Jian Sheng Chen

Models of care for the secondary prevention of osteoporotic fractures: a systematic review and meta-analysis.

Most people presenting with incident osteoporotic fractures are neither assessed nor treated for osteoporosis to reduce their risk of further fractures, despite the availability of effective treatments. We evaluated the effectiveness of published models of care for the secondary prevention of osteoporotic fractures. We searched eight medical literature databases to identify reports published between 1996 and 2011, describing models of care for secondary fracture prevention. Information extracted from each publication included study design, patient characteristics, identification strategies, assessment and treatment initiation strategies, as well as outcome measures (rates of bone mineral density (BMD) testing, osteoporosis treatment initiation, adherence, re-fractures and cost-effectiveness). Meta-analyses of studies with valid control groups were conducted for two outcome measures: BMD testing and osteoporosis treatment initiation. Out of 574 references, 42 articles were identified as analysable. These studies were grouped into four general models of care—type A: identification, assessment and treatment of patients as part of the service; type B: similar to A, without treatment initiation; type C: alerting patients plus primary care physicians; and type D: patient education only. Meta-regressions revealed a trend towards increased BMD testing (p = 0.06) and treatment initiation (p = 0.03) with increasing intensity of intervention. One type A service with a valid control group showed a significant decrease in re-fractures. Types A and B services were cost-effective, although definition of cost-effectiveness varied between studies. Fully coordinated, intensive models of care for secondary fracture prevention are more effective in improving patient outcomes than approaches involving alerts and/or education only.

Atypical antipsychotic medications and risk of falls in residents of aged care facilities.

Objectives: To determine whether use of atypical antipsychotics (olanzapine and risperidone) is associated with lower risk of falls than use of typical antipsychotics.

Antiresorptive therapies for osteoporosis: a clinical overview

Antiresorptive therapies are used to increase bone strength in individuals with osteoporosis and include five principal classes of agents: bisphosphonates, estrogens, selective estrogen receptor modulators (SERMs), calcitonin and monoclonal antibodies such as denosumab. However, no head-to-head studies have compared different antiresorptive agents using fracture as an end point. Bisphosphonates, which have proven antifracture efficacy and a good safety profile, are the most widely used first-line antiresorptive therapy and are recommended for patients with osteoporosis, a prior fragility fracture or osteopenia, as well as individuals with a high risk of fracture. Denosumab, which also has good antifracture efficacy, is another possible first-line therapy, although long-term safety data are lacking. However, no single antiresorptive therapy is currently appropriate for all patients or clearly superior to other therapies. Antiresorptive agents such as estrogens, SERMs (in postmenopausal women) and calcitonin are considered to be second-line agents that are appropriate in special circumstances. Clinicians should determine the most appropriate pharmacological therapy after a careful assessment of the risk:benefit profiles of these drugs in each patient. In addition, patients should receive a detailed explanation of the treatment goals, so that the therapeutic benefit can be maximized through good compliance and persistence.

Carpal tunnel syndrome and its relationship to occupation: a meta-analysis

OBJECTIVE To examine the association between work place exposure and CTS by meta-analysis, including analyses with respect to exposure to hand force, repetition, vibration and wrist posture. METHODS All relevant peer-reviewed articles published between January 1980 and December 2009 were identified by a systematic search using the MEDLINE, CINAHL and PubMed databases. Papers were critiqued independently by two researchers and the relevant exposure information was extracted. Using the raw data of exposed and unexposed cases, a cumulative effect of specific exposure risks were calculated for hand force, repetition, a combination of force and repetition, vibration and wrist posture using the statistical program, Stata version 11 (StataCorp, College Station, TX, USA). Heterogeneity, meta-regression, publication bias and subgroup sensitivity analyses were performed. RESULTS Thirty-seven studies from English-language literature met the inclusion criteria. Using National Institute for Occupational Health and Safety criteria for case definition, a significant positive association between CTS and hand force, repetition, use of vibratory tools and wrist posture was observed with approximate doubling of risk for all exposures. Significant heterogeneity among studies was observed for most exposures and metaregression analyses identified CTS case definition, study design, country and risk of bias score to be the significant determinants. When a more conservative definition of CTS was employed to include nerve conduction abnormality with symptoms and/or signs, risk factors significantly associated with an increased risk of CTS among exposed workers were: vibration [odds ratio (OR) 5.40; 95% CI 3.14, 9.31], hand force (OR 4.23; 95% CI 1.53, 11.68) and repetition (OR 2.26; 95% CI 1.73, 2.94). There was a non-significant trend for the association between CTS and combined exposure to both force and repetition (OR 1.85; 95% CI 0.99, 3.45) and wrist posture (OR 4.73; 95% CI 0.42, 53.32). CONCLUSION Occupational exposure to excess vibration, increased hand force and repetition increase the risk of developing CTS. Workplace strategies to avoid overexposure to these risk factors should be implemented.

The global burden attributable to low bone mineral density

Introduction The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors by calculating disability-adjusted life years (DALYs). Osteoporosis was not considered as a disease, and bone mineral density (BMD) was analysed as a risk factor for fractures, which formed part of the health burden due to falls. Objectives To calculate (1) the global distribution of BMD, (2) its population attributable fraction (PAF) for fractures and subsequently for falls, and (3) the number of DALYs due to BMD. Methods A systematic review was performed seeking population-based studies in which BMD was measured by dual-energy X-ray absorptiometry at the femoral neck in people aged 50 years and over. Age- and sex-specific mean ± SD BMD values (g/cm2) were extracted from eligible studies. Comparative risk assessment methodology was used to calculate PAFs of BMD for fractures. The theoretical minimum risk exposure distribution was estimated as the age- and sex-specific 90th centile from the Third National Health and Nutrition Examination Survey (NHANES III). Relative risks of fractures were obtained from a previous meta-analysis. Hospital data were used to calculate the fraction of the health burden of falls that was due to fractures. Results Global deaths and DALYs attributable to low BMD increased from 103 000 and 3 125 000 in 1990 to 188 000 and 5 216 000 in 2010, respectively. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). Around one-third of falls-related deaths were attributable to low BMD. Conclusions Low BMD is responsible for a growing global health burden, only partially representative of the real burden of osteoporosis.

The Effects of Calcium Supplementation on Verified Coronary Heart Disease Hospitalization and Death in Postmenopausal Women: A Collaborative Meta‐Analysis of Randomized Controlled Trials

Calcium supplementation, particularly with vitamin D, has been an approved public health intervention to reduce fracture risk. Enthusiasm for this intervention has been mitigated by meta‐analyses suggesting that calcium supplementation with or without vitamin D increases myocardial infarction (MI) risk; however, concern has been raised over the design of these meta‐analyses. We, therefore, undertook a meta‐analysis of randomized controlled trials with placebo or no‐treatment control groups to determine if these supplements increase all‐cause mortality and coronary heart disease (CHD) risk including MI, angina pectoris and acute coronary syndrome, and chronic CHD verified by clinical review, hospital record, or death certificate in elderly women. The Cochrane Central Register of Controlled Trials, MEDLINE, and EMBASE databases were searched from January 1, 1966, to May 24, 2013, for potentially eligible studies, reference lists were checked, and trial investigators were contacted where additional unpublished data were required. The search yielded 661 potentially eligible reports of which 18 met the inclusion criteria and contributed information on 63,563 participants with 3390 CHD events and 4157 deaths. Two authors extracted the data independently with trial data combined using random‐effects meta‐analysis to calculate the relative risk (RR). Five trials contributed CHD events with pooled relative RR of 1.02 (95% confidence interval [CI], 0.96–1.09; p = 0.51). Seventeen trials contributed all‐cause mortality data with pooled RR of 0.96 (95% CI, 0.91–1.02; p = 0.18). Heterogeneity among the trials was low for both primary outcomes (I2 = 0%). For secondary outcomes, the RR for MI was 1.08 (95% CI, 0.92–1.26; p = 0.32), angina pectoris and acute coronary syndrome 1.09 (95% CI, 0.95–1.24; p = 0.22) and chronic CHD 0.92 (95% CI, 0.73–1.15; p = 0.46). In conclusion, current evidence does not support the hypothesis that calcium supplementation with or without vitamin D increases coronary heart disease or all‐cause mortality risk in elderly women.

Effect of Age-Related Chronic Immobility on Markers of Bone Turnover†

The effects of acute immobilization on bone turnover are well known, but the effects of chronic hypomobility with aging have not been studied. In a cohort of 1064 frail elderly subjects, immobility was significantly associated with serum PINP but not serum CTx after adjusting for confounders. The effect of immobility may be more marked on bone formation than on bone resorption.

Hip fracture causes excess mortality owing to cardiovascular and infectious disease in institutionalized older people: A prospective 5-year study

An increasing risk of death after hip fracture has been well documented, but the duration and causes remain unclear, especially in very frail older people. This is a nested case‐control study of 229 hip fracture cases and 229 controls matched by age, gender, institution type, and follow‐up period from a cohort of 2005 institutionalized older people. The residents were assessed at baseline and followed up for hip fracture and death for at least 5 years. Time to death was measured from the same time for each case (time of the hip fracture) and the matched control. The study sample consisted of 90 males and 368 females with a mean age of 86 years (range 67 to 102 years). The hazard ratio (HR) of death for the cases compared with the controls was 3.09 [95% confidence interval (CI) 1.83–5.22, p < .001] for the first 3 months, 1.99 (95% CI 1.13–3.51, p = .02) for the period of 3 to 9 months, and 0.88 (95% CI 0.64–1.22, p = .46) for the period beyond 9 months following a fracture, after adjusting for age, gender, institution type, weight, immobility, cognitive function, comorbidities, and number of medications. The main causes of the excess mortality in the first 9 months were infections (HR = 6.66, 95% CI 1.95–22.77, p = .002) for females and cardiac disease (HR = 2.68, 95% CI 1.39–5.15, p = .003) for both males and females. Bisphosphonate use was associated with a reduction in mortality after hip fracture (p = .002). Intensive medical supervision to reduce cardiovascular and infective complications should be provided for frail older people with recent hip fracture to reduce mortality.

Hypovitaminosis D and parathyroid hormone response in the elderly: effects on bone turnover and mortality.

Objective  To investigate whether absence of secondary hyperparathyroidism in the presence of hypovitaminosis D has altered bone turnover, fracture risk and mortality.

Association between serum cholesterol and bone mineral density

BACKGROUND Hypercholesterolaemia has been associated with low bone mineral density (BMD) in some but not all studies. OBJECTIVES To examine the influence of age, menopausal status and hormone replacement therapy (HRT) on the relationship between serum cholesterol and BMD in women. PATIENTS AND MEASUREMENTS 497 female participants (age range 20-81) comprising 224 premenopausal and 273 postmenopausal women (156 on HRT and 117 no HRT) underwent measurements of bone mineral density (BMD) and serum lipid profile. RESULTS Total serum cholesterol (TC) and low density lipoprotein (LDL) levels were higher and lumbar spine BMD was lower in postmenopausal women not taking HRT compared to those taking HRT. TC and LDL were negatively associated with BMD at all measured sites among postmenopausal women not taking HRT in univariate regression analysis (all p<0.05). High density lipoprotein (HDL) had inverse relationships with BMD at all sites in pre-menopausal women and those who were exposed to HRT (p<0.05). In fully adjusted regression models the relationships between TC and BMD remained significant at the lumbar spine and whole body (p<0.05) and between LDL and lumbar spine BMD only (p<0.05). For subjects in the other groups, no significant associations between TC or LDL and BMD were found. Significant interactions between total cholesterol and LDL levels with HRT were detected among post-menopausal women in the regression analyses (all p<0.05). No such interactions were found between HDL levels and HRT. CONCLUSION There is a modest inverse relationship between lumbar spine and whole body BMD and serum TC and LDL levels and in post-menopausal women and HDL in pre-menopausal women. HRT use appears to modify these relationships. The mechanisms of this relationship require further study.