GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

Eva Pers Winning Iepsen; Julie Rehné Lundgren; Bolette Hartmann; Oluf Pedersen; Torben Hansen; Niklas R Jørgensen; Jens-Erik Beck Jensen; Jens J Holst; Sten Madsbad; Signe Sørensen Torekov

doi:10.1210/jc.2015-1176

GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

Eva Pers Winning Iepsen, Julie Rehné Lundgren, Bolette Hartmann, Oluf Pedersen, Torben Hansen, Niklas R Jørgensen, Jens-Erik Beck Jensen, Jens J Holst, Sten Madsbad, Signe Sørensen Torekov

77 Citations (Scopus)

Abstract

Context: 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. Design: Randomized control study. Setting: Outpatient research hospital clinic. Participants: Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m² and age 46 ± 2 years. Intervention: 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. Main Outcome Measures: 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) vsa2%(-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.

Original language	English
Journal	The Journal of clinical endocrinology and metabolism
Volume	100
Issue number	8
Pages (from-to)	2909 –2917
Number of pages	9
ISSN	0021-972X
DOIs	https://doi.org/10.1210/jc.2015-1176
Publication status	Published - 1 Aug 2015

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Iepsen, E. P. W., Lundgren, J. R., Hartmann, B., Pedersen, O., Hansen, T., Jørgensen, N. R., Jensen, J.-E. B., Holst, J. J., Madsbad, S., & Torekov, S. S. (2015). GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women. The Journal of clinical endocrinology and metabolism, 100(8), 2909 –2917. https://doi.org/10.1210/jc.2015-1176

GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women. / Iepsen, Eva Pers Winning; Lundgren, Julie Rehné; Hartmann, Bolette et al.
In: The Journal of clinical endocrinology and metabolism, Vol. 100, No. 8, 01.08.2015, p. 2909 –2917.

Research output: Contribution to journal › Journal article › Research › peer-review

Iepsen, EPW, Lundgren, JR, Hartmann, B , Pedersen, O , Hansen, T , Jørgensen, NR, Jensen, J-EB, Holst, JJ , Madsbad, S & Torekov, SS 2015, 'GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women', The Journal of clinical endocrinology and metabolism, vol. 100, no. 8, pp. 2909 –2917. https://doi.org/10.1210/jc.2015-1176

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title = "GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women",

abstract = "Context: 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. Design: Randomized control study. Setting: Outpatient research hospital clinic. Participants: Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m2 and age 46 ± 2 years. Intervention: 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. Main Outcome Measures: 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) vsa2%(-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.",

author = "Iepsen, {Eva Pers Winning} and Lundgren, {Julie Rehn{\'e}} and Bolette Hartmann and Oluf Pedersen and Torben Hansen and J{\o}rgensen, {Niklas R} and Jensen, {Jens-Erik Beck} and Holst, {Jens J} and Sten Madsbad and Torekov, {Signe S{\o}rensen}",

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T1 - GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

AU - Iepsen, Eva Pers Winning

AU - Lundgren, Julie Rehné

AU - Hartmann, Bolette

AU - Pedersen, Oluf

AU - Hansen, Torben

AU - Jørgensen, Niklas R

AU - Jensen, Jens-Erik Beck

AU - Holst, Jens J

AU - Madsbad, Sten

AU - Torekov, Signe Sørensen

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N2 - Context: 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. Design: Randomized control study. Setting: Outpatient research hospital clinic. Participants: Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m2 and age 46 ± 2 years. Intervention: 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. Main Outcome Measures: 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) vsa2%(-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.

AB - Context: 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. Design: Randomized control study. Setting: Outpatient research hospital clinic. Participants: Thirty-seven healthy obese women with body mass index of 34 ± 0.5 kg/m2 and age 46 ± 2 years. Intervention: 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. Main Outcome Measures: 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) vsa2%(-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.

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DO - 10.1210/jc.2015-1176

M3 - Journal article

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SN - 0021-972X

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JO - The Journal of clinical endocrinology and metabolism

JF - The Journal of clinical endocrinology and metabolism

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ER -

GLP-1 receptor agonist treatment increases bone formation and prevents bone loss in weight-reduced obese women

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