Christopher Holroyd

Epidemiology of osteoporosis

Osteoporosis represents a major public health problem through its association with fragility fractures. All osteoporotic fractures increase patient morbidity; however, fractures of the hip and vertebrae are also linked with significant mortality. The public health burden of osteoporotic fracture is likely to rise in future generations, due in part to an increase in life expectancy. Understanding the epidemiology of this disease is therefore essential in trying to develop strategies to help reduce this load. This chapter will review the epidemiology of osteoporosis, including the relationship between low bone mass and fracture. It will review the epidemiology of fractures, concentrating on the sites where the majority of age-related fractures occur. Finally it will discuss new developments in the assessment of fracture risk.

Vitamin D supplementation in pregnancy: a systematic review.

BACKGROUND It is unclear whether or not the current evidence base allows definite conclusions to be made regarding the optimal maternal circulating concentration of 25-hydroxyvitamin D [25(OH)D] during pregnancy, and how this might best be achieved. OBJECTIVES To answer the following questions: (1) What are the clinical criteria for vitamin D deficiency in pregnant women? (2) What adverse maternal and neonatal health outcomes are associated with low maternal circulating 25(OH)D? (3) Does maternal supplementation with vitamin D in pregnancy lead to an improvement in these outcomes (including assessment of compliance and effectiveness)? (4) What is the optimal type (D2 or D3), dose, regimen and route for vitamin D supplementation in pregnancy? (5) Is supplementation with vitamin D in pregnancy likely to be cost-effective? METHODS We performed a systematic review and where possible combined study results using meta-analysis to estimate the combined effect size. Major electronic databases [including Database of Abstracts of Reviews of Effects (DARE), Centre for Reviews and Dissemination (CRD), Cochrane Database of Systematic Reviews (CDSR) and the Health Technology Assessment (HTA) database] were searched from inception 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 Relevant authors were contacted for any unpublished findings and additional data if necessary. Abstracts were reviewed by two reviewers. 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)D concentration] or supplementation of participants with vitamin D or food containing vitamin D (e.g. oily fish). OUTCOMES offspring - birthweight, birth length, head circumference, bone mass, anthropometry and body composition, risk of asthma and atopy, small for gestational dates, preterm birth, type 1 diabetes mellitus, low birthweight, serum calcium concentration, blood pressure and rickets; mother - pre-eclampsia, gestational diabetes mellitus, risk of caesarean section and bacterial vaginosis. RESULTS Seventy-six 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)D and (1) offspring birthweight in meta-analysis of three observational studies using log-transformed 25(OH)D concentrations after adjustment for potential confounding factors [pooled regression coefficient 5.63 g/10% change maternal 25(OH)D, 95% confidence interval (CI) 1.11 to 10.16 g], but not in those four studies using natural units, or across intervention studies; (2) offspring cord blood or postnatal calcium concentrations in a meta-analysis of six intervention studies (all found to be at high risk of bias; mean difference 0.05 mmol/l, 95% CI 0.02 to 0.05 mmol/l); 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 terms of study design, population used, vitamin D status assessment, exposure measured and outcome definition. CONCLUSIONS The evidence base is currently insufficient to support definite clinical recommendations regarding vitamin D supplementation in pregnancy. Although there is modest evidence to support a relationship between maternal 25(OH)D status and offspring birthweight, bone mass and serum calcium concentrations, these findings were limited by their observational nature (birthweight, bone mass) or risk of bias and low quality (calcium concentrations). High-quality randomised trials are now required. STUDY REGISTRATION This study is registered as PROSPERO CRD42011001426. FUNDING The National Institute for Health Research Health Technology Assessment programme.

Does combined clinical and ultrasound assessment allow selection of individuals with rheumatoid arthritis for sustained reduction of anti-tumor necrosis factor therapy?

To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti–tumor necrosis factor (anti‐TNF) therapies.

Does combined clinical and ultrasound assessment allow selection of individuals with rheumatoid arthritis for sustained reduction of anti-TNF therapy?

To investigate whether a strategy combining clinical and ultrasound (US) assessment can select individuals with rheumatoid arthritis (RA) for sustained dose reduction of anti–tumor necrosis factor (anti‐TNF) therapies.

Placental size at 19 weeks predicts offspring bone mass at birth: findings from the Southampton Women's Survey.

OBJECTIVES In this study we investigate the relationships between placental size and neonatal bone mass and body composition, in a population-based cohort. STUDY DESIGN 914 mother-neonate pairs were included. Placental dimensions were measured via ultrasound at 19 weeks gestation. Dual X-ray absorptiometry (DXA) was performed on the neonates within the first two weeks of life. RESULTS We observed positive relationships between placental volume at 19 weeks, and neonatal bone area (BA; r = 0.26, p < 0.001), bone mineral content (BMC; r = 0.25, p < 0.001) and bone mineral density (BMD; r = 0.10, p = 0.001). Thus placental volume accounted for 6.25% and 1.2% of the variation in neonatal BMC and BMD respectively at birth. These associations remained after adjustment for maternal factors previously shown to be associated with neonatal bone mineral accrual (maternal height, smoking, walking speed in late pregnancy, serum 25(OH) vitamin D and triceps skinfold thickness). CONCLUSIONS We found that placental volume at 19 weeks gestation was positively associated with neonatal bone size and mineral content. These relationships appeared independent of those maternal factors known to be associated with neonatal bone mass, consistent with notion that such maternal influences might act through modulation of aspects of placental function, e.g. utero-placental blood flow or maternal nutrient concentrations, rather than placental size itself. Low placental volume early in pregnancy may be a marker of a reduced postnatal skeletal size and increased risk of later fracture.

Session 2: Other diseases Dietary management of osteoporosis throughout the life course

Osteoporosis-related fractures have a major impact on health at the individual and societal levels, through associated morbidity and increased mortality. Up to 50% of women and 20% of men at age 50 years may have a fragility fracture in their remaining lifetimes. Nutrition is important throughout the life course. Thus, adequate Ca and vitamin D intake has been shown to reduce risk of fracture in old age. Other factors such as protein and vitamin K may also be important, although the evidence here is less strong. In childhood Ca or vitamin D supplementation trials have demonstrated modest short-term increases in bone mass, but the long-term implications have not been established. Over recent years it has become apparent that maternal nutrition may have critical and far-reaching persistent consequences for offspring health. Thus, reduced maternal fat stores and low levels of circulating 25-hydroxyvitamin D in pregnancy are associated with reduced bone mass in the offspring; placental Ca transport may be key to these relationships. Wider maternal dietary patterns have also been shown to predict offspring bone mass. These data suggest that an interventional approach aimed at specific micronutrients, such as vitamin D, should be complemented by general optimisation of the mothers diet and lifestyle in order to maximise intrauterine bone mineral accrual and postnatal skeletal growth and thus reduce the burden of osteoporotic fractures in future generations.

Vitamin D and the postmenopausal population

Vitamin D, a hormone critical to the bodys maintenance of serum calcium and phosphorus concentrations, is currently the subject of much scientific interest. Low levels of vitamin D have been observed in many populations and epidemiological studies have suggested a link between this biochemical state and a range of diseases, such as cancer, diabetes and multiple sclerosis. While the consequence of vitamin D deficiency is well documented for bone (rickets and osteomalacia), with mixed findings relating to falls and fractures, a causal link between vitamin D deficiency and these wider health outcomes has not been established. If these relationships were found to be causal, the morbidity and mortality resulting from low levels of vitamin D could be substantial; the current evidence base, however, most robustly supports the assessment of serum 25(OH)-vitamin D in the context of specific symptoms, low bone mineral density or biochemical abnormalities, rather than as an entity to treat in its own right or as the basis for a population-wide screening programme.