Osteoarthritis: From Palliation to Prevention

Abstract

Osteoarthritis is a leading cause of disability. The traditional focus on late-stage osteoarthritis has not yielded effective disease-modifying treatments. Consequently, current clinical care focuses on palliation until joint replacement is indicated. A symposium format was used to examine emerging strategies that support the transformation of the clinical approach to osteoarthritis from palliation to prevention. Central to this discussion are concepts for diagnosis and treatment of pre-osteoarthritis, meaning joint conditions that increase the risk of accelerated development of osteoarthritis. The presentation of translational and clinical research on three common orthopaedic conditions—anterior cruciate ligament tear, intra-articular fracture, and hip dysplasia—were used to illustrate these ideas. New information regarding the use of novel quantitative magnetic resonance imaging (MRI) in the form of ultrashort echo time enhanced T2* (UTE-T2*) mapping to evaluate the potential for articular cartilage to heal subsurface damage in a mechanically sound environment was presented. These data indicate that improved diagnostics can both identify cartilage at risk and evaluate the effectiveness of early treatment strategies. With use of a new mouse model for intra-articular fracture, it was shown that inflammation correlated to fracture severity and that super-healer mice avoided early posttraumatic osteoarthritis in part through an enhanced ability to dampen inflammation. These findings suggest that there is a role for acute and sustained anti-inflammatory treatment in the prevention of osteoarthritis. For long-term treatment, contemporary gene-therapy approaches may offer an effective means for sustained intra-articular delivery of anti-inflammatory and other bioactive agents to restore joint homeostasis. To illustrate the potential of early treatment to prevent or delay the onset of disabling osteoarthritis, the positive clinical effects on articular cartilage and in long-term clinical follow-up after operative correction of structural abnormalities about the hip highlight the role for targeting mechanical factors in delaying the onset of osteoarthritis. Given that orthopaedic surgeons treat the full spectrum of joint problems, ranging from joint trauma to pre-osteoarthritic conditions and end-stage osteoarthritis, an awareness of the paradigm shift toward the prevention of osteoarthritis is critical to the promotion of improved clinical care and participation in clinical research involving new treatment strategies.

Osteoarthritis is a leading cause of pain and disability¹. The traditional focus on late-stage osteoarthritis has not yielded effective disease-modifying treatments. Consequently, clinical care has focused on palliation until joint replacement is indicated. While the pathogenesis of osteoarthritis is multifactorial, joint injuries and excessive loading are known to accelerate joint degeneration. With rising medical and disability costs attributable to osteoarthritis, there is a growing need for new strategies to prolong joint health.

This symposium from the 2013 American Orthopaedic Association Annual Meeting held in Denver, Colorado, examined emerging strategies that support the transformation of the clinical approach to osteoarthritis from palliation to prevention. Central to this discussion are concepts for diagnosis and treatment of pre-osteoarthritis, meaning joint conditions that increase the risk of accelerated development of osteoarthritis². Three common orthopaedic conditions—anterior cruciate ligament (ACL) tear, intra-articular fracture, and hip dysplasia—meet the criteria for pre-osteoarthritic conditions and were discussed to highlight relevant translational science as well as long-term clinical outcomes.

Early Diagnosis Enables Early Treatment to Reduce Osteoarthritis Risk After ACL Tear

Anterior cruciate ligament tear is common, affecting primarily teenagers and young adults^3,4, and accelerates the development of osteoarthritis to such a degree that approximately half show symptomatic radiographic knee osteoarthritis ten to twenty years later⁵. While ACL reconstruction is effective in stabilizing the joint, prior procedures have not reduced the incidence of premature knee osteoarthritis^6,7. As ACL surgery continues to evolve, future reports that reflect the outcomes of contemporary means of ACL augmentation and anatomic reconstruction with use of nonirradiated allografts may show a reduction of osteoarthritis risk. Another view is that reconstructive surgery does little to overcome progressive joint deterioration due to subtle but irreversible cartilage injuries sustained at the time of an ACL tear. Improved understanding of early changes after ACL injury and reconstruction may yield a more integrated perspective leading to effective disease-modifying therapies.

Quantitative magnetic resonance imaging (MRI) techniques for biochemical evaluation of articular cartilage (e.g., delayed gadolinium-enhanced MRI of cartilage [dGEMRIC], sodium MRI, and glycosaminoglycan chemical exchange saturation transfer imaging [gagCEST] to quantify proteoglycan content, as well as T2 mapping, and T1rho) show promise for improving the ability to identify potentially reversible early pathological changes to articular cartilage^2,8,9. While it is well known that partial-thickness and full-thickness injuries to articular cartilage generally do not heal, less is known about whether articular cartilage can repair itself after injuries that do not disrupt the articular surface. Anecdotal evidence suggests that, in the absence of supra-physiological mechanical load, surface intact articular cartilage found to be soft to the point of “blistering” after ACL injury can regain matrix stiffness (Fig. 1).

Fig. 1.

Articular cartilage shows capacity to heal subsurface injury. Left: At the time of ACL reconstruction, the entire trochlear groove was softened to the point where probing indicated bubbling of the cartilage both medial and lateral to the raised “wrinkle.” Right: In this patient with poor vastus medialis obliquus recovery, breakdown of the overloaded lateral trochlear groove was noted ten months after the examination performed at the time of ACL reconstruction. In the mechanically privileged areas, the medial cartilage was firm and smooth to probing and the “wrinkle” had firmed into a raised ridge.

Recently, ultrashort echo time enhanced T2* (UTE-T2*) mapping was developed to evaluate the subsurface matrix of articular cartilage^10,11 (Fig. 2). This novel, quantitative MRI technique shows potential to identify cartilage and menisci at risk and to evaluate whether therapeutic interventions can restore articular cartilage matrix properties. When used to evaluate human subjects after an ACL tear, deep tissue UTE-T2* showed that surface intact articular cartilage and menisci were elevated as compared with the cartilage and menisci of uninjured controls, suggesting subsurface matrix injury^11,12. More importantly, longitudinal data show preservation of cartilage morphology with reversal of the UTE-T2* changes two years after ACL reconstruction, which is suggestive of healing¹².

Fig. 2.

Novel UTE-T2* mapping shows subsurface meniscus and articular cartilage structural changes due to injury that cannot be seen with conventional magnetic resonance imaging (MRI). Left: UTE-T2* maps of the articular cartilage deep tissue (A, arrows) and meniscus (B) of a human subject after ACL tear, showing a mottled pattern that was higher than that seen in the uninjured control. Right: UTE-T2* maps of the articular cartilage (C, arrows) and meniscus (D) of the same subject two years after anatomic anterior cruciate ligament reconstruction, showing return of the laminar pattern with low signal (mapped to red), comparable to the uninjured control. (Meniscal images shown in B and D were reproduced, with permission, from Chu CR, Williams AA, West RV, Qian Y, Fu FH, Do BH, Bruno S. Quantitative magnetic resonance imaging UTE-T2* mapping of cartilage and meniscus healing after anatomic anterior cruciate ligament reconstruction. Am J Sports Med. 2014 May 8. Epub ahead of print. DOI:10.1177/0363546514532227.)

This study introduces new quantitative MRI data to support a concept that is critical to the idea that premature osteoarthritis may be preventable: that articular cartilage possesses an ability to heal if pathological stimuli such as inflammation or mechanical overload are arrested early in the disease process prior to breakdown of the articular surface. Audience response questions from the American Orthopaedic Association (AOA) symposium indicate receptivity to these ideas. When the audience was asked to choose a response to the survey statement, “Articular cartilage is able to heal itself…”, the response “…after subsurface injury (articular surface intact)” was selected by 35% of the audience after the presentation as compared with just 7% before the presentation. In addition, 92% of the audience also concluded that mechanical overload of articular cartilage interferes with articular cartilage healing.

The ability to observe early and reversible cartilage damage supports development of disease-modifying therapies. Cellular and molecular targets for intervention include administration of chondro-resuscitative substances such as growth factors, anti-apoptotic treatments, free radical scavengers, and anti-inflammatory agents^13,14. In vitro studies suggest that there is a role for acute treatment after impact injury to articular cartilage when progressive chondrocyte death and apoptosis have been observed within minutes to days^13,15. In particular, brief exposure to free radical scavengers (e.g., rotenone) two hours after an impact injury has been shown to reduce oxidative stress and prevent chondrocyte death¹³.

Chronic inflammation is a common feature of osteoarthritic joints in which subsynovial lymphocytic infiltrates are present¹⁶. Anti-inflammatory agents provide symptomatic relief. Because osteoarthritis develops over a period of years to decades, long-term oral administration of anti-inflammatory agents poses several challenges. Concerns for systemic toxicity have led to new interest in evaluating the anti-inflammatory effects of high molecular weight hyaluronan¹⁷. Corticosteroid injections have a known anti-inflammatory effect but many formulations also carry concerns for chondrotoxicity, especially when corticosteroids are combined with local anesthetics^18,19. While injection therapy reduces the risk of systemic toxicity, long-term and sustained bioactivity remains difficult to achieve without incurring substantial local morbidity from repeated injections.

Gene therapy holds high promise for sustained and prolonged administration of bioactive substances. More than a decade ago, a highly publicized death from systemic exposure to a viral vector refocused the field onto improving the margin of safety. Strategies include use of nonviral or nontoxic viral vectors, localized treatment, and adding external methods to control in vivo gene expression. Recent work showed that localized gene therapy, with use of a small (20 nm) replication-defective and nonenveloped virus (adeno-associated virus [AAV]) that is not known to cause any human disease, resulted in sustained transgene expression after a single intra-articular injection²⁰. This virus also integrates into the host genome at a specific site, thereby reducing unpredictable effects of random insertion that could theoretically include carcinogenesis. The safety profile of AAV has been further improved through external control of in vivo gene expression by selective use of promoters to “turn on” and “turn off” gene expression in response to orally administered triggers such as tetracycline²⁰. Consequently, AAV has been approved for use in several human clinical trials in which sites such as the brain, the eye, and the knee are involved.

With increasing public understanding that the human microbiome contains more bacterial and viral genes than human genes, there may be increasing acceptance of these strategies in the future. Approximately half of respondents (51%) answered “Yes,” and 29% answered “Maybe” in response to the statement: If I were shown to be “at risk” for premature osteoarthritis, and gene therapy with a nonpathogenic vector (e.g., AAV) was shown to protect my joint from deteriorating, I would consent to treatment. The response to this statement highlights the importance of using validated and quantitative methods both to identify cartilage at risk and to assess treatment effects during the development and clinical translation of new strategies to prevent or delay the onset of disabling osteoarthritis.

From Mice to Men: Reduction of Posttraumatic Osteoarthritis After Intra-Articular Fracture

Approximately 12% of patients seeking surgery for symptomatic arthritis have a history of major trauma to the involved joint²¹. Although the development of posttraumatic osteoarthritis is particularly rapid following intra-articular fracture^22,23, the diversity in fracture patterns, acuity, and severity render it difficult to study pathogenesis in humans. To identify and evaluate new treatment targets in a controlled setting, effective animal models of intra-articular fracture are needed²⁴. The development, application, and implications of a small animal intra-articular fracture model were highlighted in the symposium.

In developing this intra-articular fracture model, maintenance of a closed joint was considered to be important because surgical approaches may alter the physiologic response to injury. A mouse model would facilitate mechanistic study. Thus, a closed tibial plateau fracture model was developed with use of the commonly used wild-type or control adult C57BL/6 mice²⁵. Fractures were created with use of a computer-controlled material testing system and custom positioning jig and indenter tip. Progressive joint degeneration was observable by histologic analysis with use of a modified Mankin scale by eight weeks after injury and persisted through fifty weeks after injury.

Reduced chondrocyte viability is one of the earliest effects of intra-articular fracture, and chondrocyte viability was reduced in fractured joints as compared with control joints (p < 0.05). However, no significant difference was observed in chondrocyte viability between low-energy and high-energy fractures (p = 0.68). Furthermore, the work of Krenn et al. in humans was modified for use in the murine model to show that the inflammatory response differed between experimental and control limbs seven days after injury²⁶. Low-energy fractures had synovitis present in the lateral (fractured) portion of the joint. In high-energy fractures, synovitis expanded throughout the joint.

These data indicate that, similar to the sequelae of intra-articular fracture in humans, a closed intra-articular fracture in mice led to accelerated cartilage injury and degeneration. Furthermore, there was a well-defined inflammatory response. While the load-bearing requirements, life span, and time course for disease differ between mice and humans, mouse models, including the use of transgenic, knock-out, and special strains of mice, permit the cost-effective systematic study of events after intra-articular fracture as well as the mechanistic study of the biological factors that are important in fracture-healing and joint degeneration.

This model was then used to investigate the response of the MRL/MpJ strain (also known as “super-healer” mice) to a closed articular fracture. Although the articular fracture in the MRL/MpJ mice healed in a displaced position, no difference in modified Mankin histological scoring of cartilage degeneration was seen between fractured and contralateral control limbs at any time point. In contrast, when the injured joint and the contralateral control joint were compared in the C57BL/6 mice, posttraumatic osteoarthritis was evident in the injured joint (Fig. 3). No differences were seen between the non-fractured control joints and the contralateral control joints of the experimental subjects.

Fig. 3.

Super-healer mouse shows reduced susceptibility to posttraumatic osteoarthritis. Histologic images of the lateral compartment of the knee of C57BL/6 and MRL/MpJ mice were made at eight weeks after fracture. The C57BL/6 image (left) shows articular cartilage disruption and degeneration, and loss of (red) proteoglycan staining. The MRL/MpJ image (right) shows articular cartilage disruption and minimal loss of (red) staining. (Safranin O staining, original magnification, original magnification ×100.) Histology scale bars = 100 μm. Boxed areas show sites of histologic damage. (Reproduced from: Ward BD, Furman BD, Huebner JL, Kraus VB, Guilak F, Olson SA. Absence of posttraumatic arthritis following intra-articular fracture in the MRL/MpJ mouse. Arthritis & Rheumatism. 2008 [Mar]; 58[3]:744-53. Reproduced with permission of the original publisher, BioMed Central [open access article].)

Differences were also observed in gene expression between the MRL/MpJ and the C57BL/6 murine models after closed tibial plateau fractures²⁷. In this study, the C57BL/6 mice developed changes of posttraumatic osteoarthritis by eight weeks after injury, whereas the MRL/MpJ mice did not. Assessment of gene expression of inflammatory cytokines and chemokines from the synovial lining of injured joints found elevation of the pro-inflammatory genes for tumor necrosis factor-alpha (TNF-α), interleukin-1 alpha (IL-1α), and interleukin-1 beta (IL-1β). TNF-α expression was elevated early in the C57BL/6 mice and remained elevated (relative to the expression in the MRL/MpJ mice) for seven days after fracture. The increased expression ranged from threefold to fifteenfold over that in the non-fracture controls. IL-1α expression was elevated in both the C57BL/6 and MRL/MpJ mice after fracture in a similar manner. IL-1β had the most dramatic differences in expression, with a 720-fold increase in expression in the C57BL/6 mice and a seventy-fourfold increase in the MRL/MpJ mice at Day 0 (four hours after fracture). The expression remained elevated in the C57BL/6 mice through Day 7 but had returned to normal in the MRL/MpJ mice by Day 3 (Fig. 4).

Fig. 4.

Fig. 4, A, B, and C Gene expression and serum levels of cytokines in C57BL/6 and MRL/MpJ mice following intra-articular fracture (fx). A: A greater than threefold change in expression from pre-fracture to post-fracture was considered significant. B and C: Enzyme-linked immunosorbent assay was used to assess the serum levels of IL-1α (B) and IL-1β (C) in C57BL/6 and MRL/MpJ mice following fracture. IL-1β peaks at Day 1 after injury, consistent with higher synovial levels after injury, while IL-1α levels have a delayed peak at three days after injury. (Reproduced, with modification, from: Lewis JS Jr., Furman BD, Zeitler E, Huebner JL, Kraus VB, Guilak F, Olson SA. Genetic and cellular evidence of decreased inflammation associated with reduced incidence of posttraumatic arthritis in MRL/MpJ mice. Arthritis & Rheumatism. 2013 [Mar]:65[3]:660-70. Reproduced with permission of the original publisher, BioMed Central [open access article].)

Synovial fluid analysis showed that TNF-α and IL-1α levels in the fractured joints were similar to those in the contralateral control joints. The TNF-α synovial fluid response was barely detectable. Synovial fluid IL-1β was significantly elevated in the injured joints of C57BL/6 and MRL/MpJ mice but not in the contralateral control joints. The IL-1β level of the C57BL/6 mice remained elevated through seven days, while that of the MRL/MpJ mice returned to prefracture levels by Day 3 after injury. Serum IL-1α and IL-1β levels in both mice strains mirrored the elevation in the synovial fluid levels. At all time points, the C57BL/6 mice had slightly higher serum levels.

By Day 7, the fractured joints in the C57BL/6 mice had significantly greater synovitis scores than did the fractured joints in the MRL/MpJ mice (p < 0.05). By Days 28 and 56, the synovitis resolved in both strains of mice. Immunohistochemistry showed differences between the C57BL/6 and the MRL/MpJ mice with regard to localization of activated macrophages in the synovium. The C57BL/6 mice showed substantially more positive staining for activated macrophages at Day 7. Despite resolution of synovitis, macrophage infiltration continued through Day 28 after fracture in C57BL/6 mice.

The findings from the MRL/MpJ analysis indicate that reduced intra-articular inflammation is associated with protection from the development of posttraumatic osteoarthritis. The MRL/MpJ animals showed an initial pro-inflammatory response to injury and early synovitis; however, they were able to limit the inflammatory response after injury. These data suggest that early increases in IL-1 may be involved in the development of posttraumatic osteoarthritis in wild-type C57BL/6 mice. Similarly activated macrophages may play a role in the joint degeneration seen after intra-articular fracture.

These investigations suggest that intra-articular inflammation after a fracture has occurred plays a part in the development of posttraumatic osteoarthritis. The concept of a therapeutic agent that targets DNA translation, or blocks specific inflammatory pathways, is common today in oncology and cardiology^28,29. Results from the audience response questions indicated that a high percentage of symposium attendees understood that fracture severity correlated to inflammation (97%) and that super-healer mice were able to limit inflammation after sustaining a fracture (86%). Models that allow us to study basic mechanisms in the development of posttraumatic osteoarthritis can therefore highlight new potential treatment opportunities to delay the onset of posttraumatic osteoarthritis for patients with joint injuries.

Thirty Years of Experience in Joint-Preservation Surgery

Joint preservation surgery has a long history in improving function and delaying osteoarthritis through the correction of mechanical forces about the hip, and it also has an exciting future with newer arthroscopic techniques to address soft-tissue injuries and femoroacetabular impingement. While surgical treatment has classically been performed for developmental dysplasia of the hip (the most common cause of osteoarthritis of the hip in North America), there is increasing recognition of the potential role of a variety of anatomical conditions leading to femoroacetabular impingement as a leading etiological factor in hip osteoarthritis. This was reflected in the near equal distribution of the audience selecting either developmental dysplasia of the hip or femoroacetabular impingement as the most common cause of osteoarthritis of the hip in North America and Europe. Any discussion of the newest effective strategies for hip preservation surgery will benefit from a brief description of the driving concepts, and pertinent diagnostic techniques, as well as the therapeutic techniques themselves.

The conceptual framework for methods to prevent and treat osteoarthritis of the hip postulates that hip osteoarthritis has primarily a mechanical origin and is rarely a primary disease of articular cartilage, although genetic variability in cartilage resistance certainly exists. Therefore, abnormal mechanics driven by predisposing anatomy and activity leads to progressive articular damage. Felson has categorized risk factors for osteoarthritis as including impairment of joint protectors, conditions of excessive loading, or combinations of both³⁰.

Worldwide, hip osteoarthritis is strongly associated with developmental conditions, particularly developmental dysplasia of the hip, Legg-Calvé-Perthes disease, and slipped capital femoral epiphysis, as well as anatomic variants such as femoral and acetabular retroversion, coxa profunda, and reduced femoral head-neck offset. The newest insights into mechanically based hip disease include the concepts of instability and femoroacetabular impingement. The acetabular rim is usually the locus of earliest damage³¹. Instability is from rim overload by the femoral head—typically during hip extension, adduction, or external rotation. Developmental acetabular dysplasia, which results in an oblique acetabular weight-bearing zone, exemplifies mechanical instability, which may be macroscopic in infancy and less obvious but still problematic in adulthood.

Femoroacetabular impingement, first described well by Ganz and colleagues, is a condition in which a “conflict” occurs between the proximal part of the femur and the acetabulum, causing articular damage³². Hip impingement may occur within the hip capsule or may be extra-articular. Intra-articular femoroacetabular impingement may be an inclusion type (cam), in which an aspherical head or neck jams and tears the tissues of the rim and acetabulum with hip motion, or an impaction type (pincer), in which a retroverted socket or neck, an overly deep socket, or a normal femoral neck in a ligamentously lax hip crushes the rim tissues in flexion, abduction, or internal rotation. Recent work implicates cam-type deformities rather than pincer-type deformities for joint tissue damage that raises the risk for the development of early osteoarthritis. In addition, femoroacetabular impingement and instability may coexist in mechanically at-risk hips.

A careful clinical history will reveal problematic situations in accordance with the dynamic aspect of conditions leading to hip osteoarthritis. The contemporary physical examination should include stressing the hip joint. Static imaging has been the gold standard in diagnosing orthopaedic conditions, and several recently popularized projections increase the usefulness of radiographs for initial evaluation of most hip problems³³. Supplementing the imaging of the anteroposterior aspect of the pelvis with orthogonal views of the proximal aspect of the femur, such as the Dunn lateral view (which often demonstrates anterolateral “cam” lesions) and the faux profile view (a true lateral view of the acetabulum to evaluate anterior coverage), provides a sound initial set of static images.

Important advances in static imaging include computed tomography (CT) scanning of the pelvis, with cuts through the distal aspect of the femora to evaluate femoral version and with recently introduced low-radiation protocols now commonly used. Imaging with noncontrast and contrast-enhanced dedicated hip MRI protocols may be used in lieu of CT. Biochemical MRI with the dGEMRIC technique with use of 1.5-T and 3-T magnets has been useful in assessing the loss of glycosaminoglycan from articular cartilage and may reveal chondral damage not otherwise detected by structural MRI³⁴.

Another major change in imaging to assess mechanical hip problems has been the increasing use of dynamic methods. While CT reconstructions with collision software can simulate impingement, real-time ultrasound can delineate intra-articular and extra-articular impingement involving various hip structures^35,36. Ultrasound imaging requires some specialized equipment and training but is relatively inexpensive, comfortable for patients, quick, safe, and potentially also extremely useful for screening purposes.

An improved understanding of the natural history of anatomical patterns predisposing to osteoarthritis has paralleled contemporary characterization of the roles of instability and impingement in causing articular damage. Consequently, early and increasingly precise treatment directed at correcting problematic mechanics has been developed. These techniques have been potentiated by surgical techniques for deformity correction, such as the acetabulum-reorienting periacetabular osteotomy for correcting acetabular dysplasia and the direct structural reshaping by head-neck osteochondroplasty for relief of inclusion-type femoroacetabular impingement^37,38.

Important advances in surgical approaches have further increased the effectiveness of hip-preserving surgery by allowing direct exposure of the structures requiring correction while at the same time reducing operative morbidity. Open approaches for periacetabular osteotomy have moved far beyond the classical Smith-Petersen iliofemoral approach, which was associated with the risk of abductor weakness and heterotopic ossification, to the now standard direct anterior abductor-sparing approach, which allows excellent exposure for osteotomy cuts and anterior arthrotomy. Recently, the transsartorial rectus-sparing approach to periacetabular osteotomy has allowed extremely rapid functional recovery in patients having periacetabular osteotomy that does not require arthrotomy³⁹. The transtrochanteric surgical dislocation approach, devised by Ganz et al., is now standard for nondestructive, extensive, open intra-articular hip preservation surgery around the world^40-42.

Newer approaches to the hip joint allow surgery to be performed directly on articular cartilage, but biological obstacles to chondral repair remain a strong incentive to correct mechanical problems before irreversible chondral damage occurs^2,13,14,43. Experience provided by the surgical dislocation approach has facilitated the development of less invasive arthroscopic surgery to address a subset of intra-articular hip disorders that can be safely accessed through percutaneous portals^38,44. Hybrid surgical treatment programs are employed, when indicated, with combinations of osseous realignment via osteotomy and intra-articular surgery by arthrotomy or arthroscopy during the same anesthesia session^37,38,44.

Arthroscopic approaches to the hip to address chondral and labral pathology as well as bone changes for both cam-type and pincer-type femoroacetabular impingement have increased exponentially in the past decade. In comparison with the more invasive open procedures, these minimally invasive techniques have lowered perioperative morbidity and potentiated treatment of symptomatic patients earlier in the disease process. Reports on results of surgical treatment for hip impingement are appearing in increasing numbers. Follow-up is relatively short, even for the open surgical cases that predated the arthroscopic approach favored for the common “cam” subtype of impingement^34,44-46. Common themes are the poorer results noted in older patients, especially those with preexisting arthrosis, and in those in whom the mechanically important deformity has been incompletely corrected or overcorrected⁴⁷.

However, data from the outcomes of open procedures with regard to prolonging joint function for developmental dysplasia of the hip support the promise of early intervention. Developmental dysplasia of the hip remains common worldwide, making discussion of outcomes of realignment pelvic osteotomy highly relevant. Steppacher et al. reported on the mean twenty-year follow-up of Ganz’s original group of patients who underwent periacetabular osteotomy, with 61% of hips surviving⁴⁰. Matheney et al.⁴¹ and Søballe and Troelsen³⁹ reported midterm periacetabular osteotomy outcomes similar to the Bern experience⁴⁰. Risk factors associated with poor midterm and long-term periacetabular osteotomy outcomes in these three centers included preexisting osteoarthritis, incongruent joints, severe dysplasia, labral tears, older age at surgery, and overcorrection or undercorrection.

Newer strategies to treat and prevent osteoarthritis in the hip recognize the importance and interaction of anatomic, dynamic, and biological factors. Instability and impingement are common agents of articular damage in the hip, where the degree of chondral injury at the time of treatment remains a dominant factor in determining outcomes. Arthroscopic techniques show promise for earlier recognition and treatment of structural lesions that are placing mechanical stress on articular cartilage, thus further reducing the risk of osteoarthritis. Given the positive long-term outcomes with open procedures for developmental dysplasia of the hip, prospective clinical trials incorporating advanced structural imaging in addition to patient-reported outcomes to evaluate outcomes following hip arthroscopy for treatment of femoroacetabular impingement are important research priorities.

Summary

Orthopaedic surgeons treat the full spectrum of joint diseases, ranging from joint trauma to pre-osteoarthritic conditions and end-stage osteoarthritis. New information on the ability of articular cartilage to heal subsurface damage in a mechanically sound environment, the role of inflammation in osteoarthritis, and long-term clinical outcomes following operative correction of joint mechanics were presented. These data support a clinical paradigm shift toward early intervention strategies to delay the onset of disabling osteoarthritis. This symposium highlighted orthopaedic research at the forefront in transforming the clinical approach to osteoarthritis from palliation to prevention.