Methotrexate to treat hand osteoarthritis with synovitis (METHODS): an Australian, multisite, parallel-group, double-blind, randomised, placebo-controlled trial.

BACKGROUND: Hand osteoarthritis is a disabling condition with few effective therapies. Hand osteoarthritis with synovitis is a common inflammatory phenotype associated with pain. We aimed to examine the efficacy and safety of methotrexate at 6 months in participants with hand osteoarthritis and synovitis. METHODS: In this multisite, parallel-group, double-blind, randomised, placebo-controlled trial, participants (aged 40-75 years) with hand osteoarthritis (Kellgren and Lawrence grade ≥2 in at least one joint) and MRI-detected synovitis of grade 1 or more were recruited from the community in Melbourne, Hobart, Adelaide, and Perth, Australia. Participants were randomly assigned (1:1) using block randomisation, stratified by study site and self-reported sex, to receive methotrexate 20 mg or identical placebo orally once weekly for 6 months. The primary outcome was pain reduction (measured with a 100 mm visual analogue scale; VAS) in the study hand at 6 months assessed in the intention-to-treat population. Safety outcomes were assessed in all randomly assigned participants. This trial was registered with the Australian New Zealand Clinical Trials Registry (ACTRN12617000877381). FINDINGS: Between Nov 22, 2017, and Nov 8, 2021, of 202 participants who were assessed for eligibility, 97 (48%) were randomly assigned to receive methotrexate (n=50) or placebo (n=47). 68 (70%) of 97 participants were female and 29 (30%) were male. 42 (84%) of 50 participants in the methotrexate group and 40 (85%) of 47 in the placebo group provided primary outcome data. The mean change in VAS pain at 6 months was -15·2 mm (SD 24·0) in the methotrexate group and -7·7 mm (25·3) in the placebo group, with a mean between-group difference of -9·9 (95% CI -19·3 to -0·6; p=0·037) and an effect size (standardised mean difference) of 0·45 (0·03 to 0·87). Adverse events occurred in 31 (62%) of 50 participants in the methotrexate group and 28 (60%) of 47 participants in the placebo group. INTERPRETATION: Treatment of hand osteoarthritis and synovitis with 20 mg methotrexate for 6 months had a moderate but potentially clinically meaningful effect on reducing pain, providing proof of concept that methotrexate might have a role in the management of hand osteoarthritis with an inflammatory phenotype. FUNDING: National Health and Medical Research Council of Australia.

METHODS - A randomised controlled trial of METhotrexate to treat Hand Osteoarthritis with Synovitis: study protocol for a randomised controlled trial.

BACKGROUND: Hand osteoarthritis is a common and disabling problem without effective therapies. Accumulating evidence suggests the role of local inflammation in causing pain and structural progression in hand osteoarthritis, and hand osteoarthritis with synovitis is a commonly encountered clinical phenotype. Methotrexate is a well-established, low-cost, and effective treatment for inflammatory arthritis with a well-described safety profile. The aim of this multicentre, randomised, double-blind, placebo-controlled trial is to determine whether methotrexate reduces pain over 6 months in patients with hand osteoarthritis and synovitis. METHODS: Ninety-six participants with hand osteoarthritis and synovitis will be recruited through the Osteoarthritis Clinical Trial Network (Melbourne, Hobart, Adelaide, and Perth), and randomly allocated in a 1:1 ratio to receive either methotrexate 20 mg or identical placebo once weekly for 6 months. The primary outcome is pain reduction (assessed by 100 mm visual analogue scale) at 6 months. The secondary outcomes include changes in physical function and quality of life assessed using Functional Index for Hand Osteoarthritis, Australian Canadian Osteoarthritis Hand Index, Health Assessment Questionnaire, Michigan Hand Outcomes Questionnaire, Short-Form-36, tender and swollen joint count, and grip strength, and structural progression assessed using progression of synovitis and bone marrow lesions from magnetic resonance imaging and radiographic progression at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups. DISCUSSION: This study will provide high-quality evidence to address whether methotrexate has an effect on reducing pain over 6 months in patients with hand osteoarthritis and synovitis, with major clinical and public health importance. While a positive trial will inform international clinical practice guidelines for the management of hand osteoarthritis, a negative trial would be highly topical and change current trends in clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR), ACTRN12617000877381. Registered 15 June 2017, https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=373124.

Effect of low-dose amitriptyline on reducing pain in clinical knee osteoarthritis compared to benztropine: study protocol of a randomised, double blind, placebo-controlled trial.

BACKGROUND: Knee osteoarthritis is a major cause of pain and disability. Pain control is poor, with most patients remaining in moderate to severe pain. This may be because central causes of pain, a common contributor to knee pain, are not affected by current treatment strategies. Antidepressants, such as amitriptyline, have been used to treat chronic pain in other conditions. The aim of this randomised, double blind, controlled trial, is to determine whether low dose amitriptyline reduces pain in people with painful knee osteoarthritis over 3 months compared to benztropine, an active placebo. METHODS/DESIGN: One hundred and sixty people with painful radiographic knee osteoarthritis will be recruited via clinicians, local and social media advertising. Participants will be randomly allocated in a 1:1 ratio to receive either low dose amitriptyline (25 mg) or active placebo (benztropine mesylate, 1 mg) for 3 months. The primary outcome is change from baseline in knee pain (WOMAC pain subscale) at 12 weeks. Secondary outcomes include change in function (total WOMAC) and the proportion of individuals achieving a substantial response (≥ 50% reduction in pain intensity, measured by Visual Analog Scale, VAS, from no pain to worst pain imaginable, 0-100 mm) and moderate response (≥ 30% reduction in pain intensity, measured by VAS) at 12 weeks. Intention to treat analyses will be performed. Subgroup analyses will be done. DISCUSSION: This study will provide high level evidence regarding the effectiveness of low dose amitriptyline compared to benztropine in reducing pain and improving function in knee OA. This trial has the potential to provide an effective new therapeutic approach for pain management in knee osteoarthritis, with the potential of ready translation into clinical practice, as it is repurposing an old drug, which is familiar to clinicians and with a well described safety record. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry prior to recruitment commencing ( ACTRN12615000301561 , March 31, 2015, amended 14 December 2018, February 2021). Additional amendment requested 18 July 2021.

The bulge sign - a simple physical examination for identifying progressive knee osteoarthritis: data from the Osteoarthritis Initiative.

OBJECTIVE: To examine whether the presence of bulge sign or patellar tap was associated with frequent knee pain, progression of radiographic OA (ROA) and total knee replacement (TKR). METHODS: This study included 4344 Osteoarthritis Initiative participants examined at baseline for bulge sign and/or patellar tap. The clinical signs were categorized as no (none at baseline and 2 years), resolved (present at baseline only), developed (present at 2 years only) and persistent (present at both time points). Frequent knee pain and progression of ROA over 4 years and TKR over 6 years were assessed. Binary logistic regression was used to examine the associations. RESULTS: A total of 12.7% of participants had bulge sign only, 2.0% had patellar tap only and 3.3% had both. A positive baseline bulge sign was associated with an increased risk of frequent knee pain [OR 1.31 (95% CI 1.04, 1.64), P = 0.02] and TKR [OR 1.47 (95% CI 1.06, 2.05), P = 0.02]. Developed bulge sign was associated with an increased risk of frequent knee pain [OR 1.75 (95% CI 1.34, 2.29), P < 0.001] and progressive ROA [OR 1.67 (95% CI 1.11, 2.51), P = 0.01]. Persistent bulge sign was associated with an increased risk of frequent knee pain [OR 1.60 (95% CI 1.09, 2.35), P = 0.02], progressive ROA [OR 1.84 (95% CI 1.01, 3.33), P = 0.045] and TKR [OR 2.13 (95% CI 1.23, 3.68), P = 0.007]. Patellar tap was not examined for its association with joint outcomes due to its low prevalence. CONCLUSION: The presence of bulge sign identifies individuals at increased risk of frequent knee pain, progression of ROA and TKR. This provides clinicians with a quick, simple, inexpensive method for identifying those at higher risk of progressive knee OA who should be targeted for therapy.

Knee effusion volume assessed by magnetic resonance imaging and progression of knee osteoarthritis: data from the Osteoarthritis Initiative.

Objective: To examine whether baseline knee joint effusion volume and the change in effusion volume over 1 year are associated with cartilage volume loss, progression of radiographic OA (ROA) over 4 years and risk of total knee replacement over 6 years. Methods: This study included 4115 Osteoarthritis Initiative participants with knee joint effusion volume quantified by MRI at baseline. The change in effusion volume over 1 year was assessed. Cartilage volume loss and progression of ROA over 4 years were assessed using MRI and X-ray and total knee replacement over 6 years was assessed. Multiple linear regression and binary logistic regression were used for data analyses. Results: Baseline knee effusion volume (per 5 ml) was positively associated with a loss of medial and lateral cartilage volume [regression coefficient 0.13%/year (95% CI 0.10, 0.17) and 0.13%/year (95% CI 0.10, 0.16), respectively, both P < 0.001], progression of ROA [odds ratio (OR) 1.28 (95% CI 1.20, 1.37), P < 0.001], and risk of knee replacement [OR 1.12 (95% CI 1.05, 1.20), P = 0.001]. A 5 ml increase in knee effusion volume over 1 year was positively associated with medial cartilage volume loss [regression coefficient 0.09%/year (95% CI 0.04, 0.15), P = 0.001], progression of ROA [OR 1.21 (95% CI 1.11, 1.33), P < 0.001] and risk of knee replacement [OR 1.24 (95% CI 1.12, 1.37), P < 0.001]. Conclusions: Knee joint effusion volume assessed from MRI provides a continuous and sensitive measure that was associated with cartilage volume loss, progression of ROA and risk of total knee replacement. It may provide a method to identify individuals with an inflammatory OA phenotype who are at higher risk of disease progression.

The interaction between physical activity and amount of baseline knee cartilage.

OBJECTIVES: Conflicting reports of the effect of physical activity on knee cartilage may be due to the heterogeneity of populations examined and, in particular, the underlying health of the knee joint. This study examined the influence of recreational and occupational physical activity on cartilage volume loss. METHODS: A total of 250 participants with no significant musculoskeletal disease were recruited. A gender-specific median cartilage volume split was used to define people in the lowest and highest 50% of baseline cartilage volume. Baseline recreational and occupational activity was examined by questionnaire, while cartilage volume was assessed by MRI at baseline and 2.4 years later. RESULTS: Significant interactions were demonstrable between physical activity and cartilage volume loss based on stratification of baseline cartilage volume (all P ⩽ 0.03). There was a dose-response relationship between frequently performed baseline occupational activities and medial cartilage volume loss in both the low (B = 0.2% per annum, 95% CI: 0.0, 0.04% per annum) and high (B = -0.2% per annum, 95% CI: -0.4, 0.0% per annum) baseline cartilage volume groups (P = 0.001 for interaction). Individuals with low baseline cartilage volume who were active in their occupation and/or recreational activity had greater medial cartilage volume loss than their more inactive counterparts (2.4% per annum vs 1.5% per annum, P = 0.02). CONCLUSION: Whereas people with less baseline cartilage volume are more at risk of structural knee damage with either heavy occupational or recreational workloads or both, individuals with high baseline cartilage volume may advantageously modify their risk for knee OA by participating in more frequent occupational physical activities.

Statins and tendinopathy: a systematic review.

OBJECTIVES: To systematically review the evidence on whether statin therapy, commonly used in clinical practice to treat hypercholesterolaemia for primary and secondary prevention of cardiovascular disease, contributes to tendinopathy; and to examine causality according to the Bradford Hill criteria. STUDY DESIGN: A systematic review of studies examining the relationship between statin therapy and tendinopathy. Included studies were rated based on their methodological quality. A best evidence synthesis was used to summarise the results, and Bradford Hill criteria were used to assess causation. DATA SOURCES: Ovid MEDLINE, CINAHL Plus, PubMed and Embase databases. STUDY SELECTION: We included adult human studies published in the English language between January 1966 and October 2015. Study designs eligible for inclusion were randomised controlled trials and cross-sectional, cohort or case-control studies. DATA SYNTHESIS: Four studies (three cohort studies and one case-control study) were included, with a mean methodological quality score of 67%. Three studies were deemed high quality. Tendon rupture was the primary outcome in three studies, and rotator cuff disease in the other. All studies found no positive association between statin therapy and tendon rupture for the total study population. There was evidence that simvastatin reduces the risk of tendinopathy. CONCLUSION: To date, there is a paucity of evidence to implicate statin therapy as a well established risk factor or causal mechanism for tendon rupture in the general population. There is strong evidence that simvastatin reduces the risk of tendinopathy.

Modic changes in the lumbar spine and their association with body composition, fat distribution and intervertebral disc height - a 3.0 T-MRI study.

BACKGROUND: Vertebral endplate (Modic) abnormalities are important structural lesions in the spine, but their association with body composition and fat distribution have not been examined. Moreover, no study has examined whether Modic change are related to other structural features of low back pain, such as reduced intervertebral disc height. METHODS: Seventy-two community-based individuals not selected for low back pain had lumbar vertebral Modic change and intervertebral disc height assessed from MRI. Dual energy x-ray absorptiometry measured body composition and fat distribution. RESULTS: The predominance of Modic change was type 2. Modic change was associated with an increased fat mass index (OR 1.20, 95 % CI 1.01 to 1.43), and tended to be associated with a reduced fat-free mass index (OR 0.62, 95 % CI 0.37 to 1.03, p = 0.07). While an increased percentage of gynoid fat was associated with a reduced risk (OR 0.62, 95 % CI 0.43 to 0.89), an increased percentage of android fat was associated with an increased risk of Modic change (OR 2.11, 95 % CI 1.18 to 3.76). Modic change was also associated with reduced intervertebral disc height at L2/3, L4/5 and L5/S1 (OR range 1.4 to 1.8; all p ≤ 0.03). CONCLUSION: Modic type 2 change is associated with reduced intervertebral disc height and an increased fat mass index. Whereas gynoid fat distribution protected against Modic type 2 change, an android pattern increased the risk of this lesion. Modic type 2 change, which histologically represent fat replacement, might have a metabolic component to its aetiology.

Lumbar disc degeneration is associated with modic change and high paraspinal fat content - a 3.0T magnetic resonance imaging study.

BACKGROUND: Degenerative disc disease of the lumbar spine is common, with severe disease increasing the risk for chronic low back pain. This cross-sectional study examined whether disc degeneration is representative of a 'whole-organ' pathology, by examining its association with bone (vertebral endplate) and soft tissue (paraspinal muscle fat) abnormalities. METHODS: Seventy-two community-based individuals unselected for low back pain, had Magnetic Resonance Imaging (MRI). Lumbosacral disc degeneration was determined via the Pfirrmann grading system, a validated method to assess the intervertebral disc, distinguishing the nucleus and annulus, the signal intensity and the height of the intervertebral disc. Modic change and high paraspinal muscle fat content was also measured from MRI. RESULTS: Severe disc degeneration was associated, or tended to be associated with type 2 Modic change from L2 to L5 (OR range 3.5 to 25.3, p ≤ 0.06). Moreover, severe disc degeneration at all intervertebral levels was associated with or tended to be associated with high fat content of the paraspinal muscles (OR range 3.7 to 14.3, p ≤ 0.09). CONCLUSION: These data demonstrate that disc degeneration of the lumbar spine is commonly accompanied by Modic change and high fat content of paraspinal muscles, thus representing a 'whole-organ' pathology. Longitudinal studies are required to determine the temporal relationship between these structural abnormalities. Understanding this may have the potential to identify novel targets for the treatment and prevention of lumbosacral disc degeneration.

Weight change and change in tibial cartilage volume and symptoms in obese adults.

INTRODUCTION: There is a paucity of data examining the effects of weight change on knee joint structures and symptoms. This study examined the effect of weight change on change in knee cartilage volume and symptoms in an obese cohort. METHODS: 112 obese subjects (Body Mass Index ≥30 kg/m(2)) were recruited from various community sources to examine the effect of obesity on musculoskeletal health. Tibial cartilage volume, determined by MRI, and knee symptoms, determined by the Western Ontario and McMaster Osteoarthritis Index (WOMAC) were collected at baseline and an average of 2.3 years later. RESULTS: Percentage weight change was associated with change in medial tibial cartilage volume (ß -1.2 mm(3), 95% CI -2.3 to -0.1 mm(3), p=0.03) that was consistent throughout the spectrum of weight loss through to mild weight gain. Percentage weight change was not associated with change in the lateral tibial (p=0.93) or patella (p=0.32) cartilage volumes. Percentage weight change was associated with change in all WOMAC subscales (all p≤0.01): pain (ß -1.8 mm, 95% CI -3.2 to -0.4 mm), stiffness (ß -1.6 mm, 95% CI -2.5 to -0.7 mm) and function (ß -6.9 mm, 95% CI -11.6 to -2.1 mm). CONCLUSIONS: The linearity of effect implies that weight loss is associated with reduced medial cartilage volume loss and improved knee symptoms, while weight gain is associated with increased medial cartilage volume loss and worse knee symptoms. These results suggest that in obese people, small amounts of weight change may have the potential for a disease modifying effect on both knee joint structure and symptoms. While weight loss is an important primary management strategy in obese individuals, avoidance of further weight gain should also be a clinical goal.

Weight change following knee and hip joint arthroplasty-a six-month prospective study of adults with osteoarthritis.

BACKGROUND: Inconsistent findings of weight change following total knee (TKA) and hip (THA) arthroplasty may largely be attributable to heterogeneous cohorts and varied definitions of weight loss. This study examined weight change following TKA and THA for osteoarthritis (OA). METHODS: 64 participants with hip or knee OA were recruited from orthopaedic joint arthroplasty waiting lists at a single major Australian public hospital between March and October 2011. The Short Form (SF) 12 survey was used to assess baseline physical and mental functioning. 49 participants completed 6 month follow-up (20 from the THA group and 29 from the TKA group). RESULTS: The majority of subjects lost weight (>0 kg) 6 months following THA (70 %) and TKA (58.6 %). When at least a 5 % reduction in total body weight was used to define clinically significant weight loss, the proportion of people with weight loss was 37.9 % for TKA and 25 % for THA. Greater weight loss occurred 6 months following TKA compared with THA (7.2 % versus 3.7 % of body weight; p = 0.04). Worse pre-operative physical functioning (SF-12) was associated with greater weight loss following TKA (ß = 0.22 kg, 95 % CI 0.02-0.42 kg; p = 0.04). CONCLUSION: Most people lost weight (>0 kg) 6 months following TKA and THA and a considerable proportion of people achieved ≥5 % loss of body weight. The magnitude of weight loss was greater following TKA than THA, with worse pre-operative function being a predictor of more weight loss. Further attention to weight management is required to assist a greater number of people to achieve a larger magnitude of weight loss following knee and hip joint arthroplasty.

The longitudinal relationship between changes in body weight and changes in medial tibial cartilage, and pain among community-based adults with and without meniscal tears.

INTRODUCTION: Meniscal tears are commonly found on MRI and increase the risk for radiographic knee osteoarthritis (OA). While meniscectomy is recommended when knee pain is severe or functionally disabling, it is unclear how to best treat meniscal tears without these symptoms. The aim of this longitudinal study was to examine the effect of weight change on knee cartilage and pain in a cohort of community-based adults with and without meniscal tears detected by MRI. METHODS: 250 adults with no history of knee OA or knee injury were recruited from the general community and weight-loss clinics. MRI of the knee, Western Ontario and McMaster University Osteoarthritis Index (WOMAC), weight and height were measured at baseline and again at follow-up approximately 2 years later. RESULTS: Medial meniscal tears were present in 36 (18%) of the cohort. In those with medial meniscal tears, after adjustment for confounders, percentage weight change was significantly associated with percentage change in medial tibial cartilage volume (ß 0.2% 95% CI 0.08% to 0.3% p=0.002) and knee pain (ß 11.6% 95% CI 2.1% to 21.1% p=0.02). That is, for every 1% gain in weight, there was an associated 0.2% increased loss of medial tibial cartilage volume and 11.6% increase in pain. In those with no medial meniscal tear, neither change in medial tibial cartilage volume (ß 0.02% 95% CI -0.01% to 0.10% p=0.53) or pain (ß 1.9% 95% CI -2.2% to 6.1% p=0.36) were significantly associated with change in weight. CONCLUSIONS: This study demonstrated that among adults with medial meniscal tears, weight gain is associated with increased cartilage loss and pain, while weight loss is associated with the converse. This suggests attention to weight is particularly important in the management of people with medial meniscal tears.

Increase in vastus medialis cross-sectional area is associated with reduced pain, cartilage loss, and joint replacement risk in knee osteoarthritis.

OBJECTIVE: Although there is evidence for a beneficial effect of increased quadriceps strength on knee symptoms, the effect on knee structure is unclear. We undertook this study to examine the relationship between change in vastus medialis cross-sectional area (CSA) and knee pain, tibial cartilage volume, and risk of knee replacement in subjects with symptomatic knee osteoarthritis (OA). METHODS: One hundred seventeen subjects with symptomatic knee OA underwent magnetic resonance imaging of the knee at baseline and at 2 and 4.5 years. Vastus medialis CSA was measured at baseline and at 2 years. Tibial cartilage volume was measured at baseline and at 2 and 4.5 years. Knee pain was assessed by the Western Ontario and McMaster Universities Osteoarthritis Index at baseline and at 2 years. The frequency of knee joint replacement over 4 years was determined. Regression coefficients (B) and odds ratios were determined along with 95% confidence intervals (95% CIs). RESULTS: After adjusting for confounders, baseline vastus medialis CSA was inversely associated with current knee pain (r = -0.16, P = 0.04) and with medial tibial cartilage volume loss from baseline to 2 years (B coefficient -10.9 [95% CI -19.5, -2.3]), but not with baseline tibial cartilage volume. In addition, an increase in vastus medialis CSA from baseline to 2 years was associated with reduced knee pain over the same time period (r = 0.24, P = 0.007), reduced medial tibial cartilage loss from 2 to 4.5 years (B coefficient -16.8 [95% CI -28.9, -4.6]), and reduced risk of knee replacement over 4 years (odds ratio 0.61 [95% CI 0.40, 0.94]). CONCLUSION: In a population of patients with symptomatic knee OA, increased vastus medialis size was associated with reduced knee pain and beneficial structural changes at the knee, suggesting that management of knee pain and optimizing vastus medialis size are important in reducing OA progression and subsequent knee replacement.

An approach to neck pain for the family physician.

BACKGROUND: Neck pain is a common presentation in general practice. Nevertheless, recommendations for the investigation and management of neck pain lack a strong evidence base and are predominantly extrapolated from low back pain studies. OBJECTIVE: This review provides an investigation and treatment paradigm to help primary care physicians assess and manage cervical spine pain. DISCUSSION: Although sinister causes of neck pain are rare, clinicians must be mindful of red flags that may indicate serious pathology. The medical interview, rather than the physical examination, remains the most critical step in determining the likely cause of cervical spine pain, whereas biochemical tests and imaging are not part of routine assessment. The classification of neck pain into acute or chronic patterns, extrapolated from the low back pain literature, may help stratify the need for intervention and the likely prognosis of neck pain. A more concerted research effort is needed to help better understand and develop evidence-based guidelines for the management of neck pain.

The associations between body and knee height measurements and knee joint structure in an asymptomatic cohort.

BACKGROUND: It has been suggested that knee height is a determinant of knee joint load. Nonetheless, no study has directly examined the relationship between anthropometric measures of height and knee joint structures, such as cartilage. METHODS: 89 asymptomatic community-based adults aged 25-62 with no diagnosed history of knee arthropathy were recruited. Anthropometric data (knee height and body height) were obtained by standard protocol, while tibial cartilage volume and defects, as well as bone area were determined from magnetic resonance imaging. Static knee alignment was measured from the joint radiograph. RESULTS: All anthropometric height measures were associated with increasing compartmental tibial bone area (p ≤ 0.05). Although knee height was associated with tibial cartilage volume (e.g. ß = 27 mm³ 95% CI 7- 48; p = 0.009 for the medial compartment), these relationship no longer remained significant when knee height as a percentage of body height was analysed. Knee height as a percentage of body height was associated with a reduced risk of medial tibial cartilage defects (odds ratio 0.6; 95% confidence interval 0.4 - 1.0; p = 0.05). CONCLUSION: The association between increased anthropometric height measures and increased tibial bone area may reflect inherently larger bony structures. However the beneficial associations demonstrated with cartilage morphology suggest that an increased knee height may confer a beneficial biomechanical environment to the chondrocyte of asymptomatic adults.

The associations between indices of patellofemoral geometry and knee pain and patella cartilage volume: a cross-sectional study.

BACKGROUND: Whilst patellofemoral pain is one of the most common musculoskeletal disorders presenting to orthopaedic clinics, sports clinics, and general practices, factors contributing to its development in the absence of a defined arthropathy, such as osteoarthritis (OA), are unclear.The aim of this cross-sectional study was to describe the relationships between parameters of patellofemoral geometry (patella inclination, sulcus angle and patella height) and knee pain and patella cartilage volume. METHODS: 240 community-based adults aged 25-60 years were recruited to take part in a study of obesity and musculoskeletal health. Magnetic resonance imaging (MRI) of the dominant knee was used to determine the lateral condyle-patella angle, sulcus angle, and Insall-Salvati ratio, as well as patella cartilage and bone volumes. Pain was assessed by the Western Ontario and McMaster University Osteoarthritis Index (WOMAC) VA pain subscale. RESULTS: Increased lateral condyle-patella angle (increased medial patella inclination) was associated with a reduction in WOMAC pain score (Regression coefficient -1.57, 95% CI -3.05, -0.09) and increased medial patella cartilage volume (Regression coefficient 51.38 mm3, 95% CI 1.68, 101.08 mm3). Higher riding patella as indicated by increased Insall-Salvati ratio was associated with decreased medial patella cartilage volume (Regression coefficient -3187 mm3, 95% CI -5510, -864 mm3). There was a trend for increased lateral patella cartilage volume associated with increased (shallower) sulcus angle (Regression coefficient 43.27 mm3, 95% CI -2.43, 88.98 mm3). CONCLUSION: These results suggest both symptomatic and structural benefits associated with a more medially inclined patella while a high-riding patella may be detrimental to patella cartilage. This provides additional theoretical support for the current use of corrective strategies for patella malalignment that are aimed at medial patella translation, although longitudinal studies will be needed to further substantiate this.

Associations of Joint Line Tenderness and Patellofemoral Grind With Long-Term Knee Joint Outcomes: Data From the Osteoarthritis Initiative.

OBJECTIVE: To examine whether joint line tenderness and patellofemoral grind from physical examination were associated with cartilage volume loss, worsening of radiographic osteoarthritis, and the risk of total knee replacement. METHODS: This study examined 4,353 Osteoarthritis Initiative participants. For each measurement of joint line tenderness and patellofemoral grind, the patterns were defined as no (none at baseline and at 1 year), fluctuating (present at either time point), and persistent (present at both time points). Cartilage volume loss and worsening of radiographic osteoarthritis over 4 years were assessed using magnetic resonance imaging and radiographs, and total knee replacement over 6 years was assessed. RESULTS: A total of 35.0% of participants had joint line tenderness, and 15.8% had patellofemoral grind. Baseline patellofemoral grind, but not joint line tenderness, was associated with increased cartilage volume loss (1.08% per year versus 0.96% per year; P = 0.02) and an increased risk of total knee replacement (odds ratio [OR] 1.55 [95% confidence interval (95% CI) 1.11-2.17]; P = 0.01). While the patterns of joint line tenderness were not significantly associated with joint outcomes, participants with persistent patellofemoral grind had an increased rate of cartilage volume loss (1.30% per year versus 0.90% per year; P < 0.001) and an increased risk of total knee replacement (OR 2.10 [95% CI 1.30-3.38]; P = 0.002) compared with those participants without patellofemoral grind. CONCLUSION: Patellofemoral grind, but not joint line tenderness, may represent a clinical marker associated with accelerated cartilage volume loss over 4 years and an increased risk of total knee replacement over 6 years. This simple clinical examination may provide clinicians with an inexpensive way to identify those at higher risk of disease progression who should be targeted for surveillance and management.

The associations between the dominant and nondominant peak external knee adductor moments during gait in healthy subjects: evidence for symmetry.

OBJECTIVES: There is growing interest in the role of the knee adduction moment in the pathogenesis of knee pain and osteoarthritis. It is unclear whether the knee adduction moment is similar between the dominant and nondominant legs during locomotion. This study examined whether asymmetry exists in the peak knee adductor moments during gait in healthy adults. DESIGN: Cross-sectional study. SETTING: Musculoskeletal Research Centre, La Trobe University, Melbourne, Victoria, Australia. PARTICIPANTS: Three-dimensional Vicon gait analyses were performed for 17 healthy men and women. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: The external dominant and nondominant peak knee adduction moments during early and late stance were analyzed to determine whether any significant differences occurred between limbs. RESULTS: Peak knee adductor moments for dominant and nondominant limbs were significantly correlated during early (R=0.61, P=0.009) and late (R=0.72, P=0.001) stance. After adjustment for age and sex, there was an associated 0.58 (P=0.030) and 0.98 (P=0.009) unit increase in the peak knee adduction moment in the nondominant leg, for every 1 unit increase in the dominant leg during the early and late stance phases of gait, respectively. Further evidence for symmetry was provided by the symmetry index, which was 0.04% and 0.62% for early and late stance, respectively. CONCLUSIONS: In healthy subjects, the magnitude of the dominant limb peak external knee adduction moments during stance, and in particular late stance, appears representative of the magnitude of the moment in the nondominant limb. These findings imply symmetry between these moments and may have important implications when collecting data for limb analyses among healthy subjects. Whether gait symmetry protects against the onset of unilateral (or increases the risk for bilateral) pathological joint changes will need to be confirmed longitudinally.

Knee pain as a predictor of structural progression over 4 years: data from the Osteoarthritis Initiative, a prospective cohort study.

BACKGROUND: There is evidence that knee pain not only is a consequence of structural deterioration in osteoarthritis (OA) but also contributes to structural progression. Clarifying this is important because targeting the factors related to knee pain may offer a clinical approach for slowing the progression of knee OA. The aim of this study was to examine whether knee pain over 1 year predicted cartilage volume loss, incidence and progression of radiographic osteoarthritis (ROA) over 4 years. METHODS: Osteoarthritis Initiative participants with no ROA (Kellgren-Lawrence grade ≤ 1) (n = 2120) and with ROA (Kellgren-Lawrence grade > 2) (n = 2249) were examined. Knee pain was assessed at baseline and 1 year using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC). Knee pain patterns were categorised as no pain (WOMAC pain < 5 at baseline and 1 year), fluctuating pain (WOMAC pain > 5 at either time point) and persistent pain (WOMAC pain > 5 at both time points). Cartilage volume, incidence and progression of ROA were assessed using magnetic resonance imaging and x-rays at baseline and 4-years. RESULTS: In both non-ROA and ROA, greater baseline WOMAC knee pain score was associated with increased medial and lateral cartilage volume loss (p ≤ 0.001), incidence (OR 1.07, 95% CI 1.01-1.13) and progression (OR 1.07, 95% CI 1.03-1.10) of ROA. Non-ROA and ROA participants with fluctuating and persistent knee pain had increased cartilage volume loss compared with those with no pain (p for trend ≤ 0.01). Non-ROA participants with fluctuating knee pain had increased risk of incident ROA (OR 1.62, 95% CI 1.04-2.54), corresponding to a number needed to harm of 19.5. In ROA the risk of progressive ROA increased in participants with persistent knee pain (OR 1.82, 95% CI 1.28-2.60), corresponding to a number needed to harm of 9.6. CONCLUSIONS: Knee pain over 1 year predicted accelerated cartilage volume loss and increased risk of incident and progressive ROA. Early management of knee pain and controlling knee pain over time by targeting the underlying mechanisms may be important for preserving knee structure and reducing the burden of knee OA.