Greater BMD increase with denosumab vs ZOL in patients switching from oral bisphosponates

Study Type: Therapy
OE Level of Evidence: 1
Journal Level of Evidence: N/A
Synopsis
643 postmenopausal women with osteoporosis who had used oral bisphosphonate for a minimum of 2 years were randomized to either subcutaneous injections of denosumab 60mg - one at baseline and another at 6 months - or intravenous injection of zoledronic acid 5mg. The purpose of this study was to evaluate if denosumab offered noninferior or superior efficacy and safety to zoledronic acid for increasing bone mineral density in this patient population. The increase in Please login to view the rest of this report. Please login to view the rest of this report.
Funding: Industry funded
Sponsor: Amgen Inc.
Conflicts: Company Employee
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Why was this study needed now?
Bisphosphonate therapy has become standard in the management of osteoporosis. Many oral bisphosphonates, such as alendronate and ibandronate, utilize inconvenient dosing schedules, which can lead to non-adherence and suboptimal outcomes. Patients have previously demonstrated a preference for zoledronate, administered as a yearly intravenous injection, and previous research has demonstrated similar outcomes for patients switching to zoledronate from other bisphosphonates. Denosumab, an anti-RANKL human monoclonal antibody treatment more recently developed, has demonstrated improved bone mineral density in those switching from alendronate than in those continuing treatment with alendronate, and there is interest in whether the same would be found in those switching from oral bisphosphonates to zoledronate.
What was the principal research question?
In postmenopausal women with osteoporosis who are transitioning from oral bisphosphonate therapy, does subcutaneous denosumab offer noninferior efficacy to intravenous zoledronic acid for the increase in lumbar spine and total hip bone mineral density after 12 months?
Population: 643 postmenopausal women, over the age of 55, with osteoporosis (T-score of -2.5 or lower) and prior oral bisphosphonate therapy for a minimum of 2 years. Additional inclusion criteria were that participants were evaluable on dual-energy x-ray absorptiometry (DEXA), and had serum concentration of C-telopeptide of type-1 collagen of 500pg/mL or less. Cases of prior zoledronic acid or denosumab use, or fluoride, strontium ranelate or IV bisphosphonate use within the previous 5 years were excluded. In addition to allocated anti-osteoporosis drug, patients received daily supplementation of 1000mg or greater calcium and 800IU or greater vitamin D.
Intervention: Denosumab group: Patients received two subcutaneous injections of 60mg denosumab, one at baseline and one at 6 months. At baseline, a placebo intravenous injection was also administered. (n=321 randomized; 313 completed) (Mean age: 68.5+/-7.1)
Comparison: ZOL group: Patients received an intravenous injection of 5mg zoledronic acid. Patients were also administered subcutaneous injections of placebo at baseline and at 6 months. (n=322 randomized; 312 completed) (Mean age: 69.5+/-7.7)
Outcomes: The primary outcome was the percent change from baseline in lumbar spine bone mineral density on DEXA after 12 months. The secondary outcome was the percent change from baseline in BMD of the total hip. Prespecified noninferiority margins were -0.46% for change in lumbar spine BMD and -0.51% for change in total hip BMD. Tertiary outcomes were percent changes from baseline in BMD of the femoral neck and distal one-third radius. Serum concentrations of C-telopeptide of type-1 collagen (CTX), procollagen type 1 N-terminal telopeptide (P1NP), intact parathyroid hormone (iPTH), and albumin-adjusted calcium were also measured. Adverse events were documented.
Methods: RCT; Patient- and assessor blind; multicentre (11 sites)
Time: Patients were assessed at 12-month follow-up
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The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.