Review Question - QID 5769

Prolia, or denosumab, is a newly approved drug used to treat osteoporosis and has a mechanism of action similar to osteoprotegerin (inhibits binding of RANKL to RANK).

RANKL (Receptor activator of nuclear factor kappa-B ligand) is a key molecule for osteoclast differentiation and activation. Inhibition of RANKL activity with anti-RANKL antibody reduces osteoclastogenesis, resulting in inhibition of bone resorption.

Capozzi et al. author a review article on denosumab. They state the medication confers improved bone mineral density and prevents new fragility fractures similar to alendronate. However, denosumab presents less risk of atypical femoral fractures and osteonecrosis of the jaw.

Yasuda et al. present a review that details the creation of three elegant animal models to mimic metabolic bone disease and how the animal models can create a template to help cure human metabolic bone disease. These enable modeling of osteoporosis, hypercalcemia, and osteopetrosis by treating normal mice with soluble RANKL (sRANKL), adenovirus expressing sRANKL, and anti-mouse RANKL neutralizing antibody, respectively. They report that these animal models can be established in about 14 days using normal mice.

Illustration A demonstrates the mechanism of action of bisphosphonates and denosumab.

Incorrect Answers:
1: Romosozumab is the first humanized anti-sclerostin monoclonal antibody that has been demonstrated to increase bone formation.
2: Zoledronic acid (Reclast) is a nitrogen containing bisphosphonates that inhibits osteoclast resorption by inhibiting the enzyme farnesyl diphosphate synthase.
4: Teriparatide (Forteo) comprises the first 34 amino acids of the 84 amino acid parathyroid hormone (PTH) and can reproduce the primary effects of PTH by activating adenyl cyclase.
5: Blosozumab is an investigational monoclonal anti-sclerostin antibody showing osteoanabolic properties with the potential to improve clinical outcomes in patients with osteoporosis.