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Osteoporosis drugs for prevention of clinical fracture in white postmenopausal women: a network meta-analysis of survival data

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Abstract

Summary

By Bayesian random effects network meta-analysis stratified by prevalent vertebral fracture (PVF), we conclude that different effective drugs should be used to prevent fragility fractures according to postmenopausal women with or without PVF and that there are two drugs (i.e., parathyroid hormone (1-84) and abaloparatide) less tolerated than placebo.

Introduction

No studies have compared various osteoporosis drugs in postmenopausal women (PMW) either with or without prevalent vertebral fracture (PVF). We aimed to compare them in the two different subgroups.

Methods

We searched different databases to select relevant studies. We performed Bayesian random effects network meta-analysis to synthesize hazard ratio (HR) and 95% confidence interval (CI) for clinical fracture stratified by PVF and to synthesize risk ratio (RR) for tolerability and vertebral fracture.

Results

We included 33 trials involving 79,144 PMW. In the PVF ≥ 50% subgroup, teriparatide (HR 0.39, 95% CI 0.28–0.57), romosozumab (HR 0.49, 95% CI 0.29–0.75), risedronate (HR 0.62, 95% CI 0.50–0.79), zoledronate (HR 0.67, 95% CI 0.47–0.96), and alendronate (HR 0.69, 95% CI 0.47–0.97) reduced clinical fracture risk. In the other subgroup, abaloparatide (HR 0.56, 95% CI 0.33–0.92), romosozumab (HR 0.67, 95% CI 0.47–0.95), and denosumab (HR 0.68, 95% CI 0.50–0.85) reduced clinical fracture risk. Five drugs reduced vertebral fracture risk in the PVF ≥ 50% subgroup whereas seven did in the other subgroup. All drugs did not increase withdrawal risk except for parathyroid hormone (1-84) (PTH) (RR 1.9, 95% CI 1.4–2.6) and abaloparatide (RR 1.6, 95% CI 1.2–2.3).

Conclusion

Different effective drugs should be used to prevent fragility fractures according to PMW with or without PVF, and romosozumab is the only one which can reduce clinical and vertebral fractures in both of the two populations. PTH and abaloparatide are less tolerated than placebo whereas the eight other drugs assessed in the study have the same tolerability as placebo.

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Abbreviations

PMOW:

Postmenopausal osteoporotic women

PMW:

Postmenopausal women

HR:

Hazard ratio

RR:

Risk ratio

OR:

Odds ratio

CI:

Confidence interval

SUCRA:

Surface under the cumulative ranking curve

RCT:

Randomized controlled trial

PTH:

Parathyroid hormone (1-84)

PVF:

Prevalent vertebral fracture

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Author information

Author notes

  1. L.-L. Ding and F. Wen contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopedics, The People’s Hospital of Rongchang District, Chongqing, 402460, China

    L.-L. Ding, F. Wen, H. Wang, D.-H. Wang & X. Tan

  2. Department of Orthopedics, Yueyang Second People’s Hospital, Hunan Normal University, Yueyang, 414000, Hunan, China

    Q. Liu & J.-X. Hu

  3. Department of Gynecology, The People’s Hospital of Rongchang District, Chongqing, 402460, China

    Y.-X. Mo & M. Qiu

Authors
  1. L.-L. Ding
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  2. F. Wen
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  4. D.-H. Wang
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Correspondence to M. Qiu or J.-X. Hu.

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Electronic supplementary materials

Appendix 1

Full search strategy in PubMed, and trials included for quantitative synthesis. (PDF 70 kb)

Appendix 2

Study characteristics and quality assessment. (XLSX 18 kb)

Appendix 3

Heterogeneity assessment for clinical fracture in the subgroup of the proportion of PVF ≥ 50%. (PDF 91 kb)

Appendix 4

Heterogeneity assessment for clinical fracture in the subgroup of the proportion of PVF < 50%. (PDF 149 kb)

Appendix 5

Heterogeneity assessment for tolerability with all trials included. (PDF 151 kb)

Appendix 6

Heterogeneity assessment for vertebral fracture in the subgroup of the proportion of PVF ≥ 50%. (PDF 61 kb)

Appendix 7

Heterogeneity assessment for vertebral fracture in the subgroup of the proportion of PVF < 50%. (PDF 121 kb)

Appendix 8

Inconsistency test for clinical fracture in the subgroup of the proportion of PVF ≥ 50%. (PDF 56 kb)

Appendix 9

Inconsistency test for clinical fracture in the subgroup of the proportion of PVF < 50%. (PDF 84 kb)

Appendix 10

Inconsistency test for tolerability with all trials included. (PDF 89 kb)

Appendix 11

Inconsistency test for vertebral fracture in the subgroup of the proportion of PVF ≥ 50%. (PDF 29 kb)

Appendix 12

Inconsistency test for vertebral fracture in the subgroup of the proportion of PVF < 50%. (PDF 85 kb)

Appendix 13

Network meta-analysis forest plot of vertebral fracture for the subgroup of the proportion of PVF ≥ 50%. (PDF 130 kb)

Appendix 14

Network meta-analysis forest plot of vertebral fracture for the subgroup of the proportion of PVF < 50%. (PDF 173 kb)

Appendix 15

Sensitivity network meta-analysis for clinical fracture in the subgroup of the proportion of PVF < 50%. (PDF 83 kb)

Appendix 16

Sensitivity network meta-analysis for tolerability. (PDF 83 kb)

Appendix 17

Sensitivity network meta-analysis for vertebral fracture in the subgroup of the proportion of PVF < 50%. (PDF 83 kb)

Appendix 18

Comparison-adjusted funnel plots of clinical fracture for the subgroup of the proportion of PVF ≥ 50% (A), clinical fracture for the subgroup of the proportion of PVF < 50% (B), tolerability for all trials (C), vertebral fracture for the subgroup of the proportion of PVF ≥ 50% (D), and vertebral fracture for the subgroup of the proportion of PVF < 50% (E). (PDF 181 kb)

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Ding, LL., Wen, F., Wang, H. et al. Osteoporosis drugs for prevention of clinical fracture in white postmenopausal women: a network meta-analysis of survival data. Osteoporos Int 31, 961–971 (2020). https://doi.org/10.1007/s00198-019-05183-4

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  • DOI: https://doi.org/10.1007/s00198-019-05183-4

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