title: 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).
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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.
authors: Department of Medicine, University of California, San Francisco, San Francisco, California 94143, USA. anne.schafer@ucsf.edu
authors: Anne L
authors: AL
authors: Schafer
authors: Deborah E
authors: DE
authors: Sellmeyer
authors: Ann V
authors: AV
authors: Schwartz
authors: Clifford J
authors: CJ
authors: Rosen
authors: Eric
authors: E
authors: Vittinghoff
authors: Lisa
authors: L
authors: Palermo
authors: John P
authors: JP
authors: Bilezikian
authors: Dolores M
authors: DM
authors: Shoback
authors: Dennis M
authors: DM
authors: Black
mesh_terms: D052242:Adiponectin / Q000097:blood*; D050154:Adiposity / Q000187:drug effects* / Q000502:physiology; D000368:Aged; D000369:Aged, 80 and over; D019386:Alendronate / Q000494:pharmacology / Q000627:therapeutic use*; D001835:Body Weight / Q000187:drug effects* / Q000502:physiology; D015519:Bone Density / Q000187:drug effects / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood*; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D010281:Parathyroid Hormone / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D052242:Adiponectin; D050071:Bone Density Conservation Agents; D010281:Parathyroid Hormone; D015675:Osteocalcin; D019386:Alendronate