Table 2.

Major efficacy outcomes

	Intervention		Control		Effect size (95% CI)	I2	p-value
	Events/ n	%	Events/ n	%
SRE INCIDENCE					RR for reduced	SREs
Zoledronic acid vs. placebo
Kritikosc [34]	10/26	38	13/26	50	0.77 (0.41-1.4)
Zoledronic acid + chemotherapy vs. chemotherapy
Zarogoulidis[31, 35]	4/87	5	3/57	5	0.87 (0.20-3.8)
Rosen [7] [6] [27]	124/259	48	74/123	60	0.80 (0.66-0.96)
Hirai [36]	15/50	30	20/50	39	0.75 (0.44-1.3)
Scagliottid [37-39]	5/226	2	3/211	1	0.74 (0.39-1.4)
Pooled M-H	148/622	24	100/441	23	0.81(0.67-0.97)	0	0.02
Zoledronic acid vs. ibandronate
Francini [25]	5/26	19	7/27	30	0.74 (0.27-2.0)
PAIN CONTROL					RR for better pain control
Clodronate vs. radioisotope
Su [30]	23/28	82	16/19	84	0.98 (0.75-1.3)
Li [28]	8/15	53	9/16	56	0.95 (0.50-1.8)
Pooled M-H	31/43	72	25/35	71	0.97 (0.74-1.3)	0	0.80
Bisphosphonate alone (clodronate or pamidronate) vs. other modalities a
Su [30]	23/28	82	16/19	84	0.98 (0.75-1.3)
Li [28]	8/15	53	64/102	63	0.85 (0.52-1.4)
Zhang [29]	11/13	85	33/40	83	1.0 (0.78-1.4)
Pooled M-H	42/56	75	113/161	70	0.95 (0.78-1.2)	0	0.62
Bisphosphonate combined (clodronate or pamidronate) vs. other modalities b
Su [30]	18/20	90	16/19	84	1.1 (0.84-1.4)
Li [28]	18/24	75	64/102	63	1.2 (0.91-1.6)
Zhang [29]	24/27	89	33/40	83	1.1 (0.89-1.3)
Zheng [32]	41/46	89	16/25	64	1.4 (1.0-1.9)
Pooled M-H	101/117	86	129/186	69	1.2 (1.0-1.4)	0	0.01
Bisphosphonate (combined) vs. bisphosphonate (alone)
Su [30]	18 /20	90	23/28	82	1.1 (0.87-1.4)
Li [28]	18/24	75	8/15	53	1.4 (0.83-2.4)
Zhang [29]	24/27	89	11/13	85	1.1 (0.80-1.4)
Pooled M-H	60/71	85	48/56	86	1.2 (0.96-1.4)	0	0.14
Zoledronic acid vs. ibandronate
Francini [25]	11/18	61	9/16	56	1.1 (0.62-1.9)
Ibandronate vs. clodronate
Guo [26]	36/46	78	31/42	74	1.1(0.88-1.4)
SURVIVAL					Mean difference (days)
Zoledronic acid + chemotherapy vs. chemotherapy	n	days e	n	days e
Zarogoulidis [31, 35]	87	578	57	384	194.0 (80.9-307.2)
Rosen [7][6][27]	259	187	123	157	30.0 (−65.6-125.6)
Pandyaf [33]	100	266	52	206	60.0 (−108.2-228.2)
Hirai [36]	50	312	50	291	21.0 (−61.7-103.7)
Pooled I-V	496		282		72.0 (−8.9-152.9)	55	0.08
TIME TO DISEASE PROGRESSION					Mean difference (days)
Zoledronic acid + chemotherapy vs. chemotherapy	n	days e	n	days e
Zarogoulidis [31, 35]	87	265	144	150	115.0 (47.9-182.1)
Pandya [33]	100	132	150	131	0.00 (−0.04-0.04)
Hirai [36]	50	81	100	78	3.0 (−39.4-45.4)
Scagliottid [37-39]	226	270	437	339	−69.0 (−109.8- −28.2)
Pooled I-V	463		831		5.2 (−41.5-51.9)	87	0.83

n= sample size; SRE, Skeletal Related Events; M-H, Mantel-Haenzel; I-V, Inverse Variance;

^aOther modalities include: chemotherapy, radiation and /or radioisotopes;

^bCombined: bisphosphonates with chemotherapy, radiation and/or radioisotopes;

^cAssuming total number of patients equally distributed between groups;

^dAll patients had completed primary treatment (surgery, chemotherapy or radiotherapy);

^eMedian survival time in days; fDid not include patients with bone metastases.