title: Suppressed bone turnover in obesity: a link to energy metabolism? A case-control study.
abstract: BACKGROUND
  Observations in rodents suggest that osteocalcin (OC) participates in glucose metabolism. Based on human studies, it remains unclear whether circulating OC is simply a bone turnover marker (BTM) or also a mediator in interactions between the skeleton and glucose homeostasis.
  
  
  OBJECTIVE
  The objective of the study was to determine the responses of BTMs, including OC, to oral glucose tolerance test (OGTT) in a case-control setting.
  
  
  METHODS
  Thirty-four normoglycemic young adults [mean age 19 y (SD 2.3)] with severe childhood-onset obesity and their gender- and age-matched nonobese controls underwent a standard 2-hour OGTT.
  
  
  METHODS
  Glucose, insulin, and six BTMs including total and carboxylated OC (cOC) were determined at baseline and at 30, 60, 90, and 120 minutes during OGTT.
  
  
  RESULTS
  The obese and control subjects were similar in height; the mean body mass indices were 40.4 and 21.9 kg/m(2), respectively. The homeostasis model assessment index was 2.7 times greater in the obese subjects. All BTMs, except bone-specific alkaline phophatase, were lower in the obese subjects compared with the controls: the differences at baseline were 40%, 35%, 17%, 31%, and 32% for N-terminal propeptides of type I collagen, cross-linked telopeptides of type I collagen, tartrate-resistant acid phosphatase, total OC, and carboxylated OC (P < .05 for all) after adjusting for whole-body bone area. All BTMs decreased during OGTT. The relative values for the OGTT responses for total, but not for cOC (measured as area under the curve) differed between the two groups (P = .029 and P = .139, respectively): the decrease in total OC during the OGTT was less pronounced in the obese subjects. Responses in other BTMs were similar between the groups. No associations were observed between glucose metabolism and OCs during OGTT with linear regression.
  
  
  CONCLUSIONS
  Bone turnover markers were substantially lower in obese subjects compared with controls. Total OC and cOC showed less pronounced decrease during the OGTT in obese subjects compared with controls, whereas other BTMs responded similarly in the two groups. The role of OC, if anything, in glucose homeostasis is indirect and may be mediated via other factors than glucose or insulin.
authors.affiliation: Children's Hospital (H.V., P.P., M.L.-N., T.S., S.A., O.M.), Helsinki University Central Hospital, Obesity Research Unit (K.H.P.), Research Programs Unit, Diabetes and Obesity, University of Helsinki, and Department of Medicine, Division of Endocrinology, Helsinki University Central Hospital and Institute for Molecular Medicine Finland, University of Helsinki, and Department of Obstetrics and Gynecology (K.L.), Helsinki University Central Hospital, FI-00029 Helsinki, Finland; Institute of Biomedicine (K.K.I.), Department of Cell Biology and Anatomy, University of Turku, FI-20520 Turku, Finland; Novartis Pharma (P.P.), CH-4002 Basel, Switzerland; Novo Nordisk Farma Oy (T.S.), FI-02240 Espoo, Finland; Folkhälsan Research Center (O.M.), FI-00250 Helsinki, Finland; and Department of Molecular Medicine and Surgery (O.M.), Karolinska Institutet, SE-171 77 Stockholm, Sweden.
authors.forename: Heli
authors.initials: H
authors.lastname: Viljakainen
authors.forename: Kaisa K
authors.initials: KK
authors.lastname: Ivaska
authors.forename: Päivi
authors.initials: P
authors.lastname: Paldánius
authors.forename: Marita
authors.initials: M
authors.lastname: Lipsanen-Nyman
authors.forename: Tero
authors.initials: T
authors.lastname: Saukkonen
authors.forename: Kirsi H
authors.initials: KH
authors.lastname: Pietiläinen
authors.forename: Sture
authors.initials: S
authors.lastname: Andersson
authors.forename: Kalevi
authors.initials: K
authors.lastname: Laitinen
authors.forename: Outi
authors.initials: O
authors.lastname: Mäkitie
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D016723:Bone Remodeling; D001842:Bone and Bones / Q000378:metabolism; D016022:Case-Control Studies; D004734:Energy Metabolism; D005260:Female; D005951:Glucose Tolerance Test; D006801:Humans; D008297:Male; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D015675:Osteocalcin / Q000097:blood / Q000378:metabolism*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D015675:Osteocalcin