. 2008 Spring;10(2):99–110.

Table 2.

Clinical Trials Evaluating Bisphosphonates for the Prevention of Bone Loss in Prostate Cancer Patients Without Bone Metastases Receiving ADT^*

Study/	Annualized Mean Percentage Change in BMD^‡
Regimen^†	LS	TH	FN	Comments and AEs
Greenspan 2007¹⁸
Alendronate	3.7^§	0.7^§	1.6^§	All patients received calcium and vitamin D supplementation 91% of men were osteopenic or osteoporotic at baseline AEs: no differences between groups
70 mg PO q 1 wk	(P < .001)^∥	(P < .031)^∥	(P = .008)^∥
× 12 mo (n = 56)
vs
placebo	− 1.4^§	0.7^§	− 0.7^§
(n = 56)	(P < .045)^∥	(P < .052)^∥	(P = .081)^∥
ADT duration
≥ 6 mo at entry
Smith 2001²²
Pamidronate	No change	No change	No change	All patients received calcium and vitamin D supplementation AEs: acute-phase reactions (ie, arthralgias, fever) more common in pamidronate group (24% vs 0%); no between-group differences for all other common AEs; no pamidronate-related renal failure or ONJ
60 mg IV q 12 wk
× 48 wk
(n = 21)
vs
control group	− 3.3	− 1.8	No change
(n = 22)	(P < .001)^¶	(P = .005)^¶	(P = .56)^¶
ADT initiation
at entry
Casey 2006²⁰
Zoledronic acid	3.3 (n = 68)	0.9 (n = 66)	1.8 (n = 66)	AEs: mild-to-moderate hot flashes, fatigue, nausea, vomiting (most common); no zoledronic acid-related renal failure or ONJ
4 mg IV q 3 mo
× 1 y
(n = 68)
vs
control group	− 1.5 (n = 71)	− 2.0 (n = 69)	− 1.7 (n = 72)
(n = 72)	(P = .0005)^¶	(P = .0012)^¶	(P = .0001)^¶
ADT initiation
at entry
Israeli 2006⁶
Zoledronic acid	4.7	1.6	NR	All patients received calcium and vitamin D supplementation AEs: flulike illness (15% vs 3%), fatigue (10% vs 6%), pyrexia (10% vs 0%) (most common); no between-group differences in grades 3 and 4 AEs; no zoledronic acid-related renal failure or ONJ
4 mg IV q 3 mo
× 48 wk
(n = 106)
vs
placebo	− 2	− 2.1	NR
(n = 109)	(P < .0001)^¶	(P < .0001)^¶
ADT duration
≤ 12 mo at entry
Ryan 2006¹⁹
Zoledronic acid	4.6	1.4	1.3	All patients received calcium and vitamin D supplementation Patients stratified according to ADT duration at study entry (< 6 mo vs 6−12 mo); no significant interaction between effect of zoledronic acid and duration of ADT AEs: nausea more common in zoledronic acid group (P = .028); no between-group differences for all other common AEs (ie, hot flashes, fatigue, bone pain, arthralgias); no zoledronic acid-related renal failure or ONJ
4 mg IV q 3 mo
× 1 y
(n = 50)
vs
placebo	− 2.1	− 2.4	− 2.4
(n = 51)	(P < .0001)^¶	(P < .0001)^¶	(P = .0004)^¶
ADT duration
≤ 12 mo at entry
Smith 2003²³
Zoledronic acid	5.6	1.1	1.2	All patients received calcium and vitamin D supplementation AEs: no between-group differences; no zoledronic acid-related renal failure or ONJ
4 mg IV q 3 mo
× 1 y
(n = 42)
vs
placebo	− 2.2	− 2.8	− 2.1
(n = 37)	(P < .001)^¶	(P < .001)^¶	(P < .001)^¶
ADT initiation
at entry
Michaelson 2007²¹
Zoledronic acid	4	0.7	2	AEs: no serious AEs related to treatment in either group
4 mg IV
× 1 dose in 12 mo
(n = 22)
vs
placebo	− 3.1	− 1.9	− 0.1
(n = 22)	(P < .001)^¶	(P = .004)^¶	(P = .06)^¶
ADT duration
≥ 12 mo at entry

ADT consisted of LHRH agonist, LHRH agonist ± antiandrogen, or orchidectomy.

^†

Patients (n) assessable for efficacy analysis.

^‡

BMD measured by dual-energy x-ray absorptiometry, unless otherwise specified.

^§

Interim, 12-month results.

^∥

P value provided for within-group comparison of baseline and 12-month BMD.

^¶

P value provided for between-group comparison.

ADT, androgen deprivation therapy; AE, adverse event; BMD, bone mineral density; FN, femoral neck; IV, intravenous; LHRH, luteinizing hormone-releasing hormone; LS, lumbar spine; NR, not reported; ONJ, osteonecrosis of the jaw; TH, total hip.