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)

Anne L. Schafer, Deborah E. Sellmeyer, Ann V. Schwartz, Clifford J. Rosen, Eric Vittinghoff, Lisa Palermo, John P. Bilezikian, Dolores M. Shoback, Dennis M. Black

Research output: Contribution to journalArticle

Abstract

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 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. 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.

Original languageEnglish (US)
Pages (from-to)E1982-E1989
JournalJournal of Clinical Endocrinology and Metabolism
Volume96
Issue number12
DOIs
StatePublished - Dec 1 2011

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

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