Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis

Chen, Po‐Wei; Su, Hsiao-Yuan; Tu, Yu‐Kang; Wu, Chih-Hsing; Yeh, Jih‐I; Chen, Liyu; Peng, Chung Kang; Loh, Ching‐Hui; Huang, Huei‐Kai; Lin, Shu‐Man

doi:10.1007/s00198-022-06616-3

Cited by 7 publications

(8 citation statements)

References 37 publications

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“… 41 42 43 44 A recent meta-analysis from two post hoc analyses of randomized controlled trials and five observational studies showed that bisphosphonate use was associated with a 23% decreased risk of diabetes (relative risk 0.77, 95% confidence interval 0.65 to 0.90); although only minimal benefit (0.93, 0.74 to 1.18) in the subgroup of post hoc analyses of randomized controlled trials. 45 Proposed mechanisms suggest bisphosphonates might improve glucose homeostasis by inhibiting the mevalonate pathway of endothelial cells, decreasing the number of macrophages in visceral adipose tissues, or through interaction with multiple active osteokines (eg, osteocalcin and osteopontin). 42 46 47 Although more studies are needed to evaluate the exact mechanism of bisphosphonates on risk of type 2 diabetes, the use of oral bisphosphonates as compactor drug in the current study provides a more conservative estimate of the association between denosumab and risk of type 2 diabetes.…”

Section: Discussionmentioning

confidence: 99%

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Lyu

Zhao

Zhang

et al. 2023

BMJ

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Objective To estimate the effect of denosumab compared with oral bisphosphonates on reducing the risk of type 2 diabetes in adults with osteoporosis. Design Population based study involving emulation of a randomized target trial using electronic health records. Setting IQVIA Medical Research Data primary care database in the United Kingdom, 1995-2021. Participants Adults aged 45 years or older who used denosumab or an oral bisphosphonate for osteoporosis. Main outcome measures The primary outcome was incident type 2 diabetes, as defined by diagnostic codes. Cox proportional hazards models were used to estimate adjusted hazard ratios and 95% confidence intervals, comparing denosumab with oral bisphosphonates using an as treated approach. Results 4301 new users of denosumab were matched on propensity score to 21 038 users of an oral bisphosphonate and followed for a mean of 2.2 years. The incidence rate of type 2 diabetes in denosumab users was 5.7 (95% confidence interval 4.3 to 7.3) per 1000 person years and in oral bisphosphonate users was 8.3 (7.4 to 9.2) per 1000 person years. Initiation of denosumab was associated with a reduced risk of type 2 diabetes (hazard ratio 0.68, 95% confidence interval 0.52 to 0.89). Participants with prediabetes appeared to benefit more from denosumab compared with an oral bisphosphonate (hazard ratio 0.54, 0.35 to 0.82), as did those with a body mass index ≥30 (0.65, 0.40 to 1.06). Conclusions In this population based study, denosumab use was associated with a lower risk of incident type 2 diabetes compared with oral bisphosphonate use in adults with osteoporosis. This study provides evidence at a population level that denosumab may have added benefits for glucose metabolism compared with oral bisphosphonates.

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Section: Discussionmentioning

confidence: 99%

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Lyu

Zhao

Zhang

et al. 2023

BMJ

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“…This meta-analysis, centered on evaluating the clinical efficacy of bisphosphonates in treating osteoporosis among diabetic patients, corresponds with prior investigations examining bisphosphonates' effects on glycemic control and diabetes risk. Although our results highlight substantial enhancements in BMD and bone metabolism markers, distinctions arise concerning glycemic control and diabetes risk, areas not directly investigated in our study [13]. Additionally, while prior meta-analyses suggest that alendronate combined with atorvastatin is a superior treatment for osteoporosis in diabetes mellitus, exhibiting enhanced effectiveness, higher BMD, and fewer adverse events compared to alendronate alone, our study did not investigate the differences between combination therapy and monotherapy [14].…”

Section: Discussionmentioning

confidence: 67%

“…Given the increasing prevalence of diabetes and its associated complications, understanding the effects of bisphosphonates on bone health in diabetic individuals is crucial. However, there are still few systematic reviews on the influence of bisphosphonates on bones in diabetes patients with osteoporosis [13,14]. Therefore, the primary objective of this study is to systematically review original research evaluating the effects of bisphosphonates on individuals with osteoporosis in diabetes.…”

Section: Introductionmentioning

confidence: 99%

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis

Yang,

Jin

2024

Horm Metab Res

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The aim of the study was to explore the clinical efficacy of bisphosphonates in patients with osteoporosis in diabetes patients by meta-analysis. Six databases were systematically searched from inception to January 30,2023. Studies evaluating the treatment of diabetic osteoporosis with bisphosphonates were included. Key outcome measures, such as bone mineral density (BMD), bone metabolism markers, pain improvement, and safety assessments, were extracted and analyzed. STATA MP V17.0 was used to calculate the combined effect size. After searching Chinese and English databases, 15 studies met the inclusion criteria of this study. The results of the meta-analysis showed that the BMD of patients with osteoporosis in diabetes increased significantly after bisphosphonate treatment, and the lumbar BMD increased by 0.08 g/cm² (95% CI: 0.05–0.11). Femoral neck BMD increased by 0.06 g/cm² (95% CI: 0.01–0.11); Ward’s triangle BMD increased 0.07 g/cm² (95% CI: 0.04–0.09); and trochanter BMD increased by 0.06 g/cm² (95% CI: 0.04–0.08). In addition, bone alkaline phosphatase increased 1.95 μg/l (95% CI: 1.18–2.72), while serum tartrate-resistant acid phosphatase-5b decreased 1.28 U/l (95% CI: –1.81–0.75). Moreover, improvements in pain were statistically significant. The effects of bisphosphonates on osteocalcin (MD: –0.07; 95% CI: –1.12–1.25), serum calcium (MD: 0.01; 95% CI: –0.03–0.04), serum phosphorus (MD: 0.04; 95% CI: –0.03–0.10) and medication safety (OR: 1.75; 95% CI: 1.29–2.37) were not statistically significant. Bisphosphonates have a significant positive effect on bone mineral density and bone metabolism in patients with osteoporosis in diabetes and have good safety.

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“…15 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, 29,30 may influence the comparisons between bisphosphonates and denosumab and complicate the use of bisphosphonates as an appropriate reference group.…”

Section: Jama Network Open | Pharmacy and Clinical Pharmacologymentioning

confidence: 99%

Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis

Huang,

Chuang,

Liao

et al. 2024

JAMA Netw Open

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ImportanceDenosumab, a humanized monoclonal antibody against receptor activator of nuclear factor κB ligand (RANKL), is a widely used antiresorptive medication for osteoporosis treatment. Recent preclinical studies indicate that inhibition of RANKL signaling improves insulin sensitivity, glucose tolerance, and β-cell proliferation, suggesting that denosumab may improve glucose homeostasis; however, whether denosumab reduces the risk of incident diabetes remains unclear.ObjectiveTo evaluate whether denosumab use is associated with a lower risk of developing diabetes in patients with osteoporosis.Design, Setting, and ParticipantsThis nationwide, propensity score–matched cohort study used administrative data from Taiwan’s National Health Insurance Research Database. Adult patients who received denosumab for osteoporosis therapy in Taiwan between 2012 and 2019 were included. To eliminate the inherent bias from confounding by indication, the patients were categorized into a treatment group (34 255 patients who initiated denosumab treatment and adhered to it) and a comparison group (34 255 patients who initiated denosumab treatment but discontinued it after the initial dose) according to the administration status of the second dose of denosumab. Propensity score matching was performed to balance patient characteristics and to control for confounders.ExposureTreatment with denosumab.Main Outcomes and MeasuresThe primary outcome was incident diabetes requiring treatment with antidiabetic drugs. A Cox proportional hazards model was used to estimate the hazard ratio (HR) for incident diabetes. Data were analyzed from January 1 to November 30, 2023.ResultsAfter propensity score matching, 68 510 patients were included (mean [SD] age, 77.7 [9.8] years; 57 762 [84.3%] female). During a mean (SD) follow-up of 1.9 (1.6) years, 2016 patients developed diabetes in the treatment group and 3220 developed diabetes in the comparison group (incidence rate, 35.9 vs 43.6 per 1000 person-years). Compared with the comparison group, denosumab treatment was associated with a lower risk of incident diabetes (HR, 0.84; 95% CI, 0.78-0.90). Several sensitivity analyses also demonstrated similar results of lower diabetes risk associated with denosumab treatment.Conclusions and relevanceThe results from this cohort study indicating that denosumab treatment was associated with lower risk of incident diabetes may help physicians choose an appropriate antiosteoporosis medication for patients with osteoporosis while also considering the risk of diabetes.

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Association of bisphosphonates with diabetes risk and glycemic control: a meta-analysis

Cited by 7 publications

References 37 publications

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Denosumab and incidence of type 2 diabetes among adults with osteoporosis: population based cohort study

Clinical Efficacy of Bisphosphonates in Treating Osteoporosis in Diabetes Patients: A Meta-Analysis

Denosumab and the Risk of Diabetes in Patients Treated for Osteoporosis

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