Efficacy of Romosozumab and Denosumab Combined Treatment in Postmenopausal Osteoporosis Patients with Multiple Fragility Fractures

Osteoporosis, whether accompanied by low bone resorption, microarchitectural deterioration, and fragility, leads to poor bone strength and increased risk of fracture. Decreased bone strength can also be due to external factors including bone formation and resorption (turnover), bone geometry (bone size and shape), and bone mineral density (BMD), including microarchitecture. Osteoporotic fractures lead to a significant decrease in quality of life with increased morbidity, mortality, and disability. More than 50 percent of postmenopausal white women will have an osteoporotic fracture, and only 33 percent of older women with a hip fracture are able to live independently.

The World Health Organization (WHO) has defined diagnostic thresholds for low bone density and osteoporosis based on measurements of bone density versus the young adult reference (T score). Postmenopausal women with osteoporosis have decreased bone loss and/or experienced associated bone loss.

Romosozumab is a drug used to treat osteoporosis. Romosozumab is an FDA-cleared humanized monoclonal antibody sclerostin inhibitor used to treat postmenopausal osteoporosis at high risk of fracture, including patients with a history of osteoporotic fractures, those who have failed or are tolerant to other available osteoporosis therapies, and those who have failed or are tolerant to other available osteoporosis therapies. It increases bone formation and impairs bone resorption.

For most postmenopausal women with osteoporosis, oral bisphosphonates are preferred as initial therapy because of their efficacy, affordability, and availability of long-term safety data. Treatment selection should be based on efficacy, safety, cost, freedom, and the individual's fracture risk.

In a 2019 meta-analysis of 107 studies evaluating pharmacological treatments in postmenopausal women with osteoporosis, alendronate, zoledronic acid, risdronate, denosumab, romosozumab, and estrogen with progestin were found to reduce the risk of hip fractures. Alendronate, zoledronic acid, rosedronate, ibandronate, denosumab, abaloparatide, teriparatide, parathyroid hormone (1.84), romosozumab, raloxifene, bazedoxifene, lasofoxifene, estrogen with progestin, tibolone, and calcitonin were found to reduce the risk of vertebral fractures. Anabolic agents (teriparatide, abaloparatide, romosozumab) and denosumab were found to have the highest relative efficacy, but few studies compared the drugs in terms of fracture prevention.