NICE (TA 204) recommends denosumab as a treatment option for the primary and secondary prevention of osteoporotic fragility fractures in postmenopausal women at increased risk of fractures but NICE guidance for the primary and secondary prevention of osteoporotic fragility fractures in postmenopausal women at increased risk of fractures (TA 160 &161) does not address the use of ibandronate because it is not licensed for this indication.
This randomised, open-label study compared the efficacy and safety of denosumab (60 mg subcutaneously every 6 months; licensed UK dose; n=417) to ibandronate (150mg orally every month; US formulation not available within the UK; n=416) in postmenopausal women with low bone mineral density (BMD) previously treated with a bisphosphonate.
The primary end point, the percentage change from baseline in BMD at the total hip at month 12, was reported to be 2.3% with denosumab and 1.1% with ibandronate, resulting in a treatment difference of 1.1% (95% CI 0.821.5, p<0.001). Increased BMD from baseline were also observed with denosumab compared with ibandronate at the femoral neck (1.7% vs 0.7%; P<0.001) and lumbar spine (4.1% vs 2.0%; P<0.001).
A similar number of women in each treatment group reported one or more on-study fracture (the study was not powered for this comparison): 15 (3.6%) denosumab and 13 (3.2%) ibandronate. The most commonly reported fractures (1% or more of women in either treatment group) were wrist fractures, four (1.0%) for denosumab and one (0.2%) ibandronate; and foot fractures three (0.7%) for denosumab and five (1.2%) for ibandronate. Two women in each treatment group reported vertebral fractures, and one ibandronate-treated participant reported a hip fracture.
A total of 245 women (59.6%) in the denosumab group and 230 women (56.1%) in the ibandronate group experienced one or more adverse event during the study (P=0.635) with the most frequently experienced adverse events (4% or more in either treatment group) being arthralgia (6.1% denosumab, 5.6% ibandronate), upper respiratory tract infection (denosumab 5.1%, ibandronate 2.2%), and urinary tract infection (3.4% denosumab, 4.6% ibandronate). The incidence of serious adverse events was 9.5% for denosumab-treated women and 5.4% for ibandronate-treated women (P=0.046) and the incidence rates of serious adverse events involving infection and malignancy were similar between treatment groups.
The authors concluded that denosumab treatment resulted in greater BMD increases than ibandronate at all measured sites in postmenopausal women previously treated with a bisphosphonate and low BMD. Despite the limitations of the open-label dosing, they note that these results suggest that transitioning to denosumab which has a different mechanism of action and less frequent administration provides greater BMD improvement than switching to another bisphosphonate.