Table 2.

Comparison of major characteristics of bisphosphonates (alendronate and zoledronic acid) versus denosumab.

	Bisphosphonates		Denosumab
	Alendronate	Zoledronic Acid
Efficacy	Vertebral and hip fracture reduction: ~ 50% (STAND and DECIDE trials comparing alendronate to denosumab showed greater BMD gains with denosumab at 12 months)	Vertebral fracture reduction: 70%. Hip fracture reduction: 41%. (Ongoing trial comparing efficacy of ZA vs denosumab)	Vertebral fracture reduction: 68%. Hip fracture reduction: 40%
Pivotal Trial	FIT [54]	HORIZON-PFT [55]	FREEDOM [20]
Safety	Risk for AFF and ONJ with prolonged exposure	Risk for AFF and ONJ with exposure to high doses and/or prolonged exposure	Risk for AFF and ONJ. Increased risk of serious skin infections
Administration	Oral, patient administered weekly	Intravenous administration once a year. Requires IV catheter placement	Subcutaneous injection every 6 months. Can be administered in office
Pharmacokinetics	Poor oral bioavailability. Non-uniform drug accumulation within bone matrix, with elimination half-life of ~ 10 years	Non-uniform drug accumulation within bone matrix, with prolonged suppression of bone turnover	No bone accumulation, effects reversible by 9 – 12 months post-dose
Pharmacodynamics	Slow suppression of bone turnover	More rapid suppression of bone turnover than oral (within days)	Rapid suppression of bone turnover (within 12 h)
Use in renal impairment	Contraindicated for GFR < 35	Contraindicated for GFR < 35	No restriction for use in renal impairment, though close monitoring of serum calcium in patients with GFR < 30 recommended
Relative cost	Low (generic available)	Moderate/High (generic available)	High

AFF: Atypical femur fractures; GFR: Glomerular filtration rate; ONJ: Osteonecrosis of the jaw.