TY - JOUR
T1 - Bone Health After Exercise Alone, GLP-1 Receptor Agonist Treatment, or Combination Treatment
T2 - A Secondary Analysis of a Randomized Clinical Trial
AU - Jensen, Simon Birk Kjær
AU - Sørensen, Victor
AU - Sandsdal, Rasmus Michael
AU - Lehmann, Eva Winning
AU - Lundgren, Julie Rehné
AU - Juhl, Christian Rimer
AU - Janus, Charlotte
AU - Ternhamar, Tummas
AU - Stallknecht, Bente Merete
AU - Holst, Jens Juul
AU - Jørgensen, Niklas Rye
AU - Jensen, Jens-Erik Beck
AU - Madsbad, Sten
AU - Torekov, Signe Sørensen
PY - 2024/6/3
Y1 - 2024/6/3
N2 - IMPORTANCE: A major concern with weight loss is concomitant bone loss. Exercise and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent weight loss strategies that may protect bone mass despite weight loss.OBJECTIVE: To investigate bone health at clinically relevant sites (hip, spine, and forearm) after diet-induced weight loss followed by a 1-year intervention with exercise, liraglutide, or both combined.DESIGN, SETTING, AND PARTICIPANTS: This study was a predefined secondary analysis of a randomized clinical trial conducted between August 2016 and November 2019 at the University of Copenhagen and Hvidovre Hospital in Denmark. Eligible participants included adults aged 18 to 65 years with obesity (body mass index of 32-43) and without diabetes. Data analysis was conducted from March to April 2023, with additional analysis in February 2024 during revision.INTERVENTIONS: After an 8-week low-calorie diet (800 kcal/day), participants were randomized to 1 of 4 groups for 52 weeks: a moderate- to vigorous-intensity exercise program (exercise alone), 3.0 mg daily of the GLP-1 RA liraglutide (liraglutide alone), the combination, or placebo.MAIN OUTCOMES AND MEASURES: The primary outcome was change in site-specific bone mineral density (BMD) at the hip, lumbar spine, and distal forearm from before the low-calorie diet to the end of treatment, measured by dual-energy x-ray absorptiometry in the intention-to-treat population.RESULTS: In total, 195 participants (mean [SD] age, 42.84 [11.87] years; 124 female [64%] and 71 male [36%]; mean [SD] BMI, 37.00 [2.92]) were randomized, with 48 participants in the exercise group, 49 participants in the liraglutide group, 49 participants in the combination group, and 49 participants in the placebo group. The total estimated mean change in weight losses during the study was 7.03 kg (95% CI, 4.25-9.80 kg) in the placebo group, 11.19 kg (95% CI, 8.40-13.99 kg) in the exercise group, 13.74 kg (95% CI, 11.04-16.44 kg) in the liraglutide group, and 16.88 kg (95% CI, 14.23-19.54 kg) in the combination group. In the combination group, BMD was unchanged compared with the placebo group at the hip (mean change, -0.006 g/cm2; 95% CI, -0.017 to 0.004 g/cm2; P = .24) and lumbar spine (-0.010 g/cm2; 95% CI, -0.025 to 0.005 g/cm2; P = .20). Compared with the exercise group, BMD decreased for the liraglutide group at the hip (mean change, -0.013 g/cm2; 95% CI, -0.024 to -0.001 g/cm2; P = .03) and spine (mean change, -0.016 g/cm2; 95% CI, -0.032 to -0.001 g/cm2; P = .04).CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the combination of exercise and GLP-1RA (liraglutide) was the most effective weight loss strategy while preserving bone health. Liraglutide treatment alone reduced BMD at clinically relevant sites more than exercise alone despite similar weight loss.TRIAL REGISTRATION: EudraCT: 2015-005585-32.
AB - IMPORTANCE: A major concern with weight loss is concomitant bone loss. Exercise and glucagon-like peptide-1 receptor agonists (GLP-1RAs) represent weight loss strategies that may protect bone mass despite weight loss.OBJECTIVE: To investigate bone health at clinically relevant sites (hip, spine, and forearm) after diet-induced weight loss followed by a 1-year intervention with exercise, liraglutide, or both combined.DESIGN, SETTING, AND PARTICIPANTS: This study was a predefined secondary analysis of a randomized clinical trial conducted between August 2016 and November 2019 at the University of Copenhagen and Hvidovre Hospital in Denmark. Eligible participants included adults aged 18 to 65 years with obesity (body mass index of 32-43) and without diabetes. Data analysis was conducted from March to April 2023, with additional analysis in February 2024 during revision.INTERVENTIONS: After an 8-week low-calorie diet (800 kcal/day), participants were randomized to 1 of 4 groups for 52 weeks: a moderate- to vigorous-intensity exercise program (exercise alone), 3.0 mg daily of the GLP-1 RA liraglutide (liraglutide alone), the combination, or placebo.MAIN OUTCOMES AND MEASURES: The primary outcome was change in site-specific bone mineral density (BMD) at the hip, lumbar spine, and distal forearm from before the low-calorie diet to the end of treatment, measured by dual-energy x-ray absorptiometry in the intention-to-treat population.RESULTS: In total, 195 participants (mean [SD] age, 42.84 [11.87] years; 124 female [64%] and 71 male [36%]; mean [SD] BMI, 37.00 [2.92]) were randomized, with 48 participants in the exercise group, 49 participants in the liraglutide group, 49 participants in the combination group, and 49 participants in the placebo group. The total estimated mean change in weight losses during the study was 7.03 kg (95% CI, 4.25-9.80 kg) in the placebo group, 11.19 kg (95% CI, 8.40-13.99 kg) in the exercise group, 13.74 kg (95% CI, 11.04-16.44 kg) in the liraglutide group, and 16.88 kg (95% CI, 14.23-19.54 kg) in the combination group. In the combination group, BMD was unchanged compared with the placebo group at the hip (mean change, -0.006 g/cm2; 95% CI, -0.017 to 0.004 g/cm2; P = .24) and lumbar spine (-0.010 g/cm2; 95% CI, -0.025 to 0.005 g/cm2; P = .20). Compared with the exercise group, BMD decreased for the liraglutide group at the hip (mean change, -0.013 g/cm2; 95% CI, -0.024 to -0.001 g/cm2; P = .03) and spine (mean change, -0.016 g/cm2; 95% CI, -0.032 to -0.001 g/cm2; P = .04).CONCLUSIONS AND RELEVANCE: In this randomized clinical trial, the combination of exercise and GLP-1RA (liraglutide) was the most effective weight loss strategy while preserving bone health. Liraglutide treatment alone reduced BMD at clinically relevant sites more than exercise alone despite similar weight loss.TRIAL REGISTRATION: EudraCT: 2015-005585-32.
KW - Humans
KW - Female
KW - Male
KW - Middle Aged
KW - Liraglutide/therapeutic use
KW - Glucagon-Like Peptide-1 Receptor/agonists
KW - Bone Density/drug effects
KW - Adult
KW - Exercise
KW - Obesity/drug therapy
KW - Weight Loss/drug effects
KW - Hypoglycemic Agents/therapeutic use
KW - Aged
KW - Combined Modality Therapy
KW - Denmark
UR - http://www.scopus.com/inward/record.url?scp=85197014814&partnerID=8YFLogxK
U2 - 10.1001/jamanetworkopen.2024.16775
DO - 10.1001/jamanetworkopen.2024.16775
M3 - Journal article
C2 - 38916894
SN - 2574-3805
VL - 7
SP - e2416775
JO - JAMA network open
JF - JAMA network open
IS - 6
M1 - e2416775
ER -