GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women

Iepsen, Eva Winning; Lundgren, Julie; Hartmann, Bolette; Pedersen, Oluf; Hansen, Torben; Jørgensen, Niklas Rye; Jensen, Jens–Erik Beck; Holst, Jens J.; Madsbad, Sten; Torekov, Signe S.

doi:10.1210/jc.2015-1176

Cited by 134 publications

(91 citation statements)

References 52 publications

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“…Despite limitations in the methods used to determine the above-mentioned changes in bone mass, changes in bone turnover markers observed in this study also supported a favorable effect of liraglutide [86]. Indeed, there were significant, 11%-16% increases in plasma concentrations of the bone formation markers P1NP and osteocalcin during liraglutide treatment, in contrast to non-significant changes in the control group.…”

Section: Glp-1 Receptor Agonistssupporting

confidence: 65%

“…There was a significant decrease in plasma vitamin D concentrations in the control group, in contrast to a non-significant decrease in the liraglutide group. There was no significant change in the plasma concentrations of the bone resorption marker CTX in either group [86]. These findings for P1NP/osteocalcin and CTX, markers of bone formation and resorption, respectively, suggest that the beneficial effect of liraglutide may be to promote bone formation rather than the prevention of bone resorption.…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 70%

“…Despite these limitations, another study provides some degree of support for the positive findings of the effect of liraglutide on fracture risk [86]. In this study, 37 non-diabetic, obese women, aged 46 ± 2 years, completed an 8-week meal replacement weight loss program and were then randomized into a liraglutide group (1.2 mg/day, which is less than half the dose of liraglutide used for weight management, n = 18) or a control (not placebo) group (n = 19).…”

Section: Glp-1 Receptor Agonistsmentioning

confidence: 95%

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Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

Harper

Pattinson

Fernando

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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Background: New evidence suggests that obesity is deleterious for bone health, and obesity treatments could potentially exacerbate this. Materials and methods: This narrative review, largely based on recent systematic reviews and meta-analyses, synthesizes the effects on bone of bariatric surgery, weight loss pharmaceuticals and dietary restriction. Results and conclusions: All three obesity treatments result in statistically significant reductions in hip bone mineral density (BMD) and increases in bone turnover relative to pre-treatment values, with the reductions in hip BMD being strongest for bariatric surgery, notably Roux-en Y gastric bypass (RYGB, 8%-11% of pre-surgical values) and weakest for dietary restriction (1%-1.5% of pre-treatment values). Weight loss pharmaceuticals (orlistat or the glucagon-like peptide-1 receptor agonist, liraglutide) induced no greater changes from pre-treatment values than control, despite greater weight loss. There is suggestive evidence that liraglutide may increase bone mineral content (BMC) -but not BMD -and reduce fracture risk, but more research is required to clarify this. All three obesity treatments have variable effects on spine BMD, probably due to greater measurement error at this site in

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Section: Glp-1 Receptor Agonistssupporting

confidence: 65%

Section: Glp-1 Receptor Agonistsmentioning

confidence: 70%

Section: Glp-1 Receptor Agonistsmentioning

confidence: 95%

See 1 more Smart Citation

Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

Harper

Pattinson

Fernando

et al. 2016

Hormone Molecular Biology and Clinical Investigation

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show abstract

“…Incretins are known suppressors of bone resorption, and it has previously been shown in vitro and in animal studies that GLP-1 reduces bone resorption (29,30,31). A recent clinical trial concluded that treatment with a GLP-1 analogue increases bone formation possibly by decreasing bone resorption in obese women (32). Patients with type 1 diabetes have normal postprandial levels of both GIP and GLP-1 (33), and traditionally, patients with type 2 diabetes are thought to have low levels of incretins, which would contribute to an impaired insulin response to hyperglycemia.…”

Section: Total (95% Ci)mentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover – a systematic review and meta-analysis

Hygum

Starup-Linde

Harsløf

et al. 2017

European Journal of Endocrinology

264

192

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Objective: To investigate the differences in bone turnover between diabetic patients and controls. Design: A systematic review and meta-analysis. Methods: A literature search was conducted using the databases Medline at PubMed and EMBASE. The free text search terms 'diabetes mellitus' and 'bone turnover', 'sclerostin', 'RANKL', 'osteoprotegerin', 'tartrate-resistant acid' and 'TRAP' were used. Studies were eligible if they investigated bone turnover markers in patients with diabetes compared with controls. Data were extracted by two reviewers. Results: A total of 2881 papers were identified of which 66 studies were included. Serum levels of the bone resorption marker C-terminal cross-linked telopeptide (−0.10 ng/mL (−0.12, −0.08)) and the bone formation markers osteocalcin (−2.51 ng/mL (−3.01, −2.01)) and procollagen type 1 amino terminal propeptide (−10.80 ng/mL (−12.83, −8.77)) were all lower in patients with diabetes compared with controls. Furthermore, s-tartrate-resistant acid phosphatase was decreased in patients with type 2 diabetes (−0.31 U/L (−0.56, −0.05)) compared with controls. S-sclerostin was significantly higher in patients with type 2 diabetes (14.92 pmol/L (3.12, 26.72)) and patients with type 1 diabetes (3.24 pmol/L (1.52, 4.96)) compared with controls. Also, s-osteoprotegerin was increased among patients with diabetes compared with controls (2.67 pmol/L (0.21, 5.14)). Conclusions: Markers of both bone formation and bone resorption are decreased in patients with diabetes. This suggests that diabetes mellitus is a state of low bone turnover, which in turn may lead to more fragile bone. Altered levels of sclerostin and osteoprotegerin may be responsible for this.

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“…A recent study in obese non-diabetic postmenopausal women taking liraglutide showed increased bone formation (elevation of P1NP without changes in CTX1) with prevention of bone loss even after weight loss due to the medication [110] . Studies in diabetic insulin-resistant rats show involvement of osteogenic activation of the Wnt pathway that can be reversed using exendin-4 [111].…”

Section: -Glp-1 and The Bonementioning

confidence: 93%

Untitled

2017

SF J Obesity Res

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GLP-1 Receptor Agonist Treatment Increases Bone Formation and Prevents Bone Loss in Weight-Reduced Obese Women

Abstract: 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.

Cited by 134 publications

References 52 publications

Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

Effects of obesity treatments on bone mineral density, bone turnover and fracture risk in adults with overweight or obesity

MECHANISMS IN ENDOCRINOLOGY: Diabetes mellitus, a state of low bone turnover – a systematic review and meta-analysis

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