Table 1.

Treatment of MM bone disease (MBD).

Study	Study Design	Patient Papulation	Treatment Drug	Treatment Schedule	Patients, n	Median Time to First SRE, months	SREs Incidence, %	ONJ Incidence, %	Renal Toxicity, %
Berenson et al. [55]	Randomization	Stage III myeloma	Pamidronate vs. placebo	90 mg pamidronate 4 h IV infusion every 4 weeks for 9 cycles	196 vs. 181	Significantly less in placebo group (p = 0.01)	24 vs. 41 (p < 0.01)	NR	NR
Rosen et al. [56]	Phase III, double-blind, comparative trial	Durie-Salmon Stage III myeloma	ZA vs. pamidronate	4 or 8 mg ZA IV or 15 min or 90 mg pamidronate IV 2 h every 3–4 w for 12 months	129 vs. 65	12.5 vs. 9.4	NR	NR	NR
Gimsing et al. [57]	Double-blind, randomized, phase 3 trial	MM patients starting antimyeloma treatment	Pamidronate	30 vs. 90 mg of pamidronate	252 vs. 252	10.2 vs. 9.2 (p = 0.63)	33.7 vs. 35.2	0.8 vs. 3.2	NR
Morgan et al. [58]	Computer-generated randomization	Newly diagnosed MM	ZA vs. clodronate	4 mg of ZA IV every 3–4 weeks or 1600 mg of clodronic acid orally daily	981 vs. 979	NR	27 vs. 35 (p = 0.0004)	4 vs. 1	Similar for the two treatment groups (p = 0.55)
Himelstein et al. [59]	Randomized, open-label	MM with at least one site of bone involvement	ZA	ZA every 12 vs. every 4 weeks	139 vs. 139	NR	55 vs. 60	NR	NR
Raje et al. [60]	Double-blind, double-dummy, randomized, controlled, phase 3	MM with at least one lytic bone lesion	Denosumab vs. ZA	120 mg of denosumab SC plus placebo IV or ZA 4 mg IV plus placebo SC every 4 weeks	859 vs. 859	22.8 vs. 24 (p = 0.01)	43.8 vs. 44.6	4.1 vs. 2.8	10 vs. 17.1

BPs, bisphosphonates; MM, multiple myeloma; NR, no report; RANKL, receptor activator of nuclear factor-kappa B ligand; SREs, skeletal-related events; ZA, zoledronic acid; IV, intravenous; SC, subcutaneous.