Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA.
J Clin Endocrinol Metab. 2011 Dec;96(12):E1982-9. doi: 10.1210/jc.2011-0587. Epub 2011 Oct 12.
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.
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.
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.
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 β = -0.25, P = 0.04) and fat mass (β = -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 (β = 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.
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.
成骨细胞分泌的蛋白骨钙素的低羧化形式对小鼠的脂肪和葡萄糖代谢有有益影响。在人体研究中，横断面研究表明存在相关关联。
我们研究了骨质疏松症治疗过程中低羧化骨钙素（ucOC）的变化是否与代谢参数的变化相关。
设计、地点、参与者和干预措施：我们测量了甲状旁腺激素和阿仑膦酸盐研究中接受 PTH(1-84)或阿仑膦酸盐治疗的绝经后骨质疏松症女性亚组血清中的 ucOC（分别为 64 例和 33 例）。
我们测量了血清脂联素、瘦素和胰岛素，并分析了体重、脂肪量和血清葡萄糖浓度的现有数据。将 3 个月时 ucOC 水平的变化评估为预测 12 个月时脂肪和葡萄糖代谢指数变化的指标。
ucOC 水平随着 PTH(1-84)的增加而增加，随着阿仑膦酸盐的使用而降低（两组治疗的 P 值均≤0.01）。校正治疗组后，ucOC 的 3 个月变化与 12 个月体重（标准化β=-0.25，P=0.04）和脂肪量（β=-0.23，P=0.06）的变化呈负相关。ucOC 的 3 个月变化与 12 个月时脂联素的变化呈正相关（β=0.30，P=0.01），与脂肪量的变化无关。治疗和 ucOC 变化之间没有相互作用会影响体重、脂肪量或脂联素的变化。
PTH(1-84)增加而阿仑膦酸盐降低 ucOC 水平。PTH(1-84)和阿仑膦酸盐诱导的 ucOC 变化与代谢指标的变化相关。这些关联与动物模型的观察结果一致，并支持 ucOC 在人类骨骼调节能量代谢中的作用。
