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1.  Nutrition and Sarcopenia: A Review of the Evidence and Implications for Preventive Strategies 
Journal of Aging Research  2012;2012:510801.
Prevention of age-related losses in muscle mass and strength is key to protecting physical capability in older age and enabling independent living. To develop preventive strategies, a better understanding is needed of the lifestyle factors that influence sarcopenia and the mechanisms involved. Existing evidence indicates the potential importance of diets of adequate quality, to ensure sufficient intakes of protein, vitamin D, and antioxidant nutrients. Although much of this evidence is observational, the prevalence of low nutrient intakes and poor status among older adults make this a current concern. However, as muscle mass and strength in later life are a reflection of both the rate of muscle loss and the peak attained in early life, efforts to prevent sarcopenia also need to consider diet across the lifecourse and the potential effectiveness of early interventions. Optimising diet and nutrition throughout life may be key to preventing sarcopenia and promoting physical capability in older age.
doi:10.1155/2012/510801
PMCID: PMC3312288  PMID: 22506112
2.  Adverse Reactions and Drug–Drug Interactions in the Management of Women with Postmenopausal Osteoporosis 
Calcified Tissue International  2011;89(2):91-104.
The pharmacological management of disease should involve consideration of the balance between the beneficial effects of treatment on outcome and the probability of adverse effects. The aim of this review is to explore the risk of adverse drug reactions and drug–drug interactions with treatments for postmenopausal osteoporosis. We reviewed evidence for adverse reactions from regulatory documents, randomized controlled trials, pharmacovigilance surveys, and case series. Bisphosphonates are associated with gastrointestinal effects, musculoskeletal pain, and acute-phase reactions, as well as, very rarely, atrial fibrillation, atypical fracture, delayed fracture healing, osteonecrosis of the jaw, hypersensitivity reactions, and renal impairment. Cutaneous effects and osteonecrosis of the jaw are of concern for denosumab (both very rare), though there are no pharmacovigilance data for this agent yet. The selective estrogen receptor modulators are associated with hot flushes, leg cramps, and, very rarely, venous thromboembolism and stroke. Strontium ranelate has been linked to hypersensitivity reactions and venous thromboembolism (both very rare) and teriparatide with headache, nausea, dizziness, and limb pain. The solidity of the evidence base depends on the frequency of the reaction, and causality is not always easy to establish for the very rare adverse reactions. Drug–drug interactions are rare. Osteoporosis treatments are generally safe and well tolerated, though they are associated with a few very rare serious adverse reactions. While these are a cause for concern, the risk should be weighed against the benefits of treatment itself, i.e., the prevention of osteoporotic fracture.
doi:10.1007/s00223-011-9499-8
PMCID: PMC3135835  PMID: 21637997
Osteoporosis; Adverse drug reaction; Drug–drug interaction; Bisphosphonate; Denosumab; SERM; Strontium ranelate; Teriparatide
3.  Epidemiology of hip fracture: Worldwide geographic variation 
Indian Journal of Orthopaedics  2011;45(1):15-22.
Osteoporosis is a major health problem, especially in elderly populations, and is associated with fragility fractures at the hip, spine, and wrist. Hip fracture contributes to both morbidity and mortality in the elderly. The demographics of world populations are set to change, with more elderly living in developing countries, and it has been estimated that by 2050 half of hip fractures will occur in Asia. This review conducted using the PubMed database describes the incidence of hip fracture in different regions of the world and discusses the possible causes of this wide geographic variation. The analysis of data from different studies show a wide geographic variation across the world, with higher hip fracture incidence reported from industrialized countries as compared to developing countries. The highest hip fracture rates are seen in North Europe and the US and lowest in Latin America and Africa. Asian countries such as Kuwait, Iran, China, and Hong Kong show intermediate hip fracture rates. There is also a north–south gradient seen in European studies, and more fractures are seen in the north of the US than in the south. The factors responsible of this variation are population demographics (with more elderly living in countries with higher incidence rates) and the influence of ethnicity, latitude, and environmental factors. The understanding of this changing geographic variation will help policy makers to develop strategies to reduce the burden of hip fractures in developing countries such as India, which will face the brunt of this problem over the coming decades.
doi:10.4103/0019-5413.73656
PMCID: PMC3004072  PMID: 21221218
Epidemiology; geographic variation; hip fracture; incidence rate; osteoporosis
4.  Regulation of Placental Calcium Transport and Offspring Bone Health 
Osteoporosis causes considerable morbidity and mortality in later life, and the risk of the disease is strongly determined by peak bone mass, which is achieved in early adulthood. Poor intrauterine and early childhood growth are associated with reduced peak bone mass, and increased risk of osteoporotic fracture in older age. In this review we describe the regulatory aspects of intrauterine bone development, and then summarize the evidence relating early growth to later fracture risk. Physiological systems include vitamin D, parathyroid hormone, leptin, GH/IGF-1; finally the potential role of epigenetic processes in the underlying mechanisms will be explored. Thus factors such as maternal lifestyle, diet, body build, physical activity, and vitamin D status in pregnancy all appear to influence offspring bone mineral accrual. These data demonstrate a likely interaction between environmental factors and gene expression, a phenomenon ubiquitous in the natural world (developmental plasticity), as the potential key process. Intervention studies are now required to test the hypotheses generated by these epidemiological and physiological findings, to inform potential novel public health interventions aimed at improving childhood bone health and reducing the burden of osteoporotic fracture in future generations.
doi:10.3389/fendo.2011.00003
PMCID: PMC3355895  PMID: 22649358
bone; placenta; osteoporosis; fracture; BMC; vitamin D; fetus; neonate
5.  Objective measures of physical capability and subsequent health: a systematic review 
Age and Ageing  2010;40(1):14-23.
Background: measures of physical capability may be predictive of subsequent health, but existing published studies have not been systematically reviewed. We hypothesised that weaker grip strength, slower walking speed and chair rising and shorter standing balance time, in community-dwelling populations, would be associated with higher subsequent risk of fracture, cognitive outcomes, cardiovascular disease, hospitalisation and institutionalisation.
Methods: studies were identified through systematic searches of the electronic databases MEDLINE and EMBASE (to May 2009). Reference lists of eligible papers were also manually searched.
Results: twenty-four papers had examined the associations between at least one physical capability measure and one of the outcomes. As the physical capability measures and outcomes had been assessed and categorised in different ways in different studies, and there were differences in the potential confounding factors taken into account, this made it impossible to pool results. There were more studies examining fractures than other outcomes, and grip strength and walking speed were the most commonly examined capability measures. Most studies found that weaker grip strength and slower walking speed were associated with increased risk of future fractures and cognitive decline, but residual confounding may explain results in some studies. Associations between physical capability levels and the other specified outcomes have not been tested widely.
Conclusions: there is some evidence to suggest that objective measures of physical capability may be predictors of subsequent health in older community-dwelling populations. Most hypothesised associations have not been studied sufficiently to draw definitive conclusions suggesting the need for further research.
doi:10.1093/ageing/afq117
PMCID: PMC3000177  PMID: 20843964
grip strength; walking speed; chair rises; standing balance; fracture; cognitive outcomes; cardiovascular disease; systematic review
6.  Long-term treatment with bisphosphonates and their safety in postmenopausal osteoporosis 
Bisphosphonates are the leading drugs for the treatment of osteoporosis. In randomized controlled trials (RCTs), alendronate, risedronate, and zoledronate have shown to reduce the risk of vertebral, nonvertebral, and hip fractures, whereas RCTs with ibandronate show antifracture efficacy at vertebral sites. Bisphosphonates are generally well tolerated and safe. Nevertheless, adverse events have been noted, and it is important to consider the strength of the evidence for causal relationships. Effects on the gastrointestinal tract and kidney function are well recognized, as are transient acute-phase reactions. Atrial fibrillation was first identified as a potential adverse event in a zoledronate trial, but subsequent trials and analyses failed to substantiate an association with bisphosphonates. Case reports have suggested a relationship between oral bisphosphonates and esophageal cancer, but this has not been demonstrated in epidemiologic studies. A possible association between bisphosphonate use and osteonecrosis of the jaw (ONJ) has also been suggested. However, the risk of ONJ in patients with osteoporosis appears to be very low, with no evidence from prospective RCTs of a causal association. There are reports of occasional occurrence of subtrochanteric or diaphyseal fractures in osteoporotic patients, but an association with bisphosphonate therapy is not substantiated by epidemiologic studies or prospective RCTs.
PMCID: PMC2909499  PMID: 20668715
bisphosphonates; osteoporosis; safety
7.  Maternal Diet, Behaviour and Offspring Skeletal Health 
Osteoporotic fracture has a major impact upon health, both in terms of acute and long term disability and economic cost. Peak bone mass, achieved in early adulthood, is a major determinant of osteoporosis risk in later life. Poor early growth predicts reduced bone mass, and so risk of fracture in later life. Maternal lifestyle, body build and 25(OH) vitamin D status predict offspring bone mass. Recent work has suggested epigenetic mechanisms as key to these observations. This review will explore the role of the early environment in determining later osteoporotic fracture risk.
doi:10.3390/ijerph7041760
PMCID: PMC2872349  PMID: 20617058
osteoporosis; epigenetic; early life origins; fracture; bone mass; vitamin D; neonate; fetus

Results 1-8 (8)