Department of Obstetrics, Gynecology, and Pediatrics, Gynecology Units, Policlinico of Modena, 41100 Modena, Italy
Address correspondence to: Dott. Angelo Cagnacci, M.D., Dipartimento Integrato di Scienze Ginecologiche Ostetriche e Pediatriche, Unità di Ginecologia e Ostetricia, Policlinico di Modena, via del Pozzo 71, 41100 Modena, Italy. E-mail: cagnacci{at}unimore.it.
To the editor:
Stone et al. (1) have recently reported that in older women low serum levels of vitamin B12 are associated with increased hip bone loss. They did not find a relation between vitamin B12 and bone mineral density (BMD) or its change in time, as should have been expected, but only that women in the first quintile of vitamin B12 values (levels 280 pg/ml) experience a greater bone loss than those of the other four quintiles. The study is weakened by the much more frequent intake of unspecified multivitamins in the group of women of the upper four vitamin B12 quintiles (50% vs. 18%). Vitamin B12 and its coenzyme folic acid are important for homocysteine metabolism, and their deficiency is associated with an increase of homocysteine levels. Familial hyperhomocysteinemia is associated with skeletal abnormalities, and recent data have shown that more modest elevation of homocysteine is also associated with a higher risk of osteoporotic fractures (2, 3). Similarly, a higher risk of osteoporosis is associated with mutations of genes involved in homocysteine metabolism, leading to hyperhomocysteinemia (4). Interestingly, this event was reported only in women depleted of folates and not explained only by homocysteine levels (4). It is surprising that the authors never mentioned this possibility and, worse than that, that they did not measure homocysteine and folate levels in their samples. By a cross-sectional investigation performed in younger postmenopausal women, we have recently reported that lumbar spine BMD is linearly and positively related to serum levels of folate but not vitamin B12 or homocysteine (5). The lowest quartile of folate was associated not only with the lowest BMD values, but also with the lowest levels of vitamin B12 and the highest values of homocysteine. However, at multivariate analysis, only levels of folate and weight were the significant determinants of BMD. Recent data suggest that folate may exert both cardiovascular and bone effects independent of homocysteine (6, 7). Both vitamin B12 and folate have been reported to decrease with age. Accordingly, vitamin B12-deficient individuals are very likely also folate-deficient individuals. We wonder whether the conclusion of Stone et al. (1) would have been different in case homocysteine, and in particular folate, were evaluated. For possible future inferential studies aimed to the prevention of osteoporosis, it is critical to know whether it is vitamin B12 or folate levels that are related to bone mineralization, and which one of the two has the major impact in the general population.
Received May 17, 2004.
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