Anderson Paul H, Sawyer Rebecca K, Moore Alison J, May Brian K, O'Loughlin Peter D, Morris Howard A
School of Medicine, Faculty of Health Sciences, University of Adelaide, Adelaide, South Australia, Australia.
J Bone Miner Res. 2008 Nov;23(11):1789-97. doi: 10.1359/jbmr.080616.
The association between increased risk of hip fracture and low vitamin D status has long been recognized. However, the level of vitamin D required to maintain bone strength is controversial. We used a rodent model of vitamin D depletion to quantify the 25-hydroxyvitamin D (25D) levels required for normal mineralization. Six groups of 10-wk-old male Sprague-Dawley rats (n = 42) were fed a diet containing 0.4% calcium and various levels of dietary vitamin D(3) for 4 mo to achieve stable mean serum 25D levels ranging between 10 and 115 nM. At 7 mo of age, animals were killed, and the histomorphometry of distal and proximal femora and L(2) vertebra was analyzed. Total RNA was extracted from whole femora for real-time RT-PCR analyses. In the distal femoral metaphysis, trabecular bone mineral volume (BV/TV) showed a significant positive association with circulating 25D levels (r(2) = 0.42, p < 0.01) in the animals with serum 25D levels between 20 and 115 nM. Osteoclast surface (Oc.S) levels were positively associated with RANKL:OPG mRNA ratio, higher in groups with lower serum 25D levels, and were independent of serum 1,25D levels. Serum 25D levels <80 nM gave rise to osteopenia as a result of increased osteoclastogenesis, suggesting that levels of 25D >80 nM are needed for optimal bone volume. These data indicate that serum 25D levels are a major determinant of osteoclastogenesis and bone mineral volume and are consistent with the levels of 25D recommended to reduce the risk of fracture in humans.
髋部骨折风险增加与维生素D水平低之间的关联早已为人所知。然而，维持骨强度所需的维生素D水平仍存在争议。我们使用维生素D缺乏的啮齿动物模型来量化正常矿化所需的25-羟基维生素D（25D）水平。将六组10周龄雄性Sprague-Dawley大鼠（n = 42）喂养含0.4%钙和不同水平膳食维生素D(3)的饮食4个月，以实现稳定的平均血清25D水平在10至115 nM之间。在7月龄时处死动物，分析股骨远端和近端以及L(2)椎骨的组织形态计量学。从整个股骨中提取总RNA进行实时RT-PCR分析。在血清25D水平为20至115 nM的动物中，股骨远端干骺端的小梁骨矿物质体积（BV/TV）与循环25D水平呈显著正相关（r(2) = 0.42，p < 0.01）。破骨细胞表面（Oc.S）水平与RANKL:OPG mRNA比值呈正相关，在血清25D水平较低的组中更高，且与血清1,25D水平无关。血清25D水平<80 nM由于破骨细胞生成增加导致骨质减少，表明最佳骨量需要25D水平>80 nM。这些数据表明血清25D水平是破骨细胞生成和骨矿物质体积的主要决定因素，并且与推荐用于降低人类骨折风险的25D水平一致。
