Table 1.

Characteristic	Diel et al.[2], Annals of Oncology, 19:2007		Powles et al.[1], Breast Cancer Research, 8:R13		Gnant et al.[3], [4], The Lancet, 12:631		Coleman et al.[5], New Eng J of Med, 365:1396		Kristensen et al.[6], Acta Oncologica, 47:740		Saarto et al.[9], Acta Oncologica, 43:650
Bisphosphonate used	Clodronate	Placebo	Clodronate	Placebo	Zoledronic acid	Placebo	Zoledronic acid	Placebo	Pamidronate	Placebo	Clodronate	Placebo
Dosing schedule and route	1600 mg orally daily for 2 years	No	1600 mg orally daily for 2 years	Yes	4 mg IV every 6 month for 3 years	No	4 mg IV every 3–4 weeks for 6 cycles then every 3–6 months for 5 years	No	150 mg orally twice daily for 4 yrs	No	1,600 mg orally daily for 3 yrs	No
Use of anti-estrogens	47% received tamoxifen	45% received tamoxifen	80% of cohort received tamoxifen		100% of cohort received either Tamoxifen or anastrozole		78.3% on endocrine or endocrine+chemotherapy	78.6% on endocrine or endocrine+chemotherapy	Endocrine therapy excluded	Endocrine therapy excluded	100% of cohort received tamoxifen or toremifene
Cohort size	157	145	530	539	900	903	1681	1678	460	493	139	143
Mean age	NR	NR	52.8	52.7	44.5	44.5	NR	NR	b	b
52
T-stage
T1	38%	37%	26%	26%	75.7%	76.7%	32.2%	31.2%	41%	44%	51%	46%
T2	45%	46%	57%	57%	21.2%	21.7%	50.6%	51.7%	50%	50%	42%	46%
T3 or greater	17%	16%	9%	10%			17.0%	17.1%	7%	5%	7%	6%
Unknown			8%	7%	2.1%	2.6%	0.2%	0.1%	2%	1%	0	3
Lymph node positive	51%	54%	37%	38%	30.5%	30.5%	97.8%	97.7%	75%	75%	99%	99%
Menopausal status
Pre-menopausal	36%	39%	50%	49%	NR	NR	44.7%	44.8%	67%	66%	48%	57%
Post-menopausal	64%	61%	50%	51%	NR	NR			33%	34%	52%	43%
Post-menopausal <5yrs							14.7%	14.5%
Post-menopausal >5yrs							30.9%	31.1%
Unknown							9.8%	9.5%	0%	0.2%
ER status
Positive	75%	71%	46%	45%	94.6%	93.3%	78.5%	78.4%	13.5%	17.2%	61%	68%
Negative	25%a	29%a	26%	25%	3.3%	3.9%	20.8%	21.1%	60.4%	52.9%	35%	23%
Unknown			28%	30%	2.1%	2.6%	0.8%	0.4%	26.1%	29.8%	4%	9%
PR status
Positive	62%	63%	21%	22%	89.9%	89.5%	NR	NR	11%	11%	50%	60%
Negative	38%a	67%a	15%	14%	7.6%	8.3%	NR	NR	29%	28%	45%	31%
Unknown			64%	65%	2.5%	2.2%	NR	NR	60%	61%	5%	9%
Pretreatment evidence of bone metastasis	Yes	Yes	No	No	No	No	No	No	No	No	No	No
	Positive		Positive		Positive		Negative		Negative		Negative
	–Increased OS at 8.5 years post-treatment. –No difference in DFS or incidence of metastases at 8.5 years post-treatment.		–Decreased incidence of bone metastases at 5 years post-treatment. –Trend for better OS at 5 years post-treatment.		–Reduced incidence of DFS events at 5 years post-treatment. –No difference in OS.		–No differences in OS, DFS at 5 years post-treatment.		–no differences in OS, DFS or incidence of metastases at 5 years post-treatment		–no significant differences in OS or frequency of metastases at 10 years post-treatment –decreased DFS and increased extraskeletal metastases in clodronate group at 10 years post-treatment

NR—Not Reported.

^aNot originally reported therefore may contain negative and unknown categories.

^bMean age for treatment groups was not reported however was stratified across 4 groups originally; for pamidronate and control cohorts there were 61.3% and 63.1% of patients younger than age 50 respectively.