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Bone modifying agents for bone loss in patients with aromatase inhibitor as adjuvant treatment for breast cancer; insights from a network meta-analysis

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Abstract

Purpose

The data of head-to-head comparisons of the anti-fracture efficacy of bone modifying agents (BMAs) in patients with hormone receptor-positive breast cancer receiving aromatase inhibitor (AI) are not available. Therefore, we conducted a network meta-analysis to compare the efficacy of different BMAs in patients with breast cancer receiving adjuvant AI.

Methods

We performed a network meta-analysis to compare the change of bone mineral densities (BMDs) and the risk of fracture in the selected studies using a random effect model. The primary outcomes are the change of BMD of lumbar spine (LS) and total hip (TH) from the baseline (ΔBMD, %) at 1 and 2 years and the risk of fracture.

Results

We identified and included a total of 16 randomized controlled trials for this analysis. All BMAs included (risedronate, zoledronate, and denosumab) were associated with a significant increase in BMD of LS and TH at 1 and 2 years compared with no upfront treatment group. Among BMAs, zoledronate and denosumab use resulted in significantly higher BMD of LS and TH at 1 and 2 years compared with risedronate. The risk of fracture was significantly lower in the patients who received denosumab or risedronate compared with the patients without upfront treatment (Relative risk (RR) [95% CI] 0.51 [0.38–0.67] and 0.54 [0.35–0.83], respectively).

Conclusion

Among the bisphosphonates, zoledronate increased BMD the most, but risedronate, not zoledronate, use was associated with lower risk of fracture. Denosumab increased BMD not only of LS but also of the cortical-bone-rich hip, and showed a significant reduction of fracture risk.

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Abbreviations

AI:

Aromatase inhibitor

BMA:

Bone modifying agent

BMD:

Bone mineral density

ΔBMD:

BMD change from baseline (%)

CI:

Confidence interval

RR:

Relative risk

LS:

Lumbar spine

TH:

Total hip

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Authors and Affiliations

  1. Department of Medicine, Icahn School of Medicine at Mount Sinai, Mount Sinai Beth Israel, New York, NY, USA

    Hirotaka Miyashita, Toshiki Kuno, Christina Cruz & Se-Min Kim

  2. Mount Sinai Bone Program, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Hirotaka Miyashita & Se-Min Kim

  3. Department of Medicine, Nippon Medical School Hospital, Tokyo, Japan

    Sera Satoi

  4. Mount Sinai Beth Israel Comprehensive Cancer Center, New York, NY, USA

    Stephen Malamud

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  1. Hirotaka Miyashita
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Correspondence to Hirotaka Miyashita or Se-Min Kim.

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Hirotaka Miyashita declares that he has no conflict of interest. Sera Satoi declares that she has no conflict of interest. Toshiki Kuno declares that he has no conflict of interest. Christina Cruz declares that she has no conflict of interest. Stephen Malamud declares that he has no conflict of interest. Se-Min Kim declares that he has no conflict of interest.

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10549_2020_5640_MOESM1_ESM.pdf

Supplementary Figure 1A: Forrest plot comparing the BMD change (%, lumbar spine) with each BMA at 2 year (MD: mean difference, CI: confidence interval). Supplementary Figure 1B: Forrest plot comparing the BMD change (%, total hip) with each BMA at 1 year (MD: mean difference, CI: confidence interval). Supplementary Figure 1C: Forrest plot comparing the BMD change (%, total hip) with each BMA at 2 year (MD: mean difference of ΔBMD, CI: confidence interval). Supplementary Figure 2: Forrest plot comparing the BMD change (%) of lumbar spine (2A and 2B) and of total hip (2C and 2D) with each BMA at 1 and 2 year after excluding a study with the greatest heterogeneity (MD: mean difference, CI: confidence interval). Supplementary Figure 3: Forrest plot comparing the BMD change (%) of lumbar spine (3A and 3B) and of total hip (3C and 3D) with each BMA at 1 and 2 year after excluding a study with the largest number of patients (MD: mean difference, CI: confidence interval). Supplementary Figure 4: Forrest plot comparing the risk of fracture with each BMA in patients with low BMD at baseline (T score < -1.0) (RR: relative risk of fracture, CI: confidence interval). Supplementary file1 (PDF 751 kb)

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Miyashita, H., Satoi, S., Kuno, T. et al. Bone modifying agents for bone loss in patients with aromatase inhibitor as adjuvant treatment for breast cancer; insights from a network meta-analysis. Breast Cancer Res Treat 181, 279–289 (2020). https://doi.org/10.1007/s10549-020-05640-3

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