Denosumab and zoledronic acid for patients with postmenopausal osteoporosis

Osteoporosis is characterized by low bone mineral density (BMD), deterioration of bone microarchitecture, and a consequent increase in bone fragility and risk of fracture.1 Osteoporosis is most prevalent in postmenopausal women over 50 as estrogen levels decline. BMD is determined by the delicate balance of bone resorption (osteoclast activity) and bone formation (osteoblast activity), with osteoporosis occurring when bone resorption exceeds bone formation. There are several therapies available for the prevention and management of postmenopausal osteoporosis. Nitrogen-containing bisphosphonates are highly potent inhibitors of osteoclastic bone resorption and have proven to be effective at reducing vertebral fracture risk. Bisphosphonates such as alendronate and risedronate have been used for treatment of postmenopausal osteoporosis for many years and are taken orally with a daily dosage regimen. Zoledronic acid (Aclasta) is a newer bisphosphonate administered intravenously once-yearly. Recent advancements in the field of bone biology have led to the development of a new class of postmenopausal osteoporosis therapy. Denosumab (Prolia) is a human recombinant monoclonal antibody that binds to RANKL, a protein that acts as an essential mediator of osteoclast formation, thereby inhibiting osteoclast formation, function, and survival. Denosumab is administered subcutaneously at six-month intervals. Due to the complex dosing regimen of oral bisphosphonates, compliance rates may be low, making therapies such as zoledronic acid and denosumab attractive treatment options. Both denosumab and zoledronic acid have been approved for listing within Canada's publicly funded drug plans for women aged 75 years or older who have had a previous fragility fracture and a BMD T-score ? -2.5, or more than 2.5 standard deviations below the mean peak bone mass.11,12 In addition, the patient must be contraindicated for bisphosphonate therapy due to hypersensitivity or abnormality of the esophagus. Despite these criteria, there is limited e