Bisphosphonates Preserve Bone Mineral Density and Suppress Bone Turnover Markers in Early Menopausal Women: A Systematic Review and Meta‐Analysis of Randomized Trials
Bibliographic record
Abstract
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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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.014 | 0.032 |
| Meta-epidemiology (narrow) | 0.003 | 0.001 |
| Meta-epidemiology (broad) | 0.019 | 0.026 |
| Bibliometrics | 0.006 | 0.006 |
| Science and technology studies | 0.001 | 0.001 |
| Scholarly communication | 0.003 | 0.002 |
| Open science | 0.002 | 0.001 |
| Research integrity | 0.002 | 0.002 |
| Insufficient payload (model declined to judge) | 0.004 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".