After 4 years of treatment, the supplemented group had a 60% lower risk of developing cancer than the placebo group [113]. However, a recent re-analysis has indicated that this inverse association between vitamin D levels and cancer incidence disappeared after adjustment for BMI and physical activity [9, 112]. In another randomised trial, the Women’s Health Initiative, no YH25448 chemical structure effect of calcium and 400 IU vitamin D/day was found on the incidence of colorectal TEW-7197 purchase or breast cancer, which were secondary outcomes [114]. However, the dose of

400 IU used in that trial may have been inadequate to raise 25(OH) vitamin D blood levels significantly, particularly after factoring in adherence levels. A recent review of randomised vitamin D supplementation trials with cancer incidence as a secondary endpoint concluded that the results were null [112]. Moreover, the recent large-scale “Cohort Consortium Vitamin D Pooling Project of Rarer Cancers” showed no evidence linking higher serum 25(OH) vitamin D levels to reduced risks of less common cancers, including endometrial, gastric, kidney, pancreatic and ovarian cancers [115]. In summary, the available evidence that vitamin D reduces cancer incidence is inconsistent and inconclusive. Randomised controlled trials assessing vitamin

D supplementation for cancer prevention are in progress. Their results are to be awaited before promoting vitamin D supplementation to reduce cancer risk. As a general conclusion, the importance of vitamin D for bone health and the prevention of osteomalacia and c-Met inhibitor osteoporosis are well recognized. More recently, vitamin D deficiency has been associated with other chronic conditions, including cardiovascular disease, autoimmune diseases and cancer. However, most evidence for the importance of vitamin D in these conditions

comes from laboratory studies and observational investigations. Suplatast tosilate Randomised controlled trials are needed to determine whether long-term supplementation with vitamin D has a favourable impact on the development or clinical course of non-skeletal diseases [116]. Bisphosphonates BPs are the mainstay in the treatment of osteoporosis and other metabolic bone diseases such as Paget’s disease, as well as in tumoural conditions such as multiple myeloma, bone metastases and cancer-induced hypercalcaemia. Their efficacy and safety have been thoroughly established on the basis of multiple large pivotal trials dealing with their main indications. Their daily use in clinical medicine since 1969 has confirmed the general conclusions of the trials. Their strong affinity for the skeleton partially explains their excellent safety profile for other systems of the body. Even at high pharmacologic doses, their bone affinity grossly precludes tissue uptake outside the skeleton.