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Musculoskeletal pain is common and typically occurs at multiple sites. Pain has been shown to be associated with falls risk; however, whether an increased risk for falls associated with multisite pain (MSP) translates into an increased risk of fractures has not been investigated. This study aimed to examine the association of number of painful sites with prevalent and incident fractures. Data from a longitudinal population-based study of older adults (mean age 63 years) were utilized. Follow-up was performed at 2.6, 5.1, and 10.7 years later, respectively. Presence/absence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire at baseline. Participants were classified into three groups according to the total number of painful sites: zero to two, three to four, and five to seven. Fractures were self-reported at each time point. BMD was measured by DXA. Falls risk was calculated based on the Short-Form Physiological Profile Assessment. Log-binomial regression was used for the analyses. There were 450 fractures at baseline and 154 new fractures reported during a mean follow-up period of 10.7 years (range 9.2 to 12.5 years). In multivariable analyses, number of painful sites was associated with prevalent fractures at any and nonvertebral site. Furthermore, participants with five to seven painful sites had an increased risk of incident fractures at any site (RR 1.69; 95% CI, 1.13 to 2.53); major site, including the femur, radius, ulnar, vertebral, rib, and humerus (RR 2.17; 95% CI 1.12 to 4.22); and vertebral site (RR 6.44, 95% CI, 1.64 to 25.33) compared with those with pain at zero to two sites. These associations remained statistically significant after further adjustment for falls risk and BMD. Pain at multiple sites was associated with incident fracture risk in a dose-response manner, suggesting that widespread pain is an independent contributor to fracture risk. The potential for pain management in fracture prevention warrants further exploration. © 2019 American Society for Bone and Mineral Research., (© 2019 American Society for Bone and Mineral Research.)

Objective: To identify and validate knee pain phenotypes in an older population across different pain-related domains over 10.7 years., Methods: A total of 963 participants (mean age 63 years) from a population-based older adult cohort study were studied at baseline and followed up at 2.6 (n = 875), 5.1 (n = 768) and 10.7 years (n = 563). Baseline demographic, psychological, lifestyle and comorbidities data were obtained and MRI was performed to measure knee structural pathology. WOMAC pain and pain at multiple sites were assessed by questionnaires at each time-point. Latent class analysis was used to identify knee pain phenotypes, considering sex, BMI, emotional problems, education level, comorbidities, number of painful sites and knee structural pathology., Results: Three pain phenotypes were identified: Class 1: high prevalence of emotional problems and low prevalence of structural damage (25%); Class 2: high prevalence of structural damage and low prevalence of emotional problems (20%); Class 3: low prevalence of emotional problems and low prevalence of structural damage (55%). Participants within Class 1 and 2 had greater BMI, more comorbidities, a higher prevalence of radiographic knee OA and knee structural pathology compared with Class 3. Furthermore, compared with Class 2 and 3, WOMAC pain and number of painful sites were consistently greater at each time-point over 10.7 years in Class 1. Results were similar when the analyses were restricted to participants with radiographic knee OA., Conclusion: Psychological and structural factors interact with each other to exacerbate pain perception, suggesting that tailored treatment approaches for older people with knee pain in clinical practice are needed.

Background: Bisphosphonates are a class of drugs that slow bone loss and are a promising candidate to treat knee osteoarthritis (OA) patients. In a pilot study, we demonstrated that zoledronic acid reduced knee pain and size of subchondral bone marrow lesions (BMLs) over 6 months in knee OA patients with significant knee pain and BMLs. A longer, larger study is required to assess whether decreases in BML size will translate to reductions in cartilage loss over time. We are currently conducting a multicentre, randomised, double-blind, placebo-controlled trial over 24 months that aims to compare the effect of annual infusions of zoledronic acid to placebo on knee structural change (assessed using magnetic resonance imaging (MRI)) and knee pain in knee OA patients., Methods: Two hundred sixty-four patients with clinical knee OA, significant knee pain and subchondral BMLs present on MRI will be recruited in Hobart, Melbourne, Sydney and Adelaide. They will be randomly allocated to the two arms of the study, receiving an annual identical intravenous infusion of either 100 mL of fluid containing zoledronic acid (5 mg/100 mL) or placebo (0.9% NaCl 100 mL), at baseline and 1 year later. MRI of the study knee will be performed at screening, month 6 and 24. Knee structure, symptoms and function will be assessed using validated methods. The primary outcome is absolute change in tibiofemoral cartilage volume (mm 3 ) over 24 months. Secondary outcomes include improvement in knee pain over 3, 6, 12, 18, and 24 months and reductions in BML size over 6 and 24 months. The primary analyses will be intention-to-treat analyses of primary and secondary outcomes. Per protocol analyses will be performed as the secondary analyses., Discussion: This study will provide high-quality evidence to assess whether zoledronic acid has a novel disease modifying effect in OA by slowing cartilage loss and reducing pain. If zoledronic acid proves effective, it suggests great potential for cost savings through a delay or reduced need for joint replacement surgery, and potential for great improvements in quality of life for OA suffers., Trial Registration: Australian New Zealand Clinical Trials Registry: ACTRN12613000039785 , registered on 14 January 2013.

The objective of this study was to investigate the associations of knee structural abnormalities with different patterns of pain. A total of 891 participants (average age 63 years; range 50 to 80 years) participated in this study. Presence of pain at the neck, back, hands, shoulders, hips, knees, and feet was assessed by questionnaire. Participants were categorized as having no pain at any site (no pain), pain only at the knee (KP), pain at other sites but not the knee (OP), and pain at the knee and other sites (KOP). T1-weighted or T2-weighted MRI of the right knee was performed to measure cartilage defects, bone marrow lesions (BMLs), and effusion-synovitis. Osteophytes and joint space narrowing were assessed by X-ray. KP, KOP, and OP were, respectively, present in 3, 43, and 42% of the participants. In multivariable analyses, KOP was associated with the presence of cartilage defects, BMLs, and osteophytes (OR 3.57 (95% CI 1.78 to 7.14), 2.37 (1.27 to 4.43), and 2.87 (1.10 to 7.51), respectively) in those with radiographic knee OA. KP was also associated with presence of these structural abnormalities as well as effusion-synovitis, and these associations were much stronger. The associations between structural abnormalities and KOP were weaker than those with KP in those with radiographic knee OA. This suggests that mechanisms mediating the association between structural pathology, localized, and generalized pain may be different, and central sensitization is possibly involved in generalized pain. Pain at other sites needs to be considered in the management and treatment of OA-related pain.

Introduction: There is increasing evidence to suggest that bone marrow lesions (BMLs) play a key role in the pathogenesis of osteoarthritis (OA). However, there is a lack of long term data. The aim of this study was to describe the natural history of knee BMLs, their association with knee pain and examine predictors of BML change over eight years., Methods: A total of 198 subjects (109 adult offspring of subjects who had a knee replacement and 89 community-based controls) were studied. Knee pain and BML size were assessed at two and ten year visits., Results: At the two year visit, 64% of participants (n = 127) had 229 BMLs (34% patella, 26% femoral and 40% tibial). Over eight years, 24% (55/229) increased in size, 55% (125/229) remained stable and 21% (49/229) decreased in size or resolved completely. Of the participants without BMLs at baseline, 52% (37/71) developed incident BMLs., Conclusion: In this midlife cohort, the proportion of BMLs increasing in size was similar to those decreasing in size with the majority remaining stable. Change in BMLs was predicted by BMI and strenuous activity. An increase in BML size or a new BML resulted in an increase in pain especially in males and those with a family history of OA.

The objective of this study was to describe the cross-sectional and longitudinal relationship between hip bone marrow lesions (BMLs), high cartilage signal, and hip and knee pain. One hundred ninety-eight participants in the Tasmanian Older Adult Cohort Study with right hip MRI conducted at two time points, approx. 2.3 years apart, were included. Short T1 Inversion Recovery MR images were used to quantitatively measure hip BML size and determine high cartilage signal presence. Hip and knee pain were individually assessed using the Western Ontario and McMaster Universities Osteoarthritis index pain score. Fifty-five participants (28%) had either femoral and/or acetabular BMLs. Cross-sectionally, the presence of large femoral, acetabular, or any hip BMLs was associated with higher odds of hip pain (OR = 4.42, 95% CI = 1.37-19.7; OR = 5.23, 95% CI = 1.17-22.9; OR = 4.43, 95% CI = 1.46-13.2, respectively). High cartilage signal was strongly associated with hip BMLs (OR = 6.45, 95% CI = 3.37-12.6), but not with pain. Longitudinally, incident acetabular (Mean diff = +5.90, 95% CI = +3.78 to +8.15) and femoral BMLs (Mean diff = +1.18, 95% CI = 0.23-1.94) were associated with worsening hip pain, while resolving femoral BMLs were associated with a decrease in knee pain (Mean diff = -3.18, 95% CI = -5.99 to -0.50). The evidence is consistent for hip, but not knee pain, and strongly suggests that large hip BMLs are associated with hip pain. Furthermore, high cartilage signal is asymptomatic, but strongly associated with hip BMLs. These findings suggest that hip BMLs play an important role in hip osteoarthritis.

Background: A socioeconomic gradient exists in the utilisation of total hip replacements (THR) and total knee replacements (TKR) for osteoarthritis. However, the relations between socioeconomic status (SES) and time to THR or TKR is unknown. Aim: To describe the association between SES and time to THR and TKR. Methods: One thousand and seventy‐two older adults residing in Tasmania, Australia, were studied. Incident primary THR and TKR were determined by data linkage to the Australian Orthopaedic Association National Joint Replacement Registry. At baseline, each participant's area‐level SES was determined using the Index of Relative Socioeconomic Advantage and Disadvantage (IRSAD) from the Australian Bureau of Statistics' 2001 census data. The IRSAD was analysed in two ways: (i) categorised into quartiles, whereby quartile 1 represented the most socioeconomically disadvantaged group; and (ii) the cohort dichotomised at the quartile 1 cut‐point. Results: The mean age was 63.0 (±7.5) years and 51% were women. Over the median follow up of 12.9 (interquartile range: 12.2–13.9) years, 56 (5%) participants had a THR and 79 (7%) had a TKR. Compared with the most disadvantaged quartile, less disadvantaged participants were less likely to have a THR (i.e. less disadvantaged participants had a longer time to THR; hazard ratio (HR): 0.56; 95% confidence interval (CI) 0.32, 1.00) but not TKR (HR: 0.90; 95% CI 0.53, 1.54). However, the former became non‐significant after adjustment for pain and radiographic osteoarthritis, suggesting that the associations may be mediated by these factors. Conclusions: The present study suggests that time to joint replacement was determined according to the symptoms/need of the participants rather than their SES. [ABSTRACT FROM AUTHOR]

Background: Hip effusion-synovitis may be relevant to osteoarthritis (OA) but is of uncertain etiology. The aim of this study was to describe the cross-sectional and longitudinal associations of hip effusion-synovitis with clinical and structural risk factors of OA in older adults.Methods: One hundred ninety-six subjects from the Tasmanian Older Adult Cohort (TASOAC) study with a right hip STIR (Short T1 Inversion Recovery) Magnetic Resonance Imaging (MRI) on two occasions were included. Hip effusion-synovitis CSA (cm2) was assessed quantitatively. Hip pain was determined by WOMAC (Western Ontario and McMaster Universities Osteoarthritis) while hip bone marrow lesions (BMLs), cartilage defects (femoral and/or acetabular) and high cartilage signal were assessed on MRI. Joint space narrowing (0-3) and osteophytes (0-3) were measured on x-ray using Altman's atlas.Results: Of 196 subjects, 32% (n = 63) had no or a small hip effusion-synovitis while 68% (n = 133) subjects had a moderate or large hip effusion-synovitis. Both groups were similar but those with moderate or large hip effusion-synovitis were older, had higher BMI and more hip pain. Cross-sectionally, hip effusion-synovitis at multiple sites was associated with presence of hip pain [Prevalence ratio (PR):1.42 95%CI:1.05,1.93], but not with severity of hip pain. Furthermore, hip effusion-synovitis size associated with femoral defect (βeta:0.32 95%CI:0.08,0.56). Longitudinally, and incident hip cartilage defect (PR: 2.23 95%CI:1.00, 4.97) were associated with an increase in hip effusion-synovitis CSA. Furthermore, independent of presence of effusion-synovitis, hip BMLs predicted incident (PR: 1.62 95%CI: 1.13, 2.34) and worsening of hip cartilage defects (PR: 1.50 95%CI: 1.20, 1.86). While hip cartilage defect predicted incident (PR: 1.11 95%CI: 1.03, 1.20) and worsening hip BMLs (PR: 1.16 95%CI: 1.04, 1.30).Conclusions: Hip effusion-synovitis at multiple sites (presumably reflecting extent) may be associated with hip pain. Hip BMLs and hip cartilage defects are co-dependent and predict worsening hip effusion-synovitis, indicating causal pathways between defects, BMLs and effusion-synovitis. [ABSTRACT FROM AUTHOR]

Objectives: To identify distinct pain trajectories over 10.7 years and to examine predictors of identified pain trajectories in an older population and those with radiographic knee osteoarthritis (ROA).Methods: 963 participants (aged 50-80 years) from a population-based cohort had baseline demographic, psychological, lifestyle and comorbidities data collected. T1-and T2-weighted magnetic resonance imaging (MRI) of the right knee was performed to measure knee structural pathology-cartilage defects, bone marrow lesions (BMLs) and effusion-synovitis. Group-based trajectory modelling (GBTM) was applied to identify trajectories of knee pain over 10.7 years measured by Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC).Results: Three distinct pain trajectories were defined: 'Minimal pain' (n = 501, 52%), 'Mild pain' (n = 329, 34%) and 'Moderate pain' (n = 165, 14%). In multivariable analysis, having cartilage defects, BMLs and effusion-synovitis were associated with an increased risk of being in the 'Mild pain' (relative risk [RR]: 1.40 to 1.92) and 'Moderate pain' trajectory (RR: 1.72 to 2.26), compared with the 'Minimal pain' trajectory. Being obese and having more painful sites were associated with 'Mild pain' and 'Moderate pain' trajectories, while unemployment, lower education level and presence of emotional problems were associated with 'Moderate pain' trajectory group. Similar results were found for those with ROA.Conclusion: Distinct pain trajectories identified suggest that homogeneous subgroups exist, which might be useful for phenotypic assessment for pain management, particularly in knee osteoarthritis. Structural pathology was associated with worse pain trajectories, suggesting that peripheral stimuli are critical for the development and maintenance of pain severity. Environmental and psychological factors may exacerbate pain perception. [ABSTRACT FROM AUTHOR]

Aim: To describe the associations of between-person and within-person variability in serum 25-hydroxyvitamin D (25(OH)D), physical activity (PA), and knee pain and dysfunction with muscle mass, strength, and muscle quality over 10 years in community-dwelling older adults.Method: Participants (N = 1033; 51% women; mean age 63 ± 7.4 years) were measured at baseline, 2.5, 5, and 10 years. Lower limb lean mass (LLM) was assessed using dual energy X-ray absorptiometry, lower limb muscle strength (LMS) using a dynamometer, and lower limb muscle quality (LMQ) calculated as LMS/LLM. Knee pain and dysfunction were assessed using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) index. PA was measured using pedometers. Linear-mixed effect regression models, with adjustment for confounders, were used to estimate the association of within-person and between-person variability in PA, 25(OH)D, and WOMAC scores with muscle mass, strength, and muscle quality.Results: Both between-person and within-person increases in PA were associated with LLM, LMS, and LMQ (all P < 0.05). Within-person and between-person increases in knee pain and dysfunction were associated with LLS and LMQ, but not with LLM (all P < 0.05). Between-person effects showed that higher average 25(OH)D was associated with a higher 10-year average LLM, LMS, and LMQ (all P < 0.05), whereas within-person increases in average 25(OH)D were associated with a higher LMS and LMQ, but not with LLM.Conclusions: Variability in 25(OH)D, pain, and dysfunction within an individual over time is related to muscle changes in that individual. Increasing one's own PA level further increases muscle mass, strength, and quality supporting the clinical recommendation of promoting PA to reduce age-related muscle loss. [ABSTRACT FROM AUTHOR]

Aims To describe the longitudinal associations between physiological falls risk, and between-person and within-person effects of 25-hydroxyvitamin D (25OHD), physical activity (PA), knee pain and dysfunction in community-dwelling older people. Methods Data for 1053 participants (51% women; mean age 63 ± 7.4 years) studied at baseline, 2.5, 5, and 10 years were analysed. Falls risk (Z-score) was measured using the Physiological Profile Assessment. Knee pain and dysfunction were assessed using the Western Ontario and McMaster Universities Osteoarthritis index (WOMAC). Moderate-to-vigorous PA (MVPA) was measured using accelerometer. Linear mixed-effect regression models, with adjustment for confounders, were used to estimate the association between physiological falls risk and between-person and within-person effects of PA, 25OHD and WOMAC score. Results Between-person effects showed that 10-year average physiological falls risk was lower in participants who had a higher 10-year average 25OHD (β = −0.005 per nmol/l, 95% CI: −0.008, −0.002), log-MVPA (β = −0.16 per minute, 95% CI: −0.22, −0.10) and lower mean WOMAC score (β = 0.005 per-unit score, 95% CI: 0.003, 0.01). Within-person effects showed that a higher physiological falls risk at any time-point was associated with higher than average WOMAC score (β = 0.002 per-unit score, 95% CI: 0.0003, 0.004) and lower than average log-MVPA (β = −0.15 per minute, 95% CI: −0.24, −0.06), but not 25OHD, at the same time-point. Conclusion Having higher WOMAC global score above an individual's average increases the risk of falling, whereas, increasing one's own MVPA level further reduces their risk of falling. The presence of between-person but not within-person associations for 25OHD suggests the former may be confounded by other factors. [ABSTRACT FROM AUTHOR]