作者：Schafer AL;Sellmeyer DE;Schwartz AV;Rosen CJ;Vittinghoff E;Palermo L;Bilezikian JP;Shoback DM;Black DM
背景：成骨细胞分泌的羧化不全型骨钙素对小鼠的脂肪和糖代谢具有有利作用。在人类受试者，横断面研究也表明存在相关的关联。
目的：研究骨质疏松治疗期间羧化不全骨钙素（ucOC）的变化是否与代谢参数的改变相关。
设计、地点、受试者和干预：测定了甲状旁腺激素和阿仑膦酸钠研究中接受PTH（1-84）或阿仑膦酸钠治疗的绝经后骨质疏松症女性的血清ucOC（分别n = 64和n= 33）。
主要终点指标：测定血清脂联素、瘦素和胰岛素，分析体重、脂肪量和血糖浓度的现有数据。评估ucOC水平3个月的变化是否可作为12个月时脂肪和葡萄糖代谢变化的预测指标。
结果：PTH（1-84）升高ucOC水平，阿仑膦酸钠降低ucOC水平（P均</ = 0.01）。调整治疗组后，ucOC 3个月的变化与体重（标准化β= -0.25，p = 0.04）和脂肪量（β= -0.23，P = 0.06）12个月的变化呈负相关。 ucOC 3个月变化与脂联素12个月的变化呈正相关（β= 0.30，P = 0.01），且独立于脂肪量的变化。治疗药物和ucOC变化对于体重、脂肪量或脂联素的变化无相互作用。
结论： PTH（1-84）增加而阿仑膦酸钠降低ucOC水平。PTH（1-84）和阿仑膦酸钠诱导的ucOC变化与代谢指标的变化相关。这与动物模型的观察结果一致，并表明ucOC在人体能量代谢的骨骼调控中发挥作用。
Context:The undercarboxylated form of the osteoblast-secreted protein osteocalcin has favorable effects on fat and glucose metabolism in mice. In human subjects, cross-sectional studies suggest a relevant association.Objective:We investigated whether changes in undercarboxylated osteocalcin (ucOC) during osteoporosis treatment are associated with changes in metabolic parameters.Design, Setting, Participants, and Interventions:We measured ucOC in sera from a subset of osteoporotic postmenopausal women who were treated with PTH(1-84) or alendronate (n = 64 and n = 33, respectively) during the Parathyroid Hormone and Alendronate study.Main Outcome Measures:We measured serum adiponectin, leptin, and insulin and analyzed existing data on body weight, fat mass, and serum glucose concentration. Three-month changes in ucOC levels were evaluated as predictors of 12-month changes in indices of fat and glucose metabolism.Results:ucOC levels increased with PTH(1-84) and decreased with alendronate administration (P </= 0.01 for both treatment groups). Three-month change in ucOC was inversely associated with 12-month changes in body weight (standardized beta = -0.25, P = 0.04) and fat mass (beta = -0.23, P = 0.06), after adjustment for the treatment group. Three-month change in ucOC was positively associated with a 12-month change in adiponectin (beta = 0.30, P = 0.01), independent of change in fat mass. There were no interactions between treatment and change in ucOC on changes in weight, fat mass, or adiponectin.Conclusions:PTH(1-84) increases and alendronate decreases ucOC levels. Changes in ucOC induced by PTH(1-84) and alendronate are associated with changes in metabolic indices. These associations are consistent with observations from animal models and support a role for ucOC in the skeletal regulation of energy metabolism in humans.
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