Review Question - QID 214088

Denosumab is an antibody-based therapy that targets receptor activator of nuclear factor kappa-Β ligand (RANKL) and reduces osteoclast function. It is associated with jaw osteonecrosis.

Denosumab is an antibody-based therapy used in the treatment of osteoporosis and is used in the treatment of cancers such as Giant Cell Tumors of bone. It functions by binding to RANKL, thereby indirectly inhibiting the activation of osteoclasts. The result is increased bone mineralization. The function of denosumab is similar to OPG. Benefits of therapy include reduced vertebral fractures by 68%, hip fractures by 40%, nonvertebral fractures by 20%.

Chawla et al. published results from a phase-2 study on the safety of denosumab in skeletally mature patients with Giant Cell Tumor of Bone (GCTB). Complications identified included jaw osteonecrosis (1%), hypocalcemia (15%), hypophosphatemia (3%), and back and extremity pain (3%). Severe adverse events were identified in 9% of patients. They recommend the use of denosumab for the treatment of GCTB.

Kyrgidis et al. systematically reviewed risk factors for the development of osteonecrosis among cancer patients. They found that denosumab is not different compared to zoledronic acid for the development of osteonecrosis of the jaw. However, prescribing clodronate or pamidronate may reduce the risk compared to zoledronic acid and denosumab. The greatest risk factor however was dental extraction for osteonecrosis in cancer patients.

Branstetter et al. analyzed the histologic effect of denosumab on GCTB. They found a 90% decrease or greater of all tumor giant cells and a reduction in tumor stromal cells in all patients. 65% of patients had increased fibro-osseous and/or new woven bone formation. They conclude that denosumab has potential as a treatment of GCTB.

Illustration A demonstrates the RANK-RANKL-OPG pathway and the interaction of denosumab with RANKL preventing osteoclast activation.

Incorrect Answers:
Answer 2: Teriparatide is a recombinant human parathyroid hormone and can be used to treat jaw osteonecrosis.
Answer 3: Pamidronate, a bisphosphonate, is an anti-osteoclastic medication with an association with jaw osteonecrosis, however, it is not an antibody-based therapy.
Answer 4: Salmon calcitonin can be used to increase bone mineral density, however, is not associated with jaw osteonecrosis.
Answer 5: Conjugated Estrogen-progestin hormone replacement can be used to treat osteoporosis and increase bone mineral density, however, is not associated with jaw osteonecrosis.