Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials

ABSTRACT Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the...

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Main Authors: Aria Ahadzadeh Ardebili, Timothy Fu, Nicole Dunnewold, Fariba Aghajafari, Emma O. Billington
Format: Article
Language:English
Published: Wiley 2023-06-01
Series:JBMR Plus
Subjects:
Online Access:https://doi.org/10.1002/jbm4.10748
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author Aria Ahadzadeh Ardebili
Timothy Fu
Nicole Dunnewold
Fariba Aghajafari
Emma O. Billington
author_facet Aria Ahadzadeh Ardebili
Timothy Fu
Nicole Dunnewold
Fariba Aghajafari
Emma O. Billington
author_sort Aria Ahadzadeh Ardebili
collection DOAJ
description ABSTRACT Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long‐term fracture risk. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen‐containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta‐analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%–5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%–3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%–2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%–6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%–5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%–5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N‐telopeptide (−52.2%, 95% CI −60.3% to −44.2%, p < 0.00001, n = 3 studies) and bone‐specific alkaline phosphatase (−34.2%, 95% CI −42.6% to −25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta‐analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
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spelling doaj.art-bdc411c942ad4703863acef632b6ef752023-06-05T12:53:13ZengWileyJBMR Plus2473-40392023-06-0176n/an/a10.1002/jbm4.10748Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized TrialsAria Ahadzadeh Ardebili0Timothy Fu1Nicole Dunnewold2Fariba Aghajafari3Emma O. Billington4Cumming School of Medicine University of Calgary Calgary Alberta CanadaCumming School of Medicine University of Calgary Calgary Alberta CanadaHealth Sciences Library University of Calgary Calgary Alberta CanadaCumming School of Medicine University of Calgary Calgary Alberta CanadaCumming School of Medicine University of Calgary Calgary Alberta CanadaABSTRACT Most women do not qualify for pharmacologic osteoporosis treatment until more than a decade after menopause, by which time they will have lost up to 30% of their bone mass and may have already sustained fractures. Short or intermittent courses of bisphosphonate therapy, initiated around the time of menopause, might prevent excessive bone loss and lower long‐term fracture risk. We undertook a systematic review and meta‐analysis of randomized controlled trials (RCTs) to determine the effects of nitrogen‐containing bisphosphonates on fracture incidence, bone mineral density (BMD), and bone turnover markers in early menopausal women (ie, perimenopausal or <5 years postmenopausal) over ≥12 months. Medline, Embase, CENTRAL, and CINAHL were searched in July 2022. Risk of bias was evaluated using the Cochrane Risk of Bias 2 tool. Random effect meta‐analysis was undertaken using RevMan v5.3. In total, 12 trials were included (n = 1722 women); five evaluated alendronate, three risedronate, three ibandronate, and one zoledronate. Four were at low risk of bias; eight raised some concerns. Fractures were infrequent in the three studies that reported them. Compared with placebo, bisphosphonates improved BMD over 12 months (mean percentage difference, 95% confidence interval [CI]) at the spine (4.32%, 95% CI, 3.10%–5.54%, p < 0.0001, n = 8 studies), the femoral neck (2.56%, 95% CI, 1.85%–3.27%, p = 0.001, n = 6 studies), and the total hip (1.22%, 95% CI 0.16%–2.28%, p = 0.002, n = 4 studies). Over treatment durations of 24 to 72 months, bisphosphonates improved BMD at the spine (5.81%, 95% CI 4.71%–6.91%, p < 0.0001, n = 8 studies), femoral neck (3.89%, 95% CI 2.73%–5.05%, p = 0.0001, n = 5 studies) and total hip (4.09%, 95% CI 2.81%–5.37%, p < 0.0001, n = 4 studies). Bisphosphonates reduced urinary N‐telopeptide (−52.2%, 95% CI −60.3% to −44.2%, p < 0.00001, n = 3 studies) and bone‐specific alkaline phosphatase (−34.2%, 95% CI −42.6% to −25.8%, p < 0.00001, n = 4 studies) more than placebo at 12 months. This systematic review and meta‐analysis shows that bisphosphonates improve BMD and lower bone turnover markers in early menopause, warranting further investigation of these agents for osteoporosis prevention. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.https://doi.org/10.1002/jbm4.10748ANTIRESORPTIVESCLINICAL TRIALSDXAMENOPAUSEOSTEOPOROSIS
spellingShingle Aria Ahadzadeh Ardebili
Timothy Fu
Nicole Dunnewold
Fariba Aghajafari
Emma O. Billington
Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
JBMR Plus
ANTIRESORPTIVES
CLINICAL TRIALS
DXA
MENOPAUSE
OSTEOPOROSIS
title Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
title_full Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
title_fullStr Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
title_full_unstemmed Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
title_short Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
title_sort bisphosphonates preserve bone mineral density and suppress bone turnover markers in early menopausal women a systematic review and meta analysis of randomized trials
topic ANTIRESORPTIVES
CLINICAL TRIALS
DXA
MENOPAUSE
OSTEOPOROSIS
url https://doi.org/10.1002/jbm4.10748
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