Table 3.

Comparison of bisphosphonates and denosumab [34].

Characteristic	Bisphosphonates	Denosumab
Target	Farnesyl pyrophosphate synthase inhibitors (nitrogen-containing bisphosphonates, e.g., zoledronic acid)	MoAb to RANKL
Site of action	Taken up by bone matrix	Systematically on osteoclast formation (blood and extracellular fluid)
Structure	Small molecule	MoAb
Effect on osteoclasts	Inhibits resorption by osteoclasts; inhibits osteoclast survival by inducing osteoclast apoptosis	Inhibits differentiation of precursors into osteoclasts; inhibits osteoclast function and survival
How given	Oral (alendronate) or intravenously (zoledronic acid and pamidronate)	Subcutaneous
Clearance from body	Initially cleared by kidney, and long-term via bone remodeling	Cleared via RES (half-life ~26 days)
Contraindications	• Pregnancy • Severe renal impairment (see dosing guidelines for individual bisphosphonates) • Hypocalcemia • Hypersensitivity to any component	• Pregnancy • Hypocalcemia • Hypersensitivity to any active component or excipient

Adapted from [34] with permission.

BMD bone mineral density, MoAb monoclonal antibody, RANKL receptor activator of nuclear factor kappa-B ligand, RES reticuloendothelial system.