It is clear that adequate calcium intake is essential for bone health [8] and [9] as well as having other benefits, including possibly protecting against obesity [67]. However, calcium intake above the level required by bones

is likely to be excreted through the urine [7] and there is even evidence that higher levels of calcium intake (greater than around 1100 mg) may increase the risk of hip fractures [10]. Higher levels of serum calcium may have other adverse consequences including increased cardiovascular and mortality risk [68]. Hypocalcaemia is also associated with muscle weakness and fatigue and a small study of patients with primary hyperparathyroidism NVP-BGJ398 molecular weight found the post-surgical reduction in serum calcium was PD0325901 datasheet correlated with improved strength [69]. Our use of a genetic variant of serum calcium provides additional insight into the effects of long-term

raised serum calcium levels on measures of physical capability. As a result, greatly exceeding the UK recommendation of 700 mg calcium per day for adults [70] is not advised, and a preference for food sources over pharmacological supplements may lead to smaller effects on serum levels [68] and [71]. Whilst further studies are needed to infer causality between BMD and physical capability, attention should still be paid to the modifiable factors of bone mass, such as exercise programs [27], that would be beneficial to osteoporosis risk [23] and [24] as well as to the maintenance of good physical capability. The results of this large multi-cohort study of older adults suggest elevated serum Thalidomide calcium levels may lead to lower grip strength but provide no evidence for its effect on other measures of physical capability. Genetic markers of BMD and osteoarthritis risk provided null or inconsistent associations with measures of physical capability. We thank Kate Birnie, Vanessa Cox, Jorgen Engmann, Nikki Graham, Karen Jameson and Andrew Wong for providing data. We acknowledge the support of Medical Research Council and Arthritis Research (UK). Boyd Orr Funding: The Boyd Orr DNA bank was funded by the Wellcome Trust (grant number: GR068468MA). Follow-up of the Boyd Orr cohort was supported by grants

from the Wellcome Trust, World Cancer Research Fund, Research into Ageing and the British Heart Foundation. The Caerphilly Prospective study was conducted by the former MRC Epidemiology Unit (South Wales) and funded by the Medical Research Council of the United Kingdom. The School of Social and Community Medicine, University of Bristol now maintains the archive. Samples from the English Longitudinal Study of Ageing (ELSA) DNA Repository (EDNAR), received support under a grant (AG1764406S1) awarded by the National Institute on Ageing (NIA). ELSA was developed by a team of researchers based at the National Centre for Social Research, University College London and the Institute of Fiscal Studies. The data were collected by the National Centre for Social Research.