Change in Undercarboxylated Osteocalcin Is Associated with Changes in Body Weight, Fat Mass, and Adiponectin: Parathyroid Hormone (1-84) or Alendronate Therapy in Postmenopausal Women with Osteoporosis (the PaTH Study)

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. (J Clin Endocrinol Metab 96: E1982-E1989, 2011)