Osteoporosis constitutes a major public health problem through its association with age-related fractures, most notably those of the proximal femur. Substantial geographic variation has been noted in the incidence of hip fracture throughout the world, and estimates of recent incidence trends have varied widely; studies in the published literature have reported an increase, plateau, and decrease, in age-adjusted incidence rates for hip fracture among both men and women. Accurate characterisation of these temporal trends is important in predicting the health care burden attributable to hip fracture in future decades. We therefore conducted a review of studies worldwide, addressing secular trends in the incidence of hip and other fractures. Studies in western populations, whether in North America, Europe or Oceania, have generally reported increases in hip fracture incidence through the second half of the last century, but those continuing to follow trends over the last two decades have found that rates stabilise, with age-adjusted decreases being observed in certain centres. In contrast, some studies suggest that the rate is rising in Asia. This synthesis of temporal trends in the published literature will provide an important resource for preventing fractures; understanding the reasons for the recent declines in rates of hip fracture may help understand ways to reduce rates of hip fracture worldwide.

1. ABSTRACT Background It is unclear whether the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25(OH)-vitamin D during pregnancy, and how this might best be achieved. CRD42011001426. Aim/ Research Questions What are the clinical criteria for vitamin D deficiency in pregnant women?What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)-vitamin D?Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)?What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy?Is supplementation with vitamin D in pregnancy likely to be cost-effective? Methods We performed systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases were searched up to June 2012 covering both published and grey literature. Bibliographies of selected papers were hand-searched for additional references. Relevant authors were contacted for any unpublished findings and additional data if necessary. Inclusion and exclusion criteria Subjects Pregnant women or pregnant women and their offspring. Exposure Either assessment of vitamin D status (dietary intake, sunlight exposure, circulating 25(OH)-vitamin D concentration) or supplementation of participants with vitamin D or vitamin D containing food e.g. oily fish. Outcomes Offspring: Birth weight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes, low birth weight, serum calcium concentration, blood pressure and rickets. Mother: Preeclampsia, gestational diabetes, risk of caesarean section and bacterial vaginosis. Results 76 studies were included. There was considerable heterogeneity between the studies and for most outcomes there was conflicting evidence. The evidence base was insufficient to reliably answer question 1 in relation to biochemical or disease outcomes. For questions 2 and 3, modest positive relationships were identified between maternal 25(OH)-vitamin D and 1) offspring birth weight in meta-analysis of 3 observational studies using log-transformed 25(OH)-vitamin D concentrations after adjustment for potential confounding factors (pooled regression coefficient 5.63g/10% change maternal 25(OH)D, 95% CI 1.11,10.16), but not in those 4 studies using natural units, or across intervention studies; 2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of 6 intervention studies (all found to be at high risk of bias; mean difference 0.05mmol/l, 95% CI 0.02, 0.05); and 3) offspring bone mass in observational studies judged to be of good quality, but which did not permit meta-analysis. The evidence base was insufficient to reliably answer questions 4 and 5. Limitations Study methodology varied widely in ...