SynthesisOsteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA2014
Comparative gastrointestinal safety of bisphosphonates in primary osteoporosis: a network meta-analysis.
Synthesis in Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 8 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
23 citing papers in PubMed, 8 syntheses or guidelines pooled it, 45 citations in OpenAlex.
- Adverse effects of the PENTO(CLO) protocol in the prevention and management of iatrogenic head and neck bone necrosis in cancer patients: A systematic review and meta-analysis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2026Pooled it
- Alendronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.The Cochrane database of systematic reviews · 2025Pooled it
- Etidronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.The Cochrane database of systematic reviews · 2024Pooled it
- Additional effects of herbal medicine combined with bisphosphonates for primary osteoporosis: a systematic review and meta-analysis.Frontiers in pharmacology · 2024Pooled it
- Risedronate for the primary and secondary prevention of osteoporotic fractures in postmenopausal women.The Cochrane database of systematic reviews · 2022Pooled it
- Oral Treatment With Bisphosphonates of Osteoporosis Does Not Increase the Risk of Severe Gastrointestinal Side Effects: A Meta-Analysis of Randomized Controlled Trials.Frontiers in endocrinology · 2020Pooled it
- European guidance for the diagnosis and management of osteoporosis in postmenopausal women.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2019Guideline
- Qianggu capsule for the treatment of primary osteoporosis: evidence from a Chinese patent medicine.BMC complementary and alternative medicine · 2017Pooled it
- "Acute-phase reactions to zoledronate in clinical practice: a prospective single center study of 1,150 patients."Endocrine · 2026Article
- Targeting the osteoporotic bone microenvironment: Mechanistic insight and therapeutic biomaterials for accelerating bone regeneration.Bioactive materials · 2026Review
- Tipping point analysis in network meta-analysis.Research synthesis methods · 2025Article
- Pediatric and adult osteoporosis: a contrasting mirror.Annals of pediatric endocrinology & metabolism · 2024Article
- Review
- Article
- Adherence and preference of intravenous zoledronic acid for osteoporosis versus other bisphosphonates.European journal of hospital pharmacy : science and practice · 2019Review
- Treatment with once-weekly alendronate oral jelly compared with once-weekly alendronate oral tablet for Japanese patients with primary osteoporosis: An open-label, prospective, observational study.Health science reports · 2019Article
- Zoledronic Acid (ReclastDrugs · 2016Review
- The position of strontium ranelate in today's management 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 · 2015Review
- Gastrointestinal and renal side effects of bisphosphonates: differentiating between no proof of difference and proof of no difference.Journal of endocrinological investigation · 2015Article
- Review
Corrections and comments
- Commented on by
- Commented on by
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
unlabelledWe completed a network meta-analysis of published papers to compare bisphosphonate gastrointestinal safety. We found that zoledronic acid had the highest chance of causing gastrointestinal adverse events. Etidronate had the highest chance of discontinuation due to an adverse event. No difference was found for serious adverse events.
introductionBisphosphonates are first-line treatment for osteoporosis. Gastrointestinal (GI) adverse events (AE) are the primary reason for non-adherence. Little is known about the comparative GI safety of bisphosphonates. PURPOSE: Leverage published clinical trial data to examine the comparative GI safety of bisphosphonates.
methodsWe completed a systematic review of all English-language clinical trials that assessed bisphosphonate safety and/or efficacy in primary osteoporosis through to 2012. Randomized, blinded, and controlled studies were eligible. The primary outcome was any GI-related AE. Subanalyses were completed for upper GI symptoms, serious GI, nausea, esophageal-related events, and discontinuation due to AE. A Bayesian-based network meta-analysis was completed to allow for indirect comparisons. Results were reported as the probability that a specific drug had the highest number of events.
resultsWe identified 50 studies: 32 alendronate, 12 risedronate, 5 etidronate, and 7 zoledronic acid. Zoledronic acid had the highest probability of having the highest number of any GI AE (91%) and nausea (70%). Etidronate (70%) and zoledronic acid (28%) had the highest probability of having the greatest attrition due to AE. Etidronate had the highest probability (56%) of having the greatest number of upper GI symptoms among oral bisphosphonates.
conclusionZoledronic acid had the highest probability of causing the greatest number of GI AE, possibly related to nausea. These results question the assumption that annual zoledronic acid will translate into better adherence. Little difference was found between alendronate and risedronate for serious AE. More research into real-world implications of the comparative safety of bisphosphonates is needed.
Indexed as
Identifiers
What OpenQuestion holds
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.