Allan A. Young

Proteoglycan 4 downregulation in a sheep meniscectomy model of early osteoarthritis

Osteoarthritis is a disease of multifactorial aetiology characterised by progressive breakdown of articular cartilage. In the early stages of the disease, changes become apparent in the superficial zone of articular cartilage, including fibrillation and fissuring. Normally, a monolayer of lubricating molecules is adsorbed on the surface of cartilage and contributes to the minimal friction and wear properties of synovial joints. Proteoglycan 4 is the lubricating glycoprotein believed to be primarily responsible for this boundary lubrication. Here we have used an established ovine meniscectomy model of osteoarthritis, in which typical degenerative changes are observed in the operated knee joints at three months after surgery, to evaluate alterations in proteoglycan 4 expression and localisation in the early phases of the disease. In normal control joints, proteoglycan 4 was immunolocalised in the superficial zone of cartilage, particularly in those regions of the knee joint covered by a meniscus. After the onset of early osteoarthritis, we demonstrated a loss of cellular proteoglycan 4 immunostaining in degenerative articular cartilage, accompanied by a significant (p < 0.01) decrease in corresponding mRNA levels. Early loss of proteoglycan 4 from the cartilage surface in association with a decrease in its expression by superficial-zone chondrocytes might have a role in the pathogenesis of osteoarthritis.

Patterns of loosening of polyethylene keeled glenoid components after shoulder arthroplasty for primary osteoarthritis: results of a multicenter study with more than five years of follow-up.

BACKGROUND The aim of this study was to radiographically analyze the long-term glenoid migration patterns following total shoulder arthroplasty to better understand the factors responsible for loosening. METHODS Complete radiographic follow-up of more than five years was available for 518 total shoulder arthroplasties performed for primary glenohumeral osteoarthritis with use of an anatomically designed prosthesis with a cemented, all-polyethylene, keeled glenoid component. Radiographs were assessed for humeral head subluxation, periprosthetic radiolucent lines, and shifting of the position of the glenoid component. The type of migration of the glenoid was defined according to the direction of tilt, or as subsidence in the case of medial migration. RESULTS Definite radiographic evidence of glenoid loosening was observed in 166 shoulders (32%) and was characterized by radiolucency of ≥2 mm over the entire bone-cement interface in thirty shoulders and by a migration of the glenoid component (shift or subsidence) in 136 shoulders. Three predominant patterns of migration of the glenoid component were observed: superior tilting in fifty-two shoulders (10%), subsidence in forty-one shoulders (7.9%), and posterior tilting in thirty-three shoulders (6.4%). Superior tilting of the glenoid was associated with three risk factors: low positioning of the glenoid component, superior tilt of the glenoid component on the immediate postoperative coronal plane radiographs, and superior subluxation of the humeral head (p < 0.05 for all). Subsidence of the glenoid component was associated with the use of reaming to optimize the seating and positioning of the glenoid component (p < 0.001). Posterior tilting of the glenoid component was associated with preoperative posterior subluxation (i.e., a Walch type-B glenoid) and with excessive reaming (p < 0.01 for both). CONCLUSIONS The three patterns of migration observed in this study underscore the potential importance of the supporting bone beneath the glenoid component. In some shoulders, use of a keel or pegs to provide fixation of a polyethylene component in the absence of good support from subchondral bone may not be sufficient to resist compressive and eccentric forces, resulting in loosening. Preserving subchondral bone may be important for long-term longevity of the glenoid component.

Results of anatomic nonconstrained prosthesis in primary osteoarthritis with biconcave glenoid.

BACKGROUND Biconcave glenoids in primary osteoarthritis represent a challenge because of the associated static posterior instability of the humeral head and secondary posterior glenoid erosion. This study evaluated the influence of different preoperative radiographic measurements on the outcome of total shoulder arthroplasty (TSA), particularly regarding the development of complications. MATERIALS AND METHODS We retrospectively evaluated 92 anatomic TSAs performed in 75 patients with primary osteoarthritis and a biconcave glenoid. All patients underwent preoperative imaging with an axial computed tomography arthrogram. Measurements were taken for posterior bone erosion depth and ratio as well as humeral head subluxation. Clinical outcomes were evaluated with the Constant score. RESULTS At an average follow up of 77 months (range, 14-180 months), 15 revisions (16.3%) were performed for glenoid loosening (6.5%), posterior instability (5.5%), or soft tissue problems (4.3%). At the final follow-up, the mean Constant score improved significantly from 32.4 to 68.8 points (P = .0001). Subjectively, 66.3% of patients were very satisfied or satisfied. Glenoid loosening was observed in 20.6% and was significantly associated with posterior bone erosion in depth (P = .005) and wear ratio (P = .02), humeral head subluxation (P = .01), and neoglenoid (P = .002) and intermediate glenoid retroversion (P = .001). Dislocation was correlated only with neoglenoid retroversion (P = .01). CONCLUSIONS Performing TSA in patients with osteoarthritis and biconcave glenoids resulted in acceptable clinical outcomes but a very high rate of complications. We found that the preoperative measurement of the neoglenoid retroversion was best for predicting postoperative complications in terms of glenoid loosening and dislocation.

Open Latarjet procedure for management of bone loss in anterior instability of the glenohumeral joint.

Glenoid bone loss is commonly observed in anterior glenohumeral instability and varies greatly in both its extent and significance. In 2000, Burkhart and De Beer reported a recurrence rate of 4% after arthroscopic Bankart repair for anterior instability in patients without significant bone deficiency, whereas the rate of recurrence was 67% in the presence of bony deficiency. They defined significant glenoid bone loss as an ‘‘inverted pear glenoid’’ in which there was greater than 25% loss of the inferior glenoid diameter. In the setting of anterior instability with significant glenoid bone loss, with large Hill-Sachs lesions, or with combined glenoid and humeral bony deficiencies, we have found the Latarjet procedure is effective in restoring stability to the shoulder. In 1954, Latarjet described a coracoid bone block technique to prevent anterior dislocation, suggesting that the horizontal limb of the coracoid process be fixed to the anteroinferior margin of the glenoid with a screw. Augmentation of the anteroinferior glenoid with this procedure has obvious advantages in cases of glenoid bone loss. However, this ‘‘bone blocking effect’’ only partly contributes to the stabilizing mechanism of the Latarjet procedure. Although the precise mechanism is still unknown, the success of the intervention is explained by a triple effect first proposed by Patte:

Surgical treatment of anterior instability in rugby union players: clinical and radiographic results of the Latarjet-Patte procedure with minimum 5-year follow-up.

BACKGROUND Anterior instability in rugby players is characterized by the common finding of a bony lesion, which has been identified as a potential cause of recurrence after soft-tissue reconstruction. The Latarjet-Patte procedure is effective in the treatment of recurrent anterior instability in collision sports such as rugby union. METHODS We retrospectively assessed 34 rugby players (37 shoulders) stabilized with the Latarjet-Patte procedure. The mean follow-up was 12 years. All patients underwent clinical and radiographic assessment preoperatively and at final follow-up. Functional evaluation was performed with the Walch-Duplay and Rowe scores. A visual analog scale score for the evaluation of pain and the subjective shoulder value were recorded. In addition, all patients completed a questionnaire regarding the return to playing rugby. RESULTS No recurrence of either dislocation or subluxation occurred. Persistent apprehension on clinical examination was present in 5 patients (14%). A bony lesion of the glenoid was present in 73% and a Hill-Sachs lesion in 68%. Sixty-five percent of the patients returned to playing rugby; only 1 patient did not return to playing rugby because of his shoulder. The mean Walch-Duplay and Rowe scores were 86 and 93 points, respectively. The mean subjective shoulder value was 90%. Radiographic healing of the bone block was observed in 89% of cases. At final follow-up, 11 patients (30%) had minor arthritic changes, with no cases of moderate or severe arthritis. CONCLUSION The Latarjet-Patte procedure provides a reliable method for stabilizing the shoulder, resulting in a return to playing rugby in a high number of cases without increasing the risk of long-term arthritic degradation.

Early results of reverse shoulder arthroplasty in patients with rheumatoid arthritis.

BACKGROUND Rheumatoid arthritis affecting the shoulder is typically associated with rotator cuff compromise and can also result in severe glenoid erosion. Since reverse shoulder arthroplasty is capable of addressing both rotator cuff disorders and glenoid bone deficiencies, our aim was to evaluate the outcome of reverse shoulder arthroplasty in patients with rheumatoid arthritis and either or both of these associated conditions. METHODS We performed eighteen primary reverse total shoulder arthroplasties in sixteen patients with rheumatoid arthritis involving the shoulder as well as associated rotator cuff compromise and/or severe erosion of the glenoid bone between 2002 and 2007. Patients were assessed with use of the Constant score, patient satisfaction score, subjective shoulder value, range of shoulder motion, and imaging studies. RESULTS The mean Constant score improved from 22.5 to 64.9 points at a mean of 3.8 years (range, 2.1 to 7.0 years) postoperatively. The patients were either very satisfied or satisfied with the outcome of the surgery in seventeen of the eighteen shoulders. The mean subjective shoulder value was 68.6% postoperatively. Active forward elevation improved from 77.5° to 138.6°, and external rotation with the arm in 90° of abduction improved from 16.9° to 46.1°. The mean Constant score improved from 28.0 points to 74.3 points in shoulders in which the teres minor muscle was normal before the surgery, and it improved from 20.8 to 54.6 points in shoulders with an atrophic teres minor muscle. Scapular notching was observed in ten of the eighteen shoulders. A fracture involving the acromion, acromial spine, coracoid, or greater tuberosity was observed either intraoperatively or postoperatively in four of the eighteen shoulders. One case of transient axillary nerve injury was noted. There were no cases of dislocation, infection, or component loosening. None of the patients required revision surgery for any reason. CONCLUSIONS Comparatively good outcomes were observed in the short to intermediate term after reverse shoulder arthroplasty in patients with rheumatoid arthritis. However, surgeons should be aware of the risk of intraoperative and postoperative fractures in this patient group.

Secondary rotator cuff dysfunction following total shoulder arthroplasty for primary glenohumeral osteoarthritis: results of a multicenter study with more than five years of follow-up.

BACKGROUND Secondary rotator cuff dysfunction is a recognized complication following shoulder arthroplasty. We hypothesized that the rate of secondary rotator cuff dysfunction would increase with follow-up and result in less satisfactory clinical and radiographic outcomes. Our aim was to investigate the rate of secondary rotator cuff dysfunction following shoulder arthroplasty for primary osteoarthritis and identify factors associated with the dysfunction. METHODS Between 1991 and 2003, in ten European centers, 704 total shoulder arthroplasties were performed for primary glenohumeral osteoarthritis. Complete radiographic and clinical follow-up of more than five years was available for 518 shoulders. The diagnosis of secondary rotator cuff dysfunction was made when moderate or severe superior subluxation of the prosthetic humeral head was present on radiographs. Multivariate logistic regression identified factors associated with the development of rotator cuff dysfunction. Kaplan-Meier survivorship analysis was performed, with the end point being secondary rotator cuff failure. Clinical outcome was assessed with use of the Constant score, a subjective assessment of the shoulder, and an evaluation of shoulder motion. RESULTS At an average of 103.6 months (range, sixty to 219 months) after shoulder arthroplasty, the rate of secondary rotator cuff dysfunction was 16.8%. Survivorship free of secondary cuff dysfunction was 100% at five years, 84% at ten years, and 45% at fifteen years. Duration of follow-up (p < 0.0001), implantation of the glenoid implant with superior tilt (p < 0.001), and fatty infiltration of the infraspinatus muscle (p < 0.05) were risk factors for the development of secondary cuff dysfunction. Patients with secondary rotator cuff dysfunction had significantly worse clinical outcomes (Constant score, subjective assessment, and range of motion; p < 0.0001) and radiographic results (radiolucent line score, radiographic loosening, glenoid component migration; p < 0.0001). CONCLUSIONS In this study, rates of secondary rotator cuff dysfunction with moderate or severe superior subluxation of the prosthetic humeral head increased with the duration of follow-up and significantly influenced the clinical and radiographic outcome of total shoulder arthroplasty performed for primary glenohumeral osteoarthritis. Preoperative fatty infiltration of the infraspinatus muscle and implantation of the glenoid component with superior tilt were prognostic factors.

Modulation of aggrecan and ADAMTS expression in ovine tendinopathy induced by altered strain

OBJECTIVE To evaluate histologic, immunohistochemical, and molecular changes in tendon induced by altered strain in a large-animal model. METHODS A full-thickness partial-width laceration of the infraspinatus tendon was created in 5 sheep, while 5 sham-operated sheep were used as controls. Sheep were killed after 4 weeks, and 4 differentially stressed tendon regions (tensile or near bone attachment from overstressed or stress-deprived halves) were evaluated for histopathology, proteoglycan (PG) accumulation, and characterization of glycosaminoglycans and aggrecan catabolites. Gene expression of matrix components, enzymes, and inhibitors was analyzed by reverse transcriptase-polymerase chain reaction. RESULTS Histopathologic changes were detected in both overstressed and stress-deprived tensile tendon, but only in stress-deprived tendon near bone. In overstressed and stress-deprived tensile tendon, levels of keratan sulfate, chondroitin 4-sulfate, and chondroitin 6-sulfate were increased. In overstressed tensile tendon, levels of ADAMTS-generated aggrecan catabolites were increased. There was increased matrix metalloproteinase 13 (MMP-13) and decreased fibromodulin and decorin expression in all regions. Increased MMP-1, MMP-9, MMP-14, and ADAMTS-1 expression, and decreased type II collagen expression were restricted to stress-deprived tendon. In stress-deprived bone-attachment regions, messenger RNA (mRNA) for aggrecan was decreased, and ADAMTS was increased. In overstressed tensile tendon, aggrecan mRNA was increased, and ADAMTS was decreased. CONCLUSION The distinct molecular changes in adjacent tissue implicate altered strain rather than humoral factors in controlling abnormal tenocyte metabolism, and highlight the importance of regional sampling. Tendon abnormalities induced by increased strain are accompanied by increased aggrecan, decreased ADAMTS, and low PG expression, which may negatively impact the structural integrity of the tissue and predispose to rupture.

Regional assessment of articular cartilage gene expression and small proteoglycan metabolism in an animal model of osteoarthritis

Osteoarthritis (OA), the commonest form of arthritis and a major cause of morbidity, is characterized by progressive degeneration of the articular cartilage. Along with increased production and activation of degradative enzymes, altered synthesis of cartilage matrix molecules and growth factors by resident chondrocytes is believed to play a central role in this pathological process. We used an ovine meniscectomy model of OA to evaluate changes in chondrocyte expression of types I, II and III collagen; aggrecan; the small leucine-rich proteoglycans (SLRPs) biglycan, decorin, lumican and fibromodulin; transforming growth factor-β; and connective tissue growth factor. Changes were evaluated separately in the medial and lateral tibial plateaux, and were confirmed for selected molecules using immunohistochemistry and Western blotting. Significant changes in mRNA levels were confined to the lateral compartment, where active cartilage degeneration was observed. In this region there was significant upregulation in expession of types I, II and III collagen, aggrecan, biglycan and lumican, concomitant with downregulation of decorin and connective tissue growth factor. The increases in type I and III collagen mRNA were accompanied by increased immunostaining for these proteins in cartilage. The upregulated lumican expression in degenerative cartilage was associated with increased lumican core protein deficient in keratan sulphate side-chains. Furthermore, there was evidence of significant fragmentation of SLRPs in both normal and arthritic tissue, with specific catabolites of biglycan and fibromodulin identified only in the cartilage from meniscectomized joints. This study highlights the focal nature of the degenerative changes that occur in OA cartilage and suggests that altered synthesis and proteolysis of SLRPs may play an important role in cartilage destruction in arthritis.

Glycosaminoglycan content of knee cartilage following posterior cruciate ligament rupture demonstrated by delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC). A case report.

Following joint trauma and during the early stages of cartilage degeneration, typical changes become apparent in tissue structure and composition, including the loss of glycosaminoglycan1,2. These changes often are not apparent on conventional magnetic resonance imaging or visible at arthroscopy, thereby precluding diagnosis. Delayed gadolinium-enhanced magnetic resonance imaging of cartilage, or dGEMRIC, is an emerging in vivo method for the assessment of the biochemical composition of articular cartilage and provides a surrogate measure of glycosaminoglycan content3,4. When injected intravenously, the anionic contrast agent gadolinium diethylene triamine penta-acetic acid (Gd-DTPA2–) penetrates cartilage both from the synovial surface and from the subchondral bone3,5. Given sufficient time, the anionic contrast agent distributes inversely to the fixed negative charge associated with the cartilage glycosaminoglycan content in accordance with the Donnan principle of equilibrium. Gd-DTPA2-therefore distributes in relatively higher concentrations in regions of low glycosaminoglycan, and vice versa. Gd-DTPA2-has a concentration-dependent effect on the magnetic resonance imaging parameter T1; therefore, T1 imaging in the presence of Gd-DTPA2– (T1Gd) reflects the cartilage Gd-DTPA2–concentration and, hence, glycosaminoglycan concentration. We present the case of a patient (one of the authors [A.A.Y.]) who sustained an injury to the posterior cruciate ligament of the knee while enrolled as a “normal” control subject in a dGEMRIC study of the knee. This incidental occurrence provided us with a unique opportunity to visualize the temporal and spatial changes that occur in cartilage biochemistry following an acute posterior cruciate ligament rupture. Athirty-year-old man (one of the authors [A.A.Y.]) was involved in a motor-vehicle accident in which he sustained a direct blow to the anterior aspect of the proximal portion of the right tibia at 90° of knee flexion (a typical “dashboard” type of …