OBJECTIVE: Osteoporosis in men is a common but often neglected health problem. We aim to compare the efficacy and safety of denosumab, zoledronic acid and alendronate in men with osteoporosis.
METHODS: In this randomized, comparative, open-label study, 390 men with osteoporosis or osteopenia were included. They were randomized to receive the treatment of denosumab, alendronate, or zoledronic acid for 12 months. The percentage changes in bone mineral density (BMD), trabecular bone score (TBS) and bone turnover biomarkers (BTMs) during the treatment were evaluated. Safety parameters were observed.
RESULTS: The baseline characteristics were well balanced among the three groups. After 12 months of treatment, denosumab, alendronate and zoledronic acid significantly increased BMD by 4.83 ± 0.89%, 4.32 ± 0.77%, 5.18 ± 0.73% at lumbar spine, by 2.75 ± 0.51%, 2.50 ± 0.61% and 2.83 ± 0.59% at total hip, TBS was significantly increased by 2.44 ± 0.52%, 2.00 ± 0.64%, 2.29 ± 0.55%, respectively, without significant differences among the three groups. Serum levels of BTMs decreased significantly and similarly in all three groups (all P < .05 vs. baseline). Denosumab and alendronate group had fewer adverse events than zoledronic acid group. Denosumab had similar efficacy in patients with different gonadal functions. In patients previously receiving bone resorption inhibitors, denosumab continued to increase BMD and TBS, but the increments were reduced by approximately 30% in BMD at lumbar spine compared with treatment-naive patients.
CONCLUSION: Denosumab, alendronate and zoledronic acid significantly and similarly reduced BTMs, increased BMD and TBS in men with osteoporosis, whether the gonadal function of patients was normal or decreased. Previous anti-bone resorption therapy may partially diminish the efficacy of denosumab.
| Specialty | Score |
|---|---|
| Internal Medicine | |
| Geriatrics | |
| Rheumatology | |
| Endocrine | |
| Family Medicine (FM)/General Practice (GP) | |
| General Internal Medicine-Primary Care(US) |
This excellent prospective trial demonstrates the efficacy of all three agents. If ones patient fits the profile of these participants, there are excellent efficacious choices.
This article is relevant to internal medicine because osteoporosis in men is underdiagnosed and undertreated, particularly after fragility fractures or in patients receiving androgen-deprivation therapy. The study provides useful comparative evidence that denosumab, alendronate, and zoledronic acid produced similar short-term improvements in BMD, trabecular bone score, and bone turnover markers. For hospitalists, the main practical value is not immediate inpatient drug selection, but improving recognition, discharge planning, and outpatient referral/treatment discussions after fragility fractures. Important limitations are the open-label design, 12-month follow-up, use of surrogate outcomes rather than fracture reduction, and limited power for subgroup conclusions.
Fracture prevention is the more important outcome.
What's new is the direct comparison of agents without apparent direct influence from a pharmaceutical company. Revealing. Too bad not double-blinded.
Interesting open-label trial comparing oral vs IV bisphosphonate vs denosumab. There are limited trial data in men with low BMD and limited head-to-head trials. The results are not surprising. The sample size was insufficient to show differences between agents. Uniquely they looked at BMD response stratified by gonad function. Limitations of the trial are use of proxy outcome (i.e., BMD not fractures).
, McMaster University