The global burden of musculoskeletal conditions for 2010: an overview of methods.

The objective of this paper is to provide an overview of methods used for estimating the burden from musculoskeletal (MSK) conditions in the Global Burden of Diseases 2010 study. It should be read in conjunction with the disease-specific MSK papers published in Annals of Rheumatic Diseases. Burden estimates (disability-adjusted life years (DALYs)) were made for five specific MSK conditions: hip and/or knee osteoarthritis (OA), low back pain (LBP), rheumatoid arthritis (RA), gout and neck pain, and an 'other MSK conditions' category. For each condition, the main disabling sequelae were identified and disability weights (DW) were derived based on short lay descriptions. Mortality (years of life lost (YLLs)) was estimated for RA and the rest category of 'other MSK', which includes a wide range of conditions such as systemic lupus erythematosus, other autoimmune diseases and osteomyelitis. A series of systematic reviews were conducted to determine the prevalence, incidence, remission, duration and mortality risk of each condition. A Bayesian meta-regression method was used to pool available data and to predict prevalence values for regions with no or scarce data. The DWs were applied to prevalence values for 1990, 2005 and 2010 to derive years lived with disability. These were added to YLLs to quantify overall burden (DALYs) for each condition. To estimate the burden of MSK disease arising from risk factors, population attributable fractions were determined for bone mineral density as a risk factor for fractures, the occupational risk of LBP and elevated body mass index as a risk factor for LBP and OA. Burden of Disease studies provide pivotal guidance for governments when determining health priority areas and allocating resources. Rigorous methods were used to derive the increasing global burden of MSK conditions.

The association between use of antidepressants and bone quality using quantitative heel ultrasound.

Osteoporosis and depression are major public health problems worldwide. Studies have reported an association between antidepressant use, mainly selective serotonin reuptake inhibitors (SSRIs), and bone mineral density (BMD), but the issue remains unclear.

(1)H-NMR analysis of the human urinary metabolome in response to an 18-month multi-component exercise program and calcium-vitamin-D3 supplementation in older men

The musculoskeletal benefits of calcium and vitamin-D3 supplementation and exercise have been extensively studied, but the effect on metabolism remains contentious. Urine samples were analyzed by (1)H-NMR spectroscopy from participants recruited for an 18-month, randomized controlled trial of a multi-component exercise program and calcium and vitamin-D3 fortified milk consumption. It was shown previously that no increase in musculoskeletal composition was observed for participants assigned to the calcium and vitamin-D3 intervention, but exercise resulted in increased bone mineral density, total lean body mass, and muscle strength. Retrospective metabolomics analysis of urine samples from patients involved in this study revealed no distinct changes in the urinary metabolome in response to the calcium and vitamin-D3 intervention, but significant changes followed the exercise intervention, notably a reduction in creatinine and an increase in choline, guanidinoacetate, and hypoxanthine (p < 0.001, fold change > 1.5). These metabolites are intrinsically involved in anaerobic ATP synthesis, intracellular buffering, and methyl-balance regulation. The exercise intervention had a marked effect on the urine metabolome and markers of muscle turnover but none of these metabolites were obvious markers of bone turnover. Measurement of specific urinary exercise biomarkers may provide a basis for monitoring performance and metabolic response to exercise regimes.

Age- and sex-related patterns of first fracture and fracture prevalence

There are few data documenting the pattern of prevalent fracture across the entire adult age range, so we aimed to address this gap by investigating the prevalence of fractures in an Australian cohort. All-cause (ever) fractures were identified for males and females enrolled in the Geelong Osteoporosis Study (Australia) using a combination of radiology-confirmed and self-reported data. First fractures were used to generate age-related frequencies of individuals who had ever sustained a fracture. Of 1,538 males and 1,731 females, 927 males and 856 females had sustained at least one fracture since birth. The proportion of all prevalent fractures in the 0-10 year age group was similar for both sexes (~10 %). In males, the proportion with prevalent fracture increased to 34.1 % for age 11-20 year. Smaller increases were observed into mid-life, reaching a plateau at ~50 % from mid to late life. The age-related prevalence of fracture for females showed a more gradual increase until mid-life. For adulthood prevalent fractures, approximately 20 % of males had sustained a first adulthood fracture in the 20-30 year age group, with a gradual increase up to the oldest age group (49.1 %), while females showed an exponential pattern of increase from the 20-30 year age group (6.8 %) to the oldest age group (60.4 %). In both sexes, those who had not sustained a fracture in childhood or early adulthood generally appeared to remain fracture-free until at least the sixth decade. When considering the prevalence of adulthood fractures across the age groups, males showed a gradual increase while females showed an exponential increase.

Adulthood fracture and quality of life : A population-based study of Australian men

Background: Our objective was to investigate associations between adulthood fracture and quality of life (QOL) in men. Methods: For 448 men aged 50-85 years and enrolled in the Geelong Osteoporosis Study, we measured QOL using the validated (Australian) World Health Organization Quality of Life-Brief Version (WHOQOL-Bref) in the domains of physical health, psychological health, social relationships, and the environment. Self-reported adulthood fractures were categorized as recent or non-recent ( ≤ 10 years or > 10 years pre-QOL assessment, respectively). Lifestyle and health information were self-reported. Results: One hundred seventy four men (38.8%) sustained at least one fracture, 26% of which had occurred within the last 10 years. Compared with men who had never had an adulthood fracture, a non-recent fracture was more likely associated with poorer QOL in the physical health domain (age-adjusted odds ratio [OR] 0.47, 95% confidence interval [95%CI] 0.27-0.83), but not in any other domain. Men who had sustained a recent fracture reported a lower QOL in the domain of psychological health (age-adjusted OR 0.48, 95%CI 0.24-0.97), with a trend observed for lower QOL in the domains of physical health and environment. No further associations were observed. All results were sustained in further models that were adjusted for smoking, alcohol, physical inactivity, and body mass index. Conclusions: We present novel data examining associations between fracture status and QOL in a populationbased sample of Australian men using the WHOQOL-Bref. Recent fractures were associated with poorer QOL in the domain of psychological health while non-recent fractures were more likely associated poorer QOL for physical health. These findings have important implications for healthcare post-fracture.

Knowledge change regarding osteoporosis prevention: translating recommended guidelines into user-friendly messages within a community forum.

Osteoporosis is a skeletal disorder characterised by low bone mineral density and increased fracture risk. Nationally the total costs of this chronic disease are currently estimated at $2.754 billion annually. Effective public health messages providing clear recommendations are vital in supporting prevention efforts. This research aimed to investigate knowledge change associated with the translation of preventive guidelines into accessible messages for the community.

Serum sclerostin and DKK1 in relation to exercise against bone loss in experimental bed rest

The impact of effective exercise against bone loss during experimental bed rest appears to be associated with increases in bone formation rather than reductions of bone resorption. Sclerostin and dickkopf-1 are important inhibitors of osteoblast activity. We hypothesized that exercise in bed rest would prevent increases in sclerostin and dickkopf-1. Twenty-four male subjects performed resistive vibration exercise (RVE; n = 7), resistive exercise only (RE; n = 8), or no exercise (control n = 9) during 60 days of bed rest (2nd Berlin BedRest Study). We measured serum levels of BAP, CTX-I, iPTH, calcium, sclerostin, and dickkopf-1 at 16 time-points during and up to 1 year after bed rest. In inactive control, after an initial increase in both BAP and CTX-I, sclerostin increased. BAP then returned to baseline levels, and CTX-I continued to increase. In RVE and RE, BAP increased more than control in bed rest (p ≤ 0.029). Increases of CTX-I in RE and RVE did not differ significantly to inactive control. RE may have attenuated increases in sclerostin and dickkopf-1, but this was not statistically significant. In RVE there was no evidence for any impact on sclerostin and dickkopf-1 changes. Long-term recovery of bone was also measured and 6-24 months after bed rest, and proximal femur bone mineral content was still greater in RVE than control (p = 0.01). The results, while showing that exercise against bone loss in experimental bed rest results in greater bone formation, could not provide evidence that exercise impeded the rise in serum sclerostin and dickkopf-1 levels.

Citalopram and sertraline exposure compromises embryonic bone development

Selective serotonin reuptake inhibitors (SSRIs) are the most commonly prescribed treatments for depression and, as a class of drugs, are among the most used medications in the world. Concern regarding possible effects of SSRI treatment on fetal development has arisen recently as studies have suggested a link between maternal SSRI use and an increase in birth defects such as persistent pulmonary hypertension, seizures and craniosynostosis. Furthermore, SSRI exposure in adults is associated with decreased bone mineral density and increased fracture risk, and serotonin receptors are expressed in human osteoblasts and osteoclasts. To determine possible effects of SSRI exposure on developing bone, we treated both zebrafish, during embryonic development, and human mesenchymal stem cells (MSCs), during differentiation into osteoblasts, with the two most prescribed SSRIs, citalopram and sertraline. SSRI treatment in zebrafish decreased bone mineralization, visualized by alizarin red staining and decreased the expression of mature osteoblast-specific markers during embryogenesis. Furthermore, we showed that this inhibition was not associated with increased apoptosis. In differentiating human MSCs, we observed a decrease in osteoblast activity that was associated with a decrease in expression of the osteoblast-specific genes Runx2, Sparc and Spp1, measured with quantitative real-time PCR (qRT-PCR). Similar to the developing zebrafish, no increase in expression of the apoptotic marker Caspase 3 was observed. Therefore, we propose that SSRIs inhibit bone development by affecting osteoblast maturation during embryonic development and MSC differentiation. These results highlight the need to further investigate the risks of SSRI use during pregnancy in exposing unborn babies to potential skeletal abnormalities.Molecular Psychiatry advance online publication, 8 September 2015; doi:10.1038/mp.2015.135.

Fracture prediction from repeat BMD measurements in clinical practice

Summary: We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment. We report that repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy. Introduction: In clinical practice, many patients selectively undergo repeat bone mineral density (BMD) measurements. We investigated whether repeat BMD measurements in clinical populations are useful for fracture risk assessment and whether this is affected by preceding change in BMD or recent osteoporosis therapy. Methods: We identified women and men aged ≥50 years who had a BMD measurement during 1990–2009 from a large clinical BMD database for Manitoba, Canada (n = 50,215). Patient subgroups aged ≥50 years at baseline with repeat BMD measures were identified. Data were linked to an administrative data repository, from which osteoporosis therapy, fracture outcomes, and covariates were extracted. Using Cox proportional hazards models, we assessed covariate-adjusted risk for major osteoporotic fracture (MOF) and hip fracture according to BMD (total hip, lumbar spine, femoral neck) at different time points. Results: Prevalence of osteoporosis therapy increased from 18 % at baseline to 55 % by the fourth measurement. Total hip BMD was predictive of MOF at each time point. In the patient subgroup with two repeat BMD measurements (n = 13,481), MOF prediction with the first and second measurements was similar: adjusted-hazard ratio (HR) per SD 1.45 (95 % CI 1.34–1.56) vs. 1.64 (95 % CI 1.48–1.81), respectively. No differences were seen when the second measurement results were stratified by preceding change in BMD or osteoporosis therapy (both p-interactions >0.2). Similar results were seen for hip fracture prediction and when spine and femoral neck BMD were analyzed. Conclusion: Repeat BMD measurements are a robust predictor of fracture in clinical populations; this is not affected by preceding BMD change or recent osteoporosis therapy.

Vibration or balance training on neuromuscular performance in osteopenic women

Maintaining neuromuscular function in older age is an important topic for aging societies, especially for older women with low bone density who may be at risk of falls and bone fracture. This randomized controlled trial investigated the effect of resistive exercise with either whole-body vibration training (VIB) or coordination/balance training (BAL) on neuromuscular function (countermovement jump, multiple 1-leg hopping, sit-to-stand test). 68 postmenopausal women with osteopenia or osteoporosis were recruited for the study. 57 subjects completed the 9-month, twice weekly, intervention period. All subjects conducted 30 min of resistance exercise each training day. The VIB-group performed additional training on the Galileo vibration exercise device. The BAL-group performed balance training. An "intent-to-treat" analysis showed greater improvement in the VIB-group for peak countermovement power (p=0.004). The mean [95% confidence interval] effect size for this parameter was a  + 0.9[0.3 to 1.5] W/kg greater change in VIB than BAL after 9 months. In multiple 1-leg hopping, a significantly better performance in the VIB-group after the intervention period was seen on a "per-protocol" analysis only. Both groups improved in the sit-to-stand test. The current study provides evidence that short-duration whole-body vibration exercise can have a greater impact on some aspects of neuromuscular function in post-menopausal women with low bone density than proprioceptive training.

Effects of depression and serotonergic antidepressants on bone: mechanisms and implications for the treatment of depression

Osteoporosis is a chronic skeletal disease marked by microarchitectural deterioration of the bone matrix and depletion of bone mineral density (BMD), with a consequent increased risk for fragility fractures. It has been frequently associated with depression, which is also a chronic and debilitating disorder with high prevalence. Selective serotonin reuptake inhibitors (SSRIs), first-line agents in the pharmacological treatment of mood and anxiety disorders, have also been shown to negatively affect bone metabolism. SSRIs are the most prescribed antidepressants worldwide and a large number of persons at risk of developing osteoporosis, including older patients, will receive these antidepressants. Therefore, a proper musculoskeletal evaluation of individuals who are being targeted for or using SSRIs is a priority. The aim of this article is to review the evidence regarding the effects of depression and serotonergic antidepressants on bone and its implications for clinical care.