Comparison of anti-fracture effectiveness of zoledronate, ibandronate and alendronate versus denosumab in a registry-based cohort study

Abstract

Summary This registry-based study of 3068 patients with osteoporosis compared the anti-fracture effectiveness of denosumab versus bisphosphonates. Denosumab was associated with significantly greater risk reduction than alendronate or ibandronate for vertebral and any fractures. No difference in fracture risk reduction was found between zoledronate and denosumab. Purpose To analyse the fracture risk of patients with osteoporosis receiving bisphosphonates or denosumab in a real-world setting. Methods This registry-based cohort study evaluated patients taking denosumab, bisphosphonates or both sequentially. Fractures were analysed using rates, rate ratios and hazard ratios (HR), including both therapies as time-varying co-variates. Fracture risk hazards were adjusted (aHR) for baseline T-Scores and trabecular bone score (TBS) and were additionally analysed with inverse probability treatment weighting. Results A total of 3068 patients (89% female; median age at treatment onset, 69 years [63 to 76]) received denosumab (median duration 2.8 years, [2.2 to 4.7]), bisphosphonates (3.4 years, [2.1 to 5.7]) or both sequentially. Thus, 11,078 subject-years were assessed for bisphosphonates (41% alendronate, 36% ibandronate, 23% zoledronate) and 4216 for denosumab. Moreover, 48,375 subject-years were observed before treatment onset, in addition to 2593 years of drug holidays. A total of 1481 vertebral fractures (435 under therapy), 1508 non-vertebral fractures (499 under therapy) and 202 hip fractures (67 under therapy) occurred after age 50. The risks of vertebral, non-vertebral and hip fractures were significantly lower under all bisphosphonates, denosumab and drug holidays than before treatment onset (all p < 0.001). After adjusting for age, baseline T-scores and TBS, denosumab was associated with lower risk than alendronate or ibandronate for vertebral fractures (aHR 0.47 (0.35 to 0.64) and 0.70 [0.53 to 0.91], p < 0.001 and p = 0.009, respectively) and any fractures (aHR 0.62 [0.51 to 0.76] and 0.77 [0.64 to 0.92], p < 0.001 and p = 0.004). With propensity weighting, denosumab was associated with a lower hip fracture risk compared to alendronate (HR 0.54 [0.29 to 0.98], p = 0.044). No difference in fracture risk reduction (vertebral, non-vertebral or hip) was found between zoledronate and denosumab. Conclusions When adjusting for disease severity, denosumab was associated with significantly greater risk reduction than alendronate and ibandronate for vertebral fractures. No difference in fracture risk reduction was found between zoledronate and denosumab. Supplementary Information The online version contains supplementary material available at 10.1007/s00198-023-06863-y.

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

“…Alendronate (ALN) is a representative drug of the third generation of bisphosphonates 37 . Compared with the first two generations of drugs, it has stronger anti-bone resorption and no bone mineralization inhibition 38 . Zhou et al 39 observed that in C57BL mice, the use of alendronate alone can significantly increase serum glucagon-like peptide-1 levels compared with the diabetes group.…”

The effect of romosozumab on bone mineral density depending on prior treatment: a prospective, multicentre cohort study in Switzerland

“…This registry consecutively enrols subjects referred for a dual-energy X-ray absorptiometry (DXA) scan, and to date, three outpatient centres in Bern, Zurich, and Lucerne include patients undergoing romosozumab therapy. Previously described variables are assessed for each patient [12][13][14], and additional data are collected for patients receiving romosozumab, including cardiovascular risk factors and outcomes. The primary objective of this initial analysis was to identify predictive factors, in particular prior therapies, for changes in BMD after 12 months of therapy with romosozumab.…”

Molecular and Cellular Mechanisms of Osteoporosis

“…However, it was shown that high doses of RANKL inhibitors can transform accumulating osteomorphs into active osteoclasts that lead to bone resorption, which is accompanied by fractures [136]. The effectiveness of denosumab has been studied in comparison with bisphosphonates and found that it was associated with a significantly greater reduction in the risk of vertebral and other fractures than alendronate or ibandronate, but no differences were found compared with zoledronate [153]. Clinical studies have shown that long-term therapy with denosumab for up to 10 years was associated with an increase in bone mineral density (BMD), a low incidence of fractures, and a low level of side effects [154].…”