Turner Andrew G, Anderson Paul H, Morris Howard A
School of Pharmacy and Medical Sciences, University of South Australia, and Chemical Pathology Directorate, SA Pathology, Frome Road, Adelaide 5000 SA, Australia.
Scand J Clin Lab Invest Suppl. 2012;243:65-72. doi: 10.3109/00365513.2012.681963.
Current data demonstrate that vitamin D deficiency contributes to the aetiology of at least two metabolic bone diseases, osteomalacia and osteoporosis. Osteomalacia, or rickets in children, results from a delay in mineralization and can be resolved by normalization of plasma calcium and phosphate homeostasis independently of vitamin D activity. The well characterized endocrine pathway of vitamin D metabolism and activities is solely responsible for vitamin D regulating plasma calcium and phosphate homeostasis and therefore for protecting against osteomalacia. In contrast a large body of clinical data indicate that an adequate vitamin D status as represented by the serum 25-hydroxyvitamin D concentration protects against osteoporosis by improving bone mineral density and reducing the risk of fracture. Interestingly adequate serum 1,25-dihydroxyvitamin D concentrations do not reduce the risk of fracture. In vitro human bone cell cultures and animal model studies indicate that 25-hydroxyvitamin D can be metabolised to 1,25-dihydroxyvitamin D by each of the major bone cells to activate VDR and modulate gene expression to reduce osteoblast proliferation and stimulate osteoblast and osteoclast maturation. These effects are associated with increased mineralization and decreased mineral resorption. Dietary calcium interacts with vitamin D metabolism at both the renal and bone tissue levels to direct either a catabolic action on bone through the endocrine system or an anabolic action through a bone tissue autocrine or paracrine system.
目前的数据表明,维生素D缺乏至少会导致两种代谢性骨病——骨软化症和骨质疏松症的病因。骨软化症,或儿童佝偻病,是由矿化延迟引起的,可通过使血浆钙和磷酸盐稳态正常化来解决,而与维生素D活性无关。维生素D代谢和活性的内分泌途径已得到充分表征,它唯一负责调节血浆钙和磷酸盐稳态,从而预防骨软化症。相比之下,大量临床数据表明,以血清25-羟基维生素D浓度表示的充足维生素D状态可通过提高骨密度和降低骨折风险来预防骨质疏松症。有趣的是,血清1,25-二羟基维生素D浓度充足并不能降低骨折风险。体外人骨细胞培养和动物模型研究表明,主要的骨细胞都可以将25-羟基维生素D代谢为1,25-二羟基维生素D,以激活维生素D受体(VDR)并调节基因表达,从而减少成骨细胞增殖并刺激成骨细胞和破骨细胞成熟。这些作用与矿化增加和矿物质吸收减少有关。膳食钙在肾脏和骨组织水平与维生素D代谢相互作用,通过内分泌系统对骨产生分解代谢作用,或通过骨组织自分泌或旁分泌系统产生合成代谢作用。