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Vitamin B12 deficiency and osteoporosis

Clinical studies suggested a link between low B12 and high tHcy concentrations to low bone mineral density (BMD) and fragility fractures, typical symptoms of osteoporosis. It has been shown that B12 stimulates proliferation and functional maturation of human bone marrow stromal osteoprogenitor cells and osteoblastic cells as assessed by [3H]-thymidine incorporation and bone alkaline phosphatase activity (1). A suppressed activity of osteoblasts might contribute to osteoporosis and fractures in patients with B12 deficiency. Cultured human osteoclasts were activated when the medium was depleted of folate, B12, and vitamin B6 (2). Therefore, B12 seems to affect bone resorption. Lower concentrations of the bone formation markers, bone alkaline phosphatase and osteocalcin, were reported in B12-deficient patients compared with subjects with adequate vitamin status (3).

Clinical studies investigating B12 status, fracture risk, and BMD are not consistent. Some studies found an association between B12 and fracture risk or BMD whereas others did not observe such an association (4). Bone turnover or BMD might be improved by B12 supplementation.

A few studies have reported decreased BMD in vegetarians (5) others did not (6). An association between B12 status and BMD in vegetarians was first observed in a group of formerly macrobiotic-fed adolescents (7). Decreased levels of total B12 and high concentrations of MMA were associated with low BMD. The EPIC-Oxford study including 9,420 vegetarians and 1,126 vegans revealed an increased fracture risk in vegans only (8). In one study on vegetarians (9), low B12 status (holoTC < 35 pmol/L and MMA > 271 nmol/L) was significantly associated with higher plasma concentrations of the bone turnover markers bone alkaline phosphatase, osteocalcin, pro-collagen type I N-terminal propeptide and C-terminal telopeptides of collagen type 1.


1.     Kim GS, Kim CH, Park JY, Lee KU, Park CS. Effects of vitamin B12 on cell proliferation and cellular alkaline phosphatase activity in human bone marrow stromal osteoprogenitor cells and UMR106 osteoblastic cells. Metabolism 1996;45:1443-6.
2.     Herrmann M, Schmidt J, Umanskaya N, Colaianni G, Al MF, Widmann T et al. Stimulation of osteoclast activity by low B-vitamin concentrations. Bone 2007;41:584-91.
3.     Carmel R, Lau KH, Baylink DJ, Saxena S, Singer FR. Cobalamin and osteoblast-specific proteins. N Engl J Med 1988;319:70-5.
4.     Herrmann M, Peter SJ, Umanskaya N, Wagner A, Taban-Shomal O, Widmann T et al. The role of hyperhomocysteinemia as well as folate, vitamin B(6) and B(12) deficiencies in osteoporosis: a systematic review. Clin Chem Lab Med 2007;45:1621-32.
5.     Fontana L, Shew JL, Holloszy JO, Villareal DT. Low bone mass in subjects on a long-term raw vegetarian diet. Arch Intern Med 2005;165:684-9.
6.     Wang YF, Chiu JS, Chuang MH, Chiu JE, Lin CL. Bone mineral density of vegetarian and non-vegetarian adults in Taiwan. Asia Pac J Clin Nutr 2008;17:101-6.
7.     Dhonukshe-Rutten RA, van Dusseldorp M, Schneede J, de Groot LC, van Staveren WA. Low bone mineral density and bone mineral content are associated with low cobalamin status in adolescents. Eur J Nutr 2005;44:341-7.
8.     Appleby P, Roddam A, Allen N, Key T. Comparative fracture risk in vegetarians and nonvegetarians in EPIC-Oxford. Eur J Clin Nutr 2007;61:1400-6.
9.     Herrmann W, Obeid R, Schorr H, Hübner U, Geisel J, Sand-Hill M et al. Enhanced bone metabolism in vegetarians - the role of vitamin B12 deficiency. Clin Chem Lab Med 2009;47:1381-7.