Ray Debarti, Goswami Ravinder, Gupta Nandita, Tomar Neeraj, Singh Namrata, Sreenivas Vishnubhatla
Department of Endocrinology and Metabolism, All India Institute of Medical Sciences, New Delhi, India.
Clin Endocrinol (Oxf). 2009 Sep;71(3):334-40. doi: 10.1111/j.1365-2265.2008.03500.x.
Osteomalacia (OSM) and rickets are widely prevalent in developing countries especially in females. The factors associated with such predisposition are not known.
To identify nutritional, endocrine and genetic factors related to calcium and vitamin D metabolism that are associated with OSM/rickets in females.
We studied 98 patients with OSM or rickets and their relatives including male and female sibs and parents (n = 221) for the presence of biochemical OSM {low serum 25-hydroxyvitamin D [25(OH)D], raised intact PTH (iPTH) and raised alkaline phosphatase} and associated nutritional and genetic factors. Polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) was used for genotyping vitamin D receptor (VDR) (BsmI and FokI) and PTH gene (BstBI and DraII) single nucleotide polymorphisms (SNPs) in 74 families. The differences in the factors associated with calcium and vitamin D among the different groups were analysed by analysis of variance (ANOVA). Logistic regression analysis and the transmission disequilibrium test (TDT) were carried out to assess association between nutritional and genetic factors, and the disease, respectively.
Most of the patients were female (91.8%). The mean serum 25(OH)D level of the female patients was comparable to that of the female sibs (14.4 +/- 5.7 vs. 18.3 +/- 9.7 nmol/l). The frequency of biochemical OSM was fivefold higher in female than in male sibs (24.4%vs. 4.9%). Female sibs also had significantly lower 25(OH)D, dietary calcium intake and sunshine exposure than male sibs. The frequency of biochemical OSM was comparable between mothers and fathers. The odds of biochemical OSM in the family members was reduced by 11% per 15-min daily sunshine exposure [odds ratio (OR) = 0.89, 95% confidence interval (CI) = 0.81-0.98, P = 0.02] and decreased by 20% per 100 mg dietary calcium intake (OR = 0.80, 95% CI = 0.67-0.96, P = 0.02). VDR/PTH gene SNPs showed no association with OSM/rickets on TDT analysis.
Among the immediate family members of patients with OSM/rickets, female sibs have features of biochemical OSM in up to 24.4%. Female sibs, unlike male sibs, share with patients features of markedly low serum 25(OH)D levels, poor dietary calcium intake and poor exposure to sunshine. Genetic factors such as VDR and PTH gene SNPs were not associated with OSM/rickets.
骨软化症（OSM）和佝偻病在发展中国家广泛流行，尤其是在女性中。与这种易感性相关的因素尚不清楚。
确定与女性骨软化症/佝偻病相关的钙和维生素D代谢的营养、内分泌和遗传因素。
我们研究了98例骨软化症或佝偻病患者及其亲属，包括男性和女性兄弟姐妹及父母（n = 221），以检测生化性骨软化症（低血清25-羟基维生素D [25(OH)D]、升高的完整甲状旁腺激素（iPTH）和升高的碱性磷酸酶）以及相关的营养和遗传因素。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）对74个家庭的维生素D受体（VDR）（BsmI和FokI）和甲状旁腺激素基因（BstBI和DraII）单核苷酸多态性（SNP）进行基因分型。通过方差分析（ANOVA）分析不同组之间与钙和维生素D相关因素的差异。进行逻辑回归分析和传递不平衡检验（TDT），分别评估营养和遗传因素与疾病之间的关联。
大多数患者为女性（91.8%）。女性患者的平均血清25(OH)D水平与女性兄弟姐妹相当（14.4±5.7 vs. 18.3±9.7 nmol/l）。女性兄弟姐妹中生化性骨软化症的发生率比男性兄弟姐妹高五倍（24.4%对4.9%）。女性兄弟姐妹的25(OH)D、膳食钙摄入量和日照暴露也显著低于男性兄弟姐妹。母亲和父亲之间生化性骨软化症的发生率相当。家庭成员中，每日日照暴露每增加15分钟，生化性骨软化症的几率降低11% [比值比（OR）= 0.89，95%置信区间（CI）= 0.81 - 0.98，P = 0.02]，膳食钙摄入量每增加100 mg，几率降低20%（OR = 0.80，95% CI = 0.67 - 0.96，P = 0.02）。TDT分析显示VDR/PTH基因SNP与骨软化症/佝偻病无关联。
在骨软化症/佝偻病患者的直系亲属中，高达24.4%的女性兄弟姐妹具有生化性骨软化症的特征。与男性兄弟姐妹不同，女性兄弟姐妹与患者一样，具有血清25(OH)D水平明显降低、膳食钙摄入量低和日照暴露少的特征。VDR和PTH基因SNP等遗传因素与骨软化症/佝偻病无关。
