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Current Concepts Review   |    
Joint Chondrolysis
Matthew T. Provencher, MD, CDR, MC USN1; Maryam Navaie, DrPH2; Daniel J. Solomon, MD3; Jessica C. Smith, BA2; Anthony A. Romeo, MD4; Brian J. Cole, MD, MBA4
1 Department of Orthopaedic Surgery, Naval Medical Center, San Diego, 34800 Bob Wilson Drive, Suite 112, San Diego, CA 92134
2 Advance Health Solutions, LLC, 7660 Fay Avenue, Suite H530, La Jolla, CA 97037. E-mail address for M. Navaie: mnavaie@advancehealthsolutions.com
3 Marin Orthopedics and Sports Medicine, 7100 Redwood Boulevard, Novato, CA 94945
4 Division of Sports Medicine, Rush University Medical Center, 1611 West Harrison Street, Suite 300, Chicago, IL 60612. E-mail address for B.J. Cole: bcole@rushortho.com
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Disclosure: None of the authors received payments or services, either directly or indirectly (i.e., via his or her institution), from a third party in support of any aspect of this work. One or more of the authors, or his or her institution, has had a financial relationship, in the thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work. No author has had any other relationships, or has engaged in any other activities, that could be perceived to influence or have the potential to influence what is written in this work. The complete Disclosures of Potential Conflicts of Interest submitted by authors are always provided with the online version of the article.

  • Disclosure statement for author(s): PDF

Investigation performed at Advance Health Solutions, La Jolla, California; Rush University Medical Center, Chicago, Illinois; Naval Medical Center San Diego, San Diego, California; and Marin Orthopedics and Sports Medicine, Novato, California
Disclaimer: The views expressed in this article are those of the authors and do not reflect the official policy or position of the Department of the Navy, Department of Defense, or the United States government.

Copyright © 2011 by The Journal of Bone and Joint Surgery, Inc.
J Bone Joint Surg Am, 2011 Nov 02;93(21):2033-2044. doi: 10.2106/JBJS.J.01931
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Abstract

Although the disease was first described in the hip, reports of chondrolysis in nearly all diarthrodial joints have since emerged with considerable variations in the literature.

Despite speculation among clinicians and researchers about the implicit causal pathways and etiologic contributors associated with chondrolysis, definitive answers remain elusive.

The term chondrolysis has been applied to varied levels of joint cartilage destruction from focal chondral defects to diffuse cartilage loss, revealing a lack of consistency in the application of diagnostic criteria to guide differential disease classification.

Differentiating between the various potential etiologies associated with chondrolysis provides opportunities for the prevention of the disease.

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    Topics

    chondrolysis
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    References

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    Editorial Department, The Journal of Bone & Joint Surgery
    Posted on January 25, 2012
    Commenting on this article is closed
    The Journal of Bone & Joint Surgery, Inc.

    No additional comments concerning this article will be published.

    Matthew T. Provencher, M.D., CDR, MC USN [1], Maryam Navaie, Dr.P.H. [2], Daniel J. Solomon, M.D. [3], Jessica C. Smith, B.A. [2], Anthony A. Romeo, M.D. [4], Brian J. Cole, M.D., M.B.A. [4]
    Posted on January 24, 2012
    Final Response to Benjamin Busfield, M.D.
    [1] Department of Orthopedic Surgery, Naval Medical Center San Diego, San Diego, CA [2] Advance Health Solutions, LLC, La Jolla, CA [3] Marin Orthopedics and Sports Medicine, Novato, CA [4] Division o

    Despite Dr. Benjamin Busfield's apparent need for self-repetition [1], it is the collective position of all co-authors of the Current Concepts Review (CCR) on Joint Chondrolysis [2] that we have deliberately and very thoroughly addressed all of his queries and questions.  Therefore, we see no added value to the medical literature for ongoing and repetitive banter on said subject matter.  Our declarations specific to potential Conflicts of Interest (COI) related to both of our scientific peer-reviewed publications to which Dr. Busfield refers [2,3] remain accurate and truthful.  No further discussions are merited regarding this matter.  Unlike Dr. Busfield who continues to receive payment for his 'expert opinion' services and commentaries from plaintiffs' counsel in support of ongoing chondrolysis-related litigation as per his COI statement, none of us have such overt COIs that clearly sway one's opinions.  We value our limited time and, as such, we choose to dedicate our well-recognized expert opinions on conducting serious, objective, unbiased, and quality research with meaningful implications for accurate education and best practices to guide orthopaedic patient care.  Since commentaries are not rigorously evaluated using the scientific peer-review process, if Dr. Busfield believes that he can further enlighten the orthopaedic and epidemiologic communities with his scientific abilities, we encourage him to conduct his own research on chondrolysis and prepare it for peer-review submission such that his arguments can be meritorious and actually additive to our present understanding of this challenging disorder. REFERENCES:  [1] Busfield BT. Questions Left Unanswered. J Bone Joint Surg Am., Commentary Posted January 12, 2012. [2] Provencher MT, Navaie M, Solomon DJ, Smith JC, Romeo AA, Cole BJ. Joint chondrolysis. J Bone Joint Surg Am. 2011;93(21):2033-2044. [3] Solomon DJ, Navaie M, Stedje-Larsen ET, Smith JC, Provencher MT. Glenohumeral chondrolysis after arthroscopy: A systematic review of potential contributors and causal pathways. Arthroscopy. 2009;25(11):1329-1342. 

    Benjamin T. Busfield MD
    Posted on January 12, 2012
    Questions Left Unanswered
    Orthopedic Surgeon, East Bay Physicians Medical Group, 4053 Lone Tree Way Suite 101 Antioch, CA 94531

    I have waited with great anticipation for the reply to my letter to the editor on the recent Current Concepts Review titled “Joint Chondrolysis.”[1] I appreciate the time the authors have taken to prepare such a lengthy reply. The multi-part reply includes such topics as formulating a medical diagnosis, gender inequalities in Orthopedic surgery, gender influencing treatment recommendations, how surgeons can stay current in our field, biases in research, and various principles in epidemiology. Despite the considerable effort put forth by the word count of the reply, my most essential concerns were unaddressed. I raised several issues in my initial letter to the editor and not all were addressed in the lengthy, sometimes patronizing, reply. The most important issue with this article is this: Why does this article use an 18 month time cut-off for their chondrolysis diagnostic criteria and subsequent analysis of the literature, yet conclude that a 12 month cut-off be used for diagnosis? In their reply letter, the authors discussed several times about their “proposed 12 to 18 months temporal criteria.” This was not the conclusion of their article. The authors clearly state on page 2040 of their article: “thus, we recommend that the term chondrolysis be applied to patients who are seen within 12 months after an operative intervention or potential cartilage insult, with pain, stiffness, limited joint motion, and severe diffuse articular cartilage loss evidenced by radiographs, magnetic resonance imaging, or arthroscopic evaluation.”[1] The “Joint Chondrolysis” CCR was inconsistent in its use of time cut-offs to a chondrolysis diagnosis, as was the subsequent reply letter from the authors. This should not be overlooked as no paper in the literature has made such an assertion, and we might misdiagnose patients with too rigid a criterion. Ironically, this could actually create a pooling effect the authors addressed in their article. The CCR conclusion statement is hardly original: It is largely a rephrasing of the Beck and Hansen PAGCL diagnostic criteria, with the addition of a time cut-off.[2] Time cut-offs are not typical of diagnoses. Given the lack of a large prospective study of PAGCL patients studied to determine the natural history, the true time course to clinical onset is not known. The time to presentation is very likely to be multifactorial given the importance of unknown factors in patients. At least the authors could have been consistent in their time cut-off within their article and their conclusion. What qualifies the authors to re-analyze the literature with their diagnostic criteria for chondrolysis and re-classify the diagnosis of these patients? Certainly the authors could reasonably re-evaluate the patients from the McNickle et al study because, as some of the same authors of the CCR article, they would have access to the actual patient charts.[3] However, I question if these authors had access for the painstaking effort of looking in depth at the unpublished patient information for each of the articles they reviewed to make a true diagnosis as the original authors had the ability to do. Review articles tend to review existing literature, not re-classify the data. Why group pediatric hip chondrolysis cases with PAGCL patients? This is very likely two different pathologies presenting in vastly different patient populations. This also begs the issue of the authors merging of the terms chondrolysis and PAGCL. The term PAGCL, as I correctly stated in my initial letter to the editor that was disputed in the author reply, was indeed a term coined by Beck and Hansen.[2] PAGCL was a new diagnosis in the shoulder at that time that occurred after arthroscopy and was associated with use of intra-articular pain pumps with local anesthetics. Numerous subsequent retrospective studies have confirmed this association in both the knee and the shoulder, and numerous laboratory studies have demonstrated the chondrotoxicity of local anesthetics. For obvious reasons, no prospective study can ethically be performed for patients receiving intra-articular pain pumps and local anesthetics to give us the highest level of evidence. I find the inconsistent conclusion of this article and the grouping of all chondrolysis cases to be questionable, which creates significant concern as it has been published in our most respected journal. The advent of intra-articular pain pumps with local anesthetics in the 1990’s directly correlated with the development of PAGCL cases. All recent authors on this topic recommend against the use of intra-articular pain pumps and local anesthetics. As a non-academic surgeon in a multispecialty group, I lack the resources that Advance Health Solutions can provide for research. It seems that both the “Joint Chondrolysis” CCR and the Solomon et al. paper were both co-authored by members of this corporation.[1,4] As a “Dr.P.H.” and researcher, Dr. Maryam Navaie clearly has a better foundation in epidemiology than I have. I appreciate her explanation of the terms and principles in epidemiology. Regarding Advance Health Solutions, what is the nature of this corporation that is now co-authoring articles in our Orthopedic literature? In one of the author responses with Dr. Maryam Navaie as the lead author, she cited a judge’s ruling and attempted to discredit the Wiater et al paper which was published in the Journal of Bone and Joint Surgery.[5] I find this highly inappropriate and feel this has no place in a scholarly discussion. This judge’s ruling appears to be in favor of the I-Flow Corporation, a pain pump manufacturer. With a command of legal documents that side with the defense in ongoing litigation against pain pump manufacturers for PAGCL, I am concerned about possible bias on the part of Advance Health Solutions. Clearly an article that minimizes the role of pain pumps and local anesthetics as a cause of PAGCL would be looked upon favorably by the defense counsels of the pain pump manufacturers and could assist in deflecting blame toward their products. As the Orthopedic literature has committed to do with changes in the author disclosure forms, it is appropriate that we have complete transparency with regards to potential bias. The disclosure statement for the “Joint Chondrolysis” CCR states that none of the authors “received payments or services, either directly or indirectly (i.e., via his or her institution)” but there is disclosure of a “financial relationship” in the “thirty-six months prior to submission of this work, with an entity in the biomedical arena that could be perceived to influence or have the potential to influence what is written in this work.”[1] There were no conflicts of interest reported in the Solomon et al. paper in 2009, the other paper on chondrolysis with contributions from Advance Health Solutions and largely the same authors as the “Joint Chondrolysis” CCR.[4] If Advance Health Solutions has had pain pump manufacturers as clients with confidentiality agreements, are the company and Dr. Maryam Navaie held to our literature standard of full disclosure for publications? Are corporations also subject to the disclosure standards? I look forward to a more comprehensive reply based on the issues I have raised from the authors of the “Joint Chondrolysis” Current Concepts Review because it impacts our understanding, as well as patient care, of PAGCL and intra-articular pain pumps. REFERENCES:[1] Provencher MT, Navaie M, Solomon DJ, Smith JC, Romeo AA, Cole BJ. Joint chondrolysis. J Bone Joint Surg Am. 2011 Nov 2;93(21):2033-44. [2] Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007 Oct;35(10):1628-34. [3] McNickle AG, L'Heureux DR, Provencher MT, Romeo AA, Cole BJ. Postsurgical glenohumeral arthritis in young adults. Am J Sports Med. 2009 Sep;37(9):1784-91. [4] Solomon DJ, Navaie M, Stedje-Larsen ET, Smith JC, Provencher MT. Glenohumeral chondrolysis after arthroscopy: a systematic review of potential contributors and causal pathways. Arthroscopy. 2009 Nov;25(11):1329-42. [5] Wiater BP, Neradilek M, Polissar NL, Matsen, FA. Risk Factors for Chondrolysis of the Glenohumeral Joint: A Study of Three Hundred and Seventy-five Shoulder Arthroscopic Procedures in the Practice of an Individual Community Surgeon. J Bone Joint Surg. Am., Apr 2011; 93 (7); 615-625.

    Anthony A. Romeo, M.D. [1] and Maryam Navaie, Dr.P.H. [2]
    Posted on January 07, 2012
    Improving Orthopaedic Care and Public Health Practice Amidst the Chondrolysis Controversy
    Division of Sports Medicine, Rush University Medical Center, Chicago, IL [2] Advance Health Solutions, LLC, La Jolla, CA

    Dr. Benjamin Busfield’s comment [1] on our Current Concepts Review (CCR) on Joint Chondrolysis [2] brings forth important implications for orthopaedic care and public health practice. On both of these fronts, there is a synergistic duality of purpose: prevention and intervention. From a prevention standpoint, determining the etiology of chondrolysis is of critical importance. However, prevention can only be truly achieved if risk factors can be objectively identified, comprehensively categorized (e.g., mechanical, chemical, and thermal) and successfully eliminated. In our CCR, we provide an extensive list of all reported factors delineated in the global literature to be associated with the incidence of chondrolysis. Although exposure to many of these suggested contributors can potentially be mitigated, this does not mean that we will be successful in achieving our goal of preventing chondrolysis. Some chondrolysis patients do not have exposure to the more heavily investigated etiologic contributors such as intra-articular pain pumps or thermal or radiofrequency devices. Moreover, a risk factor such as genetic predisposition cannot be mitigated. Thus, from a public health practice vantage point, the current knowledge base impacting our ability to prevent chondrolysis remains limited, suggesting the need for further research and discovery. Fortunately, chondrolysis is a rare condition and thus its reach is confined. From an intervention standpoint, efforts must continue to be directed at improving treatment options in the care paradigm for chondrolysis. Orthopaedic surgery is a complex and dynamic profession. Advances in research, both clinical and basic science, lead to frequent modifications of current clinical practice. Patients benefit from these advances as their surgeons incorporate constructive changes into care provision and treatment offerings. Therefore, the surgeon, as part of his sacred trust with his or her patients, should sense an obligation to develop an ongoing and consistent method that enhances awareness about improved approaches to treatment. Fortunately, at the leadership level, the orthopaedic community has emphasized continuing medical education. Many courses provide substantial peer-to-peer education, both in the form of didactic lectures as well as surgical skills labs. These courses are offered frequently and in many locations to provide a reasonable opportunity for surgeons to enhance and grow their current understanding of the conditions for which patients are seeking their help. In addition, the published literature provides surgeons with exposure to thought leaders and experts in the diverse medical field that encompasses all of orthopaedics. Developing relationships with these experts not only improves the surgeon’s personal skill set, it also provides a resource when presenting problems are outside of the surgeon’s experience or expertise level, clinically and/or technically. A competent, empathetic surgeon must be capable of asking for help, meaning soliciting a suitable partner in the care and treatment of a patient when the problem is beyond his or her abilities. As surgeons, we have many factors that ultimately lead to our recommendations for treatment. Understanding the primary reason the patient is seeking help, focusing on the history of the problem and examining the patient to establish a working diagnosis, then supplementing our suspicions with ancillary tests allow us to provide the most effective treatment strategies to our patients. This is facilitated when the indications for treatment are clear and standardized, such as displaced fracture of a bone. But what happens when the indications are somewhat subjective, and the surgeon has personal bias regarding the patient and the potential outcome after intervention? Unfortunately, the physician may alter his or her recommendations based on this bias. For example, if a surgeon has certain surgical expertise, the patient population in his region may be more likely to receive a specific type of surgical intervention at a higher rate than in other areas [3]. Another indicator that has been documented to impact treatment and the surgeon-patient relationship is gender bias [4-9]. The American Academy of Orthopaedic Surgeons (AAOS) began tracking the gender of orthopaedic surgeons in 2000. Since that time, AAOS has documented that the proportion of board certified, practicing orthopaedic surgeons who are female has increased from only 2.7% to the current 3.3%, a ratio nearly identical to that found in 2002 [4]. Another disconcerting trend is the fact that while the percentage of women in medical school has increased from 11% in 1970 to 48% in 2001, the percentage of women in orthopaedics has only increased from 0.6% to approximately 9% in that same period [10]. By best estimates, approximately 90% percent of all orthopaedic surgeons in the United States are men [4]. However, a substantial number of patients that these surgeons evaluate and provide treatment recommendations for are women. There is a considerable body of literature on the effect of gender regarding physician decision-making [4-7]. For example, in one study by Borkhoff et al. [11], the effect of the patient’s gender with respect for recommendations regarding total knee arthroplasty for osteoarthritis was evaluated. Their study demonstrated that orthopaedic surgeons were 22 times more likely to recommend total knee replacement to their male patients than their female patients; remarkably, the same study protocol revealed that a family physician was only two times more likely to recommend total knee replacement to their male patients than their female patients. Issues specific to gender-related care disparities in orthopaedics is concerning and requires much more research to understand the true impact on our patient population [12]. Would this type of gender bias affect chondrolysis patients in their search for answers to severe shoulder problem as has been described [13]? Will men be provided with more definitive treatment at an earlier time in the disease progression relative to women [5,6,11]? What communication skills are necessary for better understanding of our female patients and their concerns and how do we develop those skills with >90% of surgeons being male? Clearly, if there are barriers to effective care based on either subtle or overt bias, such as gender, every effort should be made to understand and eliminate this bias through continued education and research that increase awareness. Another practice implication of importance is that both interpersonal skills and technical skills are required for the most effective patient-surgeon relationship [13]. Technical expertise will allow the patient to respect the surgeon. Empathy and interpersonal communication skills will give patients confidence that the surgeon is caring for them as a unique human being, and it will foster reciprocity in affection for the surgeon as a person. To develop an effective patient-surgeon relationship in the health care decision-making process, both technical competence and empathy are required at the surgeon level, and these qualities need to be displayed through effective communication during patient encounters [14-17]. Ultimately, demonstrating these attributes will make it possible to develop the trust that is essential for any successful long-term relationship between the patient and the surgeon. REFERENCES: [1] Busfield BT. With the Natural History of Chondrolysis Unknown, How Can We Make Diagnostic Time Cut-Offs? J Bone Joint Surg Am., Comment Posted November 8, 2011. [2] Provencher MT, Navaie M, Solomon DJ, Smith JC, Romeo AA, Cole BJ. Joint chondrolysis. J Bone Joint Surg Am. 2011;93(21):2033-2044. [3] Watkins-Castillo S, Frankowski J, Schmalz H. Orthopaedic Practice and Medical Income in the US 2004-2005. American Academy of Orthopaedic Surgeons; 2004. [4] Hawker GA, Wright JG, Coyte PC, et al. Differences between men and women in the rate of use of hip and knee arthroplasty. N Engl J Med. 2000;342(14):1016-1022. [5] Katz JN, Wright EA, Guadagnoli E, et al. Differences between men and women undergoing major orthopedic surgery for degenerative arthritis. Arthritis Rheum. 1994;37(5):687-694. [6] Petterson SC, Raisis L, Bodenstab A, Snyder-Mackler L. Disease-specific gender differences among total knee arthroplasty candidates. J Bone Joint Surg Am. 2007;89(11):2327-2333. [7] Gooberman-Hill R, Sansom A, Sanders CM, et al. Unstated factors in orthopaedic decision-making: a qualitative study. BMC Musculoskelet Disord. 2010;11:213. [8] Bible JE, Lee RS, Friedlaender GE. The need for increased access to the U.S. health-care system. J Bone Joint Surg Am. 2009;91(2):476-484. [9] Agency for Healthcare Research and Quality. National Healthcare Disparities Report, 2008. U.S. Department of Health and Human Services. AHRQ Publication No. 09-0002. March 2009. www.ahrq.gov/qual/qrdr08.htm.[10] Hariri S, York SC, O'Connor MI, Parsley BS, McCarthy JC. Career plans of current orthopaedic residents with a focus on sex-based and generational differences. J Bone Joint Surg Am. 2011;93(5):e16. [11] Borkhoff CM, Hawker GA, Kreder HJ, et al. The effect of patients’ sex on physicians’ recommendations for total knee arthroplasty. CMAJ. 2008;178(6):681-687. [12] Dykes DC, White AA. Getting to equal: strategies to understand and eliminate general and orthopaedic healthcare disparities. Clin Orthop Relat Res. 2009;467:2598-2605. [13] Miller L. Improving orthopedic patient care: 7 tips for developing physician-patient partnerships. Becker's Orthopedic, Spine & Pain Management Review. http://www.beckersorthopedicandspine.com/orthopedic-spine-practices-improving-profits/item/10201-improving-orthopedic-patient-care-7-tips-for-developing-physician-patient-partnerships. Published December 19, 2011. Accessed January 5, 2012. [14] Vranceanu A-M, Cooper C, Ring D. Integrating patient values into evidence-based practice: effective communication for shared decision-making. Hand Clin. 2009;25(1):83-96,vii. [15] Bryant D, Bednarski E, Gafni A. Incorporating patient preferences into orthopaedic practice: should the orthopaedic encounter change? Injury. 2006;37(4):328-334. [16] Freeland AE, Freeland JT. Patient communication. Orthopedics. 2006;29(7):571-572. [17] Slover J, Shue J, Koenig K. Shared decision-making in orthopaedic surgery. Clin Orthop Relat Res. Epub November 5, 2011.

    Maryam Navaie, Dr.P.H. [1], Jessica C. Smith, B.A. [1], Anthony A. Romeo, M.D. [2]
    Posted on January 06, 2012
    Avoiding the Misuse of Epidemiologic Concepts in Chondrolysis Research: Implications for the Evidence-Base in Orthopaedics
    [1] Advance Health Solutions, LLC, La Jolla, CA [2] Division of Sports Medicine, Rush University Medical Center, Chicago, IL

    As mentioned in part one of our comment responding to Dr. Benjamin Busfield [1], one of the themes of his inquiry [2] on our Current Concepts Review (CCR) on Joint Chondrolysis [3] is centered on the delineation of potential causal factors associated with chondrolysis. This is a subject matter that is best addressed by the branch of medicine known as epidemiology that deals with the incidence, distribution, and control of diseases. Of course as a discipline, epidemiology is a much broader profession that encompasses the study of events, characteristics or determinants that describe health patterns in populations. It is the cornerstone method of public health research that heavily influences policy decisions by helping to establish the evidence-base in medicine, another relevant theme raised by Dr. Busfield that will be addressed by us in a separate (i.e., part 3) responsive commentary. In judiciously reviewing Dr. Busfield’s comments and his research on said subject matter [4-6], it is clear to us that Dr. Busfield has been grappling with the following core epidemiologic tenets in relation to chondrolysis for some time: (1) what constitutes a risk factor, and (2) what are the etiologic contributors or potential “causal” factors associated with the syndrome? To facilitate a better understanding specific to these foundational epidemiologic concepts, the terms risk factor, confounding and bias will be defined herein given their inter-relational underpinnings to causal inference. Although explanatory descriptions of what constitutes a risk factor have been published recently [7], a brief reiteration of this key epidemiologic concept seems warranted. A risk factor is an aspect of personal behavior or lifestyle, an environmental exposure, or an inborn or inherited characteristic, that, on the basis of epidemiologic evidence, is known to be associated with health-related condition(s) considered important to prevent. Unfortunately, the term risk factor is rather loosely used in the orthopaedic literature when making reference to potential etiologies of chondrolysis, where any of the following meanings are haphazardly applied: (1) an attribute or exposure that is associated with an increased probability of a specified outcome, such as the occurrence of chondrolysis; (2) an attribute or exposure that increases the probability of occurrence of chondrolysis or other specified outcome such as an alternative cartilage pathology -not necessarily a causal factor, rather a risk marker; and (3) a determinant that can be modified by an intervention, thereby reducing the probability of occurrence of chondrolysis or other specified outcomes. Such determinants may be referred to as modifiable risk factors [8,9]. As described elsewhere by Navaie [7], inferring that a potential contributor is a true risk factor for a disease is a complex process given many uncertainties. Three criteria must be met before a given factor can be considered a risk factor for a particular disease: (1) the factor must be observed to covary with the disease, (2) the presence of the factor must precede the occurrence of the disease, and (3) the observed association must not be entirely due to sources of error, the involvement of other extraneous risk factors, or other problems with the study design or data analysis. In chondrolysis-related research in human subjects, which is based almost exclusively on case reports or case series, it is the aforementioned third criterion that is often violated in clinical arguments. This violation stems from dependency on purposive study samples with skewed data presentation and highly subjective interpretations of results by clinical investigators. The end result is a poor threshold of validity that limits the benefits of the research to the orthopaedic practitioner as well as his or her patients. The operative definition of confounding is a relationship between the effects of two or more causal factors empirically observed in a set of data such that it is not logically possible to separate the contribution that any single causal factor has made to an effect. Thus, confounders are factors (e.g., exposures, interventions, treatments) that explain or produce all or part of the difference between the measure of association and the measure of effect. Specifically, the apparent effect of the exposure, intervention or treatment of interest is distorted because the effect of extraneous factors is mistaken for, or mixed with, the actual exposure effect (which may be null). The distortion that is introduced by a confounding factor can be substantial, leading to overestimation or underestimation of an effect, depending on the direction of the associations that the confounding factor has with exposure and disease [8]. Bias is deviation of results or inferences from the truth, or processes leading to such deviation. In essence, bias can occur pursuant to any trend in the collection, analysis, interpretation, publication, or review of data that leads to conclusions that are systematically different from the truth. Among the multitude of ways in which deviation from the truth can occur are the following: (1) systematic (one-sided) variation of measurements from the true values; (2) variation of statistical summary measures (e.g., means, rates, odds ratios and other measures of association) from their true values as a result of systematic variation of measurements, other flaws in data collection, or flaws in study design or analysis; (3) deviation of inferences from the truth as a result of flaws in study design, data collection, or the analysis or interpretation of results; (4) a tendency of procedures in study design, data collection, analysis, interpretation, review, or publication to yield results or conclusions that depart from the truth; and (5) prejudice leading to the conscious or unconscious selection of study procedures that depart from the truth in a particular direction or to one-sidedness in the interpretation of results [8-11]. With regards to research on chondrolysis, the most problematic and prevalent bias in the existing literature is selection bias stemming from the process used in identifying and selecting a study group (e.g., case reports of chondrolysis) that can have a major impact on the internal validity of the study and the legitimacy of the conclusion [11]. Selection biases are distortions that result from procedures used to select subjects and from factors that influence study participation. The common element of such biases is that the relation between exposure and disease (e.g., chondrolysis) is different for those who participate and for all those who theoretically should have been eligible for study, including those who do not participate. Because estimates of effect (e.g., odds ratios, risk ratios) are conditioned on participation, the associations observed in a study represent a mix of forces that determine participation and forces that determine disease occurrence [8]. Demonstrative misunderstandings of epidemiologic principles related to risk factors, confounding and bias are evident throughout Dr. Busfield’s commentary on our CCR with statement such as “the current body of literature universally implicates intra-articular anesthetics as a major cause of PAGCL” or “Hansen et al. [12] clearly demonstrated a risk factor: use of intra-articular pain pumps with local anesthetics” or his advocacy for use of the term “pain pump chondrolysis (PPCL)”. Contrary to Dr. Busfield’s assertions, all published studies on chondrolysis, uniformly reveal that chondrolysis is multi-factorial in etiology. Dr. Busfield’s apparent confusion highlights the importance of understanding confounding variables, which have been comprehensively elucidated for the shoulder joint [3,13,14] as well as for other diarthrodial joints [3]. If one’s goal was to add an element of entertainment rather than science to scholarly discussions on chondrolysis, one could introduce other casuistic terms such as “proud anchor chondrolysis”, “radiofrequency chondrolysis”, “thermal chondrolysis”, “chlorhexidine-induced chondrolysis” or even “surgically-induced chondrolysis”. None of these terms would be meaningful or accurate based on the totality of our exiting medical evidence-base [3]. Indeed, “multi-factorial chondrolysis” would be the most scientifically correct term but this is already apparent to any astute and informed reader of the existing literature by the term ‘chondrolysis’ in use today. An example of a misunderstanding related to both confounding and bias by Dr. Busfield is his reference to Hansen et al [12]. The selection of the study sample by Hansen et al. was guided, as they describe, “after a suspected common etiologic factor from these 10 patients” (i.e., all patients with intra-articular pain pumps). Moreover, “the chart review only identified the operative factors noted in Table 2 to determine any differences”. Table 2 in Hansen et al. is rather limited when compared with a more comprehensive delineation of all relevant potential etiologic factors which would have likely resulted in a different study sample [13]. What’s more, Hansen et al. make appropriate concessions regarding bias and confounding by stating in their conclusions that “It is likely that other unrecognized factors are also involved. Thermal and/or radiofrequency, suture material, and reabsorbable suture anchors may have played a role not yet completely understood at this time”. We caution Dr. Busfield in his selective interpretation of published research without adequate attention to the full contextual premise presented in the cited research. The pervasiveness of strong selection bias in chondrolysis research among human subjects is further evidenced in a more recent publication by Wiater et al. with claims to have isolated the singular cause of chondrolysis [15]. Upon closer examination, the results of that study are clearly indicative of a clustering effect, which is defined as findings based on a cohort resulting from the aggregation of relatively uncommon events or diseases (i.e., shoulder chondrolysis) in space and/or time in amounts that are believed or perceived to be greater than could be expected by chance [8,15]. Moreover, in this same study, the sample was purposively selected for litigation and later shown in Federal court to have been manipulated by vested parties who had clear conflicts of interest resulting in skewed presentation of results to favor arguments posed by plaintiff’s counsel [16], thereby introducing additional layers of bias that reduce the scientific objectivity and credibility of the study. Other core epidemiologic concepts that bear relevance to Dr. Busfield’s commentary include a differentiation between the terms accuracy and precision. Accuracy in estimation implies that the value of the parameter, that is, the object of measurement, is captured with little error. Errors in estimation are typically classified as either random or systematic. Although random errors in the sampling and measurement of subjects can lead to systematic errors in the final estimates, important principles of study design emerge from separate consideration of sources of random and systematic errors. Systematic errors in estimates are commonly referred to as biases; the opposite of bias is validity, so that an estimate that has little systematic error may be described as valid. Analogously, the opposite of random error is precision, and an estimate with little random error may be described as precise. Validity and precision are both components of accuracy [8]. Dr. Busfield asks whether “an overly strict analysis criteria [could] be responsible for the pooling effect” described in our CCR. As we delineate in the article, sensitivity analyses were performed to address matters related to accuracy and precision. Sensitivity analysis is a method to determine the robustness of an assessment by examining the extent to which results are affected by changes in methods, values of variables, or assumptions. The aim is to identify variables whose values are most likely to change the results or to find a solution that is relatively stable for the most commonly occurring values of these variables [17]. For further edification on this matter, we refer Dr. Busfield to results depicted in Figure 1 of our CCR. REFERENCES: [1] Provencher MT, Solomon DJ, Romeo AA, Cole BJ. Moving Towards Adoption of A Standardized Set of Diagnostic Criteria for Joint Chondrolysis: Focusing on Best Practices to Improve Patient Care. J Bone Joint Surg Am., Comment Posted December 17, 2011. [2] Busfield BT. With the Natural History of Chondrolysis Unknown, How Can We Make Diagnostic Time Cut-Offs? J Bone Joint Surg Am., Commentary Posted November 8, 2011. [3] Provencher MT, Navaie M, Solomon DJ, Smith JC, Romeo AA, Cole BJ. Joint chondrolysis. J Bone Joint Surg Am. 2011;93(21):2033-2044. [4] Busfield BT, Romero DM. Pain pump use after shoulder chondrolysis as a cause of glenohumeral chondrolysis. Arthroscopy. 2009;25(6):647-652. [5] Busfield BT, Lee GH, Carrillo M, Ortega R, Kharrazi FD. Subacromial pain pump use with arthroscopic shoulder surgery: a short-term prospective study of complications in 583 patients. J Shoulder Elbow Surg. 2008;17(6):860-862. [6] Busfield BT, Kalur LB. Safety and litigation update for shoulder pain pumps. AAOS Now. September 2009. http://www.aaos.org/news/aaosnow/sep09/clinical8.asp. Accessed December 11, 2011. [7] Navaie M. Leveraging epidemiologic principles to drive evidence-based medicine [letter to the editor]. J Bone Joint Surg Am. 2001 May 20. http://www.jbjs.org/article.aspx?volume=93&page=615. Accessed November 27, 2011. [8] Rothman KJ, Greenland S, Lash TL. Modern Epidemiology. 3rd ed. Philadelphia, PA: Lippincott Williams & Wilkins; 2008. [9] Last JM. A Dictionary of Epidemiology. 4th ed. New York, NY: Oxford University Press; 2001. [10] Schlesselman JJ. Case-Control Studies: Design, Conduct, and Analysis. New York: Oxford University Press; 1982. [11] Gordis L. Epidemiology. 3rd ed. Philadelphia, PA: Elsevier Saunders; 2004. [12] Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007;35(10):1628-1634. [13] Solomon DJ, Navaie M, Stedje-Larsen ET, Smith JC, Provencher MT. Glenohumeral chondrolysis after arthroscopy: A systematic review of potential contributors and causal pathways. Arthroscopy. 2009;25(11):1329-1342. [14] Scheffel PT, Clinton J, Lynch JR, et al. Glenohumeral chondrolysis: a systematic review of 100 cases from the English language literature. J Shoulder Elbow Surg. 2010;19(6):944-949. [15] Wiater BP, Neradilek MB, Polissar NL, Matsen FA 3rd. Risk factors for chondrolysis of the glenohumeral joint: a study of three hundred and seventy-five shoulder arthroscopic procedures in the practice of an individual community surgeon. J Bone Joint Surg Am. 2011;93(7):615-625. [16] Opinion and Order delivered by Ann Aiken, Chief Judge. McClellan v. I-Flow Corp. Case 6:07-cv-01671- AA. Document 365. May 3, 2010. http://or.findacase.com/research/wfrmDocViewer.aspx/xq/fac.20100503_0000123.DOR.htm/qx. Accessed December 11, 2011. [17] Goldsmith CH. Sensitivity Analysis. In: Encyclopedia of Biostatistics. John Wiley & Sons; 2005.

    Matthew T. Provencher, M.D., CDR, MC USN [1], Daniel J. Solomon, M.D. [2], Anthony A. Romeo, M.D. [3], Brian J. Cole, M.D. [3]
    Posted on December 17, 2011
    Moving Towards Adoption of A Standardized Set of Diagnostic Criteria for Joint Chondrolysis: Focusing on Best Practices to Improve Patient Care
    [1] Department of Orthopedic Surgery, Naval Medical Center San Diego, San Diego, CA [2] Marin Orthopedics and Sports Medicine, Novato, CA [3] Division of Sports Medicine, Rush University Medical Cente

    We appreciate the opportunity to provide additional clarity regarding multiple clinical, epidemiologic and public health-related points raised by Dr. Busfield in his constructively intended commentary entitled: “With the Natural History of Chondrolysis Unknown, How Can We Make Diagnostic Time Cut-Offs?” [1]. In order to minimize potential confusion while we comprehensively address the rather complex dimensions of the ongoing scholarly discussions related to our Current Concepts Review (CCR) on Joint Chondrolysis [2], we are rendering our response to Dr. Busfield in two parts. Part one of our response focuses on the provision of details specific to orthopaedic-related queries raised by Dr. Busfield. Part two of our response presents lucidity on epidemiologic and public-health-related matters posed by Dr. Busfield. After careful review and consideration of Dr. Busfield’s commentary, we have identified five thematic queries raised by him in relation to our CCR. These queries include requests for: (1) further justification for our proposed 12 to 18 month temporal criterion as a means of standardizing the differential diagnosis of chondrolysis relative to other cartilage pathologies, (2) identification of alternative diagnoses for pooled or misdiagnosed cases of chondrolysis, (3) delineation of potential causal factors associated with chondrolysis, (4) discussion specific to topics related to the safety, efficacy and marketing of intra-articular pain pumps (IAPP) in relation to chondrolysis, and (5) further deliberation regarding current and future directions for the treatment of chondrolysis. We will now address each of Dr. Busfield’s concerns. In his positional commentary, Dr. Busfield’s first query asks for the provision of further justification specific to our proposed 12 to 18 month temporal criteria for the differential diagnosis of chondrolysis. Dr. Busfield suggests that we arbitrarily designated this time to presentation “cut-off” for the diagnosis of chondrolysis without adequate reliance on the literature. We would like to reiterate that the goal of our CCR was to improve the orthopaedic community’s understanding of chondrolysis and how it typically presents, not to provide an exact temporal cut-off for definitional purposes. After thoroughly reviewing all case reports and case series of chondrolysis across publications worldwide between 1930 and 2010, trends specific to the temporality of chondrolysis presentation within the entire cohort of 830 joint chondrolysis cases became evident despite considerable patient-level heterogeneity. Five orthopaedic surgeons, not simply one, independently performed detailed examinations of all reported clinical data for the 830 reported cases of chondrolysis. Our rationale for including this many surgeons to render clinical evaluations of each reported case of chondrolysis was to bolster the accuracy of diagnostic case classification, as discussed in our CCR. Pooling or misclassification of various cartilage pathologies as chondrolysis was most commonly seen with time periods extending beyond 18 months in the literature. Thus, contrary to any perceived notions that this temporal timeframe was arbitrarily selected without adequate deference to the existing literature, our proposed timeframe was in fact generated after careful examination of the totality of the literature on chondrolysis across not only the shoulder joint but all other diarthrodial joints. Dr. Busfield’s assertion regarding the arbitrariness of our proposed timeframe would be a more legitimate concern had we selected a singular study or a singular case or a singular joint to generate the temporal range we suggest as a diagnostic criterion for differentiating chondrolysis from other cartilage pathologies. For Dr. Busfield’s further edification on this matter, we refer him to the extensive references cited in our CCR which offer the most comprehensive list of relevant literature specific to chondrolysis published to date. To enhance scholarly discussions specific to the utility of considering time to symptom onset as a criterion to guide proper diagnostication, we want to build further on Dr. Busfield’s poignant statement that the natural history of chondrolysis is unknown at present. One of the key implications of this fact, particularly for the shoulder joint, is the importance of recognizing that there is a relationship between cases that present with global cartilage loss, profound subjective symptoms, and significant motion loss within a timeframe that most commonly occurs between 12 to 18 months of a documented surgical procedure (typically arthroscopy). For example, pre-existing osteoarthritis may be missed in cases diagnosed with chondrolysis following closed treatment and placement of an IAPP if no index arthroscopy was performed [3]. Although Dr. Busfield appears to be questioning the utility of our proposed 12 to 18 month timeframe as a criterion to benefit surgeons in diagnosis determination, we would like to emphasize the importance of this temporal criterion in the context of other variables that would lead to an alternative diagnosis. For example, factors such as presentation at an older age, disease progression in a more indolent fashion, and symptoms of a lesser magnitude are likely to be indicative of alternative diagnoses (e.g., osteoarthritis) compared with opposing indications of such variables among patients believed to have chondrolysis, namely younger age, rapid and diffuse loss of articular cartilage with severe motion loss and consistent somatic pain. Unfortunately, given the inherent limitations of secondary data, several studies in our CCR did not present a time between index surgery and onset of symptoms. However, among the majority of the case reports we examined, even with a delay between symptom onset and presentation, nearly all cases of chondrolysis could be identified by 18 months. The temporal relationship between the suspected etiology and the development of cartilage loss was key to the diagnosis in that chondrolysis as the condition presents rapidly, represents extensive joint destruction, and is inherently indicative of a highly toxic and synovitic environment. Furthermore, the range of 12 to 18 months takes into consideration potential delays in diagnosis due to the need for radiographic or arthroscopic confirmation of the diagnosis. Moving forward, as chondrolysis is better recognized and the potential etiological factors are further elucidated, we believe orthopaedic clinicians will most likely make the diagnosis within 12 months of cartilage insult. Dr. Busfield’s second query centers on the provision of additional clarity related to the identification of alternative diagnoses for pooled or misdiagnosed cases of chondrolysis. Specifically, Dr. Busfield refers to the 2007 publication by Hansen et al. [4] and suggests that those authors “coined” the diagnosis of chondrolysis, bringing attention to this “new” diagnosis. In the absence of our CCR, limited knowledge could have made such erroneous statements understandable. However, with the publication of our CCR, more accurate and informed statements are made possible. Our CCR provides a comprehensive historical depiction of chondrolysis revealing that the use of the term was present in the literature as early as 1971 [5]. Hence, it is neither appropriate nor accurate to credit Hansen et al. for “coining” the term chondrolysis. We believe the added value of Hansen et al.’s study to the literature on chondrolysis, albeit limited to the shoulder, is that it provides information on some important diagnostic aspects. Historically, following an arthroscopic procedure of the glenohumeral joint, patients who developed early problems with pain and motion loss were not necessarily evaluated for acute loss of articular cartilage as one potential cause of their aberrant post-operative course. Delays in radiographic diagnosis are largely due to the lack of an objective test performed during the earlier phases of the disease progression. Our collective clinical experiences and subject knowledge led us to concur that chondrolysis must start with chondrocyte death and matrix dissolution that likely pre-dates radiographic or even arthroscopic detection [6]. The distinction, as it pertains to the shoulder, is largely due to other cases that are reported in the literature as chondrolysis despite the presence of only focal cartilage loss that is typically in association with mechanical factors [2,6]. Pathoanatomy in these cases looks macroscopically much different than in patients with global cartilage loss and typically presents with a different clinical picture compared to the aggressive presentation of patients with chondrolysis. Osteoarthritis is another example that does not fit the clinical paradigm of chondrolysis. In brief, we agree with Hansen et al. that the differential diagnosis of chondrolysis is important to distinguish from other etiologies of cartilage wear and joint demise. The diagnosis of chondrolysis is apparent when the appropriate clinical history, physical examination, and radiographic findings are utilized in concert to determine the presence of the condition. Our CCR serves to further increase present understanding about these important diagnostic criteria such that cases of chondrolysis can be identified with greater accuracy. The theme of the third line of inquiry by Dr. Busfield revolves around delineation of potential causal factors associated with chondrolysis. As Dr. Busfield appropriately recognizes, there are many unknown factors relative to the pathophysiology of chondrolysis as it advances over time. We defer to our co-author, Dr. Navaie, for meaningful responsive commentary specific to epidemiologic principles of relevance related to the definitional specificity of risk factors and correct interpretations of causal inference. In her response to Dr. Busfield, Dr. Navaie summarizes these concepts in relation to the totality of the evidence-base depicted in our CCR. In a related commentary to the concept of causality, we would like to address Dr. Busfield’s assertion that the inclusion of patients with focal cartilage damage in the McNickle et al. [7] case series (coauthored by three of the authors of our CCR) refutes our current position that diffuse cartilage loss is a necessary criterion for the differential diagnosis of chondrolysis. The McNickle et al. article includes a sample of 20 patients who were retrospectively identified over a five-year period (2003–2008). In the years that have followed the 2009 McNickle et al. publication, emerging research has revealed new information about the potential etiologies and causal pathways related to chondrolysis [2]. This new information led us to re-examine how selected authors of our CCR had previously diagnosed and categorized the case series in McNickle et al. Upon re-examination, we collectively determined that 80% (16/20) of the joints had correctly been diagnosed as chondrolysis based on the time to diagnosis (all within 12 to 18 months) and the extent of cartilage damage (all diffuse loss with bone on bone). In contrast, 20% (4/20) of the joints were determined to have been misclassified or pooled because damage to the articular cartilage was focal (see Table 2 in McNickle et al.). Among these misdiagnosed cases (see Table 1 in McNickle et al.), two had bipolar radiofrequency devices used in the joint, and another two had prominent metal anchors which required removal within one year of placement. During our CCR study, five orthopedic surgeons concurred that those four cases should have been diagnosed as either post-anchor arthropathy or focal osteochondral damage. Continuing with the theme of causality, Dr. Busfield also refers to a second study conducted by four co-authors of our CCR (Dr. Busfield inadvertently lists only two), that being the 2009 publication by Solomon et al. [6]. We appreciate Dr. Busfield’s review of that body of research, one which remains the most comprehensive systematic review of post-arthroscopic glenohumeral chondrolysis (PAGCL) published to date. In his commentary, Dr. Busfield accurately refers to some of that study’s results by stating that among PAGCL cases (n=88), 68% (n=53) had surgical implants/anchors, 67% (n=59) received local anesthetics through an IAPP, and 45% (n=41) had thermal radiofrequency devices [see Table 3 in Solomon et al.]. However, his interpretations and subsequent argumentative inferences are inaccurate because these percentages do not refer to the presence of mutually exclusive etiologic contributors. Hence, contrary to Dr. Busfield’s interpretation that IAPP can be isolated as the cause of chondrolysis pursuant to results from Solomon et al. along with others that he purposively cites (e.g., Hansen et al), there is insufficient evidence to suggest that a more appropriate term for PAGCL is pain pump chondrolysis (PPCL). We refer Dr. Busfield to Table 1 in our CCR for further edification about the fact that, at present, based on the totality of evidence in the medical literature, for all published cases of chondrolysis irrespective of joint, the etiologic contributors are multi-factorial. Simply stated, it is not possible to implicate a sole cause of chondrolysis at this time based on existing evidence. Even in pre-clinical studies investigating the use of the IAPP, there are conflicting and inconsistent effects [8,9]. In addition, several in vitro studies investigated the effects of local anesthetics on the metabolism and viability of chondrocytes stripped of their matrix [10,11,12]. This modeling is far different from the intact organ of the osteochondral unit situated within a diarthrodial joint. It is of further interest to note that more dated studies [13] have reported the use of saline as used in arthroscopic medium to have a chondrotoxic effect in an in vitro environment. Thus, we cannot recommend the term PPCL given the many other factors that have been documented to be associated with chondrolysis. The science delineating the interplay between patient factors, surgical factors, and chemical or thermal factors has not been clearly elucidated, and therefore the correct term for the condition remains simply chondrolysis. Along the same theme, Dr. Busfield describes a hypothetical “young” patient who had arthroscopic labral repair with the use of an IAPP presenting with chondrolysis two years after index surgery as a case that refutes the utility of a temporal criterion for the differential diagnosis of chondrolysis. However, his case illustration presents at least three identified possible etiologic contributors to chondrolysis including (1) arthroscopic surgery suggestive of potential mechanical damage to cartilage; (2) labral repair, a procedure that involves several intra-articular manipulations including articular cartilage debridement at the glenoid edge, arthroscopic saline lavage with varying fluid temperatures, alterations in the biomechanics of the glenohumeral joint and the risk for subclinical infections; and (3) use of IAPP suggestive of potential chemically-induced damage to cartilage. Moreover, as the radiographic studies would clearly demonstrate in this young patient, the timeframe is not within the range of 12 to 18 months for the onset of the condition. Alternatively, there was a delay in diagnosis which could have been made earlier than two years (again, as we propose, by 12 to 18 months). With a comprehensive history, physical examination, and objective findings, the hypothetical patient would potentially be diagnosed with chondrolysis at the onset of the disease in terms of initial presentation and manifestation prior to the 12 to 18 month “cut-off”. To re-state, our CCR aims to help clinicians filter cases that are not truly chondrolysis so that attention can be directed to identifying all potential etiologies as well as effectively treating and preventing the disorder. Dr. Busfield’s statement that our recommended diagnostic criteria “serve no purpose” suggests that the methodology, results, and discussion sections of our CCR were not carefully reviewed with an unbiased mindset. The fourth query by Dr. Busfield focuses on themes specific to topics related to safety, efficacy, and marketing of IAPP with presumed relevance to legal and regulatory concerns in relation to chondrolysis. This mode of inquiry is clearly beyond the scope of our CCR and its published content. Moreover, we are unclear as to Dr. Busfield’s argumentative comments that do not specifically relate to our CCR. Therefore, we will confine our responsive commentary to salient issues presented in our publication. Dr. Busfield’s final query raises concerns about further deliberation regarding current and future directions for the treatment of chondrolysis. We concur that there is a group of patients that are relatively young, who present with rapid progressive cartilage loss in association with several potentially aggravating factors, that remain difficult to clinically manage given existing treatment options. Evaluating chondrolysis across several joints allows for a more comprehensive comparison of suitable treatments that could not be identified as well when evaluating the shoulder joint alone. Based on our analysis of 830 reported cases of chondrolysis, we support limiting the use of potential etiologic contributors including the use of IAPPs, thermal devices, chlorhexidine, radiofrequency probes, and local anesthetics. The rationale for our position is not imbedded in our belief that any of these potential contributors are the sole “cause” of chondrolysis, as medical evidence remains inconclusive. Instead, our convictions as surgeons rest on our primary goal in patient care, namely improving health outcomes among our patients while minimizing potential hazards during care provision. As we continue our research to better understand the underlying etiology of chondrolysis, we pay heed to Dr. Busfield’s advocacy that the orthopaedic community should continue to evaluate treatment alternatives for our patients who present with chondrolysis. Ultimately, differentiating the various conditions associated with cartilage loss, as defined in our CCR, will help us achieve our common goal as orthopedists: to appropriately treat patients with advanced cartilage damage and disability. We also believe that disease prevention for cartilage damage from any source is a sentinel goal of our CCR. To successfully prevent chondrolysis, it is critical to properly and objectively identify associated factors and conditions that may or may not be responsive to the variety of arthroplasty and non-arthroplasty treatment options currently available to treat these entities [15]. REFERENCES: [1] Busfield BT. With the Natural History of Chondrolysis Unknown, How Can We Make Diagnostic Time Cut-Offs? J Bone Joint Surg Am., Commentary Posted November 8, 2011. [2] Provencher MT, Navaie M, Solomon DJ, Smith JC, Romeo AA, Cole BJ. Joint chondrolysis. J Bone Joint Surg Am. 2011;93(21):2033-2044. [3] Serrato JA Jr, Fleckenstein CM, Hasan SS. Glenohumeral chondrolysis associated with use of an intra-articular pain pump delivering local anesthetics following manipulation under anesthesia: a report of four cases. J Bone Joint Surg Am. 2011 Sep 7;93(17):e99(1-8). [4] Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007;35(10):1628-1634. [5] Jones BS. Adolescent chondrolysis of the hip joint. S Afr Med J 1971;45: 196-202. [6] Solomon DJ, Navaie M, Stedje-Larsen ET, Smith JC, Provencher MT. Glenohumeral chondrolysis after arthroscopy: A systematic review of potential contributors and causal pathways. Arthroscopy. 2009;25(11):1329-1342. [7] McNickle AG, L'Heureux DR, Provencher MT, Romeo AA, Cole BJ. Postsurgical glenohumeral arthritis in young adults. Am J Sports Med. 2009;37(9):1784-1791. [8] Gomoll AH, Kang RW, Williams JM, Bach BR, Cole BJ. Chondrolysis after continuous intra-articular bupivacaine infusion: an experimental model investigating chondrotoxicity in the rabbit shoulder. Arthroscopy. 2006;22(8):813-819. [9] Gomoll AH, Yanke AB, Kang RW, Chubinskaya S, Williams JM, Bach BR, Cole BJ. Long-term effects of bupivacaine on cartilage in a rabbit shoulder model. Am J Sports Med. 2009;37(1):72-77. [10] Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM, Pringle EK. In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg Am. 2010;92(3):599-608. [11] Karpie JC, Chu CR. Lidocaine exhibits dose- and time-dependent cytotoxic effects on bovine articular chondrocytes in vitro. Am J Sports Med. 2007;35(10):1621-1627. [12] Chu CR, Izzo NJ, Papas NE, Fu FH. In vitro exposure to 0.5% bupivacaine is cytotoxic to bovine articular chondrocytes. Arthroscopy. 2006;22(7):693-699. [13] Nole R, Munson NM, Fulkerson JP. Bupivacaine and saline effects on articular cartilage. Arthroscopy. 1985;1(2):123-127. [14] Levy JC, Virani NA, Frankle MA, Cuff D, Pupello DR, Hamelin JA. Young patients with shoulder chondrolysis following arthroscopic shoulder surgery treated with total shoulder arthroplasty. J Shoulder Elbow Surg. 2008;17:380-388. [15] Provencher MT, Romeo AA. Shoulder Instability: A Comprehensive Approach. Philadelphia: Saunders Elsevier; 2011.

    Benjamin T. Busfield MD
    Posted on November 08, 2011
    With the Natural History of Chondrolysis Unknown, How Can We Make Diagnostic Time Cut-offs?
    East Bay Physicians Medical Group, Orthopedic Surgeon 4053 Lone Tree Way Suite 101 Antioch, CA 94531

    DISCLOSURE: Dr. Busfield is a medicolegal consultant for plaintiffs in chondrolysis litigation. COMMENT: I read with great interest the recent Current Concepts Review by Provencher et al.[1] I applaud the authors for a unique review of the literature in an attempt to use uniform diagnostic criteria that included: “1) surgical, radiographic, or imaging findings demonstrating diffuse cartilage loss or joint-space narrowing due to involvement of apposing articular surfaces and 2) rapid destruction (i.e. within 18 months after an insult).”[1] What in the literature supports these new diagnostic criteria? Could overly strict analysis criteria be responsible for the pooling effect of inappropriate diagnoses labeled as chondrolysis? Why was 18 months made the cut-off in the analysis of the literature, yet the authors “recommend that the term chondrolysis be applied to patients who are seen within 12 months after an operative intervention or potential cartilage insult, with pain, stiffness, limited joint motion, and severe diffuse articular cartilage loss evidenced by radiographs, magnetic resonance imaging, or arthroscopic evaluation”[1]? This appears to be an inconsistent conclusion. To arbitrarily create a time to presentation cut off for all patients as a diagnostic criterion for post-arthroscopic glenohumeral chondrolysis (PAGCL) is not appropriate. This time cut off was not based on any particular study in the literature. Since no longitudinal study has been done on a large cohort of patients with PAGCL risk factors up to 2 years after surgery, a true time cut off can never truly be known. The point of the seminal Beck and Hansen article was to bring attention to this new diagnosis, and the classic delay to presentation.[2] It clearly demonstrated a risk factor: use of intra-articular pain pumps with local anesthetics.[2] The PAGCL patients all presented within 3-12 months of the index surgery with a pain pump.[2] To my knowledge, Beck and Hansen were the only authors that put forth diagnostic criteria of their newly coined diagnosis, and time to presentation was not included. Because of this delay to presentation and the acknowledgement of the disease as recently as 2007, diagnosis can be delayed past 12 months from a misdiagnosis such as adhesive capsulitis. Why was “involvement of apposing articular surfaces” and “diffuse cartilage loss” used as the threshold[1]? This would imply knowledge about the rate of cartilage loss and the pattern of a progressively evolving injury. The Beck and Hansen study used a minimum of 20% joint space loss with a 15% magnification rule as the threshold of joint space narrowing on radiographs.[2] Imaging, and even arthroscopic evaluation does not distinguish grossly intact cartilage from intact cartilage without viable chondrocytes. As in the Chu et al study [3], cartilage can appear grossly normal but have diffuse chondrocyte loss. One presumes that chondrocyte death precedes gross loss of cartilage, and that catching a glimpse early in the spectrum of progression of PAGCL can be misleading. What is the pattern of development of chondrolysis? Does it start of as a small area on one side of the joint, then progress to kissing lesions? Is the glenoid or humeral cartilage more susceptible leading to one side of the joint to be largely affected prior to progression to global cartilage loss? How do surgical interventions after the onset of chondrolysis affect this progression? Does early arthroscopic debridement or capsular release accelerate the disease because large areas of cartilage are not viable but not detached and thus experience more forces after surgical intervention? Clearly there is a spectrum of disease that likely is not uniform across all patients, as some patients exposed to intra-articular pain pumps with local anesthetics do not develop chondrolysis. The McNickle et al study, with three of the same authors of this recent Current Concepts Review, showed that complete loss of cartilage on both sides of the glenohumeral joint are not necessary for the diagnosis of chondrolysis: all humeral heads had grade IV with a range of area involved, whereas the glenoid cartilage changes ranged from no changes to 100% grade IV.[4] Sixteen of the 20 patients had the risk factor of an intra-articular pain pump.[4] If this was one of the studies retrospectively reviewed by the authors of the Current Concepts Review, what was the alternative diagnosis in any of these patients with the risk factor of an intra-articular pain pump if it was not PAGCL? “Non-chondrolysis” is not a diagnosis.[1] The Beck and Hansen study appropriately discussed the association of PAGCL with intra-articular pain pumps and local anesthetics.[2] Subsequent years of clinical research overwhelmingly show intra-articular pain pumps are the leading cause of PAGCL, more so than cases reported with proud or loose anchors or thermal device usage. Laboratory research has overwhelmingly proven the chondrotoxic effects of local anesthetics in vitro. According to a recent review by Piper et al 2011: “The current body of literature universally implicates intra-articular anesthetics as a major cause of PAGCL.”5In fact, the term PAGCL is largely outdated. In the 4 years since the Beck and Hansen study, there is one case report in the literature involving insertion of the intra-articular pain pump without arthroscopy for adhesive capsulitis 6 (not post-arthroscopic) and there are two case reports of this condition in the knee 7,8 (not glenohumeral). A better term for this condition would be pain pump chondrolysis (PPCL).In the study by Provencher et al, with two of the same authors of this recent Current Concepts Review, all PAGCL cases in the literature were reviewed.[9]The authors found that 68% had surgical implants, 67% received local anesthetics through pain pumps, and 45% of the surgeries involved thermal radiofrequency devices.[9] Because many arthroscopic surgeries involve placement of implants as the indication for surgery, this study is consistent with that of Scheffel et al [10]: Intra-articular pain pump with local anesthetics are the most common surgical factor in the development of PAGCL. Other variables that may play a role in the time to presentation for the patient include pain pump volume, flow rate, dose of local anesthetic, subsequent surgeries, and number of exposures to intra-articular pain pump with local anesthetics. There are patients who have multiple exposures to intra-articular pain pumps in the follow-up surgeries after the symptoms have begun. Many of these patients had chrondolysis develop prior to 2007 and the surgeons were unaware of PAGCL as a diagnosis. The authors state that pooling in the shoulder subset was associated with an “extended time to diagnosis (i.e., twelve months or more after an identifiable insult), which was indicative of more chronic conditions (e.g., osteoarthritis) for all six international cases.” [1] Again, was the diagnostic criterion 12 or 18 months after a risk factor? If a young patient had arthroscopic labral repair with the main risk factor identified as an intra-articular pain pump and presented at 18 months or even 2 years after surgery with chondrolysis, one would not conclude that the diagnosis was osteoarthritis. At this point, with all recently published authors advocating against the use of intra-articular pain pumps with local anesthetics and with laboratory research shifted to single dose local anesthetic injections, our field is left with the aftermath of a disastrous pain modality for a product whose safety profile was never established prior to use and marketing. Rather than arbitrarily creating overly strict diagnostic cut-offs for PAGCL that serve no purpose, we should be focused on treatment alternatives with prospective long term follow-up in attempt to treat these typically young patients with advanced arthritis and disability. REFERENCES: [1] Provencher MT, Navaie M, Solomon DJ, Smith JC, Romeo AA, Cole BJ. Joint chondrolysis. J Bone Joint Surg Am. 2011 Nov 2;93(21):2033-44. [2] Hansen BP, Beck CL, Beck EP, Townsley RW. Postarthroscopic glenohumeral chondrolysis. Am J Sports Med. 2007 Oct;35(10):1628-34. [3] Chu CR, Coyle CH, Chu CT, Szczodry M, Seshadri V, Karpie JC, Cieslak KM, Pringle EK. In vivo effects of single intra-articular injection of 0.5% bupivacaine on articular cartilage. J Bone Joint Surg Am. 2010 Mar;92(3):599-608. [4] McNickle AG, L'Heureux DR, Provencher MT, Romeo AA, Cole BJ. Postsurgical glenohumeral arthritis in young adults. Am J Sports Med. 2009 Sep;37(9):1784-91. [5] Piper SL, Kramer JD, Kim HT, Feeley BT. Effects of local anesthetics on articular cartilage. Am J Sports Med. 2011 Oct;39(10):2245-53.[ 6] Serrato JA Jr, Fleckenstein CM, Hasan SS. Glenohumeral chondrolysis associated with use of an intra-articular pain pump delivering local anesthetics following manipulation under anesthesia: a report of four cases. J Bone Joint Surg Am. 2011 Sep 7;93(17):e99(1-8). [7] Fester EW, Noyes FR. Postoperative chondrolysis of the knee: 3 case reports and a review of the literature. Am J Sports Med 2009 Sep;37(9):1848-54. [8] Slabaugh MA, Friel NA, Cole BJ. Rapid chondrolysis of the knee after anterior cruciate ligament reconstruction: A case report. J Bone Joint Surg 2010 92: 186-189. [9] Solomon DJ, Navaie M, Stedje-Larsen ET, Smith JC, Provencher MT. Glenohumeral chondrolysis after arthroscopy: a systematic review of potential contributors and causal pathways. Arthroscopy. 2009 Nov;25(11):1329-42. [10] Scheffel PT, Clinton J, Lynch JR, Warme WJ, Bertelsen AL, Matsen FA. Glenohumeral chondrolysis: a systematic review of 100 cases from the English language literature. J Shoulder Elbow Surg. 2010 Sep;19(6):944-9.

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