Background: A number of modifiable predictors for osteoporosis and fractures have been identified, including nutritional factors, such as vitamin D deficiency and low calcium intake. Cobalamin deficiency has been suggested to affect bone metabolism. Pernicious anaemia, which can result in cobalamin deficiency, has been identified as a risk factor for osteoporosis. Also, it is known that homocystinuria patients are of ten diagnosed with osteoporosis. Both moderate hyperhomocysteinemia and vitamin B12 deficiency are highly prevalent in old age and may play a role in diseases characteristic for old age.Objectives: 1) To show the associations of vitamin B12 and homocysteine with measures of bone health in three different populations. 2) To assess the effect of supplementation with 1000 mg crystalline cobalamin, carried either by a milk product or a capsule, on cobalamin status in mildly cobalamin deficient Dutch elderly people .Results: Data analyses in three different populations supplied the following information. Macrobiotic-fed adolescents: adolescents (9-15 y) with a low BMD had a significantly less favorable vitamin B12 status (adjusted mean, SD: 344 :t 24 pmol/L) and MMA status (adjusted mean, P5, P95: 0.31 [0.26, 0.35] f-lIDol/L) than adolescents with a normal BMD, with levels of respectively 442 (18) and 0.20 (0.16, 0.23) f-lmol/L. Free-living elderly: An increased Hcy level appeared to be a strong and independent risk factor for osteoporotic fractures in elderly men and women of the Longitudinal Aging Study Amsterdam (n=1267, mean age: 76 yrs). Relative risks (95% CI) for the highest Hcy quartile versus lowest three homocysteine quartiles were 4.6 (1.4-14.5) in men, and 1.8 (0.8-3.7) in women. Frail elderly people: Osteoporosis (defined by BMD T-score< -2.5) occurred almost five times more of ten in frail elderly women with a marginal vitamin B12 status and seven times more of ten in women with a deficient vitamin B12 status than in women with a normal status in the VFit-study. Intervention study with vitamin B12: Crystalline cobalamin added to milk is an effective alternative for cobalamin capsules in improving cobalamin status.Conclusions: We found a relevant association between vitamin B12 metabolites and bone health in various studies with different study designs and diverse populations. Since these observed associations broaden the scope for randomized clinical trials, we conducted an intervention study in which we showed that milk enriched with vitamin B12 is an as effective treatment as cobalamin capsules.