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.

Trajectories of body mass index from early adulthood to late midlife and incidence of total knee arthroplasty for osteoarthritis: findings from a prospective cohort study.

OBJECTIVE: To examine the association between body mass index (BMI) trajectories from early adulthood to late midlife and risk of total knee arthroplasty (TKA) for osteoarthritis. METHODS: 24,368 participants from the Melbourne Collaborative Cohort Study with weight collected during 1990-1994, 1995-1998, and 2003-2007, recalled weight at age 18-21 years, and height measured during 1990-1994 were included. Incident TKA from 2003 to 2007 to December 2018 was determined by linking cohort records to the National Joint Replacement Registry. RESULTS: Using group-based trajectory modelling, six distinct trajectories (TR) of BMI from early adulthood (age 18-21 years) to late midlife (approximately 62 years) were identified: lower normal to normal BMI (TR1; 19.7% population), normal BMI to borderline overweight (TR2; 36.7%), normal BMI to overweight (TR3; 26.8%), overweight to borderline obese (TR4; 3.5%), normal BMI to class 1 obesity (TR5; 10.1%), overweight to class 2 obesity (TR6; 3.2%). Over 12.4 years, 1,328 (5.4%) had TKA. The hazard ratios for TKA increased in all TR compared to TR1 [from TR2: 2.03 (95% CI 1.64-2.52) to TR6: 8.59 (6.44-11.46)]. 28.4% of TKA could be prevented if individuals followed the trajectory one lower, an average weight reduction of 8-12 kg from early adulthood to late midlife, saving $AUS 373 million/year. Most reduction would occur in TR2 (population attributable fraction 37.9%, 95% CI 26.7-47.3%) and TR3 (26.8%, 20.0-31.2%). CONCLUSIONS: Prevention of weight gain from young adulthood to late midlife in order to reduce overweight/obesity has the potential to significantly reduce the cost and burden of TKA.

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.

Once-yearly zoledronic acid and change in abdominal aortic calcification over 3 years in postmenopausal women with osteoporosis: results from the HORIZON Pivotal Fracture Trial.

This study evaluated whether zoledronic acid (ZA) inhibited the progression of abdominal aortic calcification (AAC) over 3 years in 502 postmenopausal women with osteoporosis. AAC progressed in a similar proportion of participants in the ZA (29%) and placebo (31%) groups, suggesting no effect of ZA on AAC progression. INTRODUCTION: Bisphosphonate use is associated with reduced risk of all-cause mortality and cardiovascular events. The underlying mechanisms are uncertain but may include effects on vascular calcification. This study aimed to evaluate the effect of zoledronic acid (ZA) on abdominal aortic calcification (AAC) in postmenopausal women with osteoporosis. METHODS: This was a post hoc analysis of the HORIZON Pivotal Fracture Trial that included 502 postmenopausal women (mean age 72.5 years) with osteoporosis (234 received ZA and 268 placebo). AAC scores (range, 0-8) were assessed from paired spine X-rays at baseline and after 3 years. Progression of AAC was defined as any increase in AAC score. The association between change in hip and femoral neck bone mineral density and change in AAC score was also assessed. RESULTS: At baseline, 292 (58.2%) participants had AAC (i.e., AAC score > 0), with AAC scores similar in the two intervention groups (median [interquartile range], 1 [0 to 2] for both; p = 0.98). Over 3 years, AAC progressed in a similar proportion of participants in both groups (ZA 29% and placebo 31%; p = 0.64). Change in bone mineral density and change in AAC score were not correlated. CONCLUSION: Once-yearly zoledronic acid did not affect progression of AAC over 3 years in postmenopausal women with osteoporosis. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT00049829.

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.

Relationship of weight and obesity with the risk of knee and hip arthroplasty for osteoarthritis across different levels of physical performance: a prospective cohort study.

OBJECTIVE: To examine the association between obesity and knee and hip arthroplasty for osteoarthritis across a range of physical performance. METHOD: The body mass index and physical performance (on the 36-item Short Form Health Survey) of 9135 Australian Diabetes, Obesity and Lifestyle Study participants were measured in 1999-2000. The incidence of knee and hip arthroplasty during 2002-2011 was determined by linking the cohort records to the Australian Orthopaedic Association National Joint Replacement Registry. RESULTS: Over 9.1 ± 2.3 years (mean ± sd)) of follow-up, 317 participants had knee and 202 had hip arthroplasty for osteoarthritis. Using those with neither obesity nor significantly impaired physical performance as the reference group, participants with both obesity and significantly impaired physical performance had a higher knee arthroplasty risk [hazard ratio (HR) = 5.25, 95% confidence interval (CI) 3.85-7.14] than those with obesity alone (HR = 2.49, 95% CI 1.81-3.44) or impaired physical performance alone (HR = 2.19, 95% CI 1.59-3.02). Similar results were observed for hip arthroplasty (obesity and impaired physical performance: HR = 2.67, 95% CI 1.72-4.15; obesity alone: HR = 1.65, 95% CI 1.08-2.51; impaired physical performance alone: HR = 1.83, 95% CI 1.26-2.66). Among overweight/obese patients, 5 kg greater baseline weight increased the knee arthroplasty risk across all levels of physical performance, and hip arthroplasty risk in those with the highest level of physical performance. CONCLUSION: Although impaired physical performance is an independent risk factor for knee and hip arthroplasty, greater weight increased knee arthroplasty for overweight/obese participants at all levels of physical performance, but hip arthroplasty only in those with good physical performance. Targeting weight loss has the potential to reduce the risk of knee arthroplasty and improve patient outcomes, even in those with poor physical performance.

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.

Patients' perceived health service needs for osteoarthritis (OA) care: a scoping systematic review.

OBJECTIVE: To identify and synthesise evidence regarding patients' perceived health service needs related to osteoarthritis (OA). DESIGN: A comprehensive systematic scoping review of MEDLINE, PsycINFO, EMBASE and CINAHL (1990-2016) was performed to capture information regarding patient perceived health service needs related to OA. Risk of bias and quality of included articles were assessed. Relevant data were extracted and collated to provide a systematic review of the existing literature. RESULTS: Of the 1384 identified manuscripts, 21 were relevant to areas of patient perceived need, including needs related to medical care, pharmacologic therapy, physiotherapy and exercise therapy and alternative medicine. Key findings included (1) Symptom control drove the need for both conventional and complementary services. (2) An individualized relationship was sought with a practitioner knowledgeable in OA care and who adopted a holistic approach, whether providing conventional or alternative therapies. (3) Medications were required to obtain symptomatic relief, with use tempered by recognition of potential side effects and financial cost. (4) The need for allied health services was recognised, although patient and system issues were barriers to uptake. (5) Patient's attitudes towards joint replacement, orthoses and physical aids were influenced by patient preferences and previous healthcare experiences. CONCLUSION: Patient perceived needs are similar to those suggested by clinical guideline recommendations. Better aligning patient perceived needs with healthcare requirements may improve OA outcomes and optimise healthcare system utilisation.

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.

Weight satisfaction, management strategies and health beliefs in knee osteoarthritis patients attending an outpatient clinic.

BACKGROUND: Although weight control is important in managing knee osteoarthritis (OA), it is difficult to achieve. Understanding beliefs regarding weight management in people with knee OA may improve weight control. AIMS: To examine differences in bodyweight satisfaction, weight management strategies and weight-related health-beliefs in obese, overweight and normal weight people with knee OA. METHODS: The beliefs and attitudes to weight in 102 people with symptomatic knee OA were ascertained. Participants were classified as being obese, overweight or of normal weight. RESULTS: Although obese and overweight participants were less satisfied with their bodyweight, they were more likely to want to lose weight and to report dieting compared with normal weight participants(P < 0.001 for all) and also more likely to report weight gain in the past 6 months (P < 0.001). While most participants rated food intake to be a main determinant of health, this belief was more common in normal weight participants (P = 0.04). When asked about their own weight gain, obese participants more frequently believed genetic and metabolic factors to be important than normal and overweight participants (P = 0.01). While 51 (53%) believed that increasing activity was more important than dietary change to avoid weight gain, this was more commonly believed by obese and overweight participants (P < 0.05). CONCLUSIONS: Despite desiring and attempting to lose weight, obese people with symptomatic knee OA more commonly reported weight gain. Overweight and obese participants attributed weight gain to non-modifiable factors but believed physical activity is more important than dietary change in weight management. Thus, education regarding the importance of diet as compared with non-modifiable factors and physical activity may improve weight management in obese people with knee OA.

Vastus medialis fat infiltration - a modifiable determinant of knee cartilage loss.

BACKGROUND: There is growing interest in the role of intramuscular fat and how it may influence clinical outcomes. Vastus medialis (VM) is a functionally important quadriceps muscle that helps to stabilise the knee joint. This longitudinal study examined the determinants of VM fat infiltration and whether VM fat infiltration influenced knee cartilage volume. METHODS: 250 participants without any diagnosed arthropathy were assessed at baseline between 2005 and 2008, and 197 participants at follow-up between 2008 and 2010. Ambulatory and sporting activity were assessed and magnetic resonance imaging (MRI) was used to determine knee cartilage volume and VM fat infiltration. RESULTS: Age, female gender, BMI and weight were positively associated with baseline VM fat infiltration (P ≤ 0.03), while ambulatory and sporting activity were negatively associated with VM fat infiltration (P ≤ 0.05). After adjusting for confounders, a reduction in VM fat infiltration was associated with a reduced annual loss of medial tibial (ß = -10 mm(3); 95% CI -19 to 0 mm(3); P = 0.04) and patella (ß = -18 mm(3); 95% CI -36 to 0 mm(3); P = 0.04) cartilage volume. CONCLUSION: This community-based study of healthy adults has shown that VM fat infiltration can be modified by lifestyle factors including weight loss and exercise, and reducing fat infiltration in VM has beneficial effect on knee cartilage preservation. The findings suggest that modifying VM fat infiltration via lifestyle interventions may have the potential to reduce the risk of knee OA.

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.

Retinal arteriolar narrowing and incidence of knee replacement for osteoarthritis: a prospective cohort study.

OBJECTIVES: The role of the microcirculation in the pathogenesis of osteoarthritis (OA) remains unclear. This prospective cohort study examined the association between retinal vascular calibre and incidence of knee replacement for OA. DESIGN: 1838 participants of the Australian Diabetes, Obesity and Lifestyle (AusDiab) Study had retinal vascular calibre measured using a nonmydriatic digital fundus camera in 1999-2000 and were aged ≥ 40 years at joint replacement data collection commencement. The incidence of knee replacement for OA during 2002-2011 was determined by linking cohort records to the Australian Orthopaedic Association National Joint Replacement Registry (AOANJRR). RESULTS: 77 participants underwent knee replacement for OA. They had narrower retinal arteriolar calibre compared with those without knee replacement (166.1 ± 24.8 µm vs 174.3 ± 24.5 µm, P = 0.004). For every one standard deviation reduction in retinal arteriolar calibre, the incidence of knee replacement increased by 25% (HR 1.25, 95% confidence interval (CI) 1.00-1.56). Participants in the narrower two-thirds of arteriolar calibre had twice the risk of knee replacement compared with those in the widest one-third (HR 2.00, 95% CI 1.07-3.74, P = 0.03) after adjustment for sex, body mass index (BMI), physical activity and HbA1c. There was no association for retinal venular calibre. CONCLUSIONS: Retinal arteriolar narrowing is associated with increased risk of knee replacement for OA suggesting that further work is warranted to determine the role of the microcirculation in the pathogenesis of knee OA.