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Homocysteine (Hcy) high levels are associated with fractures, bone resorption and an early onset of osteoporosis in elderly persons; a relationship between Hcy and bone formation has also been suggested but is still controversial. Frailty, an independent predictor of fractures and decreased bone mineral density is associated with altered bone metabolism in women. However, no previous works have studied the relationship among frailty, Hcy levels and bone turnover.We studied the association among Hcy, osteoporosis and N-terminal propeptide of type I procollagen (PINP), C-terminal telopeptide of type I collagen (β-CTX), parathyroid hormone (PTH), calcium and 25-hydroxyvitamin D (25(OH)D) in 631 Spanish women between the ages of 65–78 from the Toledo Study for Healthy Aging (TSHA) cohort, who were classified as highly functional (robust subjects) or non-robust (pre-frail or frail subjects) according to Fried's criteria.Hcy was independently associated with β-CTX in the entire population (B=0.22; 95% CI, 0.09–0.34; p=0.001) and in the non-robust group (B=0.24; 95% CI, 0.09–0.39; p=0.002). Hcy was also associated with PINP in the entire and non-robust populations, but the association was lost after including the levels of β-CTX, but not the other bone biomarkers, in the multivariate analysis. This suggests that the controversial relationship between Hcy and bone formation might be explained, at least to a certain extent, by the confounding effects of β-CTX.This work highlights the important implication of frailty status in the association between Hcy and increased bone turnover in older women.Homocysteine is independently associated with bone resorption in older women.Frailty is implicated in the association between homocysteine and bone resorption.Bone resorption takes part in the association of homocysteine with bone formation.