Trial reportJAMA internal medicine2014
Fracture prediction after discontinuation of 4 to 5 years of alendronate therapy: the FLEX study.
Trial report in JAMA internal medicine, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00398931 (A 5-year, Double-blind, Randomized, Placebo-controlled Extension Study to Examine the Long-term Safety and Efficacy of Oral Alendronate in Postmenopausal Women Who Previously Received Alendronate in Conjunction With the Fracture Intervention Trial), which is not on this map. Cited by 41 papers, 5 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A 5-year, Double-blind, Randomized, Placebo-controlled Extension Study to Examine the Long-term Safety and Efficacy of Oral Alendronate in Postmenopausal Women Who Previously Received Alendronate in Conjunction With the Fracture Intervention Trial
Who cites it
41 citing papers in PubMed, 5 syntheses or guidelines pooled it, 129 citations in OpenAlex.
- The 2024 UK clinical guideline for the prevention and treatment of osteoporosis.Archives of osteoporosis · 2025Guideline
- UK clinical guideline for the prevention and treatment of osteoporosis.Archives of osteoporosis · 2022Guideline
- Fracture risk following intermission of osteoporosis therapy.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019Pooled it
- Effects of Long-Term Low-Molecular-Weight Heparin on Fractures and Bone Density in Non-Pregnant Adults: A Systematic Review With Meta-Analysis.Journal of general internal medicine · 2016Pooled it
- Clinician's Guide to Prevention and Treatment of Osteoporosis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2014Guideline
- Early changes in bone turnover and bone mineral density after discontinuation of long-term oral bisphosphonates: a post hoc analysis.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2021Trial
- Comparison of BMD Changes and Bone Formation Marker Levels 3 Years After Bisphosphonate Discontinuation: FLEX and HORIZON-PFT Extension I Trials.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2019Trial
- A model of BMD changes after alendronate discontinuation to guide postalendronate BMD monitoring.The Journal of clinical endocrinology and metabolism · 2014Trial
- Impact of bisphosphonate drug holidays on bone mineral density and osteoporotic fracture risk: real-world evidence from a retrospective cohort study.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2026Article
- Critical Considerations in the Interpretation of Bone Turnover Marker Data in Hormonal Contraceptive Users. Comment on Tassi et al. Hormonal Contraception and Bone Metabolism: Emerging Evidence from a Systematic Review and Meta-Analysis of Studies on Post-Pubertal and Reproductive-Age Women.Pharmaceuticals (Basel, Switzerland) · 2025Article
- A practical use of bone turnover markers in management of patients with skeletal fragility.Endocrine · 2025Review
- The Dutch multidisciplinary guideline osteoporosis and fracture prevention, taking a local guideline to the international arena.Archives of osteoporosis · 2024Article
- The Use of Bone-Turnover Markers in Asia-Pacific Populations.Annals of laboratory medicine · 2024Review
- Review
- Review
- Dynamic Effects of the Third Generation Bisphosphonate of Risedronate on Rat Osteoporotic Fractures for Clinical Usage Guidance.Orthopaedic surgery · 2021Article
- Romosozumab Followed by Antiresorptive Treatment Increases the Probability of Achieving Bone Mineral Density Treatment Goals.JBMR plus · 2021Article
- Bisphosphonate Drug Holidays in Primary Care: When and What to Do Next?Current osteoporosis reports · 2021Review
- Vertebral fracture assessment (VFA) for osteoporosis screening in US postmenopausal women: is it cost-effective?Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2020Article
- Duration of Bisphosphonate Drug Holidays and Associated Fracture Risk.Medical care · 2020Observational
Corrections and comments
- Commented on by
Authors and funding
8 authors at 4 institutions in 1 country.
Funding
Abstract
importanceDiscontinuation of bisphosphonate therapy after 3 to 5 years is increasingly considered, but methods to monitor fracture risk after discontinuation have not been established.
objectiveTo test methods of predicting fracture risk among women who have discontinued alendronate therapy after 4 to 5 years. DESIGN, SETTING, AND
participantsThe prospective Fracture Intervention Trial Long-term Extension (FLEX) study randomized postmenopausal women aged 61 to 86 years previously treated with 4 to 5 years of alendronate therapy to 5 more years of alendronate or placebo from 1998 through 2003; the present analysis includes only the placebo group. Hip and spine dual-energy x-ray absorptiometry (DXA) were measured when placebo was begun (FLEX baseline) and after 1 to 3 years of follow-up. Two biochemical markers of bone turnover, urinary type 1 collagen cross-linked N-telopeptide (NTX) and serum bone-specific alkaline phosphatase (BAP), were measured at FLEX baseline and after 1 and 3 years. MAIN OUTCOMES AND MEASURES: Symptomatic spine and nonspine fractures occurring after the follow-up measurement of DXA or bone turnover.
resultsDuring 5 years of placebo, 94 of 437 women (22%) experienced 1 or more symptomatic fractures; 82 had fractures after 1 year. One-year changes in hip DXA, NTX, and BAP were not related to subsequent fracture risk, but older age and lower hip DXA at time of discontinuation were significantly related to increased fracture risk (lowest tertile of baseline femoral neck DXA vs other 2 tertiles relative hazard ratio, 2.17 [95% CI, 1.38-3.41]; total hip DXA relative hazard ratio, 1.87 [95% CI, 1.20-2.92]). CONCLUSIONS AND RELEVANCE: Among postmenopausal women who discontinue alendronate therapy after 4 to 5 years, age and hip BMD at discontinuation predict clinical fractures during the subsequent 5 years. Follow-up measurements of DXA 1 year after discontinuation and of BAP or NTX 1 to 2 years after discontinuation are not associated with fracture risk and cannot be recommended.
trial registrationclinicaltrials.gov Identifier: NCT00398931.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.