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Journal of Orthopaedic Research

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Writing for Clinical Orthopaedics and Related Research

Richard a. brand.

Clinical Orthopaedics and Related Research, 1600 Spruce Street, Philadelphia, PA 19103 USA

Because of the growing need for publication space, Clinical Orthopaedics and Related Research (CORR) was established in 1953 by the Association of Bone and Joint Surgeons [ 13 ] to provide an alternative source of publication to the Journal of Bone and Joint Surgery (then the only American orthopaedic journal [ 8 ]). CORR always has striven to provide readers with high-quality peer-reviewed articles in the form of original research and survey material. High quality depends on characteristics of the work and on the reporting. While there is no lack of excellent material on medical reporting and writing [ 7 , 11 , 12 , 15 , 17 , 31 ], this article (and its predecessor on which this is based [ 6 ]) is directed to CORR contributors. Toward that end, I shall provide updated guidelines to our authors for an approach to effective reporting.

Standards of reporting, no less than standards of scientific conduct (ethics) and standards of acceptable scientific methods, change. Although ethics has always played a critical part in science and scientific reporting, recent societal and regulatory expectations impose certain new requirements, while scientific advances require others. These changes have stimulated considerable discussion [ 1 , 2 , 9 , 14 , 22 – 26 ] and CORR contributors are specifically directed to the publications of the International Committee of Medical Journal Editors [ 16 ] and The Committee on Publication Ethics for general guidelines [ 1 , 2 ]. CORR adheres to these evolving guidelines, particularly regarding ethical issues. Scientific advances in recent years include use of contemporary outcome measures, more sophisticated statistical approaches, and increasing use and reporting of well-formulated research plans (particularly in clinical research such as the CONSORT guidelines [ 18 ]). Although I shall not detail these changing standards of reporting in my review, I shall explicitly note several issues.

Scientific writing, no less than any other form of writing, reflects a demanding creative process, not merely an act: the process of writing changes thought. The quality of a report, however, depends on the quality of thought in the study design and the rigor of conduct of the research. Well-posed questions or hypotheses intimately and inexorably interrelate with study design and analysis. Well-posed hypotheses or questions imply a study design and a study design implies hypotheses or questions.

The effectiveness of a report relates to focus and brevity. Attention to a few points will allow authors to focus on critical issues. Brevity is achieved in part by avoiding repetition (with a few exceptions to be noted), clear style [ 17 ], and proper grammar [ 27 , 31 ]. Few original scientific articles need be longer than 3000 words. Longer articles (eg, 4000–5000 words) may be warranted if substantially novel methods are reported, or if the article reflects a systematic survey of literature. Although writers should avoid redundancy, effectively communicating critical information often means limited repetition of the questions (or hypotheses or key issues) and answers. The questions/hypotheses should appear in the Abstract, Introduction, and Discussion, and the answers should appear in the Abstract, Results, and Discussion. Apart from these exceptions, authors should not repeat material.

Styles of writing are as numerous as authors, although most journals publish guidelines for formatting a manuscript, and many have more or less established writing styles (eg, the American Medical Association Manual of Style ) [ 3 ]. CORR uses the AMA style as a general guideline. However, few scientific and medical authors have the time to learn these styles. Therefore, within the limits of proper grammar and clear, effective communication, and our guidelines, we allow individual styles.

I shall outline the various elements of a traditional archival report (Introduction, Materials and Methods, Results, Discussion) and suggest a logical flow for each. Each of these sections should contain unique information, and the sort of information required for one should not appear in the other; often authors mix rationale and methods, methods and results, or results and discussion. Much of this information relates to clinical studies, but the principles apply to basic reports as well. Some reports, such as surveys and systematic literature reviews or meta-analyses, require individualized structures, although I shall also describe some generalizations applicable to these studies.

Introduction (500 words)

The Introduction, although typically the shortest of sections, critically states the issues and formulates the rationale for the questions or hypotheses. Its organization might differ somewhat for a clinical report, a study of new scientific data, or a description of a new method. Most studies, however, are published to (1) report entirely novel findings (only occasionally with substantive basic or clinical studies and rarely a case report), (2) confirm previously reported work (eg, case reports, small preliminary series) when such confirmation remains questionable, or (3) introduce or address controversies in the literature when data and/or conclusions conflict. Apart from certain surveys and other special articles, one of these three purposes generally should be apparent (and often explicit) in the Introduction. The first paragraph should introduce the general topic or problem and suggest its importance, a second and perhaps a third paragraph should provide the rationale for each question or hypothesis, and a final paragraph should state the questions, hypotheses, or purposes.

One may think of formulating rationale and hypotheses as Aristotelian logic (a modal syllogism) taking the form: If A, B, and C, then D, E, or F. The premises A, B, and C reflect accepted facts (rationale) whereas D, E, or F reflect logical outcomes or predictions (questions or hypotheses). The premises best come from published data, but when data are not available, published observations (typically qualitative), logical argument, or consensus of opinion can be used. The strength of these premises is roughly in descending order from data to observations or argument to opinion. D, E, or F reflect logical consequences. For any set of observations, any number of explanations (D, E, or F) logically follow. Therefore, when formulating hypotheses (explanations), researchers designing experiments and reporting results should not be wed to a single explanation.

With the rare exception of truly novel material, when establishing rationale authors should provide representative (although not necessarily exhaustive) literature. Such rationale places a work within the body of literature. Writers should merely state their premises and provide relevant citations and avoid mention of authors’ names or description of cited works; this places emphasis on ideas rather than on investigators and studies. The exceptions to this approach include a description of past methods when essential to developing rationale for a new method or a mention of authors’ names when important to establish historical precedent. Amplification of the citations may follow in the Discussion when appropriate.

New treatment approaches require a specific sort of rationale: new interventions of any sort are intended to solve certain problems with previous approaches and those problems should be explicitly noted. For example, new implants (unless conceptually novel) typically will be designed according to certain criteria to eliminate problems with previous implants. Therefore, if the intent is to report a new treatment and/or its outcome, the premises of the study should include those explicitly stated problems (with ranges of incidence from the literature when possible) and they should be properly referenced.

The final paragraph logically flows from the earlier ones and should explicitly state the questions or hypotheses to be addressed in terms of the study variables (independent, dependent). Any issue not posed in terms of study variables cannot be meaningfully addressed. Assignment of a Level of Evidence in clinical studies requires a primary research question, which in turn requires a key outcome variable. Focus demands authors avoid answers to unposed questions and answers that are well described in the literature (eg, reporting of heterotopic ossification rates when the question is whether an implant minimizes stress shielding). Descriptive purposes (eg, “The purpose of our study was to report the results…”) are appropriate only for Level IV studies (one cohort in therapeutic studies) and only when the information is novel, an uncommon situation since typically some information has been previously reported, and the data will merely confirm or refute previously published data or will address or introduce a controversy. I reiterate any well-posed question or hypothesis will be reflected by the study design and statistical analysis; every statistical analysis necessarily implies specific questions.

Materials and Methods (1000–1500 words)

In principle, the Materials and Methods should contain adequate detail for another investigator to replicate the study. This principle applies to surveys or systematic reviews as well as to archival manuscripts since search strategies should be repeatable. In practice, such detail is often neither practical nor desirable because many methods will have been published previously (and in greater detail) and because long descriptions violate the principle of brevity. Nonetheless, the Materials and Methods section typically will be the longest section.

The Materials and Methods should flow in the approximate chronological order in which the study was conducted. For a clinical study, these elements entail (1) a study design (including key variables), (2) a power analysis (for all studies statistically comparing two or more groups), (2) key patient demographics (ie, those which could be confounding variables), (3) a description of surgery if any, (4) postoperative care, (5) a description of valid and reliable methods to measure study independent variables (eg, followup clinical, radiographic, or histologic outcomes in a clinical study and independent variables in all statistical analyses), and (6) their statistical analysis. Basic studies obviously do not contain patient demographics or surgery or postoperative care but generally require the other elements.

At the outset, the reader should grasp the basic study design. The study design should complement the questions or hypotheses just raised and must similarly state the key study variables. Level IV therapeutic studies contain a single cohort, but Level I to III studies necessarily describe two or more cohorts (independent variables); these must be outlined in the study design, as well as the key dependent variables. Level I to III studies also require a power analysis of the key outcome variable of the primary research question. This analysis should be based upon a clinically meaningful (and not merely statistically significant) effect size. That is, what difference in that variable or measure would result in a substantially different clinical outcome? A judgment as to meaningful differences should be based upon the literature when available or an educated guess when not; readers may judge whether they agree or disagree with the choice.

The first paragraph or two should also contain, in addition to the study design (and power analysis when appropriate), all relevant clinical data (Appendix 1). For a given study, not all information may be essential, but authors can use the types of data in the appendix as a checklist. Minimum followup should be sufficient to meaningfully address the questions being posed. This will necessarily differ depending upon the question. Questions relating to postoperative mortality rates may require, for example, only 30 to 90 days of followup, while those for questions relating to implant loosening may require 5 years. Authors must state the minimum followup time followed by the mean (or median when more appropriate) and range.

Clinical reports must state inclusion and exclusion criteria and whether the series is consecutive or selected; if selected, criteria for selection should be stated. The reader should understand from this description all potential sources of bias such as referral, diagnosis, exclusion, recall, or treatment bias. This includes the manner in which investigators selected the patients. Consecutive inclusion implies all patients with a given diagnosis (not typically a given treatment) are included, while selective implies patients with a given diagnosis but selected according to certain explicit criteria (eg, state of disease, choice of treatment). Often in a surgical series, patients to be reported are selected for a given treatment (eg, type of surgery or implant) rather than a given diagnosis. This occurs when some patients with the diagnosis have the treatment in question, but other patients treated during the same time frame with the same diagnosis have a different treatment or treatments; in this case, authors must specify the criteria used to select and exclude the treatment in question. Referral bias will typically be known to readers based upon the institution or institutions from which the study arises, although occasionally referral bias requires amplification in Materials and Methods.

All patient studies must include a description of potentially confounding demographic information at the time of entry into the study and at the time of surgery; this information should appear in the first paragraph or two. With a single cohort, this information will reflect referral or selection bias. With more than one cohort (ie, Level I–III studies), authors should provide a statistical analysis of these potentially confounding baseline variables between the groups; thus the reader immediately knows whether the groups are biased in any important way. Potentially biasing differences should be described not only statistically but also in clinically meaningful terms.

Missing data confound many statistical analyses. Authors, particularly those of retrospective reviews, should note what data are missing and in the statistical descriptions should note how they dealt with missing data.

Any treatment (including surgery) should be briefly described, particularly when surgeons apply unique approaches or when all patients did not undergo essentially identical procedures. Previously described approaches require only brief mention with citations to those methods.

All relevant aspects of posttreatment followup care should be described, whether nonsurgical or surgical. If that treatment might reasonably be expected to influence outcome, it should be described in some detail. Authors must note whether the treatment was uniform among all patients or varied. If varied, they should specify the indications for treating patients in varying ways and, if the study involves multiple cohorts, whether the treatment applications statistically differed between the cohorts.

If authors use statistical analysis, a paragraph should appear at the end of Materials and Methods stating all statistical tests used. Statistical tests imply specific questions or hypotheses, so the methods and their descriptions should be coherent with and in the same order as the questions or hypotheses posed in the Introduction. Authors must specify the variables analyzed with each test. All statistical tests are associated with assumptions, and when it is not obvious the data would meet those assumptions, the authors either should provide the supporting data (eg, data are normally distributed, variances in groups are similar) or use alternative tests. Although it is common to choose a level of alpha of 0.05 and a beta of 0.80, these levels are somewhat arbitrary and not always appropriate. In the case where the implications of an error are very serious (eg, missing the diagnosis of a cancer), different alpha and beta levels might be appropriate in the study design to assess clinical or biological significance. Sterne and Davey Smith [ 29 ] provide historical and theoretical reasons why attempting to suggest something is important or not based on an arbitrary threshold level was not the intent of the developers and is inappropriate. We suggest readers avoid such thresholds and rather state the exact probability value in Results to demonstrate the strength of the evidence.

Results (500 words)

If the questions or issues have been adequately focused in the Introduction, the Results section need not be long. Authors may need an initial paragraph or two to persuade the reader of the validity of the methods and should have one paragraph addressing each explicitly raised question or hypothesis; finally, an additional paragraph or two might be useful to report new and unexpected findings. That is, authors should provide a one-to-one correspondence of questions and answers. Patient information in Results should be limited to that at the time of followup to answer the questions raised in the final paragraph of the Introduction while patient information at the time of entry into the study or at the time of surgery or before assessing the independent variables should appear in Materials and Methods (these descriptions, while often in the form of data, should be considered materials).

The first (topic) sentence of each paragraph should state the point or answer the question. Well-posed questions can be unambiguously answered “yes” or “no,” and well-formulated hypotheses can be unambiguously confirmed or refuted. When the reader considers only the first sentence in each paragraph in Results, the logic of the authors’ interpretations should be clear. Parenthetic reference to all figures and tables forces the writer to textually state the interpretation of the data; the important material is the authors’ interpretation of the data, not the data.

Statistical reporting of data deserves special consideration. Stating some outcome is increased or decreased (or greater or lesser) and parenthetically stating the p (or other statistical) value immediately after the comparative terms more effectively conveys information than merely stating two values and then providing a probability value (in the same or a following sentence) without stating how or in which direction the two values differ. Avoiding the terms “statistically different” or “significantly different” but providing the exact probability value lets the reader determine whether they will consider the statistical value biologically or clinically important, regardless of statistical significance. Although a matter of philosophy and style, actual p values convey more information than stating a value less than some preset level. Furthermore, as Motulsky notes, “When you read that a result is not significant, don’t stop thinking . . . First, look at the confidence interval . . . Second, ask about the power of the study to find a significant difference if it were there” [ 20 ]. This approach will give the reader a much greater sense of biological or clinical importance. Authors should avoid making inferences from nonsignificant trends unless they believe their study underpowered to answer that question; in that case, they should provide a power analysis.

Discussion (1000 words)

The Discussion in a CORR article should contain specific elements: a restatement of the problem or question, an exploration of limitations and assumptions, a comparison and/or contrast with information (data, opinion) in the literature, and a synthesis of the comparison and the author’s new data to arrive at conclusions. The restatement of the problem or questions need be only brief for emphasis.

I prefer an exploration of assumptions and limitations immediately follow the brief introductory paragraph in Discussion rather than appear at the end because interpreting what will follow depends on these limitations. Failure to explore limitations suggests the author(s) either do not know or choose to ignore them, potentially misleading the reader. Exploration of these limitations need be only brief, but all critical issues must be raised, and the reader should be persuaded by logical argument they do not jeopardize the conclusions. Given the expense and effort for substantial prospective studies, it is not surprising most published clinical studies are retrospective. Such studies often are criticized unfairly for being retrospective, but that does not necessarily negate either validity or value of a study. Carefully designed retrospective studies have always provided and will continue to provide most of the information on which clinicians make decisions. However, authors reporting retrospective studies should describe any specific limitations relating to their study; these might include loss to followup, difficulty matching cohorts (if more than one), missing data, and the various forms of bias more common with retrospective studies.

Next, the authors should compare and/or contrast their data with data reported in the literature. Some of these reports may include those cited as rationale in the Introduction. Quantitative comparisons most effectively persuade the reader the data in the study are in the ballpark, and tables or figures efficiently convey that information. However, because of the peculiarities of each study, the data or observations might not be strictly comparable, but even in such cases it would be unusual if the literature would not contain at least trends or opinions for comparison. Discrepancies should be stated and explained when possible; when an explanation of a discrepancy is not clear, that also should be stated. Conclusions based solely on data in the paper seldom are warranted because the literature almost always contains previous information. The quality of any report will depend on the substantive nature of these comparisons.

Finally, the author(s) should synthesize their data with that in the literature. No critical data should be overlooked because contrary data might effectively refute an argument. (From a logical point of view, many consistent observations do not confirm an explanation because a single inconsistent observation can disprove an explanation.) That is, the final conclusions must be consistent not only with the new data presented but also with that in the literature.

Surveys, Systematic Reviews, Meta-analyses

The format for these three types of reports necessarily differs from those reporting original data. However, many of the principles noted above apply. These articles still require an Abstract, an Introduction, and a Discussion. The Introduction still requires focused issues and a rationale for those issues. Authors should convey to readers the unique aspects of their surveys that distinguish them from other available material (eg, monographs, book chapters). The issues should be posed in the final paragraph of the Introduction. As with an archival article reporting original material, the Introduction to a survey typically need not be longer than four paragraphs. Longer Introductions tend to lose focus, so the reader is not sure what novel information will be presented.

The sections after the Introduction and before the Discussion will be unique to the particular survey but need to be organized in a coherent fashion. Headings (and subheadings when appropriate) should follow parallel (grammatical) construction and reflect explicitly raised questions (Introduction) and generally reflect analogous topics (eg, diagnostic categories, choices of methods, choices of surgical interventions). If the reader considered only the headings, the logic of the survey (as reflected in the Introduction) should be clear.

Systematic reviews and meta-analyses are special sorts of studies meeting specific criteria of conduct [ 5 , 19 , 30 , 32 ]. In these articles the questions must be carefully defined and literature searches are conducted with inclusion criteria and stated search criteria including field tags appropriate to the questions. A Materials and Methods section will specify all databases searched, including hand searches of articles later identified as appropriate for initial consideration. The number of articles found by each search must be specified as should be the number excluded by explicit exclusion criteria. Authors must then state how they selected the final group of articles reviewed. These procedures allow an independent individual to more or less replicate the review (realizing many if not most sources today are electronic and the number of articles for a given search criterion is in continual flux). For clinical articles, authors must state whether and how they judged study quality; tables are often helpful in summarizing study quality. Meta-analyses require, in addition to those elements for a systematic review, additional requirements for analysis [ 5 , 19 ]. These include a requirement for judging and accounting for study quality. Systematic reviews and meta-analyses should contain a traditional Results section that focuses on answers to the questions addressed in the Introduction (and not the material used to arrive at the answers). That is, a systematic review should synthesize the material and not merely provide summaries of individual articles. Tables or appendices may be used to provide summaries of material when necessary to support and supplement the synthesis. If select individual articles require summaries, they should appear in Materials and Methods, not in Results.

The Discussion sections of surveys, systematic reviews, and meta-analyses synthesize the reviewed literature into a coherent whole and within the context of the novel issues stated in the Introduction. The limitations should reflect those of the literature in general, however, in addition to those of a given study. Those limitations will relate to gaps in the literature, which preclude more or less definitive assessment of diagnosis or selection of treatment, for example. Controversies in the literature should be briefly explored. Only by exploring limitations will the reader appropriately place the literature in perspective. Authors should end the Discussion by summary statements similar to those that will appear at the end of the Abstract in abbreviated form.

In general, a survey requires a more extensive literature review than an archival article, although this depends on the topic and breadth of available literature. Some topics (eg, osteoporosis) could not be comprehensively referenced, even in an entire monograph. However, authors need to ensure a survey is representative of the entire body of literature, and when that body is large, many references are required.

Acknowledgments

Many individuals contribute to a study. Those who make important contributions should be so acknowledged. In conjunction with internationally recognized standards for authorship, CORR generally limits authorship to five individuals since more than that rarely make substantive contributions to at least three major elements of a study and its report. We make occasional exceptions for multidisciplinary studies or higher level (of evidence) multiinstitutional studies. Individuals making important contributions but not fulfilling criteria for authorship should be acknowledged.

Abstract (200 words)

Generally, the Abstract should be written after the entire manuscript is completed. The reason relates to how the process of writing changes thought and perhaps even intent. Only after careful consideration of the data and a synthesis with the literature can author(s) write an effective abstract.

Many readers, professional and lay alike, now access medical and scientific information via Web-based databases rather than browsing hard copy material. Regardless of access, since the reader’s introduction occurs through titles and abstracts, substantive titles and abstracts more effectively capture a reader’s attention. Because of lay access to abstracts, these should be written in accessible language and draw conclusions that would not be misinterpreted by a lay reader. Whether a reader will examine an entire article often will depend on an abstract with compelling information. A compelling abstract contains the questions or purposes, the methods, the results (most often quantitative data), and the answers to the questions (conclusions). Each of these may be conveyed in one or two statements. Comments such as “this report describes…” convey little useful information.

Clinical studies (ie, those involving data from patients) require a Level of Evidence when they relate to treatment, diagnosis, prognosis, or economic decisions. Authors must provide below the Abstract a Level of Evidence and study description for the primary research question (our Web site contains the guidelines).

While the Abstract is important in capturing a reader’s attention, the title is likely even more important owing to Internet methods of searching and browsing. Declarative titles raising or answering questions in a few brief words will far more likely do this than titles merely pointing to the topic. A title such as “Bisphosphonates Reduce Bone Loss” effectively conveys the main message and readers will more likely remember that message and read (and cite) the paper than they might if the title were “The Effect of Bisphosphonates on Bone Loss.” As noted earlier, studies with multiple cohorts or groups statistically analyzed for differences require a power analysis of effect size based on meaningful biological or clinical differences; authors should consider a title based upon those key questions or hypotheses used for the power analysis. CORR generally limits titles to 80 characters including spaces.

CORR requires authors to acknowledge potential conflicts of interest. Our required cover letter contains four choices, one of which authors must select. This statement then becomes the basis for a standard statement that in our decision letters we request authors place on their Title Page.

When reporting studies involving human or animal subjects, authors must obtain prior approval of the institutional review board or ethics committees according to the laws and regulations of their countries. Informed consent for participation in a clinical study (a different form of consent from that required for treatment) must be stated where appropriate. In the United States, Institutional Review Board approval is required for studies using any information with patient identifiers, even if patients are not seen, although expedited review may be appropriate [ 21 ]. Similarly, animal studies require approval of institutional animal welfare committees. Such approval must be stated on the Title Page and may be stated in the first paragraph of Materials and Methods.

Finally, the Title Page must contain full contact information of the corresponding author.

References should derive primarily from peer-reviewed journals, standard textbooks or monographs, or well-accepted and stable electronic sources (eg, NIH or FDA Web sites). For citations dependent on interpretation of data, authors generally should use only high-quality peer-reviewed sources. Abstracts and submitted articles should not be used because many in both categories frequently do not pass peer review [ 4 , 10 , 28 ]. Accepted articles in press in peer-reviewed journals may be used if the anticipated date of publication is within a time frame for the final citation to be completed in CORR page proofs; if in press articles contain methods or data crucial to interpret material in a submitted manuscript, authors should include a copy in the submission for review by referees and editors.

CORR uses a modified AMA reference style. The modifications include listing of all authors, rather than only the first six authors, italicization of journal titles, and elimination of issue number.

Figures and Tables

Figures and tables should generally complement, not duplicate, material in the text. They compactly present information that would be difficult to describe in text form. (Material, which may be succinctly described in text, should rarely be placed in tables or figures.) Clinical studies, for example, often contain complementary tables of demographic data, which, although important for interpreting the results, are not critical for the questions raised in the paper. Well-focused papers contain only one or two tables or figures for every question or hypothesis explicitly posed in the Introduction. Additional material may be used for unexpected results.

Well-constructed tables are self-explanatory and require only a brief title. Every column must contain a header (with units when appropriate). Brief footnotes may be necessary to explain abbreviations or levels of statistical significance.

Figures typically need some explanation, including the meaning of symbols. Some figures will illustrate methods and may not require more than a brief explanation. Data figures should be provided only to address explicitly raised questions or hypotheses (Introduction) or unanticipated findings; data not directly addressing such questions should be avoided. In addition to whatever data descriptions are required, a figure legend should contain the major point within the framework of the questions raised. A reader should be able to read the questions in the last paragraph of the Introduction and then find the answers in the first sentence of each paragraph in Results and in the figure legends. Illustrations for a single patient should all have the same number and be labeled “A,” “B,” “C,” etc. Each figure requires a separate legend and presumably makes a separate point. Legends should be written in complete sentences.

Effective writing demands three elements: focus, logical flow, and brevity. Focus is achieved by posing clear questions or hypotheses in terms of study variables and then describing the measures required only for those variables and reporting data only related to the questions or hypotheses. In the course of investigations, authors frequently collect far more data than is required for specific questions and they find it painful to discard data acquired with often great effort and expenditure of resources. Yet, attempting to report more data than required to address the questions or hypotheses merely loses readers. Logical flow is attained by following a clear structure. The four elements of an archival paper provide overall structure, but each element must also be logically structured: the Introduction with rationale and questions posed in order of importance, the Materials and Methods with a more or less chronological order of obtaining the materials and then describing the methods of assessing each variable, the Results by answering the questions in order of importance and appearance, and finally a Discussion that synthesizes the key data for each question with that in the literature. Authors should ensure each section contains only material appropriate for that section; for example, methods should not be described in Results. Brevity is achieved by avoiding repetition of material, eliminating data and discussion not required for the questions, and ensuring each section contains only the crucial information. Through these principles, authors can achieve a wider and more interested audience.

Practical Tips

• Focus the data on addressing explicit hypotheses or questions; avoid the urge to report data not directly related to the hypotheses or questions, regardless of how painstaking it was to collect.
• Read only the first sentence in each paragraph throughout the text to ascertain whether those statements contain all critical material and the logical flow is clear.
• Avoid in the Abstract comments such as “this report describes…” Such statements convey no substantive information for the reader.
• Avoid references and statistical values in the Abstract.
• Avoid using the names of cited authors except to establish historical precedent. Instead, state the point documented in the article or articles and provide citation. For the most part, it is the data or the conclusions of the authors the reader finds crucial in scientific arguments, not the names of authors.
• Avoid in the final paragraph of the Introduction descriptive purposes such as “we report our data…” Such statements fail to focus the reader’s (and writer’s!) attention on the critical issues (and do not include mention of study variables).
• Parenthetically refer to tables and figures and avoid statements in which a table or figure is either subject or object of a sentence. Parenthetic reference places emphasis on interpretation of the information in the table or figure and not the table or figure.
• Regularly count words from the Introduction through Discussion.
• Read the guidelines for publishing in CORR (or any other journal) before submission. Those guidelines generally will need to be met in any case.

Content and Organization for Materials and Methods for Studies on Living Patients

These instructions apply when there is a need for Materials and Methods and Results sections. They do not apply to case reports, Orthopaedic-Radiology-Pathology conferences, or selected other unusual articles (eg, survey articles, articles where patient material is used to address nonclinical questions).

Description of Materials and Methods generally should be in past tense. Change passive to active voice when possible but not necessarily every sentence.

No subheadings (in most cases, a subheading merely duplicates the key point of a well-formulated lead sentence).

Paragraph 1

At the beginning of Materials and Methods, authors must clearly describe the study design in the first paragraph. (Please see our published table of Levels of Evidence for examples of descriptions of clinical study designs.) The study design should complement the questions just raised in the Introduction, and the questions should be inferred from the study design. Ensure the study design describes a method to answer the primary research question. If an IRB statement is appropriate, it can go at the end of the first paragraph, but this is not required since we require it on the title page.

Level I to III must include a description of independent (two or more groups) and dependent (outcome) variables.

Level IV must include a description of dependent (outcome) variables (there is only one group).

Level I to III (one to two paragraphs)

• Study design (sometimes one paragraph) including description of experimental and control subjects
• Power analysis including clinically important effect size
• Total potentially eligible patient base (ie, with the diagnosis or the treatment) including time over which patients enrolled
• Must state whether patients consecutive or selected
• Patient selection methods with inclusion and exclusion criteria
• If a study of a treatment (eg, surgery), list all indications for treatment, any prerequisites, and contraindications
• Randomization scheme if groups randomly assigned
• Numbers of patients excluded and for what reasons (eg, QUORUM algorithm)
• Final numbers of patients studied in each group
• Relevant demographic factors (age, gender, time to operation, etc)
• Comparability of relevant demographic factors if multiple groups
• Minimum and range of followup time
• Number of patients lost to followup
• Ethical (IRB) board approval

Level IV (one paragraph)

• Numbers of patients excluded and for what reasons
• Final numbers of patients
• If historical controls from the literature for comparison, so state

Paragraph 2

Describe surgical procedures.

Paragraph 3

Describe outcome measures. Unless measures are widely used (eg, range of motion), you should cite sources that validate the measures. If subjective measures dependent upon human observation (eg, clinical examinations, radiographs, histologic slides are used), you must state numbers of observers and parenthetically note initials of observers, whether authors or others (others should be noted in Acknowledgments).

Paragraph 4

In the final paragraph (or two), explain (and justify if appropriate) all statistical tests. Specify which tests were used to analyze which sets of data. State (and justify if appropriate) level of significance. Note software used (manufacturer, city, state or country).

The author certifies that he has no commercial associations (eg, consultancies, stock ownership, equity interest, patent/licensing arrangements, etc) that might pose a conflict of interest in connection with the submitted article. (Adapted with permission of Lippincott Williams and Wilkins from Brand RA. Writing for Clinical Orthopaedics and Related Research. Clin Orthop Relat Res . 2003;413:1–7.)

VIVO Weill Cornell Medical College

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Journal of orthopaedic research : official publication of the Orthopaedic Research Society Journal

Publication venue for.

• Staphyloccocus aureus biofilm, in absence of planktonic bacteria, produces factors that activate counterbalancing inflammatory and immune-suppressive genes in human monocytes. 2024
• A translational murine model of aseptic loosening with osseointegration failure. 2024
• Assessing paraspinal muscle atrophy with electrical impedance myography: Limitations and insights. 2024
• Capacity for large language model chatbots to aid in orthopedic management, research, and patient queries. 2024
• The 2023 Orthopaedic Research Society's International Consensus Meeting on musculoskeletal infection: Summary from the host immunity section. 2023
• A multimodal assessment of cementless tibial baseplate fixation using radiography, radiostereometric analysis, and magnetic resonance imaging. 2023
• Bone-ACL-bone allograft for anterior cruciate ligament reconstruction: Short-term evaluation in a rabbit model with microcomputed tomography. .  41. 2023
• MAVRIC based T2 mapping assessment of infrapatellar fat pad scarring in patients with total knee arthroplasty. .  41. 2022
• Adaptive immune responses in patients requiring revision after Total Knee Arthroplasty. 2022
• Dermal ultrasound measurements for bone quality assessment : An investigation of advanced glycation endproducts derived from confocal fluorescence microscopy. .  41. 2022
• Assessment of reporting practices and reproducibility potential of a cohort of published studies in computational knee biomechanics. 2022
• Evaluation of sex differences in rodent anterior cruciate ligament injury. 2022
• A novel mouse model of hindlimb joint contracture with 3D-printed casts. .  40. 2022
• The role of Meteorin-like in skeletal development and bone fracture healing. .  40. 2022
• High resolution ultrasound for the evaluation of radial nerve pathology adjacent to metallic hardware. 2022
• Assessment of osteoarthritis functional outcomes and intra-articular injection volume in the rat anterior cruciate ligament transection model. .  40. 2022
• Trabecular volumetric bone mineral density of the occipital bone at preferred screw placement sites measured by quantitative computed tomography. .  40. 2021
• Neoplastic synovial lining cells that coexpress podoplanin and CD90 overproduce CSF-1, driving tenosynovial giant cell tumor. .  40. 2021
• Targeted transcriptomic analyses of RNA isolated from formalin-fixed and paraffin-embedded human menisci. 2021
• Effect of varus alignment on the bone-implant interaction of a cementless tibial baseplate during gait. 2021
• Identifying alternative antibiotics that elute from calcium sulfate beads for treatment of orthopedic infections. 2021
• Kinematic pelvic tilt during gait alters functional cup position in total hip arthroplasty. .  40. 2021
• The cervical spine demonstrates less postoperative bone loss than the lumbar spine. 2021
• Knee cartilage T 2 relaxation times 3 months after ACL reconstruction are associated with knee gait variables linked to knee osteoarthritis. .  40. 2021
• Histologic and molecular features in pathologic human menisci from knees with and without osteoarthritis. 2021
• Chronic subacromial impingement leads to supraspinatus muscle functional and morphological changes: Evaluation in a murine model. 2020
• Utility of lavage in addition to native fluid collection during fluoroscopically guided joint aspiration in infection diagnosis. .  39. 2020
• Biomechanical evaluation of total ankle arthroplasty. Part I: Joint loads during simulated level walking. .  39. 2020
• Systemic osteoprotegerin does not improve peri-implant bone volume or osseointegration in rabbits. .  39. 2020
• Biomechanical evaluation of total ankle arthroplasty. Part II: Influence of loading and fixation design on tibial bone-implant interaction. .  39. 2020
• Rate of infection following revision anterior cruciate ligament reconstruction and associated patient- and surgeon-dependent risk factors: Retrospective results from MOON and MARS data collected from 2002 to 2011. .  39. 2020
• Alendronate enhances osseointegration in a murine implant model. .  39. 2020
• Multiparametric MRI characterization of knee articular cartilage and subchondral bone shape in collegiate basketball players. .  39. 2020
• Obesity and load-induced posttraumatic osteoarthritis in the absence of fracture or surgical trauma. .  39. 2020
• A geometric ratio to predict the flexion gap in total knee arthroplasty. .  38. 2020
• Proximal-distal shift of the center of rotation in a total wrist arthroplasty is more than twice of the healthy wrist. .  38. 2020
• Expression of alarmins in a murine rotator cuff tendinopathy model. .  38. 2020
• Multivariate use of MRI biomarkers to classify histologically confirmed necrosis in symptomatic total hip arthroplasty. .  38. 2020
• 1.5 T magnetic resonance imaging generates accurate 3D proximal femoral models: Surgical planning implications for femoroacetabular impingement. .  38. 2020
• American Society for Bone and Mineral Research-Orthopaedic Research Society Joint Task Force Report on Cell-Based Therapies - Secondary Publication. .  38. 2020
• The continuum of hip range of motion: From soft-tissue restriction to bony impingement. .  38. 2020
• Amniotic Suspension Allograft Modulates Inflammation in a Rat Pain Model of Osteoarthritis. .  38. 2019
• In vitro test methods for seating and fretting corrosion behavior of modular metal-on-metal acetabular tapers. .  38. 2019
• The biomechanics of subscapularis repair in reverse shoulder arthroplasty: The effect of lateralization and insertion site. .  38. 2019
• Combined Injury to the ACL and Lateral Meniscus Alters the Geometry of Articular Cartilage and Meniscus Soon After Initial Trauma. .  38. 2019
• The MRL/MpJ Mouse Strain Is Not Protected From Muscle Atrophy and Weakness After Rotator Cuff Tear. .  38. 2019
• Skin Ultrasound Measurement as a Potential Marker of Bone Quality: A Prospective Pilot Study of Patients undergoing Lumbar Spinal Fusion. .  37. 2019
• Predicting Carpal Bone Kinematics Using an Expanded Digital Database of Wrist Carpal Bone Anatomy and Kinematics. .  37. 2019
• Identification of Inflammatory Mediators in Tendinopathy Using a Murine Subacromial Impingement Model. .  37. 2019
• Effects of a Medial Knee Unloading Implant on Tibiofemoral Joint Mechanics During Walking. .  37. 2019
• Postoperative Tendon Loading With Treadmill Running Delays Tendon-to-Bone Healing: Immunohistochemical Evaluation in a Murine Rotator Cuff Repair Model. .  37. 2019
• Effect of interposed tissue and contamination on the initial stability of a highly porous press-fit acetabular cup. .  37. 2019
• Effect of interface mechanical discontinuities on scaffold-cartilage integration. .  37. 2019
• Mechanical performance of cementless total knee replacements: It is not all about the maximum loads. .  37. 2019
• Duration of postoperative immobilization affects MMP activity at the healing graft-bone interface: Evaluation in a mouse ACL reconstruction model. .  37. 2018
• Evaluating the role of subacromial impingement in rotator cuff tendinopathy: Development and analysis of a novel murine model. .  36. 2018
• Commentary on "increased oxidative protection by high active vitamin E content and partial radiation crosslinking of UHMWPE". 2018
• The seating mechanics of head-neck modular tapers in vitro: Load-displacement measurements, moisture, and rate effects. .  36. 2018
• Fixed-bearing medial unicompartmental knee arthroplasty restores neither the medial pivoting behavior nor the ligament forces of the intact knee in passive flexion. .  36. 2018
• The onset of fretting at the head-stem connection in hip arthroplasty is affected by head material and trunnion design under simulated corrosion conditions. .  36. 2018
• Phlpp inhibitors block pain and cartilage degradation associated with osteoarthritis. .  36. 2017
• Influence of the pericellular and extracellular matrix structural properties on chondrocyte mechanics. .  36. 2017
• Collagen XI mutation lowers susceptibility to load-induced cartilage damage in mice. .  36. 2017
• Neutral glenoid alignment in reverse shoulder arthroplasty does not guarantee decreased risk of impingement. .  36. 2017
• Correlation between RUST assessments of fracture healing to structural and biomechanical properties. .  36. 2017
• Varus knee osteoarthritis: Elevated synovial CD15 counts correlate with inferior biomechanical properties of lateral-compartment cartilage. .  36. 2017
• Tissue-engineered tendon constructs for rotator cuff repair in sheep. .  36. 2017
• Substrain-specific differences in bone parameters, alpha-2-macroglobulin circulating levels, and osteonecrosis incidence in a rat model. .  35. 2017
• Bone robusticity in two distinct skeletal dysplasias diverges from established patterns. .  35. 2017
• Reducing uncertainty when using knee-specific finite element models by assessing the effect of input parameters. .  35. 2017
• Standardized fluoroscopy-based technique to measure intraoperative cup anteversion. .  35. 2017
• Pharmacological inhibition of myostatin protects against skeletal muscle atrophy and weakness after anterior cruciate ligament tear. .  35. 2017
• Clinical platform for understanding the relationship between joint contact mechanics and articular cartilage changes after meniscal surgery. .  35. 2017
• Kinematics of meniscal- and ACL-transected mouse knees during controlled tibial compressive loading captured using roentgen stereophotogrammetry. .  35. 2016
• Composite metric R 2  - R 1ρ (1/T 2  - 1/T 1ρ ) as a potential MR imaging biomarker associated with changes in pain after ACL reconstruction: A six-month follow-up. .  35. 2016
• Perlecan is required for the chondrogenic differentiation of synovial mesenchymal cells through regulation of Sox9 gene expression. .  35. 2016
• Cadaveric gait simulation reproduces foot and ankle kinematics from population-specific inputs. .  34. 2016
• Baseline cartilage quality is associated with voxel-based T 1ρ and T 2 following ACL reconstruction: A multicenter pilot study. .  35. 2016
• Progressive cell-mediated changes in articular cartilage and bone in mice are initiated by a single session of controlled cyclic compressive loading. .  34. 2016
• Hypoxic culture conditions induce increased metabolic rate and collagen gene expression in ACL-derived cells. .  34. 2015
• Development of a bovine decellularized extracellular matrix-biomaterial for nucleus pulposus regeneration. .  34. 2015
• Indian hedgehog signaling and the role of graft tension in tendon-to-bone healing: Evaluation in a rat ACL reconstruction model. .  34. 2015
• The effect of a low radiation CT protocol on accuracy of CT guided implant migration measurement: A cadaver study. .  34. 2015
• Use of a new model allowing controlled uniaxial loading to evaluate tendon healing in a bone tunnel. .  34. 2015
• Patterns of strain and the determination of the safe arc of motion after subscapularis repair--A biomechanical study. .  34. 2015
• OARSI osteoarthritis cartilage histopathology assessment system: A biomechanical evaluation in the human knee. .  34. 2015
• Novel measure of articular instability based on contact stress confirms that the anterior cruciate ligament is a critical stabilizer of the lateral compartment. .  34. 2015
• Adverse local tissue reaction (ALTR) associated with corrosion products in metal-on-metal and dual modular neck total hip replacements is associated with upregulation of interferon gamma-mediated chemokine signaling. .  33. 2015
• The effect of wrist surgery on the kinematic consistency of joint axis reconstruction in a static posture. .  33. 2015
• Effects of steroids on thrombogenic markers in patients undergoing unilateral total knee arthroplasty: a prospective, double-blind, randomized controlled trial. .  33. 2015
• Characterization of bone perfusion by dynamic contrast-enhanced magnetic resonance imaging and positron emission tomography in the Dunkin-Hartley guinea pig model of advanced osteoarthritis. .  33. 2014
• Intermittent PTH administration and mechanical loading are anabolic for periprosthetic cancellous bone. .  33. 2014
• Population average T2 MRI maps reveal quantitative regional transformations in the degenerating rabbit intervertebral disc that vary by lumbar level. .  33. 2014
• Enhancement of Achilles tendon repair mediated by matrix metalloproteinase inhibition via systemic administration of doxycycline. .  32. 2013
• Capitellum excision: Mechanical implications and clinical consequences. .  32. 2013
• Lack of ADAM10 in endothelial cells affects osteoclasts at the chondro-osseus junction. .  32. 2013
• Comparison of the effect of intra-tendon applications of recombinant human platelet-derived growth factor-BB, platelet-rich plasma, steroids in a rat achilles tendon collagenase model. .  32. 2013
• Trabecular bone adaptation to loading in a rabbit model is not magnitude-dependent. .  31. 2013
• Dose-response effect of an intra-tendon application of recombinant human platelet-derived growth factor-BB (rhPDGF-BB) in a rat Achilles tendinopathy model. .  31. 2012
• Orthopedic wear debris mediated inflammatory osteolysis is mediated in part by NALP3 inflammasome activation. .  31. 2012
• Prognosis and predictors of ACL reconstructions using the MOON cohort: a model for comparative effectiveness studies. .  31. 2012
• Rotator cuff tear reduces muscle fiber specific force production and induces macrophage accumulation and autophagy. .  30. 2012
• Epidemiology and risk factors for perioperative mortality after total hip and knee arthroplasty. .  30. 2012
• The effect of rhPTH on the healing of tendon to bone in a rat model. .  30. 2011
• Lubricin distribution in the torn human anterior cruciate ligament and meniscus. .  29. 2011
• ACL reconstruction using bone-tendon-bone graft engineered from the semitendinosus tendon by injection of recombinant BMP-2 in a rabbit model. .  29. 2011
• Interleukin-1β stimulates stromal-derived factor-1α expression in human subacromial bursa. .  29. 2011
• Diabetes mellitus alters the mechanical properties of the native tendon in an experimental rat model. .  29. 2011
• Analysis of frictional behavior and changes in morphology resulting from cartilage articulation with porous polyurethane foams. .  28. 2010
• Activation of MKK3/6, SAPK, and ATF-2/c-jun in ACL fibroblasts grown in 3 dimension collagen gels in response to application of cyclic strain. .  29. 2010
• An injectable composite material containing bone morphogenetic protein-2 shortens the period of distraction osteogenesis in vivo. .  29. 2010
• Improving bone density at the rotator cuff footprint increases supraspinatus tendon failure stress in a rat model. .  28. 2010
• A novel locus for adolescent idiopathic scoliosis on chromosome 12p. .  27. 2009
• Understanding patellofemoral pain with maltracking in the presence of joint laxity: complete 3D in vivo patellofemoral and tibiofemoral kinematics. .  27. 2009
• The effect of paraformaldehyde fixation on the delayed gadolinium-enhanced MRI of cartilage (dGEMRIC) measurement. .  27. 2009
• Tumor interstitial fluid pressure may regulate angiogenic factors in osteosarcoma. .  26. 2008
• The effects of RANKL inhibition on fracture healing and bone strength in a mouse model of osteogenesis imperfecta. .  26. 2008
• Expression profiling reveals alternative macrophage activation and impaired osteogenesis in periprosthetic osteolysis. .  26. 2008
• Role of parathyroid hormone in the mechanosensitivity of fracture healing. .  25. 2007
• Effect of crosslinking, remelting, and aging on UHMWPE damage in a linear experimental wear model. .  25. 2007
• Relationship between cartilage stiffness and dGEMRIC index: correlation and prediction. .  25. 2007
• Effects of distal radius malunion on distal radioulnar joint mechanics--an in vivo study. .  25. 2007
• Release of gentamicin from a tricalcium phosphate bone implant. .  25. 2007
• Involvement of complement receptor 3 (CR3) and scavenger receptor in macrophage responses to wear debris. .  24. 2006
• Restoration of growth plate function following radiotherapy is driven by increased proliferative and synthetic activity of expansions of chondrocytic clones. .  24. 2006
• In vivo cyclic axial compression affects bone healing in the mouse tibia. .  24. 2006
• Stromal cell-derived factor 1 (SDF-1, CXCL12) is increased in subacromial bursitis and downregulated by steroid and nonsteroidal anti-inflammatory agents. .  24. 2006
• Retrieval, experimental, and computational assessment of the performance of total knee replacements. .  24. 2006
• Canine ACL fibroblast integrin expression and cell alignment in response to cyclic tensile strain in three-dimensional collagen gels. .  24. 2006
• Effect of cyclic strain and plating matrix on cell proliferation and integrin expression by ligament fibroblasts. .  24. 2006
• Molecular signaling in intervertebral disk development. .  23. 2005
• Macrophages accumulate in the early phase of tendon-bone healing. .  23. 2005
• The effect of ankle ligament damage and surgical reconstructions on the mechanics of the ankle and subtalar joints revealed by three-dimensional stress MRI. .  23. 2005
• Magnetic resonance imaging in the evaluation of periprosthetic acetabular osteolysis: a cadaveric study. .  23. 2005
• Recruitment of osteoclast precursors by stromal cell derived factor-1 (SDF-1) in giant cell tumor of bone. .  23. 2005
• Thrombin peptide (TP508) promotes fracture repair by up-regulating inflammatory mediators, early growth factors, and increasing angiogenesis. .  23. 2004
• A silencer element in the cartilage oligomeric matrix protein gene regulates chondrocyte-specific expression. .  22. 2004
• Osteoblast-like cell adhesion to bone sialoprotein peptides. .  22. 2004
• Acceleration of cartilage repair by genetically modified chondrocytes over expressing bone morphogenetic protein-7. .  21. 2003
• In vivo load sharing among the quadriceps components. .  21. 2003
• J-integral fracture toughness and tearing modulus measurement of radiation cross-linked UHMWPE. .  20. 2002
• Biosynthetic response and mechanical properties of articular cartilage after injurious compression. .  19. 2001
• Enhanced matrix synthesis and in vitro formation of cartilage-like tissue by genetically modified chondrocytes expressing BMP-7. .  19. 2001
• Tissue reactions to particles of bone-substitute materials in intraosseous and heterotopic sites in rats: discrimination of osteoinduction, osteocompatibility, and inflammation. .  19. 2001
• Detection of c-fos expression in benign and malignant musculoskeletal lesions. .  19. 2001
• Insulin-like growth factor-I is expressed by avian flexor tendon cells. .  18. 2000
• Chondrocyte-specific enhancer regions in the COMP gene. .  18. 2000
• Inhibition of caspase-3-like activity prevents apoptosis while retaining functionality of human chondrocytes in vitro. .  18. 2000
• Differential expression of integrin subunits in canine knee ligament fibroblasts. .  17. 1999
• Writing for the Journal of Orthopaedic Research. .  17. 1999
• Characterization of chemotactic migration and growth kinetics of canine knee ligament fibroblasts. .  17. 1999
• Intravertebral body reconstruction with an injectable in situ-setting carbonated apatite: biomechanical evaluation of a minimally invasive technique. .  17. 1999
• Noninvasive technique for measuring in vivo three-dimensional carpal bone kinematics. .  17. 1999
• Publication rate of abstracts presented at the annual meeting of the Orthopaedic Research Society. .  16. 1998
• Chemotherapy and P-glycoprotein expression in chondrosarcoma. .  16. 1998
• Identification of the oim mutation by dye terminator chemistry combined with automated direct DNA sequencing. .  16. 1998
• Residual stresses in ultra-high molecular weight polyethylene loaded cyclically by a rigid moving indenter in nonconforming geometries. .  16. 1998
• Immunolocalization of cytokines and their receptors in adhesive capsulitis of the shoulder. .  15. 1997
• Optimal normalization tests for shoulder muscle activation: an electromyographic study. .  14. 1996
• Primary immunolocalization of estrogen and progesterone target cells in the human anterior cruciate ligament. .  14. 1996
• Expression of interleukin-6 in osteoarthritic chondrocytes and effects of fluid-induced shear on this expression in normal human chondrocytes in vitro. .  14. 1996
• Qualitative and quantitative analysis of orthotopic bone regeneration by marrow. .  14. 1996
• Effect of stress deprivation and cyclic tensile loading on the material and morphologic properties of canine flexor digitorum profundus tendon: an in vitro study. .  13. 1995
• Effects of fluid-induced shear on articular chondrocyte morphology and metabolism in vitro. .  13. 1995
• Osteosarcoma oncogene expression detected by in situ hybridization. .  13. 1995
• Contact areas in the thumb carpometacarpal joint. .  13. 1995
• Immunolocalization and expression of bone morphogenetic proteins 2 and 4 in fracture healing. .  13. 1995
• Clinical reproducibility of dual energy x-ray absorptiometry. .  13. 1995
• Cyclic compressive loading results in fatigue cracks in ultra high molecular weight polyethylene. .  13. 1995
• Mechanical and biochemical changes in the superficial zone of articular cartilage in canine experimental osteoarthritis. .  12. 1994
• Effect of cyclic and static tensile loading on water content and solute diffusion in canine flexor tendons: an in vitro study. .  12. 1994
• Treatment of experimental osteomyelitis with antibiotic-impregnated bone graft substitute. .  11. 1993
• Evaluation of bone-grafting materials in a new canine segmental spinal fusion model. .  11. 1993
• Effects of prefracture irradiation on the biomechanical parameters of fracture healing. .  11. 1993
• In vivo effects of naproxen on composition, proteoglycan metabolism, and matrix metalloproteinase activities in canine articular cartilage. .  11. 1993
• The inositol phosphate pathway as a mediator in the proliferative response of rat calvarial bone cells to cyclical biaxial mechanical strain. .  10. 1992
• Effects of propranolol on bone metabolism in the rat. .  9. 1991
• Mechanical characteristics of the stem-cement interface. .  9. 1991
• Measurement reproducibility of two commercial knee test devices. .  9. 1991
• Interspecies comparisons of in situ intrinsic mechanical properties of distal femoral cartilage. .  9. 1991
• Purified staphylococcal culture medium stimulates neutral metalloprotease secretion from human articular cartilage. .  9. 1991
• An investigation of a compliant interface for press-fit joint replacement. .  8. 1990
• Omental angiogenic lipid fraction and bone repair. An experimental study in the rat. .  7. 1989
• The repair of experimentally produced defects in rabbit articular cartilage by autologous chondrocyte transplantation. .  7. 1989
• Biomechanics of the craniocervical region: the alar and transverse ligaments. .  6. 1988
• The effect of cryopreservation on canine menisci: a biochemical, morphologic, and biomechanical evaluation. .  6. 1988
• Biochemical characterization of fracture callus proteoglycans. .  5. 1987
• Valgus stability of the elbow. .  5. 1987
• Immunofluorescent localization of structural collagen types in endochondral fracture repair. .  4. 1986
• Fatigue crack propagation behavior of ultrahigh molecular weight polyethylene. .  2. 1984
• RE: Talks BJ, Fernquest S, Palmer A, et al. 2019. No Evidence of Systemic Inflammation in Symptomatic Patients With Femoroacetabular Impingement. .  37. 2019
• Commentary on "Third-generation autologous chondrocyte implantation versus mosaicplasty for knee cartilage injury: 2-year randomized trial". .  34. 2016
• Research involving ultra high molecular weight polyethylene. .  13. 1995
• Diagnosis of periprosthetic joint infection. 2014
• Irrigation and debridement. 2014
• Prevention of late PJI. 2014
• Plagiarism: an assault on the integrity of scientific research. .  30. 2012
• A new feature of the journal of orthopaedic research: research perspectives. .  29. 2011
• Orthopaedic surgeons, scientists, and industry. .  26. 2008
• Patient care, professionalism, and relations with industry. .  26. 2008
• Celebrating 25 years of Advancing Orthopaedic Research. .  26. 2008
• Guidelines for describing mouse skeletal phenotype. .  21. 2003
• Scientific progress and dissemination of research results: abstracts versus peer-reviewed publications. .  16. 1998
• Scientific credibility requires complete presentation of methods. .  15. 1997
• Meniscal repair: The current state and recent advances in augmentation. 2021
• The role of the macrophage in tendinopathy and tendon healing. 2020
• Biological and Mechanical Predictors of Meniscus Function: Basic Science to Clinical Translation. 2019
• Integrating soft and hard tissues via interface tissue engineering. 2018
• Review of current understanding of post-traumatic osteoarthritis resulting from sports injuries. 2016
• Morphologic and quantitative magnetic resonance imaging of knee articular cartilage for the assessment of post-traumatic osteoarthritis. 2016
• Reproducibility in modeling and simulation of the knee: Academic, industry, and regulatory perspectives. 2023
• Clinical magnetic resonance imaging of arthroplasty at 1.5 T. 2020
• The biologic effects of implant materials. 1991

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• J Orthop Res

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Expanding Approaches to Improve Orthopaedic Care Through the Application of Artificial Intelligence

Commentary on an article by neil p. sheth, md, et al.: “effects of abaloparatide on bone mineral density in proximal femoral regions corresponding to arthroplasty gruen zones. a study of postmenopausal women with osteoporosis”.

Moran, Meghan M. PhD 1,a

1 Department of Anatomy & Cell Biology, Rush University Medical Center, Chicago, Illinois

a Email: [email protected]

Disclosure: The Disclosure of Potential Conflicts of Interest form is provided with the online version of the article ( https://links.lww.com/JBJS/I12 ).

Corresponding Article

Sheth et al. reported that pretreatment with abaloparatide can increase bone mineral density in regions of the proximal femur that are in contact with the femoral stem of an implant in postmenopausal women with osteoporosis. An interesting finding reported is that the Gruen zones most affected by stress-shielding-induced bone loss following total hip arthroplasty were positively affected by the pretreatment, along with other proximal regions of the femur. What was not explored in this study is whether this increase in bone mineral density in the proximal femur was sufficient to affect the biomechanical properties of the bone, specifically the magnitude of stress-shielding-induced bone loss. The application of bone-adaptive modeling would be an interesting next step to address this, and it could involve the application of artificial intelligence (AI).

AI has been used in medicine in various ways since the 1950s, from machine learning and chatbots that aimed to mimic human conversation to the 2020s when AI was trained to diagnose benign polyps and malignant polyps found in colonoscopies 1 . Overall, the application of AI has been slow in medicine compared with other fields, but it has been particularly slower in orthopaedics. A brief PubMed search using the key terms of “artificial intelligence in orthopaedics” yielded only 3,890 articles from 1976 to 2024. This result is much smaller than in other fields such as radiology (23,858 articles) or cancer (39,315 articles) during the same period. With the potential of AI continuously evolving, application in the field remains a moving target and can lead to confusion for researchers and clinicians.

However, in a recent review 2 , 3 essential “domains” for the use of AI in personalizing orthopaedic care and improving outcomes were highlighted: (1) personalized prediction of clinical outcomes and adverse events, (2) automated diagnostic imaging analyses, and (3) forecasting resource utilization. The first 2 domains directly apply to the article by Sheth et al. and would contribute to understanding bone-adaptive modeling and the biomechanical properties associated with total hip arthroplasty. The third domain, forecasting resource utilization, is downstream of their article, but is still pertinent to the discussion of using AI in orthopaedics.

The prediction of clinical outcomes and adverse events is difficult and continues to be a challenge. Machine learning has been used to predict bone mineral density from genomic data 3 or unplanned readmissions following total knee arthroplasty 4 . Another article used intraoperative load sensors and AI to improve accuracy and precision of force measurements during the balancing of total knee arthroplasty 5 . These few examples show a diverse application of predictive AI that, with improvements to the algorithms, sensors, and programs, can provide a sophisticated application to many areas of orthopaedic care.

Perhaps more commonly regarded is the use of AI in analysis of diagnostic imaging, which is currently used to review 2-dimensional images in preoperative planning for revision surgery 6 and follow-up after total joint arthroplasty 7 . AI-generated results can be powerful, but they currently always need to be validated by a human expert.

The ability to forecast resource utilization does not directly apply to the article by Sheth et al. but is downstream of it. One of the first steps in planning for postoperative care is performed during the preoperative phase of care. As in the article by Sheth et al., pretreating to improve bone mineral density before any implant meets the bone translates to better postoperative planning as well as lower costs for patients and hospitals. For example, machine learning and AI have already been used to improve resource utilization in rotator cuff repair surgery 8 and arthroplasties 2 . This use of AI may push orthopaedic care to be more personalized to the patient and more efficient for both patients and doctors.

Applying AI in orthopaedic research requires specific expertise and experience. It is not realistic to think that Sheth et al. can simply “apply AI” as described in the 3 domains highlighted here without a specialized team, training, and collaborations. However, by discussing specific opportunities for the application of AI in orthopaedic research, we can begin to consider the implications in a more meaningful way to advance orthopaedic care and improve patient outcomes.

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Effects of Abaloparatide on Bone Mineral Density in Proximal Femoral Regions Corresponding to Arthroplasty Gruen Zones: A Study of Postmenopausal Women with Osteoporosis

Sheth, Neil P.; Smith, James Russell; Winzenrieth, Renaud; Humbert, Ludovic; Wang, Yamei; Boxberger, John I.; Bostrom, Mathias P.

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Correction to: Involvement of RAMP1/p38MAPK signaling pathway in osteoblast differentiation in response to mechanical stimulation: a preliminary study

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Sodhi M , Rezaeianzadeh R , Kezouh A , Etminan M. Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss. JAMA. 2023;330(18):1795–1797. doi:10.1001/jama.2023.19574

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Risk of Gastrointestinal Adverse Events Associated With Glucagon-Like Peptide-1 Receptor Agonists for Weight Loss

• 1 Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada
• 2 StatExpert Ltd, Laval, Quebec, Canada
• 3 Department of Ophthalmology and Visual Sciences and Medicine, University of British Columbia, Vancouver, Canada
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• Medical News & Perspectives What to Know About Wegovy’s Rare but Serious Adverse Effects Kate Ruder, MSJ JAMA
• Comment & Response GLP-1 Receptor Agonists and Gastrointestinal Adverse Events—Reply Ramin Rezaeianzadeh, BSc; Mohit Sodhi, MSc; Mahyar Etminan, PharmD, MSc JAMA
• Comment & Response GLP-1 Receptor Agonists and Gastrointestinal Adverse Events Karine Suissa, PhD; Sara J. Cromer, MD; Elisabetta Patorno, MD, DrPH JAMA
• Research Letter GLP-1 Receptor Agonist Use and Risk of Postoperative Complications Anjali A. Dixit, MD, MPH; Brian T. Bateman, MD, MS; Mary T. Hawn, MD, MPH; Michelle C. Odden, PhD; Eric C. Sun, MD, PhD JAMA
• Original Investigation Glucagon-Like Peptide-1 Receptor Agonist Use and Risk of Gallbladder and Biliary Diseases Liyun He, MM; Jialu Wang, MM; Fan Ping, MD; Na Yang, MM; Jingyue Huang, MM; Yuxiu Li, MD; Lingling Xu, MD; Wei Li, MD; Huabing Zhang, MD JAMA Internal Medicine
• Research Letter Cholecystitis Associated With the Use of Glucagon-Like Peptide-1 Receptor Agonists Daniel Woronow, MD; Christine Chamberlain, PharmD; Ali Niak, MD; Mark Avigan, MDCM; Monika Houstoun, PharmD, MPH; Cindy Kortepeter, PharmD JAMA Internal Medicine

Glucagon-like peptide 1 (GLP-1) agonists are medications approved for treatment of diabetes that recently have also been used off label for weight loss. 1 Studies have found increased risks of gastrointestinal adverse events (biliary disease, 2 pancreatitis, 3 bowel obstruction, 4 and gastroparesis 5 ) in patients with diabetes. 2 - 5 Because such patients have higher baseline risk for gastrointestinal adverse events, risk in patients taking these drugs for other indications may differ. Randomized trials examining efficacy of GLP-1 agonists for weight loss were not designed to capture these events 2 due to small sample sizes and short follow-up. We examined gastrointestinal adverse events associated with GLP-1 agonists used for weight loss in a clinical setting.

We used a random sample of 16 million patients (2006-2020) from the PharMetrics Plus for Academics database (IQVIA), a large health claims database that captures 93% of all outpatient prescriptions and physician diagnoses in the US through the International Classification of Diseases, Ninth Revision (ICD-9) or ICD-10. In our cohort study, we included new users of semaglutide or liraglutide, 2 main GLP-1 agonists, and the active comparator bupropion-naltrexone, a weight loss agent unrelated to GLP-1 agonists. Because semaglutide was marketed for weight loss after the study period (2021), we ensured all GLP-1 agonist and bupropion-naltrexone users had an obesity code in the 90 days prior or up to 30 days after cohort entry, excluding those with a diabetes or antidiabetic drug code.

Patients were observed from first prescription of a study drug to first mutually exclusive incidence (defined as first ICD-9 or ICD-10 code) of biliary disease (including cholecystitis, cholelithiasis, and choledocholithiasis), pancreatitis (including gallstone pancreatitis), bowel obstruction, or gastroparesis (defined as use of a code or a promotility agent). They were followed up to the end of the study period (June 2020) or censored during a switch. Hazard ratios (HRs) from a Cox model were adjusted for age, sex, alcohol use, smoking, hyperlipidemia, abdominal surgery in the previous 30 days, and geographic location, which were identified as common cause variables or risk factors. 6 Two sensitivity analyses were undertaken, one excluding hyperlipidemia (because more semaglutide users had hyperlipidemia) and another including patients without diabetes regardless of having an obesity code. Due to absence of data on body mass index (BMI), the E-value was used to examine how strong unmeasured confounding would need to be to negate observed results, with E-value HRs of at least 2 indicating BMI is unlikely to change study results. Statistical significance was defined as 2-sided 95% CI that did not cross 1. Analyses were performed using SAS version 9.4. Ethics approval was obtained by the University of British Columbia’s clinical research ethics board with a waiver of informed consent.

Our cohort included 4144 liraglutide, 613 semaglutide, and 654 bupropion-naltrexone users. Incidence rates for the 4 outcomes were elevated among GLP-1 agonists compared with bupropion-naltrexone users ( Table 1 ). For example, incidence of biliary disease (per 1000 person-years) was 11.7 for semaglutide, 18.6 for liraglutide, and 12.6 for bupropion-naltrexone and 4.6, 7.9, and 1.0, respectively, for pancreatitis.

Use of GLP-1 agonists compared with bupropion-naltrexone was associated with increased risk of pancreatitis (adjusted HR, 9.09 [95% CI, 1.25-66.00]), bowel obstruction (HR, 4.22 [95% CI, 1.02-17.40]), and gastroparesis (HR, 3.67 [95% CI, 1.15-11.90) but not biliary disease (HR, 1.50 [95% CI, 0.89-2.53]). Exclusion of hyperlipidemia from the analysis did not change the results ( Table 2 ). Inclusion of GLP-1 agonists regardless of history of obesity reduced HRs and narrowed CIs but did not change the significance of the results ( Table 2 ). E-value HRs did not suggest potential confounding by BMI.

This study found that use of GLP-1 agonists for weight loss compared with use of bupropion-naltrexone was associated with increased risk of pancreatitis, gastroparesis, and bowel obstruction but not biliary disease.

Given the wide use of these drugs, these adverse events, although rare, must be considered by patients who are contemplating using the drugs for weight loss because the risk-benefit calculus for this group might differ from that of those who use them for diabetes. Limitations include that although all GLP-1 agonist users had a record for obesity without diabetes, whether GLP-1 agonists were all used for weight loss is uncertain.

Accepted for Publication: September 11, 2023.

Published Online: October 5, 2023. doi:10.1001/jama.2023.19574

Correction: This article was corrected on December 21, 2023, to update the full name of the database used.

Corresponding Author: Mahyar Etminan, PharmD, MSc, Faculty of Medicine, Departments of Ophthalmology and Visual Sciences and Medicine, The Eye Care Center, University of British Columbia, 2550 Willow St, Room 323, Vancouver, BC V5Z 3N9, Canada ( [email protected] ).

Author Contributions: Dr Etminan had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Concept and design: Sodhi, Rezaeianzadeh, Etminan.

Acquisition, analysis, or interpretation of data: All authors.

Drafting of the manuscript: Sodhi, Rezaeianzadeh, Etminan.

Critical review of the manuscript for important intellectual content: All authors.

Statistical analysis: Kezouh.

Obtained funding: Etminan.

Administrative, technical, or material support: Sodhi.

Supervision: Etminan.

Conflict of Interest Disclosures: None reported.

Funding/Support: This study was funded by internal research funds from the Department of Ophthalmology and Visual Sciences, University of British Columbia.

Role of the Funder/Sponsor: The funder had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

Data Sharing Statement: See Supplement .

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Ai makes writing easier but stories sound alike, says study published in scientific journal .

WASHINGTON, July 14 — Books and movies of the future could all start to feel the same if creative industries embrace artificial intelligence to help write stories, a study published on Friday warned.

The research, which drew on hundreds of volunteers and was published in Science Advances , comes amid rising fears over the impact of widely available AI tools that turn simple text prompts into relatively sophisticated music, art and writing.

“Our goal was to study to what extent and how generative AI might help humans with creativity,” co-author Anil Doshi of the University College London told AFP.

For their experiment, Doshi and co-author Oliver Hauser of the University of Exeter recruited around 300 volunteers as “writers.”

These were people who didn’t write for a living, and their inherent creative ability was assessed by a standard psychology test that asked them to provide 10 drastically different words.

The scientists then split them randomly into three groups to write an eight-sentence story about one of three topics: an adventure on the open seas, an adventure in the jungle, or an adventure on another planet.

Participants were also randomly placed into three groups that received varying levels of AI assistance.

The first group got no help, the second was provided a three-sentence story idea from ChatGPT, and the third could receive up to five AI-generated story ideas to help them get going.

Individual benefit, collective loss

After completing their stories, participants were asked to assess their own work’s creativity through measures including how novel it was, how enjoyable, and how much potential the idea had to be turned into a published book.

An additional 600 external human reviewers also judged the story on the same measures.

The authors found that, on average, AI boosted the quality of an individual writer’s creativity by up to 10 per cent, and the story’s enjoyability by 22 per cent, helping particularly with elements like structure and plot twists.

These effects were most significant for writers who were judged during the initial task to be the least creative, “so it has this kind of levelling the playing field effect,” said Doshi.

But on the collective level, they found AI-assisted stories looked much more similar to each other than those produced without any AI help, as writers “anchored” themselves too heavily to the suggested ideas.

Hauser said this created a “social dilemma.” On the one hand, “you make it easier for people to get in; lowering barriers is good.” But if the collective novelty of art decreases, “it could be harmful down the line.”

Doshi said the research also showed that, just like introducing pocket calculators to children too early could prevent them from learning how to do basic arithmetic, there was a danger that people could rely too much on AI tools before developing underlying skills in writing, music or more.

People need to start thinking about “where in my workflow can I insert this tool to get the most benefit, while still inserting my own voice into the project or outcome.” — AFP

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Researchers explore treatment for biofilm infections

• Written by John Keenan, UNMC strategic communications
• Published Jul 12, 2024

Kevin Garvin, MD, and Tammy Kielian, PhD

A paper published earlier this year in the Journal of Clinical Investigation by a UNMC team of researchers and collaborators suggests a path for dealing with bacterial biofilm that can form on artificial joint implants and resist the attempts of the body’s immune system to clear it.

Tammy Kielian, PhD, professor in the UNMC Department of Pathology, Microbiology and Immunology, and Kevin Garvin, MD, chair of the UNMC Department of Orthopaedic Surgery, led a team that saw success in treating a biofilm-infected surface, reducing bacterial burden dramatically without having to remove the artificial joint.

See a video on the study .

The process, developed in animal models, is a longstanding project, and the new paper is just the latest collaborative effort to explore how to deal with these biofilms, which are frustratingly able to avoid attack by the body’s immune system, Dr. Kielian said.

As a result, biofilm infections in humans currently almost always require the removal of the infected implant, which can lead to other complications.

Patients suffering from a biofilm-associated prosthetic joint infection are faced with a tremendous challenge, Dr. Garvin said.

“Typically, patients require surgery to remove the prosthesis and excise infected and necrotic tissue, followed by a six-week course of parenteral antibiotics. If the recovery is favorable, a prosthetic joint can be reimplanted.

“While the outcome of reimplantation is 80 to 90% successful, the morbidity and mortality associated with two operations and IV antibiotics are alarmingly high,” he said. “The potential of this research under the direction and leadership of Dr. Kielian will lessen the need for surgical treatment and has the potential to be one of the greatest contributions in decades for patients who suffer from a prosthetic joint infection.” 

The team worked to better understand why the immune system was not working well in these cases and to reprogram that response to be better able to recognize these biofilms, which are challenging to treat.

“The bacteria in these biofilms have many ways to trick the immune system,” Dr. Kielian said. “The biofilm is giving signals that make the immune system dysfunctional. It’s basically cloaking itself, if you will, giving the wrong signal – kind of, ‘Hey, don’t worry about killing us.’”

In the new study, the team developed a nanoparticle-delivered drug to an immune cell that normally is immune suppressive, making them better able to recognize the biofilm as being foreign and to attack it, Dr. Kielian said. “We now have good information on changes that happen in both our mouse model and human samples, and we’re using that information to try to develop new therapeutic approaches down the road.”

In the recently published paper in The Journal of Clinical Investigation, the team and lead authors Prabhakar Arumugam, PhD, and Christopher Horn, PhD, targeted one cell type that is known to be important for preventing bacterial clearance, but more work is planned.

“We’re working toward a combinational approach, because the immune responses in these infections, both in animal models as well as human patients, are very complex. But I do feel that we are making some good advances.”

Dr. Kielian said she was excited that the signals the team saw in human cells donated by patients with these infections were similar to the reactions in animal models.

“That means our mouse model is really a good system for us to continue to test new therapies,” she said. “We feel confident that this is an excellent system.”

Dr. Garvin also expressed optimism.

“In time, we hope to see clinical evaluation of this translational research and compare it to our standard treatments,” he said.

Dr. Kielian called the collaboration at UNMC a game changer, particularly with Curtis Hartman, MD, of the department of orthopaedic surgery, providing access to several samples from his patients with prosthetic joint infection.

“Dr. Hartman and I have been honored to participate in this exciting research,” Dr. Garvin said. “It is an ideal situation in which Dr. Kielian and her team have developed a scientifically favorable model that has included our patients’ tissue. We now have five surgeons who manage patients with prosthetic joint infection and are excited for the future. The patients, too, are hopeful and will be enthusiastic contributors as they hope future patients will benefit from this research.”

“Being able to collaborate with these clinicians just really elevates this work overall,” Dr. Kielian said. “Not all investigators have access to patient samples. We don’t know their identity, of course, but we appreciate the patients who agreed to have their tissues used for our research, which would otherwise be discarded. These scientific advances wouldn’t be possible without these generous people.

“And hopefully, because of them, we will have an impact on clinical practice in the future.”

Congratulations to Dr. Kielian and team on this exciting study.

Congratulations to Drs. Kielian and Garvin and their team on this impactful work!

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The research team

The research team included:

• Tammy Kielian, PhD, professor in the UNMC Department of Pathology, Microbiology and Immunology
• Kevin Garvin, MD, chair of the UNMC Department of Orthopaedic Surgery
• Prabhakar Arumugam, PhD, lead author, UNMC Department of Pathology, Microbiology and Immunology
• Christopher Horn, PhD, lead author Center for Diseases Control and Prevention
• Curtis Hartman, MD, Adult Reconstruction Fellowship director; professor, UNMC Department of Orthopaedic Surgery and Rehabilitation

• Original research
• Open access
• Published: 03 July 2024

Understanding the epidemiology and perceived efficacy of cannabis use in patients with chronic musculoskeletal pain

• Timothy Leroux 1 ,
• Prabjit Ajrawat   ORCID: orcid.org/0000-0001-8819-1347 1 ,
• Kala Sundararajan 1 ,
• Naomi Maldonado-Rodriguez 1 ,
• Bheeshma Ravi 3 ,
• Rajiv Gandhi 1 ,
• Raja Rampersaud 1 ,
• Christian Veillette 1 ,
• Nizar Mahomed 1 &
• Hance Clarke 2  

Journal of Cannabis Research volume  6 , Article number:  28 ( 2024 ) Cite this article

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The belief that cannabis has analgesic and anti-inflammatory properties continues to attract patients with chronic musculoskeletal (MSK) pain towards its use. However, the role that cannabis will play in the management of chronic MSK pain remains to be determined. This study examined 1) the rate, patterns of use, and self-reported efficacy of cannabis use among patients with chronic MSK pain and 2) the interest and potential barriers to cannabis use among patients with chronic MSK pain not currently using cannabis.

Self-reported cannabis use and perceived efficacy were prospectively collected from chronic MSK pain patients presenting to the Orthopaedic Clinic at the University Health Network, Toronto, Canada. The primary dependent variable was current or past use of cannabis to manage chronic MSK pain; bivariate and multivariable logistic regression were used to identify patient characteristics independently associated with this outcome. Secondary outcomes were summarized descriptively, including self-perceived efficacy among cannabis users, and interest as well as barriers to cannabis use among cannabis non-users.

The sample included 629 patients presenting with chronic MSK pain (mean age: 56±15.7 years; 56% female). Overall, 144 (23%) reported past or present cannabis use to manage their MSK pain, with 63.7% perceiving cannabis as very or somewhat effective and 26.6% considering it as slightly effective. The strongest predictor of cannabis use in this study population was a history of recreational cannabis use (OR 12.7, p <0.001). Among cannabis non-users ( N =489), 65% expressed interest in using cannabis to manage their chronic MSK pain, but common barriers to use included lack of knowledge regarding access, use and evidence, and stigma.

Conclusions

One in five patients presenting to an orthopaedic surgeon with chronic MSK pain are using or have used cannabis with the specific intent to manage their pain, and most report it to be effective. Among non-users, two-thirds reported an interest in using cannabis to manage their MSK pain, but common barriers to use existed. Future double-blind placebo-controlled trials are required to understand if this reported efficacy is accurate, and what role, if any, cannabis may play in the management of chronic MSK pain.

Introduction

Musculoskeletal (MSK) disorders are the most common cause of functional disability and chronic pain worldwide (Pinto et al. 2017 ; Sundstrup et al. 2016 ). Osteoarthritis (OA) is a common cause of MSK related pain and disability with persistent pain typically being the catalyst for seeking medical intervention (Pinto et al. 2017 ; Yelin et al. 2016 ). As the global population ages, the burden of chronic MSK pain is expected to rise, substantially increasing societal costs and healthcare resource utilization (Pinto et al. 2017 ; Yelin et al. 2016 ). Current pharmacological (NSAIDs, COX-2 inhibitors, acetaminophen, serotonin-norepinephrine reuptake inhibitors, anticonvulsants, opioids, gabapentinoids) and non-pharmacological (physiotherapy, acupuncture, mindfulness/psychotherapy, transcutaneous electrical nerve stimulation therapy, etc.) approaches to manage chronic MSK pain have at best delivered modest efficacy and can often cause harmful adverse events. Given the unreliability of these therapies, it is not surprising that many chronic MSK patients often seek non-opioid and non-surgical alternatives for pain management (Boehnke et al. 2019 ).

Recreational cannabis use is now legal in several countries and there is a trend towards further legalization globally. More recently, the use of cannabis as an analgesic, immunomodulatory, and anti-inflammatory agent for patients with chronic MSK pain has become relevant (Ajrawat et al. 2022 ; Meng et al. 2021 ). Studies have shown the endocannabinoid system to be expressed in various cell types within human joints, including synovial cells, chondrocytes, and bone cells (Dunn et al. 2016 ; Porta et al. 2014 ). Clinical cannabinoid research to date has largely focused on neuropathic pain or chronic non-cancer pain (CNCP), with previous studies indicating that 10-15% of chronic pain patients use cannabis to manage their pain (Piper et al. 2017 ; Haroutounian et al. 2016 ; Hazekamp et al. 2013 ; Troutt and DiDonato 2015 ). Prior systematic reviews have demonstrated cannabis’ effectiveness in managing chronic pain and potentially reducing opioid consumption (Troutt and DiDonato 2015 ; Whiting et al. 2015 ). A study observing 757 patients who used a combination of dried or oil-based cannabis formulations revealed that, after 12 months of follow-up, the percentage of individuals reporting opioid use decreased by approximately half, dropping from 40.8% to 23.9% (Meng et al. 2021 ). Another study investigated chronic osteoarthritis (OA) patients, most of whom were using either cannabidiol (CBD) or tetrahydrocannabinol (THC) products in a sublingual tincture form. The findings revealed lower pain scores, improved quality of life, and a decrease in morphine milligram equivalents (MME) among these patients with 37.5% of participants achieving 0 MME/day at the 6-month follow-up (Renslo et al. 2022 ). A third cross-sectional study investigated the use CBD on arthritic symptoms among OA, rheumatoid, and other autoimmune arthritis patients. The authors reported that while all groups lowered their medications use and improved their arthritic symptoms, the OA group had the greatest improvements in physical function and pain with CBD use (Frane et al. 2022 ). Although past studies have been promising, these effects are still poorly investigated in patients experiencing chronic MSK pain, limiting the generalizability to this large patient population.

Therefore, the purpose of the present study was 1) to determine the patient reported prevalence rate, patterns of use, and perceived efficacy of cannabis use among patients with chronic MSK pain (i.e., pain on most days for at least three months duration) referred for orthopaedic consultation and 2) to identify the interest and potential barriers to cannabis use among patients with chronic MSK pain not currently using cannabis.

Study design and setting

In this cross-sectional study, we administered an anonymous electronic survey regarding cannabis use to consecutive patients presenting with chronic MSK pain to the Orthopaedic clinic at the University Health Network (UHN), Toronto, Canada. All potentially eligible patients visiting the clinic between November 1, 2018 and April 30, 2019 were informed of the study by a designated member of the patient’s circle of care. If the patient expressed interest, a research assistant obtained electronic written consent via a tablet and confirmed the patient’s eligibility, then invited the patient to complete the tablet-based survey (Supplementary Tables 1 - 3 ). The study was approved by the UHN Research Ethics Board (REB Number: 18-5716).

Participants

Patients with chronic MSK pain who were visiting the Orthopaedic Clinic at Toronto Western Hospital, University Health Network for a first-time consultation with an orthopaedic surgeon were included. Patients were deemed eligible to participate if they met the following inclusion criteria: (1) were ≥18 years of age, (2) able to speak and comprehend English, (3) and reported having chronic MSK pain, defined as muscle, tendon, bone or joint pain on most days for at least three months duration. Patients were excluded if they had sustained an acute MSK soft-tissue injury or fracture in the past 6 months, or if they had undergone surgery in the past 6 months.

Development of survey

The survey was designed to collect data on patient demographics, current health status and pharmaceutical pain management, characteristics of MSK pain, and cannabis use. A team of surgeons and clinical experts in the field self-developed the survey. To create it, we utilized questions from the Longitudinal Evaluation in the Arthritis Program (LEAP) study as a foundation and then developed questions specific to cannabis use based on the available literature (Whiting et al. 2015 ; Walsh et al. 2013 ; Power et al. 2019 ). Although this survey was not internally or externally validated, 3-4 research personnel reviewed the questionnaire on iPads to ensure clarity, coherence, and technical functionality before administering it to patients.

All respondents completed the demographics, health status, and cannabis use sections of the survey (Supplementary Table 1 ). Respondents who reported current or past use of cannabis to manage MSK pain (“cannabis users”) also answered more detailed questions regarding their duration and frequency of cannabis use, strain/type consumed, monthly cost, mode of administration, provenance, cannabis-related side-effects, and reason for initiating use (Supplementary Table 2 ). Cannabis users were also asked to report their perception of cannabis’s effectiveness for alleviating chronic MSK pain, its effectiveness compared to other prescription medication(s) and change in use of other medications since starting to use cannabis. Respondents who reported never using cannabis to manage MSK pain (“cannabis non-users”) were asked to rate their interest in using cannabis to manage chronic MSK pain, as well as potential barriers to using cannabis for this purpose (Supplementary Table 3 ).

The primary outcome of this study was current or past cannabis use for chronic MSK pain management, defined as a response of “yes” on the question “Have you ever used cannabis to manage your musculoskeletal pain (which includes muscle, tendon, bone or joint pain)?” Secondary outcomes were stratified based on reported cannabis use for the purposes of managing chronic MSK pain. Among cannabis users, secondary outcomes included patterns of cannabis use, self-perceived effectiveness, and self-reported changes in pain medications with cannabis use. Among cannabis non-users, secondary outcomes included interest in using cannabis for the management of chronic MSK pain and barriers to its use.

Patient demographics (age, gender, ethnic group, education, labour force participation, household income, and body-mass index), comorbid conditions, use of other pain medications (over-the-counter analgesics, prescription non-steroidal anti-inflammatory drugs, muscle relaxants, narcotic drugs, antidepressant drugs, and neuroleptic drugs), pain characteristics (bodily region for which the respondent is seeking care, number of painful bodily regions, and duration of pain), history of chronic pain specialist consultation, and recreational cannabis use were assessed as potential predictors of cannabis use for the management of chronic MSK pain.

Data extraction and collection

Participants entered survey responses directly into an electronic database via a tablet-based survey application. Analyses were carried out in R Statistical Software version 3.6.1 (Rdct and R: A, 2011 ).

Statistical analysis

Patient characteristics, patterns of cannabis use, and its self-perceived effectiveness and side effects were summarized descriptively; continuous measures were summarized with means and standard deviations, and categorical measures with counts and percentages. Bivariate analysis was conducted comparing cannabis users (patients reporting current or past cannabis use to manage their chronic MSK pain) versus non-users (patients who reported never using cannabis to manage MSK pain), using the Mann-Whitney test for continuous variables and Fisher’s exact test for categorical variables. We expected that approximately 5% of patients who visit the orthopaedic clinic will use cannabis, based on data from Ste-Marie and colleagues (Liu et al. 2019 ). The minimum sample size is given by n = (z/m)^2 x p(1-p), where Z is the z-score corresponding to the desired confidence level, m is the desired level of precision, and p is the expected proportion of patients who use cannabis for therapeutic purposes. With Z = 1.96, m = 0.05, and p = 0.05, the minimum required sample size is 73 participants.

P -values from bivariate analysis were adjusted to control false discovery rate (FDR) (Benjamini and Hochberg 1995 ). To identify factors independently associated with medical cannabis use, factors found to be significantly associated with cannabis use in the bivariate analysis ( p < 0.05) were entered in a multivariable logistic regression model of cannabis use along with age, gender, and ethnicity. Model fit was assessed with the area under the receiver operator curve and McFadden’s pseudo-R 2 . Results of the multivariable logistic regression were reported as Odds Ratios (OR) with 95% confidence intervals (CI). After reviewing bivariate analysis results, the following terms were entered into the model: age; gender; ethnicity (coded as White vs. non-White); labour force participation (coded as working/looking for work/short-term disability, retired/homemaker/student/other, or not looking for work/long-term disability); self-reported depression; number of comorbid conditions reported, excluding depression and MSK pain conditions (coded as none, 1-2 conditions, or 3+ conditions); use of narcotic medication (coded as never vs. sometimes/daily); ever visiting a pain clinic or specialist; bodily region for which the respondent is seeking treatment (coded as upper extremity, lower extremity, or spine); total number of painful bodily areas (coded as 1, 2, 3, or 4+ areas), duration of MSK pain (coded as 0-1 years, 1-5 years, or 5-10 years), and history of recreational cannabis use (coded as never vs. current/former use).

Patient characteristics

One thousand patients presented to the orthopaedic clinic and were approached for study enrolment, of which 629 met the inclusion criteria and were included (Fig.  1 ). A total of 144 (23%) patients reported any (previous or current) cannabis use with the specific intention of managing their chronic MSK pain, of which 72% ( N =104) were currently using cannabis to manage their pain. Cannabis users had a mean age of 50.88 ± 15.31 years and 51% ( N =73) were females (Table 1 ). In comparison to cannabis non-users, cannabis users reported higher use of daily pain medications (Fig.  2 ).

Sample flow diagram; MSK: musculoskeletal

Distribution of daily pain medication use among patients with chronic musculoskeletal pain presenting to the orthopaedic clinic; NSAIDS: Non-steroidal anti-inflammatory drugs

In the bivariate analysis comparing cannabis users to non-users (Tables 1 and 2 ), cannabis use was associated with younger age ( p < 0.001) and employment status ( p =0.002), with users more likely to report being unemployed or on long-term disability. Cannabis users were more likely to have multiple comorbid conditions ( p = 0.002), including depression ( p < 0.001), back pain ( p < 0.001), chronic neck pain ( p < 0.001), and chronic pelvic pain ( p < 0.001). They also reported a larger number of painful bodily areas ( p < 0.001), longer pain durations ( p = 0.003), more often visited a pain clinic/specialist ( p = 0.003), and more frequently used muscle relaxants ( p = 0.002), opioids ( p = 0.002), and antidepressants ( p = 0.002). Cannabis users were also more likely to report recreational cannabis use ( p = 0.001). There were no statistically significant differences between cannabis users and non-users in sex, ethnicity, educational attainment, or income.

Patterns of cannabis use

A descriptive summary of cannabis users’ survey responses is presented in Table 3 . Twenty-seven percent reported using cannabis for two or more years, and 25% for less than six weeks. Most patients used cannabis daily (59%). Thirty-nine percent of cannabis users reported spending at least $100 per month on cannabis products (Table 3 ).

Among cannabis users, CBD was the most commonly used cannabinoid (39%), followed by 20% of users consuming a hybrid of various cannabinoids. Twenty-three percent of cannabis users were unaware of their cannabis composition. The most frequent modes of administration among cannabis users were the ingestion of oils (57%), smoking (36%), and vaporizing (32%).

Twenty-six percent of users reported that they started using cannabis for pain management on the recommendation of a physician, and an equal proportion reported that a friend or relative advised them to use cannabis to manage pain (the options were not mutually exclusive). Many users reported getting cannabis from more than one source, including a dispensary or compassion club (43% of users); a Health Canada licensed provider (34%), and from a friend or relative (33%, Table 3 ).

Perceived effectiveness

The majority of cannabis users noted effective pain management from cannabis, with 63.7% describing it as very or somewhat effective and 26.6% indicating it as slightly effective (Table 3 ). Fifty-seven percent of users indicated cannabis to be more effective than other analgesic medications at managing their chronic MSK pain (Table 3 ). Forty percent of users reported that their use of other analgesic medication had decreased since starting to use cannabis, while 58% of cannabis users indicated no change in their analgesic medication usage since initiating cannabis (Table 3 ).

Commonly reported cannabis-related side effects included dry mouth (43%), fatigue (23%), and a lack of motivation (15%). Thirty-nine percent of cannabis users experienced no cannabis-related side-effects. Many users indicated cannabis’s effectiveness in treating other symptoms, primarily sleep disturbances (44%), anxiety (26%), and headaches (18%). Forty-three percent of cannabis users experienced no other symptomatic reliefs.

Predictors of current or past use of cannabis for MSK pain

Results of the multivariable regression analysis are illustrated in Table 4 . The most significant predictor of cannabis use was current or previous recreational cannabis usage (OR:12.72, p = < 0.001). Other significant independent predictors of cannabis use included self-reported depression (2.17, p = 0.01); opioid medication use (1.78, p = 0.03); history of pain clinic/specialist visits (1.93, p = 0.01); seeking treatment for spine pain versus lower extremity pain (2.14, p = 0.01); a greater number of painful bodily areas (2.28 for three [ p = 0.04] and 2.57 for four or more areas [ p = 0.01], versus one area); and increased duration of MSK pain (2.28 for one to five years [ p = 0.04] and 2.8 for five to ten years [ p = 0.01], versus less than one year). While controlling for these factors, age, gender, ethnicity, labour force participation and number of comorbid conditions were not significant predictors of cannabis use for MSK pain management.

Non-cannabis users

Sixty-five percent of cannabis non-users reported an interest in using cannabis for managing their chronic MSK pain. Given a list of potential barriers to using cannabis, the majority of non-users “completely” or “somewhat” agreed with many of the barriers, especially a lack of knowledge regarding cannabis formulations (85%), how to use cannabis for pain management (68%), and how to access cannabis for pain management (57%,); potential cannabis-related side effects (63%); and a perception of stigma (64%) (Fig.  3 ).

Non-cannabis users’ rating of factors influencing cannabis use for the management of chronic MSK pain

In this study, more than one in five patients presenting to an orthopaedic surgeon with chronic MSK pain had used or was currently using cannabis to manage their chronic MSK pain. Consistent with previous self-reported studies, the majority of these patients perceived cannabis to provide effective pain management (Ajrawat et al. 2022 ; Meng et al. 2021 ). More than half (57%) claimed cannabis to be more effective than other analgesic medications, and 40% reported decreasing their use of other analgesic medications since starting cannabis use. Only 26% of cannabis users reported that a physician recommended the use of cannabis to manage their chronic MSK pain, and 23% were unaware of the composition of the cannabis they were consuming. Among non-users, 65% expressed an interest in using cannabis for managing their chronic MSK pain but often reported that they lacked knowledge regarding efficacy, access, usage, and composition, as well as the associated stigma.

We found that 23% of chronic MSK pain patients have used or are using cannabis to manage their pain, of which the majority are current users (72%). This rate of cannabis use among chronic MSK pain patients in the present study is considerably higher than the cannabis use rates reported in past studies with similar patient populations. For instance, two different studies, one from Canada and another from the United States, indicated that 4% of patients undergoing orthopaedic procedures used cannabis (Liu et al. 2019 ; Medina et al. 2019 ). Similarly, a 2014 Canadian study reported that approximately 3% of rheumatology patients were cannabis users (Ste-Marie et al. 2016 ). Yet, a more recent study conducted in Canada revealed that 29% of individuals with upper extremity conditions were presently utilizing cannabis, primarily for the purpose of pain management (Greis et al. 2022 ). The difference in prevalence between the previous studies from 3-6 years ago and the current study is largely due to the legalization of cannabis in Canada in October 2018, resulting in potential changes in attitudes towards and acknowledgment of use and more permissive access to cannabis without stigma and/or legal implications. In fact, a study assessing data from the National Cannabis Survey (NCS) revealed that in the months preceding legalization, 19% of Canadian respondents intended to try cannabis or increase their cannabis use following legalization (Sandhu et al. 2019 ). Complementing this, a 2014 US survey found that 13.5% of people would consume cannabis more frequently if legalized (Cohn et al. 2017 ). Additionally, the anonymous self-reported nature of the current study may have also allowed patients to feel comfortable disclosing their cannabis, resulting in the higher rate we observed.

The strongest predictors of those who would use cannabis for managing their chronic MSK pain, were patients with a history of recreational cannabis use and the presence of long-term chronic pain. These findings are consistent with previous reports examining cannabis use in various patient populations (Liu et al. 2019 ; Medina et al. 2019 ; Sandhu et al. 2019 ; Bhashyam et al. 2019 ). It was found that previous recreational cannabis use was associated with a more than tenfold increase in the odds of using cannabis to manage chronic MSK pain. This was unsurprising as current cannabis use has been shown to strongly influence one’s perceptions of risk, stigma, and acceptability (Rudski 2014 ). Features consistent with the diagnosis of a chronic pain syndrome, such as frequent pain clinic visits and longer pain duration, were also strong predictors of cannabis use in the current cohort, suggesting that patients with chronic MSK pain are possibly unsatisfied with conventional treatments and seeking alternative pain therapies. Lastly, younger age was not a predictor of using cannabis for the management of chronic MSK pain, when controlling for factors such as opioid consumption, depression status, and the duration of pain. This finding is inconsistent with past studies which have indicated that the incidence of any cannabis use (medical or recreational) generally declines with increasing age (Rotermann and Page 2018 ; Sampasa-Kanyinga et al. 2018 ). Typically, it is assumed that younger age is associated with cannabis use, which is likely because the belief among younger adults is that cannabis use is socially acceptable, not addictive, and not harmful (Kandel 2002 ; Keyhani et al. 2018 ; Ware et al. 2003 ). However, there may be several potential reasons for this discrepancy. First, the current study’s cohort is older overall (mean age >50 years) and includes fewer young adults that would typically report a greater prevalence of use as compared to elderly patients. Second, this finding may suggest a growing acceptance among older patients regarding the role of cannabis use for the purpose of managing medical issues, which may be the result of the legalization in Canada, increasing societal acceptance, and improvements in accessibility of non-inhaled cannabis products.

In this study, over 85% of cannabis users perceived it to be effective in managing their chronic MSK pain and improving their sleep and anxiety-related symptoms. Several studies have also noted similar rates of perceived effectiveness in chronic pain patients (Heng et al. 2018 ; Miller and Miller 2017 ; Mucke et al. 2018 ). One study with 937 orthopaedic outpatients found that cannabis use was significantly associated with decreased pain intensity and better lower extremity activity scores (Medina et al. 2019 ). In a prospective observational study of chronic orthopaedic pain patients, medical cannabis use was associated with significant clinical improvements in VAS pain scores, global physical health and mental health, and quality of life within three months but plateaued at the 6 and 12 month follow-up periods (Greis et al. 2022 ). Furthermore, cannabinoids were found effective in all eight studies from a systematic review that evaluated chronic pain stemming from orthopedic etiologies (Vivace et al. 2021 ). Despite preliminary evidence suggesting cannabis’ pain management potential, most studies have short-term follow-ups with relatively small sample sizes. Moreover, significant heterogeneity exists among studies with regards to dosage, routes of administration, composition, frequencies, and patient populations, justifying the need for further investigations to elucidate the true efficacy of cannabis for the management of chronic MSK pain.

Several interesting observations were noted herein: a quarter of cannabis users had no knowledge of the current cannabis product they were consuming and only a third of users procured their cannabis from a Health Canada licensed provider. A study with upper extremity orthopaedic patients indicated that approximately 46% of patients felt more comfortable discussing their cannabis use with their physician after legalization (Sims et al. 2022 ). From a recent survey study, 86% of orthopaedic patients that were characterized as cannabis users stated that they would be willing to stop consuming cannabis if their surgeon stated it would adversely impact their surgery (Carney et al. 2020 ). These observations highlight the dire need for improved oversight and regulation of the medicinal cannabis industry (Craft et al. 2020 ; Freeman and Lorenzetti 2020 ). In the present study, 23% of cannabis users were unaware of their cannabis composition. Greis and colleagues reported similar findings with 23-29% of orthopaedic patients being able to estimate the cannabis composition of their inhaled or oral cannabis products (Greis et al. 2022 ). In our study, the most frequent modes of administration among cannabis users were the ingestion of oils (57%), smoking (36%), and vaporizing (32%). Similar to our results, a previous report indicated that most orthopaedic patients preferred oral or sublingual administration of cannabis followed by inhalation to manage their chronic pain (Greis et al. 2022 ). In contrast, Carney et al reported that smoking was the most common mode of administration, followed by edible products, and vaporizing (Carney et al. 2020 ). Although most patients in the present study reported cannabis to be effective, the varying compositions, dosages, frequencies, and routes of administration, suggests that placebo may mitigate some of the perceived efficacy. As such, there is a need for large scale observational studies where the dosages and route of administration are standardized. This could then lead to meaningful placebo-controlled comparative studies in similar patient populations to determine the effectiveness on symptom management.

Historically, common first-line pharmacologic treatments such as nonsteroidal anti-inflammatory drugs (NSAIDs) have been prescribed to alleviate chronic pain. However, NSAIDs have been associated with intolerance and serious adverse events in some patients including upper gastrointestinal bleeding or perforation (Bjordal et al. 2004 ; Langman et al. 1994 ). Opioids have also been prescribed to manage chronic MSK pain when conventional treatments have failed, so it is not surprising that individuals with chronic MSK pain are amongst the highest prescription opioid users (Ashaye et al. 2018 ; Manchikanti et al. 2012 ). However, long-term opioid use has been associated with greater pain intensity, poorer outcomes, and unintendedly increases the risk of developing an opioid use disorder, diversion, and fatal overdose (Bot et al. 2014 ; Dunn et al. 2010 ; Koehler et al. 2018 ; Noble et al. 2010 ). Cannabis has been suggested as a potentially safer analgesic therapy. In the present study, approximately 40% of our patients reported that their analgesic medications were reduced after initiating cannabis. A similarly designed study by Sims and colleagues with reported that 51% of orthopaedic patients felt that cannabis was safer than their prescription analgesics. (Sims et al. 2022 ) Further, Greis et al reported that 31% of chronic orthopaedic pain patients discontinued benzodiazepines, 73% either ceased or decreased opioid consumption, and noted a 23.4% reduction in 6-month total opioid prescription with cannabis use (Greis et al. 2022 ). Moreover, a systematic review evaluating the use of cannabinoids in orthopaedic patients found that the five of the seven studies noted an opioid sparring effect and two of the seven studies reported complete cessation of opioid use at the 6 to 12 month follow-up period (Vivace et al. 2021 ). Prior surveys of American and Canadian cannabis users reported that substituting cannabis for opioids resulted in improved pain management, decreased adverse effects, and eased opioid withdrawal symptoms. (Lucas and Walsh 2017 ; Vyas et al. 2018 )

It is noteworthy that cannabis users exhibited a constellation of comorbid conditions, including a higher prevalence of depression and pain, an increased number of painful bodily areas, longer pain durations, and more frequent visits to pain clinics/specialists when compared to non-cannabis users. This observation prompts us to consider the possibility that cannabis use may have arisen as a response to elevated levels of pain and dissatisfaction with existing therapeutic modalities. It is possible that a significant proportion of cannabis users turned to cannabis to seek relief from their heightened pain burden, which appears refractory to conventional treatments. Furthermore, we observed that cannabis users, despite experiencing greater pain, tended to employ a broader array of medications, such as muscle relaxants, opioids, and antidepressants, in comparison to their non-cannabis-using counterparts. This may also highlight that cannabis may have been sought as an alternative means of pain management, especially in situations where previous therapies yielded suboptimal results.

In this cohort, approximately two-thirds of cannabis non-users expressed interest in using cannabis for managing their chronic MSK pain, but often reported that they lacked knowledge regarding efficacy, access, usage, and composition. Interestingly, stigma was not a primary concern for cannabis non-users as previously cited in the literature (Bottorff et al. 2013 ; Hathaway et al. 2011 ; Satterlund et al. 2015 ), possibly attributed to the recent cultural shifts with cannabis legalization and with the increasing number of cannabis products that do not need to be smoked for consumption (only one third of products consumed in this study were smoked), leading to greater social acceptability and normalization (Hathaway et al. 2011 ). Research indicates that individuals are learning about cannabis from acquaintances and the internet instead of healthcare professionals (Corroon and Phillips 2018 ), which is consistent with the findings of the current study whereby only a quarter of patients started using cannabis as a result of a physician’s recommendation. Although the general perception is that cannabis is safe, there is a potential for side effects and drug interactions of which patients need to be aware (Alsherbiny and Li 2018 ; Iffland and Grotenhermen 2017 ). However, a lack of confidence regarding their knowledge on cannabis safety and efficacy exists among physicians (Fitzcharles et al. 2014 ; Kondrad and Reid 2013 ), which may prevent them from either initiating or participating in discussions regarding medical cannabis use with their patients. As such, continuing education initiatives targeting physicians are important to ensure they are armed with basic, albeit necessary, information regarding medical cannabis.

With the increased legalization of cannabis across North America and the clear interest by MSK pain patients to use cannabis therapeutically, there is large knowledge gap to fill in understanding the role of cannabis, if any, in managing chronic MSK pain. Future investigations should aim to conduct high-quality multicentre double-blind placebo-controlled trials with larger sample sizes and longer durations to assess the clinical efficacy and the long-term adverse events of cannabis as a monotherapy and in conjunction with standard analgesics. Future studies should aim to determine the optimal dosage, dose-response effects, drug interactions, and the ideal composition and route of administration based on patient history and preference.

Limitations

This study has several limitations. First, the survey utilized was not validated and the inability to compare characteristics of study participants with non-participants (i.e., those who declined or weren't eligible) limits the capacity to assess the external validity of the research. Second, the prevalence of cannabis use may be understated, given the stigma often associated with cannabis use and the use of self-reported data. However, the anonymous nature of the survey may have minimized this concern. Third, recall bias may have occurred with cannabis-related information, possibly affecting data accuracy. Additionally, the higher prevalence of comorbidities among cannabis users compared to non-users, may potential influence results and perceptions. Fourth, the survey only assessed the frequency and mode of administration and did not account for the dosage and precise composition of THC and CBD within the cannabis products being consumed. Fifth, the study was conducted in an academic, urban setting and limited to patients referred for Orthopaedic consultation, which limits the generalizability of these results to the broader MSK pain population. Finally, data collection started weeks following legalization at a single time interval, therefore the patient’s patterns and perceptions of cannabis efficacy and safety may change with increased awareness, social acceptability, and/or cannabis education since the time of the survey. We aim to repeat this work in the coming years to assess changes in use over time and collect validated patient reported outcome measures between cannabis users and non-users with chronic MSK pain, which will aim to improve upon some of the limitations identified herein.

Availability of data and materials

All data generated or analysed during this study are included in this published article [and its supplementary information files].

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No funding was used for this study. Dr. Hance Clarke is supported in part by a Merit Award from the Department of Anaesthesiology and Pain Medicine at the University of Toronto.

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TL, KS, HC, NM, RG, RR, CV, BR, and NizarM contributed to the design of the study, conceptualization, methodology, and data analysis. PA, TL, HC led the interpretation of the final data and the writing of original draft of the manuscript. All authors approved the final version of the study and collectively edited the manuscript.

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Dr. Clarke is a principal investigator of an observational medical cannabis study funded by Shoppers Drug Mart. Dr. Clarke declares a previous relationship as a consultant to Scientus Pharma at the time of the grant. The consultant relationship ended in 2019 as such there are no conflicts with respect to this work and the opinions, results, and conclusions reported in this article are those of the authors and are independent of the funding sources. All other authors have no conflicts of interest or disclosures.

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Leroux, T., Ajrawat, P., Sundararajan, K. et al. Understanding the epidemiology and perceived efficacy of cannabis use in patients with chronic musculoskeletal pain. J Cannabis Res 6 , 28 (2024). https://doi.org/10.1186/s42238-024-00231-1

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Received : 15 April 2023

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DOI : https://doi.org/10.1186/s42238-024-00231-1

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