Table 2.
Main characteristics of the articles included in the present systematic review.
| Authors | Journal | Publication year | Nationality | Population | Age (years) | Hormonal therapy | Intervention | Comparator | Outcomes | Follow-up |
|---|---|---|---|---|---|---|---|---|---|---|
| Alendronate | ||||||||||
| Rhee et al. (40) | Endocr J | 2013 | Korea | n: 98 IG: 49 CG: 49 |
IG: 57.1 ± 1.0 CG: 58.5 ± 1.1 |
Anastrozole or letrozole | Alendronate 5 mg + calcitriol 0.5 µg daily | Placebo |
- LS BMD
- TH BMD - Bone turnover biomarkers - safety |
24 weeks |
| Denosumab | ||||||||||
| Ellis et al. (49) (NCT00089661) |
J Clin Oncol. | 2008 | International Collaboration | n: 252 IG: 127 CG: 125 |
IG: 59.2 ± 8.9 CG: 59.7 ± 9.7 |
Anastrozole, letrozole, or exemestane | Denosumab 60 mg sc every 6 months | Placebo |
- LS BMD
- TH BMD - FN BMD - Radius BMD - Bone turnover biomarkers - Vertebral and nonvertebral fractures - Safety - Overall survival |
24 months |
| Gnant et al. (34) (ABCSG-18) |
The Lancet | 2015 | International Collaboration | n: 3420 IG: 1711 CG: 1709 |
64 (38 – 91) | Anastrozole, letrozole, or exemestane | Denosumab 60 mg sc every 6 months | Placebo |
- Time to first fracture
- Vertebral and nonvertebral fractures - LS BMD - TH BMD - FN BMD - Disease-free survival - Bone-metastasis free survival - Overall survival |
36 months |
| Gnant et al. (35) (ABCSG-18) |
Lancet Oncol. | 2019 | International Collaboration | n: 3420 IG: 1711 CG: 1709 |
64 (38 – 91) | Anastrozole, letrozole, or exemestane | Denosumab 60 mg sc every 6 months | Placebo |
- Time to first fracture
- Vertebral and nonvertebral fractures - LS BMD - TH BMD - FN BMD - Disease-free survival - Bone-metastasis free survival - Overall survival |
96 months |
| Ibandronate | ||||||||||
| Lester et al. (41) (ARIBON) |
Clinical Cancer Research | 2008 | UK | n: 50 IG: 25 CG: 25 |
IG: 67.8 (58.9-73.4) CG: 67.5 (63.6-71.0) |
Anastrozole | Ibandronate 150 mg every month | Placebo |
- LS BMD
- TH BMD - Bone turnover biomarkers - Safety |
24 months |
| Lester et al. (42) (ARIBON) |
Journal of Bone Oncology | 2012 | UK | n: 50 IG: 25 CG: 25 |
IG: 67.8 (58.9-73.4) CG: 67.5 (63.6-71.0) |
Anastrozole | Ibandronate 150 mg every month for 24 months | Ibandronate 150 mg every month started after 24 months |
- LS BMD
- TH BMD |
60 months |
| Livi et al. (29) (BONADIUV) |
European Journal of Cancer | 2019 | Italy | n: 144 IG: 89 CG: 82 |
IG: 60.5 (54.3-67.0) CG: 59.6 (53.9-68.0) |
Anastrozole, letrozole, or exemestane | Ibandronate 150 mg every month | Placebo |
- LS BMD
- TH BMD - Safety - Disease recurrence - Overall survival |
24 months |
| Risedronate | ||||||||||
| Greenspan et al. (38) (NCT00485953) |
Osteoporosis International | 2015 | USA | n: 109 IG: 55 CG: 54 |
IG: 65 ± 1 CG: 64 ± 1 |
Anastrozole, letrozole, or exemestane | Risedronate 35 mg every week | Placebo | - LS BMD
- TH BMD - FN BMD - TB BMD - Bone turnover biomarkers |
24 months |
| Markopoulos et al. (46) (ARBI) |
Breast Cancer Research | 2010 | Greece | n: 70 IG: 37 CG: 33 |
IG: 62.6 ± 8.5 CG: 64.5 ± 9.2 |
Anastrozole | Risedronate 35 mg every week | No treatment | - LS BMD
- TH BMD |
24 months |
| Van Poznak et al. (45) (SABRE) |
Journal of Clinical Oncology | 2010 | International Collaboration | n: 154 IG: 77 CG: 77 |
IG: 63.8 CG: 64.8 |
Anastrozole | Risedronate 35 mg every week | Placebo |
- LS BMD
- TH BMD - Bone turnover biomarkers |
24 months |
| Zoledronate | ||||||||||
| Brufsky et al. (52) | The Oncologist | 2008 | International Collaboration | n: 1667 IG: 833 CG: 834 |
IG: 58 (35-87) CG: 59 (37-89) |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - Bone turnover biomarkers - Disease recurrence - Safety |
12 months |
| Brufsky et al. (48) (Z-FAST) |
Clinical Breast Cancer | 2009 | International Collaboration | n: 602 IG: 301 CG: 301 |
IG: 61.5 ± 9.33 CG: 61 ± 8.92 |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months | - LS BMD
- TH BMD - Bone turnover biomarkers - Vertebral and nonvertebral fractures - Disease recurrence |
36 months |
| Brufsky et al. (50) (Z-FAST) |
Cancer | 2012 | International Collaboration | n: 602 IG: 301 CG: 301 |
IG: 61.5 ± 9.33 CG: 61 ± 8.92 |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months | - LS BMD
- TH BMD - Bone turnover biomarkers - Vertebral and nonvertebral fractures - Disease recurrence |
60 months |
| Bundred et al. (24) (ZO-FAST) |
Cancer | 2008 | International Collaboration | n: 1065 IG: 532 CG: 533 |
IG: 57 (36-87) CG: 58 (37-81) |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - Bone turnover biomarkers - Safety |
12 months |
| Eidtmann et al. (47) (ZO-FAST) |
Ann Oncol. | 2010 | International Collaboration | n: 1065 IG: 532 CG: 533 |
IG: 57 (36-87) CG: 58 (37-81) |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - Vertebral and nonvertebral fractures - Disease recurrence - Overall survival - Safety |
36 months |
| Coleman et al. (39) (ZO-FAST) |
Ann Oncol. | 2013 | International Collaboration | n: 1065 IG: 532 CG: 533 |
IG: 57 (36-87) CG: 58 (37-81) |
Letrozole | Immediate zoledronate 4 mg ev every 6 months | Delayed zoledronate 4 mg ev every 6 months |
- LS BMD
- TH BMD - Vertebral and nonvertebral fractures - disease recurrence - overall survival - safety |
60 months |
| Llombart et al. (44) (E-ZO-FAST) |
Clinical Breast Cancer | 2012 | International Collaboration | n: 522 IG: 252 CG: 270 |
IG: 58 (40-81) CG: 58 (44-78) |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - Vertebral and nonvertebral fractures - disease recurrence - safety |
12 months |
| Safra et al. (51) (NCT00376740) |
Oncology | 2011 | Israel | n: 86 IG: 47 CG: 39 |
IG: 59.08 ± 8.5 CG: 61.18 ± 9.2 |
Letrozole following Tamoxifen | Immediate zoledronate 4 mg iv every 6 months | No treatment |
- LS BMD
- TH BMD - Vertebral and nonvertebral fractures - Disease recurrence - Overall survival |
48 months |
| Takahashi et al. (43) | Breast Cancer Research and Treatment | 2012 | Japan | n: 194 IG: 97 CG: 97 |
IG: 61.47 ± 6.80 CG: 60.45 ± 6.56 |
Letrozole | Immediate zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - Bone turnover biomarkers - Vertebral and nonvertebral fractures |
12 months |
| Hines et al. (36) N03CC (Alliance) trial) |
Breast Cancer Res Treat. | 2009 | USA | n: 551 IG: 274 CG: 277 |
IG: 59.2 ± 11.20 CG: 59.6 ± 10.25 |
Letrozole | Upfront zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - FN BMD - Vertebral and nonvertebral fractures - toxicity |
24 months |
| Wagner-Johnston et al. (37) (N03CC (Alliance) trial) |
Cancer | 2015 | USA | n: 551 IG: 274 CG: 277 |
IG: 59.2 ± 11.20 CG: 59.6 ± 10.25 |
Letrozole | Upfront zoledronate 4 mg iv every 6 months | Delayed zoledronate 4 mg iv every 6 months |
- LS BMD
- TH BMD - FN BMD - Vertebral and nonvertebral fractures - toxicity |
60 months |
BMD, bone mineral density; CG, control group; FN, femoral neck; IG, intervention group; iv, intravenous; FN, femoral neck; LS, lumbar spine; sc, subcutaneous; TB, total body; TH, total hip; UK, United Kingdom; USA, United States of America.
Primary outcomes of the study included were marked in bold.