Effects of metformin and denosumab on bone and glucose metabolism in postmenopausal women with osteoporosis and diabetes

Diabetic osteoporosis is a metabolic disease that seriously endangers human health and Previous studies have found that denosumab and metformin have certain effects on bone metabolism and glucose metabolism, respectively. However, there is still a lack of relevant research on the effect of the combined use of two drugs. In this study, we sought to analyze the therapeutic effect of these two drugs combined on the glycemic and bone metabolic parameters in the treatment of type 2 diabetes with postmenopausal osteoporosis. A prospective cohort study was designed to include 537 cases of patients with type 2 diabetes with postmenopausal osteoporosis. Patients were treated with placebo alone (placebo, n=135), metformin alone (MET, n=132), denosumab alone (DEN, n=136), and the combination group (n=134) for 30 months. Baseline data at 10 months, 20 months, and 30 months, Dual Energy X-ray Absorptiometry (DEXA), and pQCT were used to identify spine and tibia bone microstructures, respectively. The combination therapy group demonstrated significantly greater improvements in bone mineral density (tibia, radius, spine, and whole body) and bone microstructure (tibia and radius) compared to MET or DEN monotherapy (P<0.05). Bone absorption markers such as CTX and ALP were decreased, the level of bone formation markers was further increased, and the progression of glucose metabolism was improved significantly (P<0.05) compared to DEN alone or using MET alone. Denosumab monotherapy (DEN) ameliorated bone loss while exerting modest effects on glucose metabolism progression. In contrast, metformin monotherapy (MET) significantly improved glycemic control but demonstrated limited efficacy against bone loss. Crucially, the metformin-denosumab combination synergistically mitigated bone loss in diabetic postmenopausal osteoporosis patients.