Table 1.

Bone-targeted agents approved by the US Food and Drug Administration for use in mCRPC

	Zoledronic acid	Denosumab	Strontium-89	Samarium-153	Radium-223
Mechanism of action	Hydroxyapatite binder	RANK-L inhibitor;inhibits osteoclasts	DNA damage via beta-emission	DNA damage via beta and gamma-emission	DNA damage via alpha emission
Adverse effectsof interest	ONJ, renal, flu-like symptoms, hypocalcemia	Hypocalcemia, ONJ	Hematologic	Hematologic	GI
Efficacy	Significant decrease and delay in SREs and bone pain	Significant delay in SREs	Significant decrease in bone pain	Significant decrease in bone pain	Significant increase in OS, SREs
Approval	Approved by FDA in 2002	Approved by FDA in 2010	Approved by FDA in 1993	Approved by FDA in 1997	Approved by FDA in 2013
Route	IV	SC	IV	IV	IV
Dose	4 mg IV every 3–4 weeks	120 mg SC every 4 weeks	1.5–2.2 MBq/kg, 40–60 μCi/kg body weight	1.0 mCi/kg IV	50 kBq/kg IV every 4 weeks
Indication	Prevention of SREs in mCRPC with bone metastases	Prevention of SREs in mCRPC with bone metastases	Reduction of pain in mCRPC with bone metastases	Reduction of pain in mCRPC with bone metastases	mCRPC with bone metastases in the absence of visceral metastases

Abbreviations: IV, intravenous; SC, subcutaneous; FDA, US Food and Drug Administration; ONJ, osteonecrosis of the jaw; GI, gastrointestinal; SREs, skeletal-related events; OS, overall survival; mCRPC, metastatic castration-resistant prostate cancer.