title: GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women.
abstract: BACKGROUND
  Recent studies indicate that glucagon-like peptide (GLP)-1 regulates bone turnover, but the effects of GLP-1 receptor agonists (GLP-1 RAs) on bone in obese weight-reduced individuals are unknown.
  
  
  OBJECTIVE
  To investigate the role of GLP-1 RAs on bone formation and weight loss-induced bone mass reduction.
  
  
  METHODS
  Randomized control study.
  
  
  METHODS
  Outpatient research hospital clinic.
  
  
  METHODS
  Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m(2) and age 46 ± 2 years.
  
  
  METHODS
  After a low-calorie-diet-induced 12% weight loss, participants were randomized to treatment with or without administration of the GLP-1 RA liraglutide (1.2 mg/d) for 52 weeks. In case of weight gain, up to two meals per day could be replaced with a low-calorie-diet product to maintain the weight loss.
  
  
  METHODS
  Total, pelvic, and arm-leg bone mineral content (BMC) and bone markers [C-terminal telopeptide of type 1 collagen (CTX-1) and N-terminal propeptide of type 1 procollagen (P1NP)] were investigated before and after weight loss and after 52-week weight maintenance. Primary endpoints were changes in BMC and bone markers after 52-week weight maintenance with or without GLP-1 RA treatment.
  
  
  RESULTS
  Total, pelvic, and arm-leg BMC decreased during weight maintenance in the control group (P < .0001), but not significantly in the liraglutide group. Thus, total and arm-leg BMC loss was four times greater in the control group compared to the liraglutide group (estimated difference, 27 g; 95% confidence interval, 5-48; P = .01), although the 12% weight loss was maintained in both groups. In the liraglutide group, the bone formation marker P1NP increased by 16% (7 ± 3 μg/L) vs a 2% (-1 ± 4 μg/L) decrease in the control group (P < .05). The bone resorption marker CTX-1 collagen did not change during the weight loss maintenance phase.
  
  
  CONCLUSIONS
  Treatment with a long-acting GLP-1 RA increased bone formation by 16% and prevented bone loss after weight loss obtained through a low-calorie diet, supporting its role as a safe weight-lowering agent.
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Eva W
authors.initials: EW
authors.lastname: Iepsen
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Julie R
authors.initials: JR
authors.lastname: Lundgren
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Bolette
authors.initials: B
authors.lastname: Hartmann
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Oluf
authors.initials: O
authors.lastname: Pedersen
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Torben
authors.initials: T
authors.lastname: Hansen
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Niklas R
authors.initials: NR
authors.lastname: Jørgensen
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Jens-Erik B
authors.initials: JE
authors.lastname: Jensen
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Jens J
authors.initials: JJ
authors.lastname: Holst
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Sten
authors.initials: S
authors.lastname: Madsbad
authors.affiliation: Department of Biomedical Sciences (E.W.I., J.R.L., B.H., J.J.H., S.S.T.), and NNF Center for Basic Metabolic Research (E.W.I., J.R.L., B.H., O.P., T.H., J.J.H., S.S.T.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark; Department of Endocrinology (J.-E.B.J., S.M.), Hvidovre University Hospital, 2650 Hvidovre, Denmark; Department of Diagnostics (N.R.J.), Glostrup University Hospital, DK-2600 Glostrup, Denmark; and Institute of Clinical Medicine (N.R.J.), Faculty of Health and Medical Sciences, University of Copenhagen, DKK-2200 Copenhagen, Denmark.
authors.forename: Signe S
authors.initials: SS
authors.lastname: Torekov
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001862:Bone Resorption / Q000209:etiology / Q000517:prevention & control*; D031204:Caloric Restriction / Q000009:adverse effects; D005260:Female; D052216:Glucagon-Like Peptide 1 / Q000031:analogs & derivatives* / Q000627:therapeutic use; D000067757:Glucagon-Like Peptide-1 Receptor; D006801:Humans; D000069450:Liraglutide; D008875:Middle Aged; D009765:Obesity / Q000178:diet therapy / Q000188:drug therapy* / Q000503:physiopathology; D010012:Osteogenesis / Q000187:drug effects*; D018027:Receptors, Glucagon / Q000819:agonists*; D015431:Weight Loss / Q000187:drug effects / Q000502:physiology; D055815:Young Adult
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D000069450:Liraglutide; D052216:Glucagon-Like Peptide 1