Association between weight gain and knee osteoarthritis: a systematic review.

OBJECTIVE: Although weight loss is recommended to manage knee osteoarthritis (KOA), adults tend to gain weight with age which may affect KOA symptoms and progression. We conducted a systematic review and data synthesis to investigate the association between weight gain and KOA, defined by clinical features, structural progression, and total knee replacement (TKR). DESIGN: MEDLINE and EMBASE were systematically searched for controlled trials and cohort studies of participants with (or at risk of) KOA examining the relationship between weight gain and KOA clinical features (pain, function, quality of life), structural progression, and TKR. Risk of bias was assessed using the ROBINS-I tool. Results were organised by outcome, with meta-analyses performed where appropriate. RESULTS: Twenty-three studies were included. Results showed significant detrimental effects of weight gain on pain (4 of 7 studies), stiffness (2 of 2 studies), function (5 of 6 studies), and the single studies examining quality of life, and clinical and radiographic KOA. Weight gain adversely affected cartilage (6 of 9 studies), bone marrow lesions (1 of 4 studies), meniscal damage (1 of 3 studies) and effusion/synovitis (1 of 1 study). Weight gain significantly increased TKR (3 of 6 studies): meta-analysis of 2 with available data demonstrated significant increases in TKR/5 kg weight gain in women, HR 1.34 (95% CI 1.18-1.51), and in men, HR 1.25 (95% CI 1.16-1.34). CONCLUSIONS: Weight gain in adults is associated with increased clinical and structural KOA and TKR. Prevention of weight gain should be considered to improve outcomes in KOA.

Metformin as a potential disease-modifying drug in osteoarthritis: a systematic review of pre-clinical and human studies.

OBJECTIVE: Osteoarthritis causes significant pain and disability with no approved disease-modifying drugs. We systematically reviewed the evidence from both pre-clinical and human studies for the potential disease-modifying effect of metformin in osteoarthritis. METHODS: Ovid Medline, Embase and CINAHL were searched between inception and June 2021 using MeSH terms and key words to identify studies examining the association between metformin use and outcome measures related to osteoarthritis. Two reviewers performed the risk of bias assessment and 3 reviewers extracted data independently. Qualitative evidence synthesis was performed. This systematic review is registered on PROSPERO (CRD42021261052 and CRD42021261060). RESULTS: Fifteen (10 pre-clinical and 5 human) studies were included. Most studies (10 pre-clinical and 3 human) assessed the effect of metformin using knee osteoarthritis models. In pre-clinical studies, metformin was assessed for the effect on structural outcomes (n = 10); immunomodulation (n = 5); pain (n = 4); and molecular pathways of its effect in osteoarthritis (n = 7). For human studies, metformin was evaluated for the effect on structural progression (n = 3); pain (n = 1); and immunomodulation (n = 1). Overall, pre-clinical studies consistently showed metformin having a chondroprotective, immunomodulatory and analgesic effect in osteoarthritis, predominantly mediated by adenosine monophosphate-activated protein kinase activation. Evidence from human studies, although limited, was consistent with findings in pre-clinical studies. CONCLUSION: We found consistent evidence across pre-clinical and human studies to support a favourable effect of metformin on chondroprotection, immunomodulation and pain reduction in knee osteoarthritis. Further high-quality clinical trials are needed to confirm these findings as metformin could be a novel therapeutic drug for the treatment of osteoarthritis.

The interactions between MRI-detected osteophytes and bone marrow lesions or effusion-synovitis on knee symptom progression: an exploratory study.

OBJECTIVES: To investigate the longitudinal association between MRI-detected osteophyte scores and progression of knee symptoms, and whether the association was modified in the presence of bone marrow lesions (BMLs) or effusion-synovitis. METHODS: Data from Vitamin D Effects on Osteoarthritis (VIDEO) study, a randomized, double-blinded and placebo-controlled clinical trial in symptomatic knee osteoarthritis (OA) patients, were analyzed as an exploratory study. Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) was used to assess knee symptoms. Osteophytes, BMLs and effusion-synovitis were measured using MRI. RESULTS: 334 participants with MRI information and WOMAC score (baseline and follow-up) were included in the analyses, with 24.3% of them having knee pain increased 2 years later. Statistically significant interactions were found between MRI-detected osteophytes and BMLs or effusion-synovitis on increased knee symptoms. In participants with BMLs, higher baseline scores of MRI-detected osteophytes in most compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and effusion-synovitis. In participants with effusion-synovitis, higher baseline scores of MRI-detected osteophytes in almost all the compartments were significantly associated with increased total knee pain, weight-bearing pain, stiffness, and physical dysfunction, after adjustment for age, sex, body mass index, intervention and BMLs. In contrast, MRI-detected osteophyte scores were generally not associated with knee symptom progression in participants without baseline BMLs or effusion-synovitis. CONCLUSIONS: MRI-detected OPs are associated with increased total knee pain, weight-bearing knee pain, stiffness and physical dysfunction in participants presenting BMLs or effusion-synovitis, but not in participants lacking BMLs or effusion-synovitis. This suggests they could interact with bone or synovial abnormalities to induce symptoms in knee OA.

The cross-sectional and longitudinal associations of dietary patterns with knee symptoms and MRI detected structure in patients with knee osteoarthritis.

OBJECTIVES: To examine the cross-sectional and longitudinal associations of dietary patterns with knee symptoms and structures in patients with knee osteoarthritis (OA). METHODS: Participants with symptomatic knee OA were recruited from a randomised, placebo-controlled trial conducted in Tasmania (N = 259) and Victoria (N = 133). Diet was assessed by the Anti-Cancer Council of Victoria food frequency questionnaire. Factor analysis was used to identify dietary patterns. Knee symptoms were assessed using Western Ontario and McMaster Universities Arthritis Index (WOMAC) and structures using MRI. Multivariable linear regressions were used to examine associations. RESULTS: Three dietary patterns ("high-fat", "healthy" and "mixed") were identified in whole sample. Participants with higher "healthy pattern" score had lower total WOMAC, pain, function and stiffness scores at baseline but the associations were not significant over 24 months. Three ("western", "vegetable and meat" and "mediterranean") and two ("processed" and "vegetable") patterns were identified in Tasmania and Victoria, respectively. Cross-sectionally, only "mediterranean pattern" and "vegetable pattern" scores were significantly and negatively associated with total WOMAC or function scores. Longitudinally, participants with higher "western pattern" had worsening function (ß: 0.35, 95%CI: 0.03, 0.67) and total WOMAC (ß: 0.40, 95%CI: 0.07, 0.72) scores; furthermore, "vegetable pattern" was associated with decreased WOMAC stiffness score (ß: -0.47, 95%CI: -0.93, -0.02). In contrast, dietary patterns were largely not associated with structural changes. CONCLUSION: Some healthy dietary patterns were associated with reduced joint symptoms but dietary patterns were not associated with joint structure in this sample with knee OA. Further studies are required to confirm these findings.

Does preoperative neuropathic-like pain and central sensitisation affect the post-operative outcome of knee joint replacement for osteoarthritis? A systematic review and meta analysis.

BACKGROUND: Almost a third of those undergoing knee replacement for osteoarthritis have poor outcomes despite technically successful surgery. Preoperative neuropathic-like pain and/or pain sensitisation may increase the risk of pain following joint replacement. OBJECTIVE: To examine whether preoperative neuropathic-like pain and pain sensitisation predicts pain, function and satisfaction following joint replacement for knee osteoarthritis. DESIGN: Systematic review with meta-analysis. METHODS: Medline, EMBASE and CINAHL were systematically searched until March 2020. Studies detecting neuropathic-like pain and/or sensitisation using self-report questionnaires prior to knee replacement for osteoarthritis, and relating this to post-operative outcomes were identified. Data extraction, risk of bias assessment and meta-analysis were performed, where appropriate. RESULTS: Five manuscripts, including one preprint, examining six cohorts were included: four used painDETECT or modified painDETECT, one the Self-Report Leeds Assessment of Neuropathic Symptoms and Signs, and another the Central Sensitisation Inventory to identify preoperative characteristics. Three studies showed preoperative neuropathic-like pain or sensitisation was associated with more intense post-operative pain. All four studies examining the risk of significant pain after knee replacement suggested it was increased after >3 months. The only study examining patient satisfaction and function found reduced satisfaction, but no difference in function in those with preoperative sensitisation. Meta-analysis found the relative risk of increased pain following knee replacement in those with neuropathic-like pain (painDETECT ≥13) to be 2.05 (95% confidence intervals 1.51, 2.79). CONCLUSION: These results provide consistent but limited evidence that self-report tools detecting neuropathic-like pain and/or pain sensitisation, predict patients at higher risk of pain following knee replacement.

KARAOKE: Krill oil versus placebo in the treatment of knee osteoarthritis: protocol for a randomised controlled trial.

BACKGROUND: Knee osteoarthritis (OA) is a common and important cause of pain and disability, but interventions aimed at modifying structures visible on imaging have been disappointing. While OA affects the whole joint, synovitis and effusion have been recognised as having a role in the pathogenesis of OA. Krill oil reduces knee pain and systemic inflammation and could be used for targeting inflammatory mechanisms of OA. METHODS/DESIGN: We will recruit 260 patients with clinical knee OA, significant knee pain and effusion-synovitis present on MRI in five Australian cities (Hobart, Melbourne, Sydney, Adelaide and Perth). These patients will be randomly allocated to the two arms of the study, receiving 2 g/day krill oil or inert placebo daily for 6 months. MRI of the study knee will be performed at screening and after 6 months. Knee symptoms, function and MRI structural abnormalities will be assessed using validated methods. Safety data will be recorded. Primary outcomes are absolute change in knee pain (assessed by visual analog score) and change in size of knee effusion-synovitis over 24 weeks. Secondary outcomes include improvement in knee pain over 4, 8, 12, 16 and 20 weeks. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses adjusting for missing data and for treatment compliance will be performed as the secondary analyses. DISCUSSION: This study will provide high-quality evidence to assess whether krill oil 2 g/day reduces pain and effusion-synovitis size in older adults with clinical knee OA and knee effusion-synovitis. If krill oil is effective and confirmed to be safe, we will provide compelling evidence that krill oil improves pain and function, changes disease trajectory and slows disease progression in OA. Given the lack of approved therapies for slowing disease progression in OA, and moderate cost of krill oil, these findings will be readily translated into clinical practice. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry, ACTRN12616000726459. Registered on 02 June 2016. Universal Trial Number (UTN) U1111-1181-7087.

Bone marrow lesions in knee osteoarthritis: regional differences in tibial subchondral bone microstructure and their association with cartilage degeneration.

OBJECTIVE: The aim of this study was to investigate how bone microstructure within bone marrow lesions (BMLs) relates to the bone and cartilage across the whole human tibial plateau. DESIGN: Thirty-two tibial plateaus from patients with osteoarthritis (OA) at total knee arthroplasty and eleven age-matched non-OA controls, were scanned ex vivo by MRI to identify BMLs and by micro CT to quantitate the subchondral (plate and trabecular) bone microstructure. For cartilage evaluation, specimens were processed histologically. RESULTS: BMLs were detected in 75% of the OA samples (OA-BML), located predominantly in the anterior-medial (AM) region. In contrast to non-OA control and OA-no BML, in OA-BML differences in microstructure were significantly more evident between subregions. In OA-BML, the AM region contained the most prominent structural alterations. Between-group comparisons showed that the AM region of the OA-BML group had significantly higher histological degeneration (OARSI grade) (P < .0001, P < .05), thicker subchondral plate (P < .05, P < .05), trabeculae that are more anisotropic (P < .0001, P < .05), well connected (P < .05, P = n.s), and more plate-like (P < 0.05, P < 0.05), compared to controls and OA-no BML at this site. Compared to controls, OA-no BML had significantly higher OARSI grade (P < .0001), and lower trabecular number (P < .05). CONCLUSION: In established knee OA, both the extent of cartilage damage and microstructural degeneration of the subchondral bone were dependent on the presence of a BML. In OA-no BML, bone microstructural alterations are consistent with a bone attrition phase of the disease. Thus, the use of BMLs as MRI image-based biomarkers appear to inform on the degenerative state within the osteochondral unit.

Systematic scoping review of patients' perceived needs of health services for osteoporosis.

Health service planners, administrators and providers need to understand the patients' perspective of health services related to osteoporosis to optimise health outcomes. The aims of this study were to systematically identify and review the literature regarding patients' perceived health service needs relating to osteoporosis and osteopenia. A systematic scoping review was performed of publications in MEDLINE, EMBASE, CINAHL and PsycINFO (1990-2016). Descriptive data regarding study design and methodology were extracted and risk of bias assessed. Aggregates of patients' perceived needs of osteoporosis health services were categorised. Thirty-three studies (19 quantitative and 14 qualitative) from 1027 were relevant. The following areas of perceived need emerged: (1) patients sought healthcare from doctors to obtain information and initiate management. They were dissatisfied with poor communication, lack of time and poor continuity of care. (2) Patients perceived a role for osteoporosis pharmacotherapy but were concerned about medication administration and adverse effects. (3) Patients believed that exercise and vitamin supplementation were important, but there is a lack of data examining the needs for other non-pharmacological measures such as smoking cessation and alcohol. (4) Patients wanted diagnostic evaluation and ongoing surveillance of their bone health. This review identified patients' needs for better communication with their healthcare providers. It also showed that a number of important cornerstones of therapy for osteoporosis, such as pharmacotherapy and exercise, are identified as important by patients, as well as ongoing surveillance of bone health. Understanding patients' perceived needs and aligning them with responsive and evidence-informed service models are likely to optimise patient outcomes.

Knee effusion-synovitis volume measurement and effects of vitamin D supplementation in patients with knee osteoarthritis.

OBJECTIVE: To develop a measure of knee joint effusion-synovitis volume and to examine the effect of vitamin D supplementation on effusion-synovitis in people with knee osteoarthritis (OA) and low vitamin D levels over 24 months. METHOD: Symptomatic knee OA patients with low 25-(OH)D levels (12.5-60 nmol/l) were recruited for a multi-centre, randomised, placebo-controlled and double-blind trial. Participants (age 63 ± 7 years, 208 females) were allocated to either 50,000 IU monthly vitamin D3 (n = 209) or placebo (n = 204) for 24 months. Knee effusion-synovitis volume in suprapatellar and other regions was measured on magnetic resonance imaging (MRI) using OsiriX software. The intra-class correlation coefficients (ICCs) were used to test inter- and intra-rater reliabilities. The least significant change criterion was used to define the increase/decrease in effusion-synovitis volume. RESULT: The reproducibilities of effusion-synovitis volume measurement were high with ICCs ranging from 0.93 to 0.99. Over 24 months, effusion-synovitis volume remained stable in the vitamin D group but increased in placebos with a significant between-group difference (-1.94 ml, 95% confidence interval (CI): -3.54, -0.33). This effect was evident in those with baseline effusion-synovitis and with suprapatellar effusion-synovitis. The proportion with an increase in effusion-synovitis volume was lower in the vitamin D group than placebo (risk ratio (RR): 0.87, 95% CI: 0.77, 0.97). CONCLUSION: This highly reproducible effusion-synovitis volume measurement could be a promising outcome measure in OA trials. Vitamin D supplementation could retard the progression of effusion-synovitis which can potentially benefit people with an inflammatory OA phenotype.

Associations between endogenous sex hormones and MRI structural changes in patients with symptomatic knee osteoarthritis.

OBJECTIVE: To investigate the longitudinal association between endogenous sex hormones and knee osteoarthritis (OA) structures and pain. METHOD: We examined 200 participants (mean age 63.0 ± 7.3 years) from a clinical trial of vitamin D supplement for symptomatic knee OA. Serum levels of estradiol, progesterone, testosterone and sex hormone binding globulin (SHBG) were analyzed at baseline and 24 months later. Magnetic resonance imaging (MRI) scans of selected knee were obtained at both baseline and follow-up for the measurement of cartilage volume, cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis volume. Knee pain was assessed using a 100 mm visual analogue scale (VAS). Longitudinal data were analyzed using linear mixed-effects model. RESULTS: One hundred and seven males and 93 females were included in this study. For females, after adjustment for age, body mass index (BMI), and vitamin D level, progesterone was positively associated with cartilage volume (ß = 0.12 mm3 per quartile, P < 0.01). Estradiol levels were associated with lower grades of BMLs (ß = -0.46 per quartile, P = 0.03), while estradiol (ß = -1.28 per quartile, P = 0.04), progesterone (ß = -1.56 per quartile, P < 0.01) and testosterone (ß = -1.51 per quartile, P = 0.01) were inversely associated with effusion-synovitis volume. Testosterone was inversely associated with knee pain. No consistent associations were observed for males. CONCLUSION: In women but not men, low serum levels of endogenous estradiol, progesterone and testosterone are associated with increased knee effusion-synovitis and possibly other OA-related structural changes. This may contribute to observed sex differences in knee OA.

Cross-sectional and longitudinal associations between serum inflammatory cytokines and knee bone marrow lesions in patients with knee osteoarthritis.

OBJECTIVE: To describe cross-sectional and longitudinal associations between serum levels of interleukin (IL) - 6, IL-17A, IL-17F, IL-23 and knee bone marrow lesions (BMLs) in patients with knee osteoarthritis (OA). DESIGN: Patients (n = 192) with symptomatic knee OA (mean 63 years, range 50-79, female 53%) were assessed at baseline and after 24 months. At each time point, serum IL-6, IL-17A, IL-17F and IL-23 were measured using Bio-Plex® Multiplex Immunoassays with Luminex xMAP technology. Knee BMLs were scored using the modified whole organ MRI score (WORMS) from T2 weighted fat-suppressed fast spin echo magnetic resonance imaging (MRI). Multivariable linear regression and log binominal regression were used to determine the associations between cytokines and BMLs. RESULTS: Baseline IL-6 (quarters) were significantly associated with total knee BMLs (P < 0.01 for the trend) as well as associated with an increase in BML score (P = 0.05 for the trend), after adjustment for confounders. Baseline IL-17F and IL-23 (highest quarters vs others) was associated with an increase in BML score in females (P = 0.04 for IL-17F; P = 0.01 for IL-23), but not in males, in multivariable analyses. In contrast, IL-17A was not significantly associated with BMLs in either females or males. CONCLUSION: IL-6 is associated with increased knee BMLs in both females and males with OA. Serum IL-17F and IL-23 predicted increased knee BML scores in females only, suggesting that inflammation is involved in BML pathogenesis in knee OA, especially in women. TRAIL REGISTRATION: ClinicalTrials.gov identifier: NCT01176344; Australian New Zealand Clinical Trials Registry: ACTRN12610000495022.

Management options for femoroacetabular impingement: a systematic review of symptom and structural outcomes.

OBJECTIVE: The optimal therapy for femoroacetabular impingement (FAI) is unclear. The aim of this systematic review was to examine the evidence for surgical and non-surgical treatment of FAI on symptom and structural outcomes. DESIGN: MEDLINE and EMBASE were searched electronically. Surgical and non-surgical management strategies were searched with "FAI". Studies which included comparison groups and reported symptom or structural outcomes were included (Levels I-III evidence). A risk of bias assessment was performed. RESULTS: Eighteen studies comparing management strategies for FAI were identified. Most studies had high risk of bias. No study compared surgical and non-surgical treatment. When surgical approaches were compared there was evidence of superior symptom outcomes with arthroscopy compared to open surgery and with labral preservation. There was some evidence that surgical interventions are effective in reducing alpha angle (improved hip shape), but no data on whether this affects long-term outcomes. There was some weak evidence that surgery is associated with structural progression of hip osteoarthritis (OA). CONCLUSIONS: Although evidence supports improvement in symptoms after surgery in FAI, no studies have compared surgical and non-surgical treatment. Therefore no conclusion regarding the relative efficacy of one approach over the other can be made. Surgery improves alpha angle but whether this alters the risk of development or progression of hip OA is unknown. This review highlights the lack of evidence for use of surgery in FAI. Given that hip geometry may be modified by non-surgical factors, clarifying the role of non-surgical approaches vs surgery for the management of FAI is warranted.

Association between serum concentration of 25-hydroxyvitamin D and the risk of hip arthroplasty for osteoarthritis: result from a prospective cohort study.

OBJECTIVES: There is ongoing debate regarding the optimal serum concentrations of 25-hydroxy-vitamin D for musculoskeletal health, including osteoarthritis (OA). The aim of this prospective cohort study was to determine whether serum 25-hydroxy-vitamin D concentrations were associated with the risk of hip arthroplasty for OA. DESIGN: This study examined 9135 participants from the Australian Diabetes, Obesity and Lifestyle Study who had serum 25-hydroxy-vitamin D measured in 1999-2000 and were aged ≥40 years at the commencement of arthroplasty data collection. The incidence of hip arthroplasty for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over an average 9.1 (standard deviation (SD) 2.7) years of follow-up, 201 hip arthroplasties for OA were identified (males n = 90; females n = 111). In males, a one-standard-deviation increase in 25-hydroxy-vitamin D was associated with a 25% increased incidence (HR 1.25, 95% CI 1.02-1.56), with a dose response relationship evident by quartiles of 25-hydroxy-vitamin D concentration (P for trend 0.04). These results were independent of age, body mass index (BMI), ethnicity, smoking status, physical activity, season of blood collection, latitude, hypertension and diabetes, area level disadvantage or after excluding those with extreme low 25-hydroxy-vitamin D concentrations. No significant association was observed in women (HR 1.10, 95% CI 0.87, 1.39). CONCLUSIONS: Increasing serum 25-hydroxy-vitamin D concentrations were associated with an increased risk of hip arthroplasty for OA in males, while no significant association was observed in females. The mechanism for the association warrants further investigation.

Osteoarthritis bone marrow lesions at the knee and large artery characteristics.

OBJECTIVE: There is evidence to suggest vascular involvement in the initiation and progression of osteoarthritis (OA). The relationship between large artery characteristics and pathogenesis of OA has not been investigated and was the aim of this study. DESIGN: Large artery characteristics (i.e., aortic stiffness, brachial and central blood pressure (BP) variables) and bone marrow lesions (BMLs; measured by magnetic resonance imaging as a surrogate index of OA) were recorded in 208 participants (aged 63 ± 7 years; mean ± SD) with symptomatic knee OA. Relationships between large artery characteristics and BML were assessed by multiple regression adjusting for age, sex and body mass index. RESULTS: There was a high prevalence of BML presence in the study population (70%), but no significant difference between participants with and without BML for all large artery and BP variables (P > 0.05 all). Furthermore, there were no significant relationships between BML size and aortic stiffness (r = -0.033, P = 0.71), central pulse pressure (r = 0.028, P = 0.74), augmentation index (r = 0.125, P = 0.14), brachial pulse pressure (r = 0.005, P = 0.95) or brachial systolic BP (r = -0.066, P = 0.44). When participants were stratified according to high or low aortic stiffness, there was no significant difference between groups regarding the proportion of those with a BML (64% vs. 70% respectively; P = 0.69). CONCLUSIONS: Variables indicative of large artery characteristics are not significantly correlated with BML size or presence in people with symptomatic knee OA. Thus, large artery characteristics may not have a causative influence in the development of OA, but this needs to be confirmed in prospective studies.

Social disadvantage, bone mineral density and vertebral wedge deformities in the Tasmanian Older Adult Cohort.

UNLABELLED: The relationship between social disadvantage and bone mineral density (BMD) is complex and remains unclear; furthermore, little is known of the relationship with vertebral deformities. We observed social disadvantage to be associated with BMD for females, independent of body mass index (BMI). A lower prevalence of vertebral deformities was observed for disadvantaged males. INTRODUCTION: The relationship between social disadvantage and BMD appears complex and remains unclear, and little is known about the association between social disadvantage and vertebral wedge deformities. We examined the relationship between social disadvantage, BMD and wedge deformities in older adults from the Tasmanian Older Adult Cohort. METHODS: BMD and wedge deformities were measured by dual-energy X-ray absorptiometry and associations with extreme social disadvantage was examined in 1,074 randomly recruited population-based adults (51 % female). Socioeconomic status was assessed by Socio-economic Indexes for Areas values derived from residential addresses using Australian Bureau of Statistics 2001 census data. Lifestyle variables were collected by self-report. Regression models were adjusted for age, BMI, dietary calcium, serum vitamin D (25(OH)D), smoking, alcohol, physical inactivity, calcium/vitamin D supplements, glucocorticoids and hormone therapy (females only). RESULTS: Compared with other males, socially disadvantaged males were older (65.9 years versus 61.9 years, p = 0.008) and consumed lower dietary calcium and alcohol (both p ≤ 0.03). Socially disadvantaged females had greater BMI (29.9 ± 5.9 versus 27.6 ± 5.3, p = 0.002) and consumed less alcohol (p = 0.003) compared with other females. Socially disadvantaged males had fewer wedge deformities compared with other males (33.3 % versus 45.4 %, p = 0.05). After adjustment, social disadvantage was negatively associated with hip BMD for females (p = 0.02), but not for males (p = 0.70), and showed a trend for fewer wedge deformities for males (p = 0.06) but no association for females (p = 0.85). CONCLUSIONS: Social disadvantage appears to be associated with BMD for females, independent of BMI and other osteoporosis risk factors. A lower prevalence of vertebral deformities was observed for males of extreme social disadvantage. Further research is required to elucidate potential mechanisms for these associations.

The natural history of bone marrow lesions in community-based adults with no clinical knee osteoarthritis.

OBJECTIVE: Although bone marrow lesions (BML) have been implicated in the pathogenesis of osteoarthritis, their natural history in a healthy population is unknown. This study in a healthy, pain-free population aimed to examine the natural history of BML; factors associated with incidence and progression of BML over 2 years and whether incident BML are associated with the development of pain. METHODS: 271 subjects with no clinical knee osteoarthritis, being pain free at baseline, underwent magnetic resonance imaging of their dominant knee at baseline and 2 years later. The presence of BML was assessed. RESULTS: In knees initially free of BML, incident BML developed in 14% of people over the study period. Increased body mass index (BMI; odds ratio (OR) 1.15, 95% CI 1.06 to 1.2, p = 0.001) was associated with incident BML. Those who developed a BML were more likely to develop knee pain compared with those in whom no BML developed (OR 4.2, 95% CI 1.2 to 15.1, p = 0.03). Among those in whom BML were present at baseline, 46% completely resolved. There was no association between age, gender and BMI and persistence of BML over 2 years. CONCLUSION: In this healthy population, the rate of incident BML is lower than previously described in a population with osteoarthritis. Incident BML are associated with increased BMI and the development of pain. Approximately half the BML present at baseline resolved. These data suggest that in pain-free people with no clinical knee osteoarthritis, BML are reversible and may provide a target for interventions aimed at the prevention of knee osteoarthritis.

Bone marrow lesions predict increase in knee cartilage defects and loss of cartilage volume in middle-aged women without knee pain over 2 years.

OBJECTIVE: Bone marrow lesions (BML) are important in established knee osteoarthritis, predicting pain and progression of disease. Whether BML are also associated with longitudinal changes in knee structure in an asymptomatic population is unknown. METHODS: 148 healthy pain-free women in middle age with no history of knee injury or clinical knee osteoarthritis who had a magnetic resonance imaging (MRI) scan performed on their dominant knee at baseline, had another MRI 2 years later to assess whether having a BML present at baseline affected change in tibiofemoral cartilage defects and tibial cartilage volume. RESULTS: BML were present in 14.9% of women at baseline. The risk of progression of total tibiofemoral cartilage defects was significantly higher when a very large BML was present (odds ratio 5.55, 95% CI 1.04 to 29.6) compared with when no BML was present, after adjusting for potential confounders. In the lateral compartment, the rate of cartilage volume loss was significantly greater when a BML was present after adjusting for confounders (regression coefficient 39.2 mm(3), 95% CI 11.1 to 67.2, p = 0.007). CONCLUSIONS: In healthy women without pain at baseline, large BML were associated with both progression of cartilage defects in the whole tibiofemoral joint and more rapid lateral tibial cartilage loss. These data suggest that the relationship between BML and knee cartilage in healthy women is similar to that described in established osteoarthritis. It is possible that BML may predict an increased risk of knee osteoarthritis and facilitate the identification of novel interventions to prevent disease.

Bone marrow lesions predict progression of cartilage defects and loss of cartilage volume in healthy middle-aged adults without knee pain over 2 yrs.

OBJECTIVE: In knee OA, the presence of bone marrow lesions (BMLs) predicts pain and progression of disease. Their occurrence has been described in healthy, pain-free subjects, but whether their presence affects change in cartilage is unknown. METHODS: Two hundred and seventy-one healthy community-dwelling adults with no history of knee injury, knee pain or clinical knee OA had an MRI performed on their dominant knee at baseline and 2 yrs later to assess the relationship between the presence of BMLs at baseline and change in tibiofemoral cartilage defects and tibial cartilage volume over 2 yrs. RESULTS: BMLs were present in 37 (14%) subjects. Cartilage defects were more likely to progress rather than remain stable or regress in subjects with BMLs compared with those without BMLs (P = 0.04). The odds of cartilage defects progressing in the tibiofemoral compartment of the knee where BMLs were present compared with where BMLs were absent was 2.6 (95% CI 1.2, 5.3; P = 0.01). Where 'very large' BMLs were present, there was a trend for increased annual tibial cartilage volume loss (46.4 mm(3)/yr; P = 0.07). CONCLUSIONS: These data suggest that BMLs are associated with change in knee cartilage over 2 yrs in asymptomatic subjects. Increased progression of cartilage defects is seen with increasing size of BMLs. It will be important to determine in future studies whether BMLs directly cause change in cartilage over 2 yrs, or act as a marker of another factor that facilitates these changes.

Physician diagnosed arthritis, reported arthritis and radiological non-axial osteoarthritis.

OBJECTIVE: To determine the question that best predicts radiographic evidence of non-axial osteoarthritis (OA). DESIGN: The Melbourne Women's Mid-life Health Project (MWMHP), commenced in 1991, is a population-based prospective study of 438 Australian-born. Two hundred and fifty-seven (57%) women remained in longitudinal assessment in 2002 and 224 (87%) women agreed to undergo X-rays of their hands and knees between 2002 and 2003. METHODS: Annually participants were asked about aches and stiff joints and arthritis or rheumatism. In the eleventh year of follow-up X-rays were scored for evidence of OA using a validated scale, by two investigators who were blinded to questionnaire results. Information on hormone therapy use, physical activity, mood, smoking, body mass index (BMI) and age were obtained by both self-administered and face-to-face questionnaires. RESULTS: Patient reported physician diagnosed arthritis was the best predictor of radiological OA (ROA). The question had a specificity of 64%, a positive predictive value of 57% and a negative predictive value of 71%. Even the most reliable question about arthritis still had a relatively low specificity for radiologically diagnosed OA. Reporting symptoms were significantly more common in participants who were depressed, those who had a higher negative affect and those with a higher BMI. CONCLUSION: In large epidemiological studies where questionnaire assessment of OA is required, the greatest accuracy is achieved by asking about physician diagnosed arthritis. Concurrent application of a validated scale for mood is important.

The natural history of cartilage defects in people with knee osteoarthritis.

OBJECTIVES: Cartilage defects are highly prevalent in subjects with knee osteoarthritis (OA). Although they are associated with increased cartilage loss and joint replacement, there is little data on the natural history of cartilage defects. The aim of this study was to examine the progression of cartilage defects over 2 years in people with knee OA and to identify factors associated with progression. METHODS: One hundred and seventeen subjects with OA underwent magnetic resonance imaging of their dominant knee at baseline and follow-up. Cartilage defects were scored (0-4) at four sites. Bone size of the medial and lateral tibial plateau was determined. Height, weight, body mass index and physical activity were measured by standard protocols. RESULTS: The mean cartilage defect score increased significantly over the 2-year study period in all tibiofemoral compartments (all P<0.001), except the lateral tibial compartment with age and tibial plateau bone area at baseline being predictors of progression. However, there was heterogeneity with 81% progressing at any site, 15% remaining stable and 4% decreasing. CONCLUSION: Over 2 years, cartilage defects tend to progress in people with symptomatic OA, with only a small percentage decreasing in severity. Increasing age and increased bone area are risk factors for progression. Interventions aimed at preventing cartilage defects from occurring and reducing their severity may result in a reduction in the severity of OA, by reducing loss of articular cartilage and subsequent requirement for knee joint replacement.