Denosumab

Abstract

Denosumab (Prolia®) is a human recombinant monoclonal antibody that is approved for the treatment of postmenopausal osteoporosis in women at high or increased risk of fracture in the US, the EU and several other countries. Denosumab has a novel mechanism of action; it binds to receptor activator of nuclear factor κB ligand and inhibits bone resorption by inhibiting osteoclast formation, function and survival. In postmenopausal women with osteoporosis, denosumab reduced the risk of vertebral, nonvertebral and hip fractures compared with placebo over 3 years in the large, phase III FREEDOM study. In postmenopausal women with low bone mineral density (BMD) or osteoporosis, treatment with denosumab increased BMD and decreased markers of bone turnover more than alendronate in those who were essentially treatment-naive in the 1-year DECIDE study and also in the 1-year STAND study, in which women were switched from alendronate to denosumab or continued alendronate treatment. Denosumab was generally well tolerated in clinical trials, although long-term effects of very low bone turnover remain to be established. Denosumab is administered once every 6 months via subcutaneous injection, which may be a preferred method of administration and may improve adherence to treatment compared with other osteoporosis treatments. Denosumab is a valuable new option for the treatment of postmenopausal osteoporosis in women at increased or high risk of fractures, and may be useful as a first-line treatment in women at increased risk of fractures who are unable to take other osteoporosis treatments.

Osteoporosis in Chronic Obstructive Pulmonary Disease

“…Denosumab decreases bone resorption by binding to the RANKL and inhibiting the RANKL/RANK interaction on the surface of osteoclasts and osteoclast precursors. It results in inhibition of osteoclast differentiation, activity, and survival 196,211. Denosumab is administered at a dosage of 60 mg as a single subcutaneous injection into the thigh, abdomen, or upper arm once every six months for up to three years.…”

Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy

“…However, patients undergoing curettage often have recurrent disease or significant morbidity. Denosumab is a human anti-RANKL monoclonal antibody that inhibits RANKL function and therefore its osteoclast activity, and causes the repression of osteoclast recruitment, maturation and bone resorption [16,18]. Denosumab is a Food and Drug Administration (FDA)-approved drug for osteoporosis and skeletal-related events in patients with bone metastases.…”

“…Denosumab, a monoclonal antibody specifically binding RANK-ligand, inhibits bone resorption and, therefore, [16-18] is used in the treatment of osteoporosis, skeletal complications of metastatic disease, and more recently in the treatment of giant cell tumors of bone, with a high rate of clinical success [19]. To date, we are aware of only one publication presenting the application of denosumab in two cases of spinal ABCs [20].…”

Emerging therapies for the treatment of osteoporosis

“…[9] It is a human monoclonal antibody that binds receptor-activator of nuclear factor kappa B ligand (RANKL) and inhibits its action, thus inhibiting the activation of osteoclasts. [10] The first effective anabolic agent teriparatide [parathyroid hormone (PTH) 1-34] has been used clinically. However, high cost and daily subcutaneous injections are its major limitations.…”