Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA···
Effects of Glucagon-Like Peptide-1 Treatments on Bone Health in People with Obesity
GLP-1 receptor agonists may modestly reduce and shift remodeling toward resorption in people with obesity, but the bone-health picture remains uncertain.
Evidence
This English-language review searched preclinical and human literature from January 2013 to December 2024 on GLP-1 receptor agonists, weight loss, and bone outcomes in obesity.
Caveat
Human evidence is limited, rodent benefits often used doses above obesity-treatment concentrations, and fracture-related outcomes remain unresolved.
Simplified
Medications like liraglutide 3.0 mg daily (Saxenda®; Novo Nordisk) and semaglutide 2.4 mg weekly (Wegovy®; Novo Nordisk), which are glucagon-like peptide-1 receptor agonists (GLP-1Ra), have been sanctioned for prolonged weight management in people living with obesity (PwO). Although GLP-1 might enhance bone metabolism and quality, the impact of these receptor agonists on bone health remains uncertain and is the subject of this review. Data on bone health in the context of calorie restriction and bariatric surgery were also summarized. A comprehensive search of the literature on preclinical studies and human data published in English was performed from Jan 2013 to Dec 2024 to identify the various effects of GLP-1Ra on bone health. The effects of intentional weight loss procedures in PwO are well documented; significant weight reduction (~ 7-10%) through calorie restriction, with or without exercise, and bariatric/metabolic surgery results in high turnover bone loss. In different rodent models, liraglutide seems to positively influence bone material properties despite notable weight loss. However, the most favorable effects on and microarchitecture were noted at concentrations much higher than those approved for human obesity treatment. Current evidence on the effects of GLP-1Ra on bone health in PwO is limited. Although initial findings suggest that GLP-1Ra leads to a slight reduction in bone mineral density and promotes bone remodeling, favoring resorption similar to calorie restriction effects, further research is needed to explore the effects of GLP-1Ra on bone metabolism and fracture-related outcomes, as well as dual- and triple-receptor agonists of GLP-1, glucose-dependent insulinotropic polypeptide (GIP), and glucagon in PwO. The impact of glucagon-like peptide-1 receptor agonists (GLP-1Ra) on bone health remains unclear. Although preliminary findings indicate that GLP-1Ra causes modest bone mineral density reduction and enhances bone remodeling, favoring resorption similar to the effects of calorie restriction, further research is needed on fracture-related outcomes in people living with obesity.
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Declarations. Conflicts of interest: JP has received consulting fees from Kyowa Kirin, Eli Lilly, and Theramex; honoraria from Amgen, Besins, CDD, Kyowa Kirin, and Theramex; payment for expert testimony from UCB; and support for attending meetings from Kyowa Kirin and Theramex. GM and LK has no conflict of interest.
