Denosumab increases BMD and reduces bone turnover vs monthly oral bisphosphonate

Study Type: Randomized Trial
OE Level of Evidence: 2
Journal Level of Evidence: N/A
A post hoc analysis was performed combining the data from two previously conducted randomized controlled trials (RCTs) in postmenopausal women (total of 1705 patients) with low adherence to a daily/weekly BP treatment who then transitioned to either denosumab or a monthly BP treatment (ibandronate and risedronate, respectively). This study aimed to compare bone mineral density and bone turnover marker levels. Results indicated that 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: Consultant
Why was this study needed now?
Bisphosphonate therapy is commonly prescribed for postmenopausal women with osteoporosis. The major impediment to treatment efficacy, however, is adherence to dosing regimens. It has been suggested that a different class of treatment may be more effective than frequency of dosing or cycling through different bisphosphnate treatments. As such, denosumab was introduced as an antibody against RANKL. Theoretically, denosumab should reduce bone resorption and increase bone mass and strength. In two previously conducted randomized controlled trials (RCTs) results indicated that among patients with low adherence to a daily/weekly BP treatment, a transition to treatment with denosumab elicited increases in BMD and decreases in bone turnover markers when compare to transitions to ibandronate (TTI study) or risedronate (TTR study). As such, this study performed a post-hoc analysis of these RCTs to compare BMD and levels of bone turnover markers within the overall population and in a subgroup of patients with a high fracture risk.
What was the principal research question?
How do bone mineral densities and bone turnover marker levels compare between denosumab, and monthly oral bisphosphonate (BP) (ibandronate and risedronate) treatments?
Population: 1705 postmenopausal women >=55 years who had either discontinued oral daily or weekly BP treatment, or had a low adherence rate (<6 on Osteoporosis-Specific Morisky Medication Adherence Scale; OS-MMAS) were included. These patients were required to have received BP treatment within 1 month and at least 2 vertebrae (L1-L4) evaluable by dual-energy X-ray absorptiometry (DXA). In the TTI study patients were additionally required to have a BMD score of -4 to -2 (total hip/lumbar spine) and at least 1 proximal femur for DXA. All patients received daily elemental calcium (≥500 mg [TTI] and ≥1,000 mg [TTR]) and vitamin D (≥800 IU).
Intervention: Denosumab: Patients received 60 mg denosumab administered subcutaneously every 6 months (n=852; Mean age: 67.5+/-7.6; 475 higher risk patients).
Comparison: Bisphosphonate: Patients received an oral BP taken monthly for 12 months (one 150 mg ibandronate tablet or 75 mg risendronate taken on each of two consecutive days [150 mg total]) (n=851; Mean age: 67.0+/-7.3; 469 higher risk patients).
Outcomes: Outcome measures included BMD at proximal femur and lumbar spine, biochemical bone turnover marker serum C-telopeptide of type 1 collagen (sCTX-1) levels, and adverse events. Adequate adherence to treatment was defined as two scheduled denosumab injections or at least 80% of oral BPs.
Methods: RCT: Post-hoc analysis of two RCTs; multicentre; open-label; parallel-group
Time: Baseline, 6 months, 12 months.
What were the important findings?
What should I remember most?
How will this affect the care of my patients?
The authors responsible for this critical appraisal and ACE Report indicate no potential conflicts of interest relating to the content in the original publication.