Differential Metabolic Effects of Osteoporosis Therapies in Patients With Diabetes Mellitus: A Retrospective Cohort Study

INTRODUCTION: Osteoporosis is currently health problem with mortality rate that can reach 12–20%. Diabetes mellitus (DM) is one of the independent risk factors for osteoporosis. An area requiring further study during osteoporosis treatment, in which various agents are selected according to the patient, is the metabolic parameters that change with treatment. The aim of this study is to comparatively evaluate the metabolic effects of bisphosphonates and denosumab, agents commonly used in osteoporosis treatment on glucose, HbA1c, and lipid profile according to the presence of diabetes.
METHODS: The data of 4552 patients who presented to our clinics between January 2011 and March 2024 and were diagnosed with osteoporosis were retrospectively reviewed. After excluding patients lost to follow-up or with missing data, 733 adult patients were included in the study. Patients were grouped according to the antiosteoporotic medication used and the presence of a diabetes diagnosis, and laboratory results before and after treatment were analyzed.
RESULTS: Post-treatment glucose levels varied by group in both treatment arms, whereas HbA1c levels showed a statistically significant increase in non-DM (p<0.001). According to subgroup analyses, bisphosphonate use did not cause significant change in HbA1c levels in non-diabetic patients, whereas denosumab use led to a significant increase in HbA1c. In contrast, the osteoporosis medications used in the diabetic patient group did not lead to a statistically significant change in metabolic parameters, although significant post-treatment decrease in triglyceride levels was recorded in the bisphosphonate group.
DISCUSSION AND CONCLUSION: The metabolic effects of anti-osteoporotic therapies, particularly HbA1c and LDL, emerged clearly in nonDM individuals, whereas these effects were not observed in diabetic patients, likely owing to their pre-existing metabolic dysregulation. In contrast to some literature suggesting that RANKL inhibitors contribute positively to glucose metabolism, the increases in HbA1c and LDL observed in this study indicate that this issue warrants investigation through larger-scale clinical studies.

Keywords: Osteoporosis, Diabetes mellitus, Bisphosphonate, Denasumab