TY - JOUR
T1 - Change in undercarboxylated osteocalcin is associated with changes in body weight, fat mass, and adiponectin
T2 - Parathyroid hormone (1-84) or alendronate therapy in postmenopausal women with osteoporosis (the PaTH study)
AU - Schafer, Anne L.
AU - Sellmeyer, Deborah E.
AU - Schwartz, Ann V.
AU - Rosen, Clifford J.
AU - Vittinghoff, Eric
AU - Palermo, Lisa
AU - Bilezikian, John P.
AU - Shoback, Dolores M.
AU - Black, Dennis M.
PY - 2011/12
Y1 - 2011/12
N2 - 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.
AB - 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.
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U2 - 10.1210/jc.2011-0587
DO - 10.1210/jc.2011-0587
M3 - Article
C2 - 21994958
AN - SCOPUS:83155168441
SN - 0021-972X
VL - 96
SP - E1982-E1989
JO - Journal of Clinical Endocrinology and Metabolism
JF - Journal of Clinical Endocrinology and Metabolism
IS - 12
ER -