Dipeptidyl Peptidase-4 Inhibitors and Bone Fractures
Objective—Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients. Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.
Research Design and Methods—A meta-analysis was performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP-4 inhibitors with placebo or active drugs.
Results—Twenty-eight trials enrolling 11,880 and 9,175 patients for DPP-4 inhibitors and comparators, respectively, were included, reporting 63 fractures. DPP-4 inhibitors, compared with placebo or other treatments, were associated with a reduced risk of fractures (Mantel–Haenszel odds ratio [MH-OR] 0.60, 95% CI 0.37–0.99, P = 0.045), even after the exclusion of comparisons with thiazolidinediones or sulfonylureas (MH-OR 0.56, 0.33–0.93, P = 0.026).
Conclusions—The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.
Type 2 diabetes is associated with an increased risk for bone fractures. The higher risk could be determined by several factors, including falls, diabetes complications, and comorbidities. Moreover, glucose-lowering agents such as thiazolidinediones have been reported to reduce bone density and to increase the incidence of fractures in longer-term trials and in epidemiologic studies. Insulin therapy is also associated with an increased fracture risk despite its neutral effect on bone density. The increased risk of falls, due to hypoglycemia, could lead to higher fracture risk.
Glucagon-like peptide-1 (GLP-1) has been reported to induce osteoblast differentiation and inhibit osteoclastic activity; GLP-1 receptor agonists stimulate bone formation in rodents. Experimental data in animal models suggest that gastric intestinal polypeptide is also capable of increasing bone density. Drugs capable of increasing incretin levels, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, could therefore exert beneficial effects on the bone.
Abstract and Introduction
Abstract
Objective—Thiazolidinediones and insulin are associated with a higher risk of fractures in type 2 diabetic patients. Incretin hormones increase bone density in experimental models, but the effect of dipeptidyl peptidase-4 (DPP-4) inhibitors on bone fractures has not been reported so far.
Research Design and Methods—A meta-analysis was performed including all randomized clinical trials with a duration of at least 24 weeks, enrolling patients with type 2 diabetes, comparing DPP-4 inhibitors with placebo or active drugs.
Results—Twenty-eight trials enrolling 11,880 and 9,175 patients for DPP-4 inhibitors and comparators, respectively, were included, reporting 63 fractures. DPP-4 inhibitors, compared with placebo or other treatments, were associated with a reduced risk of fractures (Mantel–Haenszel odds ratio [MH-OR] 0.60, 95% CI 0.37–0.99, P = 0.045), even after the exclusion of comparisons with thiazolidinediones or sulfonylureas (MH-OR 0.56, 0.33–0.93, P = 0.026).
Conclusions—The present meta-analysis suggests that treatment with DPP-4 inhibitors could be associated with a reduced risk of bone fractures.
Introduction
Type 2 diabetes is associated with an increased risk for bone fractures. The higher risk could be determined by several factors, including falls, diabetes complications, and comorbidities. Moreover, glucose-lowering agents such as thiazolidinediones have been reported to reduce bone density and to increase the incidence of fractures in longer-term trials and in epidemiologic studies. Insulin therapy is also associated with an increased fracture risk despite its neutral effect on bone density. The increased risk of falls, due to hypoglycemia, could lead to higher fracture risk.
Glucagon-like peptide-1 (GLP-1) has been reported to induce osteoblast differentiation and inhibit osteoclastic activity; GLP-1 receptor agonists stimulate bone formation in rodents. Experimental data in animal models suggest that gastric intestinal polypeptide is also capable of increasing bone density. Drugs capable of increasing incretin levels, such as dipeptidyl peptidase-4 (DPP-4) inhibitors, could therefore exert beneficial effects on the bone.
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