The Impact of Antiosteoporotic Drugs on Glucose Metabolism and Fracture Risk in Diabetes: Good or Bad News?

Abstract

Osteoporosis and diabetes mellitus represent global health problems due to their high, and increasing with aging, prevalence in the general population. Osteoporosis can be successfully treated with both antiresorptive and anabolic drugs. While these drugs are clearly effective in reducing the risk of fracture in patients with postmenopausal and male osteoporosis, it is still unclear whether they may have the same efficacy in patients with diabetic osteopathy. Furthermore, as bone-derived cytokines (osteokines) are able to influence glucose metabolism, it is conceivable that antiosteoporotic drugs may have an effect on glycemic control through their modulation of bone turnover that affects the osteokines’ release. These aspects are addressed in this narrative review by means of an unrestricted computerized literature search in the PubMed database. Our findings indicate a balance between good and bad news. Active bone therapies and their modulation of bone turnover do not appear to play a clinically significant role in glucose metabolism in humans. Moreover, there are insufficient data to clarify whether there are any differences in the efficacy of antiosteoporotic drugs on fracture incidence between diabetic and nondiabetic patients with osteoporosis. Although more studies are required for stronger recommendations to be issued, bisphosphonates appear to be the first-line drug for treatment of osteoporosis in diabetic patients, while denosumab seems preferable for older patients, particularly for those with impaired renal function, and osteoanabolic agents should be reserved for patients with more severe forms of osteoporosis.

Low Bone Turnover Due to Hypothyroidism or Anti-Resorptive Treatment Does Not Affect Whole-Body Glucose Homeostasis in Male Mice

“…Despite low bone turnover and a reduced uptake of glucose into bone, we did not observe effects on glucose tolerance or insulin sensitivity. Our findings are supported by several clinical studies that examined patients treated with bisphosphonates and found no side effects of bisphosphonate treatment on glucose homeostasis [17,38]. Together, these data suggest that impaired glucose tolerance in hypothyroidism is not mediated via impaired glucose uptake into bone.…”

“…Lately, the skeleton has emerged as an endocrine organ secreting osteokines such as osteocalcin (OCN), receptor activator of NF-κB ligand (RANKL) and sclerostin (SOST) that can regulate systemic glucose homeostasis [14][15][16][17]. Daily injections of uncarboxylated osteocalcin improve glucose tolerance and insulin tolerance in mice fed a normal diet and can prevent the development of type 2 diabetes mellitus in mice on high-fat diet [18].…”

Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis

“…However, confounding by indication may not have been completely eliminated in that study because factors such as kidney function and upper gastrointestinal tract diseases may be associated with the selection of denosumab or bisphosphonates. Moreover, the potential association of bisphosphonates with reduced diabetes risk, as suggested by previous studies, may influence the comparisons between bisphosphonates and denosumab and complicate the use of bisphosphonates as an appropriate reference group.…”

Treatment of Diabetes and Osteoporosis—A Reciprocal Risk?

“…Teriparatide reduces the risk of cervical fractures and non-vertebral fractures [ 106 ]. Conclusions from clinical trials regarding the action of teriparatide on carbohydrate management parameters are often contradictory, and the effect on glucose homeostasis remains unknown, although the role of calcium and its effect on glucose transport to the cell and the regulation of insulin receptors are postulated [ 107 ]. Celer et al showed that the use of teriparatide in patients with postmenopausal osteoporosis increased glucose concentrations, whereas Anastasilakis et al showed that this trend decreases when teriparatide treatment is continued [ 108 , 109 ].…”