A two-year clinical outcomes study of 400 patients, comparing open surgery and arthroscopy for rotator cuff repair.

OBJECTIVES: The aim of this study was to determine whether there is any significant difference in temporal measurements of pain, function and rates of re-tear for arthroscopic rotator cuff repair (RCR) patients compared with those patients undergoing open RCR. METHODS: This study compared questionnaire- and clinical examination-based outcomes over two years or longer for two series of patients who met the inclusion criteria: 200 open RCR and 200 arthroscopic RCR patients. All surgery was performed by a single surgeon. RESULTS: Most pain measurements were similar for both groups. However, the arthroscopic RCR group reported less night pain severity at six months, less extreme pain and greater satisfaction with their overall shoulder condition than the open RCR group. The arthroscopic RCR patients also had earlier recovery of strength and range of motion, achieving near maximal recovery by six months post-operatively whereas the open RCR patients took longer to reach the same recovery level. The median operative times were 40 minutes (20 to 90) for arthroscopic RCR and 60 minutes (35 to 120) for open RCR. Arthroscopic RCR had a 29% re-tear rate compared with 52% for the open RCR group (p < 0.001). CONCLUSIONS: Arthroscopic RCR involved less extreme pain than open RCR, earlier functional recovery, a shorter operative time and better repair integrity.

Effect of taping on the shoulders of Australian football players.

BACKGROUND: Taping of the shoulder is common in many sports, particularly Australian football, a contact sport that often involves marking (catching) the ball overhead and has a high incidence of shoulder instability. HYPOTHESIS: Taping of the shoulder reduces glenohumeral joint laxity and improves proprioception without impairing function. STUDY DESIGN: Crossover study design. METHODS: 33 male players aged 18-31 years were recruited from a local Australian football club. The dominant shoulder of each player was tested with and without taping in a randomised fashion by an examiner blinded to the presence or absence of taping. The tests were (1) inferior glenohumeral joint laxity (the Orthopaedic Research Institute laxometer), (2) shoulder joint position sense accuracy using an optical tracking system, and (3) handballing accuracy. RESULTS: The methods for testing laxity and joint position sense had good intraobserver reliability and sensitivity. All subjects tolerated the taping and testing. Glenohumeral joint laxity (p=0.75), joint position sense (p=0.56) and handballing accuracy (p=0.6) were not changed by taping. CONCLUSIONS: Taping of the shoulder joint in uninjured and non-symptomatic Australian football players in a pattern that attempted not to restrict their range of overhead movement did not significantly affect the accuracy of joint position sense, inferior laxity or handball accuracy. CLINICAL RELEVANCE: These data suggest that taping of the shoulder is unlikely to decrease the incidence of injury-specifically dislocation-of the shoulder in Australian football players.

Cytokines and apoptosis in supraspinatus tendinopathy.

The role of inflammatory cells and their products in tendinopathy is not completely understood. Pro-inflammatory cytokines are upregulated after oxidative and other forms of stress. Based on observations that increased cytokine expression has been demonstrated in cyclically-loaded tendon cells we hypothesised that because of their role in oxidative stress and apoptosis, pro-inflammatory cytokines may be present in rodent and human models of tendinopathy. A rat supraspinatus tendinopathy model produced by running overuse was investigated at the genetic level by custom micro-arrays. Additionally, samples of torn supraspinatus tendon and matched intact subscapularis tendon were collected from patients undergoing arthroscopic shoulder surgery for rotator-cuff tears and control samples of subscapularis tendon from ten patients with normal rotator cuffs undergoing arthroscopic stabilisation of the shoulder were also obtained. These were all evaluated using semiquantitative reverse transcription polymerase chain-reaction and immunohistochemistry. We identified significant upregulation of pro-inflammatory cytokines and apoptotic genes in the rodent model (p = 0.005). We further confirmed significantly increased levels of cytokine and apoptotic genes in human supraspinatus and subscapularis tendon harvested from patients with rotator cuff tears (p = 0.0008). These findings suggest that pro-inflammatory cytokines may play a role in tendinopathy and may provide a target for preventing tendinopathies.

Randomised, double-blind, placebo-controlled clinical trial of a new topical glyceryl trinitrate patch for chronic lateral epicondylosis.

OBJECTIVE: This study aimed to determine whether a new glyceryl trinitrate patch preparation is effective in treating chronic lateral epicondylosis. DESIGN: Randomised double-blind controlled clinical trial. SETTING: Private practice PATIENTS: 154 adult patients with chronic lateral epicondylosis were recruited, with 136 patients completing the trial. INTERVENTIONS: 8 weeks of glyceryl trinitrate patch application (dosages of 72 mg/24 h, 1.44 mg/24 h, and 3.6 mg/24 h), or placebo patch application. MAIN OUTCOME MEASURES: Subjective global assessment of change in elbow symptoms, patient-rated tennis elbow evaluation, visual analogue pain at rest, visual analogue pain with activity, visual analogue pain intensity, grip strength, and strength testing using the Orthopaedic Research Institute-Tennis Elbow Testing System. RESULTS: At 8 weeks there was a significant decrease in elbow pain with activity in the glyceryl trinitrate 0.72 mg/24 h group compared with placebo (p = 0.04). There were no other significant differences. CONCLUSIONS: Continuous 1.25 mg/24 h topical glyceryl trinitrate treatment, when combined with daily exercise rehabilitation, has previously demonstrated efficacy in treating chronic lateral epicondylosis. There was significantly decreased elbow pain with activity at 8 weeks in the glyceryl trinitrate 0.72 mg/24 h group (p = 0.04). This short-term dose-ranging study did not demonstrate a treatment effect of a new topical glyceryl trinitrate patch in dosages of 1.44 mg/24 h or 3.6 mg/24 h, which conflicts with previous studies on topical glyceryl trinitrate treatment. TRIAL REGISTRATION NUMBER: NCT00447928.

The effectiveness of arthroscopic stabilisation for failed open shoulder instability surgery.

We identified ten patients who underwent arthroscopic revision of anterior shoulder stabilisation between 1999 and 2005. Their results were compared with 15 patients, matched for age and gender, who had a primary arthroscopic stabilisation during the same period. At a mean follow-up of 37 and 36 months, respectively, the scores for pain and shoulder function improved significantly between the pre-operative and follow-up visits in both groups (p = 0.002), with no significant difference between them (p = 0.4). The UCLA and Rowe shoulder scores improved significantly (p = 0.004 and p = 0.002, respectively), with no statistically significant differences between groups (p = 0.6). Kaplan-Meier analysis for time to recurrent instability showed no differences between the groups (p = 0.2). These results suggest that arthroscopic revision anterior shoulder stabilisation is as reliable as primary arthroscopic stabilisation for patients who have had previous open surgery for recurrent anterior instability.

Reliability of a new shoulder laxometer to assess inferior glenohumeral joint translation.

OBJECTIVE: This study tested the reliability of the ORI laxometer, a newly developed non-invasive device for testing inferior translation of the humeral head in humans. DESIGN: The instrument was designed to measure displacement between the top of the acromion and the head of the humerus when loaded in a similar fashion to the sulcus sign. PARTICIPANTS AND INTERVENTIONS: Sixteen healthy subjects (32 shoulders) were measured for inferior glenohumeral joint laxity. One observer used the laxometer in 16 subjects on three separate occasions for the intra-observer trial. Three observers measured the inferior shoulder laxity of six subjects on one occasion in the inter-observer trial. Asymptomatic and unstable shoulders were also compared in 12 subjects with shoulder instability. MAIN OUTCOME MEASUREMENTS: Translation in the glenohumeral joint RESULTS: The range of inferior translation of glenohumeral joint in these subjects was between 0.01 mm and 6.5 mm with a mean of 1.5 mm. The intraclass correlation coefficient (ICC) for inter-observer reliability was 0.74. For intra-observer reliability the ICC was 0.76. These results are considered to be good to excellent. There was no advantage gained by using data from all five cycles of testing compared with three cycles. In patients with shoulder instability, laxometer measurements were significantly greater in their unstable shoulders than in their normal shoulders. CONCLUSIONS: The laxometer is easy to use, painless and gives objective measures for inferior glenohumeral laxity, with good intra- and inter-observer reliabilities. The ORI laxometer may be useful for assessing and monitoring global glenohumeral joint laxity which usually involves inferior laxity.

A sensitive stain for aluminum in undecalcified cancellous bone.

Aluminum is known to accumulate with age in bone and other tissues of humans, even in the absence of renal disease. Our study aimed to develop a histological staining method sufficiently sensitive to detect aluminum in plastic sections of undecalcified bone biopsies from healthy volunteers as well as from patients with renal and non-renal bone diseases. We used quantitative histomorphometry to measure the percentage of trabecular surface stained by aluminum and found that our new method was approximately 50% more sensitive for detecting aluminum than the Acid Solochrome Azurine (ASA) method which in turn was significantly more sensitive than the Aluminon method. Aluminon is widely used in pathology laboratories for diagnostic purposes despite concerns in the literature about Aluminon's limited sensitivity for aluminum. Our histomorphometric results showed that the newly developed method stained approximately 10% of the trabecular surface in bone sections from healthy controls, 38% from renal patients, 26% from patients with vitamin D deficiency, and 29% from patients with osteoporosis. Histomorphometric measurements of aluminum-stained trabecular surfaces in sections stained with ASA were consistent with those obtained in Walton-stained sections but proportionately lower. Moreover, the Walton and ASA methods stained aluminum at similar locations in adjacent bone sections. As the ASA and Walton methods are considerably more sensitive for bone aluminum than the Aluminon method, we recommend that either of them should be used in place of the Aluminon method for routine diagnostic purposes.

Adductor strain and hip range of movement in male professional soccer players.

PURPOSE: To determine whether hip range of movement (ROM) can predict the occurrence of adductor strain among male professional soccer players. METHODS: 120 subjects were prospectively selected from 6 professional soccer clubs in Australia. Internal rotation, external rotation, and ROM of the hip were measured using a goniometer before and during the course of a soccer season (2003-2004). When adductor strain occurred, further assessments of the hip were performed. Injured subjects' hip ROMs were measured again at the end of the season. RESULTS: Eight of the 120 subjects had 9 adductor strains (one bilateral). There was a correlation between preseason decreased hip ROM and occurrence of adductor strain. The mean preseason hip ROM was 44.7 degrees in the injured group and 53.7 degrees in the uninjured group. Once the subjects were able to resume playing soccer, their hip ROM increased to near pre-injury levels. CONCLUSION: Decreased hip ROM may be considered an aetiological factor in the occurrence of adductor strain in male professional soccer players.

Arthroscopic estimation of the extent of chondropathy.

INTRODUCTION: Arthroscopy has been used to evaluate articular cartilage (AC) pathology in osteoarthritis (OA) for outcome measurement and validation of non-invasive imaging. However, many fundamental aspects of arthroscopic assessment remain un-validated. OBJECTIVES: This study evaluated arthroscopic estimates of extent of chondropathy. METHODS: Serial arthroscopic assessments were performed in a group of 15 sheep before and after bilateral stifle medial meniscectomy (MMx). Post-mortem assessments were performed in un-MMx sheep and 4 and 16 weeks post-MMx. Arthroscopic assessments of the extent of each grade of chondropathy were compared with a non-arthroscopic hybrid assessment that incorporated biomechanical, thickness and macroscopic assessments. RESULTS: Arthroscopy evaluated only 36% of AC and missed significant pathological changes, softening and chondro-osteophyte, occurring in peripheral regions. The patterns of change in arthroscopic assessments were similar to those of the non-arthroscopic assessment but there was a very strong tendency to over-estimate the extent of softened AC after MMx. In spite of these limitations arthroscopic assessments were responsive to change. Estimates of the extent of normal and softened AC were most responsive to change over time followed by estimates of superficial and deep fibrillation. Arthroscopy was as an excellent discriminator between normal and OA. Assessments of chondro-osteophyte and exposed bone were not responsive to change. CONCLUSIONS: Arthroscopic estimates of extent of chondropathy are prone to substantial error. While experience and training may reduce these errors other approaches may more effectively improve performance.

Microarray analysis of the tendinopathic rat supraspinatus tendon: glutamate signaling and its potential role in tendon degeneration.

Degenerative tendon injury or "tendinopathy" is one of the most common disorders of the musculoskeletal system. We used a rat model (Soslowsky LJ, Thomopoulos S, Tun S, Flanagan CL, Keefer CC, Mastaw J, and Carpenter JE. J Shoulder Elbow Surg 9: 79-84, 2000) to identify novel gene expression in the exercised-induced degenerated supraspinatus tendon by microarray and real-time PCR analyses. We identified several novel groups of differentially expressed genes, including those involved in apoptosis and related stress responses, and also genes that appear to be involved in glutamate signaling in tendon tissue, similar to recent findings by us in a microarray study of healing in the transected Achilles tendon of the rat (24). Until recently this kind of cellular communication was thought only to exist in cells of the central nervous system (CNS), where it is vital for CNS function. We further show that glutamate appears to induce a proapoptotic response in cultured tendon cells, similar to the "excitotoxic" response of cells in the CNS that become overstimulated. This may prove to be at least a partial cause of degeneration in overused tendon tissue and allow the development of treatments or "prehibilitation" regimens for tendinopathy based on currently used non-toxic glutamate antagonists.

Microarray analysis of healing rat Achilles tendon: evidence for glutamate signaling mechanisms and embryonic gene expression in healing tendon tissue.

Tendon healing is a complex process consisting of a large number of intricate pathways roughly divided into the phases of inflammation, proliferation, and remodeling. Although these processes have been extensively studied at a variety of levels in recent years, there is still much that remains unknown. This study used microarray analyses to investigate the process at a genetic level in healing rat Achilles tendon at 1, 7, and 21 days postinjury, roughly representing the inflammation, proliferation, and remodeling phases. An interesting temporal expression profile was demonstrated, identifying both known and novel genes and pathways involved in the progression of tendon healing. Both inflammatory response and pro-proliferative genes were shown to be significantly upregulated from 24 h postinjury through to 21 days. Day 7 showed the largest increase in genetic activity, particularly with the expression of collagens and other extracellular matrix genes. Interestingly, there was also evidence of central nervous system-like glutamate-based signaling machinery present in tendon cells, as has recently been shown in bone. This type of signaling mechanism has not previously been shown to exist in tendon. Another novel finding from these analyses is that there appears to be several genes upregulated during healing which have exclusively or primarily been characterized as key modulators of proliferation and patterning during embryonic development. This may suggest that similar pathways are employed in wound healing as in the tightly regulated progression of growth and development in the embryo. These results could be of use in designing novel gene-based therapies to increase the efficacy and efficiency of tendon healing.

Spontaneous recovery of injured Achilles tendon in inducible nitric oxide synthase gene knockout mice.

OBJECTIVE AND DESIGN: To determine if inducible nitric oxide synthase (iNOS) gene could affect Achilles tendon healing using iNOS gene knockout mice. METHODS: 21 iNOS knockout (iNOS(-/-)) mice and 8 of the wild type (iNOS(+/+)) mice were utilized in this study. Group 1: iNOS(+/+) mice (n = 8), group 2: iNOS(-/-) mice (n = 11) and group 3: iNOS(-/-) with a NOS inhibitor, (aminoguanidine, 500 mg/kg/day, via an intraperitoneal mini-osmotic pump for 7 days, n = 10). The right Achilles tendon was transected in all mice and harvested on day 7 for cross-sectional area and biomechanical properties. Serum nitrate concentration of the mice was measured by gas chromatography mass spectrometry (GC/MS). RESULTS: A significant reduction in cross-sectional area of the healing Achilles tendon was observed in group 3 mice compared to group 2 mice (p < 0.01). The serum nitrate concentration in both group 2 and group 3 mice was lower than that in group 1 mice (p < 0.01) iNOS gene deletion and inhibition of NOS did not affect the biomechanical properties of the healing tendons. CONCLUSIONS: iNOS gene is not solely responsible for the beneficial effects of nitric oxide (NO) on tendon healing.

Overexpression of nitric oxide synthases in tendon overuse.

Tendon disorders with a chronic nature, including the rotator cuff, are extremely common, and represent a major clinical problem. Mechanical overload has been proposed as an important etiologic factor in tendinopathies. Nitric oxide (NO), a free radical produced by nitric oxide synthases (NOSs), is a potent regulator and stimulator of biological processes including tendon degeneration and healing. It is also involved in response to mechanical stimuli in different tissues. In an animal model of acutely injured tendon healing temporal and differential expression of NOS isoforms has been demonstrated, suggesting that different patterns of NOSs expression may have different biological functions. Therefore, we hypothesized that tendon overuse may result in a differential upregulation of NOSs, particularly iNOS. An animal model of supraspinatus tendon overuse was utilized, which consisted of treadmill running. A group of animals of the same strain and age subjected to normal cage activity were used as controls. Following a 4-week exercise protocol supraspinatus tendons were harvested, RNA was extracted, and subjected to competitive reverse transcription and polymerase chain reaction (RT-PCR) to determine the expression levels of inducible-, endothelial-, and neuronal-NOS isoforms (i-, e-, and nNOS). The mRNA expression of all three NOS isoforms increased in the supraspinatus tendons as a result of overuse exercise. iNOS and eNOS mRNA expression increased fourfold (p < 0.01), and there was an increase, but statistically not significant, in nNOS mRNA expression in the overused tendons when compared with the controls. This study is the first to show that NOS isoforms are upregulated in rotator cuff tendon as a result of chronic overuse, and suggests the involvement of nitric oxide in the response of tendon tissue to increased mechanical stress.

Ovariectomy alters the structural and biomechanical properties of ovine femoro-tibial articular cartilage and increases cartilage iNOS.

OBJECTIVE: To examine the effect of oestrogen depletion produced by surgical ovariectomy on the structural and biomechanical properties of ovine femoro-tibial articular cartilage (AC), and the production of inducible nitric oxide synthase (iNOS) and nitrotyrosine by these tissues. METHODS: Six aged ewes were surgically ovariectomised (OVX), while six were used as unoperated controls. Dynamic biomechanical indentation testing of tibial plateau AC was performed at 26 weeks post-op. Histological sections of medial tibial plateau and lateral tibial plateau (LTP), medial and lateral femoral condyles (MFC, LFC) and patellar AC were examined for histopathology, toluidine blue staining intensity, and patterns of collagen birefringence intensity. Immunoreactivity for iNOS and nitrotyrosine was assessed in full-thickness biopsy plugs of LFC and patellar AC, and patellar AC explants were cultured to determine in vitro NO release. RESULTS: Phase lag was reduced overall in LTP-AC of OVX sheep (10.9+/-2.2 degrees vs 12.1+/-2.3 degrees ; P<0.0001). Cartilage thickness was reduced in the LTP of OVX sheep (P=0.0002), in association with localised changes in dynamic shear modulus. Toluidine blue staining intensity was reduced in the patella, LFC, and MFC. Histological examination revealed greater histopathology scores in the MFC of OVX animals, and altered collagen birefringence intensity plots in the LTP. Immunostaining for iNOS was increased in patella AC (P=0.008), whilst nitrotyrosine immunoreactivity was increased in patella (P=0.03) and LFC (P<0.0001) AC. NO release by patellar AC explants was also elevated. CONCLUSIONS: Oestrogen depletion induced by OVX caused regional thinning of femoro-tibial cartilage, with biomechanical and histological changes suggestive of a disturbance in the content and/or structural organisation of the proteoglycan and collagen macromolecular assembly. The observed up-regulation of cartilage iNOS suggests a possible mechanism for these matrix changes.

Arthroscopy -- a potential "gold standard" for the diagnosis of the chondropathy of early osteoarthritis.

OBJECTIVES: The aims of this study were to: 1. Evaluate the performance of arthroscopy for the diagnosis of chondropathy and to compare it to that of direct non-arthroscopic assessments; 2. Determine intra-observer reliability of arthroscopic assessments; 3. Evaluate the effects of the arthroscopic video quality and probing upon diagnostic performance. DESIGN: The ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) was used assuming that pre-MMx articular cartilage (AC) was "normal" and post-MMx AC "chondropathic". Video recordings of arthroscopic assessments of each stifle compartment were evaluated. Scores were given for the quality of the video and the amount of probing. The diagnostic performances of dynamic shear modulus (G), light microscopic assessment and superficial zone collagen birefringence assessments were evaluated and compared to that of arthroscopy. Intra-observer reliability of arthroscopic assessments was also evaluated. RESULTS: Arthroscopic assessments had high sensitivity (91-100%), specificity (62-88%) and accuracy (75-93%) for the diagnosis of chondropathy 16 weeks after MMx. Arthroscopy compared favourably with the direct non-arthroscopic assessments in the lateral compartment and was found to have extremely high intra-observer reliability (kappa 0.78-1.00). The quality of arthroscopic video recordings and the amount of probing did not significantly influence accuracy or reliability. CONCLUSIONS: Arthroscopy performs as well as direct non-arthroscopic assessments of AC for diagnosis of early OA. These results suggest that arthroscopy can be used as a "gold standard" for the validation of non-invasive assessments like magnetic resonance imaging and that arthroscopic diagnosis can be based on small amounts of video footage without AC probing.

Biomechanical, histologic and macroscopic assessment of articular cartilage in a sheep model of osteoarthritis.

OBJECTIVES: Our primary objective was to explore the full potential of the ovine medial meniscectomy (MMx) model of early osteoarthritis (OA) for studies to validate non-destructive articular cartilage (AC) assessments and therapeutic interventions. Our secondary objective was to re-evaluate the relationships between the different types of AC assessment after MMx in sheep. METHODS: Macroscopic assessments, dynamic shear modulus (G*), phase lag and AC thickness measurements were performed at a total of 5437 reference points on all six articular surfaces in four normal joints and 16 MMx ovine stifle (knee) joints. Comparisons with histologic assessments of gross structural damage, collagen organisation (birefringence) and proteoglycan content were possible at 702 of these points. RESULTS: Histologic gross structural damage and proteoglycan loss were seen throughout the joint with greatest severity (fibrillation) in closest proximity to the MMx site. Increases in AC (30-50%) thickness, reductions in G* (30-40%) and collagen birefringence intensity (15-30%) occurred more evenly throughout the joint. Macroscopic softening was evident only when G* declined by 80%. G* correlated with AC thickness (rho=-0.47), collagen organisation rho=0.44), gross structural damage (rho=-0.44) and proteoglycan content (rho=0.42). Multivariate analysis showed that collagen organisation contributed twice as much to dynamic shear modulus (t=6.66 as proteoglycan content (t=3.21). Collagen organisation (rho=0.11) and proteoglycan content (rho=0.09) correlated only weakly to phase lag. CONCLUSIONS: Macroscopic assessments were insensitive to AC softening suggesting that arthroscopic assessments of AC status might also perform poorly. Collagen integrity was more important for the maintenance of AC stiffness (G*) than proteoglycan content. The development of major AC softening and thickening throughout the joint following MMx suggested involvement of non-mechanical (e.g., protein and biochemical) chemical and cytokine mediated processes in addition to the disturbance in biomechanical loading. The ovine MMx model provides a setting in which the spectrum of AC changes associated with the initiation and progression of OA may be evaluated.

Addition of nitric oxide via nitroflurbiprofen enhances the material properties of early healing of young rat Achilles tendons.

OBJECTIVE AND DESIGN: To determine if the addition of nitric oxide (NO) via nitroflurbiprofen (NO-flurbiprofen) would enhance rat Achilles tendon healing. MATERIALS AND METHODS: Sixty-five male Sprague-Dawley rats were randomly divided into NO-flurbiprofen, flurbiprofen and vehicle groups, given drugs or vehicle subcutaneously, and their right Achilles tendon divided. Histological assessment was carried out at day 5, 10, and 15 post-operation. Healing tendon biomechanical properties and hydroxyproline content were measured at day 10. RESULTS: The healing Achilles tendon from the NO-flurbiprofen and flurbiprofen groups showed a better organization of extracellular collagenous matrix than that from the vehicle group. Flurbiprofen and NO-flurbiprofen decreased healing tendon cross-sectional area by 30% and 20%. This reduction was accompanied by a decreased failure load in the flurbiprofen group, but not the NO-flurbiprofen group. NO-flubiprofen prevented the reduction of body weight gain observed in the flubiprofen group. CONCLUSION: Both flurbiprofen and NO-flurbiprofen promoted better collagen reorganization during tendon healing. NO-flurbiprofen further improved tendon healing by increasing tendon stress and reducing the side effects (body weight loss) of flurbiprofen. The enhanced tendon healing by NO-flurbiprofen is likely due to the release of NO from the compound.

Topographical analysis of the structural, biochemical and dynamic biomechanical properties of cartilage in an ovine model of osteoarthritis.

OBJECTIVE: The relationship between the topographical variations in the structural, biochemical and dynamic biomechanical properties of articular cartilage (AC) before and 6 months after meniscectomy has not been previously reported but is clearly relevant to our understanding of the role of mechanical factors on the pathogenesis of osteoarthritis (OA). The objective of this study was to address this deficiency using an ovine model of OA induced by bilateral lateral meniscectomy. DESIGN: The dynamic effective shear modulus (G*) and phase lag were determined ex vivo at 26 individual locations over the medial and lateral tibial plateaux of non-operated and meniscectomized ovine joints 6 months after surgery using a novel hand-held dynamic indentation probe. AC thickness was measured with a needle penetration probe. The AC from the same topographical locations as indented was then analysed for sulfated glycosaminoglycans (S-GAG) as a measure of proteoglycan (PG) levels, collagen and water content. Histological evaluation of the collagen organization using quantitative analysis of birefringence intensity was performed on stained tissue sections from the same topographical locations of each animal. RESULTS: It was demonstrated that the AC of the entire lateral tibial compartment of the meniscectomized joints underwent significant local degenerative and compensatory changes as indicated by a decreased G* and an increase in phase lag and water content. This was accompanied by a decrease in PG content of the AC of the middle and inner regions. While the AC of the outer region of the lateral meniscectomized compartment showed a marked increase in PG content and a more than two-fold increase in thickness, these tissues were also found to be structurally inferior, as indicated by a decreased G* and abnormal collagen birefringence intensity. The AC thickness was elevated at all locations of the lateral and medial tibial plateau of the meniscectomized joints. Strong and significant correlations between the biomechanical and biochemical data were established for a number of the parameters examined, especially between collagen content and G*, collagen content and AC thickness, and G* and AC thickness. An inverse correlation between S-GAG content and G* was only apparent in non-operated control tissues, whereas correlations between collagen and water content, water content and G*, and water content and thickness were evident for AC of the meniscectomized tibial plateaux. Less striking changes were noted in the medial compartment where the intact meniscus remained in place. However, elevated PG content, thicker AC together with slight changes in G* suggested an early hypertrophic response in these tissues. CONCLUSION: This study has highlighted the variable response of AC in different topographical regions of meniscectomized joints to the altered mechanical stresses introduced by this surgical procedure. The AC at the joint margins, while thicker and richer in PG, was found to be biomechanically softer (lower shear modulus) than normal AC, and because of this, would be expected to undergo degenerative changes with time leading to the onset of OA.