Glucagon-like Peptide-1 Receptor Agonists and Diabetic Osteopathy: Another Positive Effect of Incretines? A 12 Months Longitudinal Study

Abstract

Diabetic osteopathy is a frequent complication in patients with type 2 diabetes mellitus (T2DM). The association between T2DM and increased fracture risk has led to study the impact of new antidiabetic drugs on bone metabolism. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are incretin mimetic drugs which have many pleiotropic properties. The relationship between GLP-1RAs and bone is very complex: while in vitro and animal studies have demonstrated a protective effect on bone, human studies are scarce. We led a 12 months longitudinal study evaluating bone changes in 65 patients withT2DM for whom a therapy with GLP-1RAs had been planned. Fifty-four T2DM patients completed the 12-month study period; of them, 30 had been treated with weekly dulaglutide and 24 with weekly semaglutide. One-year therapy with GLP-1RAs resulted in a significant reduction in weight and BMI. Bone mineral density (BMD), bone metabolism, trabecular bone score (TBS), adiponectin, and myostatin were evaluated before and after 12 months of GLP-1RAs therapy. After 12 months of therapy bone turnover markers and adiponectin showed a significant increase, while myostatin values showed a modest but significant reduction. BMD-LS by DXA presented a significant reduction while the reduction in BMD-LS by REMS was not significant and TBS values showed a marginal increase. Both DXA and REMS techniques showed a modest but significant reduction in femoral BMD. In conclusion, the use of GLP-1RAs for 12 months preserves bone quality and reactivates bone turnover. Further studies are needed to confirm whether GLP-1RAs could represent a useful therapeutic option for patients with T2DM and osteoporosis.

Keywords: Bone mineral density (BMD); Bone turnover markers; Dual-energy X-ray absorptiometry (DXA); Dulaglutide; Radiofrequency echographic multispectrometry (REMS); Semaglutide; Trabecular bone score (TBS); Type 2 diabetes mellitus (T2DM).

Fig. 1

The study flow-chart

Fig. 2

Serum levels of CTX (A) and B-ALP (B) in T2DM patients at baseline and after 12 months of therapy with GLP-1RAs

Fig. 3

Values of BMD expressed as T-score at lumbar spine (LS) and at total hip (TH) by DXA and REMS technique in T2DM patients in therapy with GLP-1RAs

Fig. 4

Mean percent changes from baseline in BMD at lumbar spine by DXA, by REMS and in TBS in T2DM patients at baseline and after 12 months of therapy with GLP-1RAs

Fig. 5

Mean percent changes from baseline in BMD at total hip by DXA and by REMS in T2DM patients at baseline and after 12 months of therapy with GLP-1RAs

Fig. 6

Mean percent changes from baseline in BMD at femoral neck by DXA and by REMS in T2DM patients at baseline and after 12 months of therapy with GLP-1RAs