Table 1.
Summary of RCTs of bisphosphonates in men receiving ADT
| Study | Study population | N | Study groups | Follow-up | Key findings |
|---|---|---|---|---|---|
| Smith et al. 2001 [72] | advanced or recurrent PCa and no bone metastases | 47 | ADT only vs ADT + Pam | 48 weeks |
-ADT only arm: decrease in BMD of LS (− 3.3%), trochanter (− 2.1%), and total hip (− 1.8%), p < 0.001 for all. -No significant change in mean BMD at any skeletal site in ADT + Pam arm. |
| Michaelson et al. 2007 [73] | Non-metastatic PCa | 40 | ADT + placebo vs ADT + Zol | 12 months | -Increase in BMD in Zol arm compared to placebo in both LS (4% vs − 3.1%, p < 0.001) and total hip (0.7% vs − 1.9%, p = 0.004), with suppression of serum NTP levels. |
| Bhoopalam et al. 2009 [74] | Non-metastatic PCa on ADT for ≤ 1 year or > 1 year | 93 | ADT + placebo vs ADT + Zol | 12 months | -Increase in LS BMD in Zol arm seen in both groups (ADT ≤ 1 year: 5.95% in Zol arm vs − 3.23% in placebo arm [p = 0.0044], ADT > 1 year: 6.08% in Zol arm vs 1.57% in placebo arm [p = 0.0005]), including patients with multiple risk factors for osteoporosis. |
| Smith et al. 2003 [75] | Non-metastatic PCa | 106 | ADT + placebo vs ADT + Zol | 12 months | -Increase in LS BMD in Zol arm compared to placebo arm (5.6% vs − 2.2%, p < 0.001) |
| Magno et al. 2005 [76] | Locally advanced PCa with osteoporosis at baseline | 60 | MAB vs MAB + Ner vs Bicalutamide vs Bicalutamide + Ner | 12 months |
-MAB only arm: significant loss in BMD of LS (− 4.9%, p = 0.002) and total hip (− 1.9%, p = 0.004). -MAB + Ner arm: no significant BMD change. -Bicalutamide arm: no significant BMD change. -Bicalutamide + Ner arm: increase in LS (+ 2.5%) and total hip (+ 1.6%) BMD—both p < 0.05. |
| Ryan et al. 2006 [77] | PCa without bone metastases, on ADT for ≤ 12 months | 120 | ADT + placebo vs ADT + Zol | 12 months | -Zol arm: increase in femoral neck, total hip, and LS BMD by 3.6% (p = 0.0004), 3.8% (p < 0.0001), and 6.7% (p < 0.0001) respectively. |
| Ryan et al. 2007 [78] | PCa with or without bone metastases, on ADT for ≤ 12 months | 42 | ADT + placebo vs ADT + Zol | 12 months | -After excluding BMD data from sites of known metastases, patients in the Zol arm had a relative increase in BMD compared to placebo, at the femoral neck (4.2%, p = 0.001) and LS (7.1%, p < 0.001). |
| Klotz et al. 2013 [79] | Non-metastatic PCa | 186 | ADT + placebo vs ADT + Alen | 12 months | -Increase in LS BMD in Alen arm compared to placebo (1.7% vs − 1.9%, p < 0.0001). |
| Choo et al. 2013 [80] | Non-metastatic PCa, undergoing RT + 2–3 years of ADT | 104 | ADT + placebo vs ADT + Ris | 24 months | -Non-significant decrease in BMD loss in Ris arm at 2 years compared to placebo. |
| Greenspan et al. 2007/2008 [81, 82] | Non-metastatic PCa | 112 | ADT + placebo vs ADT + Alen, crossover at 12 months | 24 months |
-ADT + Alen arm: increase in BMD of LS by 3.7% (p ≤ 0.001) and femoral neck by 1.6% (p = 0.008) at 1 year. -At crossover, those continuing Alen had additional BMD gains at both LS and hip, both p < 0.01; those who switched to placebo maintained BMD at LS and hip but had BMD loss at radius - p < 0.01. |
| Rodrigues et al. 2007 [83] | PCa patients who had prostatectomy and rising PSA | 94 | Placebo vs Clo vs Zol | 36 months |
Placebo arm: mean BMD loss of − 1.82. Clo arm: mean BMD loss − 0.72. Zol arm: mean BMD loss − 0.82. |
| Israeli et al. 2007 [84] | Locally advanced PCa during first year of ADT | 213 | ADT + placebo vs ADT + Zol | 12 months | -Mean BMD percentage differences were 6.7% for LS and 3.7% for total hip (p < 0.0001 for both). |
| Kachnic et al. 2013 [85] | high grade and/or locally advanced, non-metastatic PCa receiving ADT + RT | 96 | Zol vs observation | 36 months | Increase in BMD in LS (6% vs − 5%, p < 0.0001), left total hip (1% vs − 8%, p = 0.0002), and left femoral neck (3% vs − 8%, p = 0.0007) in Zol arm compared to observation arm. |
| Denham et al. 2014 [86] | Locally advanced PCa | 1071 | ADT for 6 months before RT ± additional 12 months ADT ± 18 months Zol | 3 years |
-Incidence of vertebral fractures was not increased by 18 months compared to 6 months ADT and was not affected by addition of Zol. -Incidence of non-vertebral fractures was significantly related to ADT duration (p = 0.013) but not to the addition of Zol. |
| Taxel et al. 2010 [87] | Locally advanced PCa | 40 | Placebo vs weekly risedronate | 6 months |
-The Ris group had no change in femoral neck or total hip BMD, while the placebo group decreased by 2% (p = 0.004) and 2.2% (p = 0.001), respectively. -The Ris group had an increase in LS BMD of 1.7% from baseline (p = 0.04), with no change in the placebo group. |
| Casey et al. 2010 [88] | Non-metastatic PCa | 200 | ADT + Zol for 24 months vs ADT alone for 24 months vs ADT alone for 12 months crossing over to ADT + Zol for 12 months. | 24 months |
-Significant BMD differences between patients receiving ADT alone and ADT + Zol were observed at the 12 months (p < or = 0.01 for each site) and 24 months (p < 0.05 for each site). -Initiating Zol after 12 months of ADT alone provided BMD benefits but was insufficient to completely restore BMD. |
| Kapoor et al. 2011 [89] | Non-metastatic PCa with osteoporosis or osteopenia | 41 | ADT + placebo vs ADT + Zol | 12 months | -The change in vertebral BMD in the Zol group (+ 7.93%) was significantly greater (p < 0.05) than the change in the placebo group (+ 0.82%). |
RCT randomized controlled trial, PCa prostate cancer, Pam pamidronate, Zol zoledronate, BMD bone mineral density, LS lumbar spine, PF proximal femur, NTP N-telopeptide (a bone turnover marker), MAB maximum androgen blockade, Ner neridronate, Alen alendronate, RT radiotherapy, Ris risedronate, Clo clodronate