ReviewJBMR plus2022
Bisphosphonate Drug Holidays: Evidence From Clinical Trials and Real-World Studies.
Review in JBMR plus, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers, 2 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
21 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Comparing the Efficacy of Antiosteoporotic Drugs in Preventing Periprosthetic Bone Loss Following Total Hip Arthroplasty: A Systematic Review and Bayesian Network Meta-Analysis.Orthopaedic surgery · 2024Pooled it
- [Osteoporosis-Definition, risk assessment, diagnosis, prevention and treatment (update 2024) : Guidelines of the Austrian Society for Bone and Mineral Research].Wiener klinische Wochenschrift · 2024Guideline
- Preventing Hip (Proximal Femoral) Fractures: An Evidence-Based Review for Clinicians.Journal of clinical medicine · 2026Review
- Pathophysiology, diagnosis and management of secondary osteoporosis.Nature reviews. Endocrinology · 2026Review
- Bilateral atypical femoral fractures following unsupervised long-term alendronate use: a case report.Journal of medical case reports · 2026Article
- ZM-306416 prevents ovariectomy-induced bone loss by promoting osteoblastogenesis and inhibiting osteoclastogenesis.Journal of orthopaedic surgery and research · 2026Article
- Article
- Sequential Treatment for Osteoporosis After Teriparatide: A Real-Life Long-Term Comparison Between Zoledronic Acid and Denosumab.Journal of clinical medicine · 2025Article
- Denosumab discontinuation in the clinic: implications of rebound bone turnover and emerging strategies to prevent bone loss and fractures.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Review
- Early and multiple doses of zoledronate mitigates rebound bone loss following withdrawal of receptor activator of nuclear factor kappa-B ligand inhibition.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2025Article
- Inhibition of choroidal osteoma progression using bisphosphonate and RANKL-inhibitory treatment.American journal of ophthalmology case reports · 2024Article
- Effect of Oral Bisphosphonate Drug Holiday on Mortality Following Hip Fracture.The Journal of clinical endocrinology and metabolism · 2024Article
- Increased bone mass but delayed mineralization: in vivo and in vitro study for zoledronate in bone regeneration.BMC oral health · 2024Article
- Secondary fracture prevention in Spanish primary care: results of the PREFRAOS Study.Archives of osteoporosis · 2024Observational
- Comparison of bone mineral density of osteoporotic and osteopenia menopausal women treated with oral bisphosphonates before stopping the treatment and 1 year after drug holiday period.Clinical rheumatology · 2024Article
- Approach to the Patient With Bone Fracture: Making the First Fracture the Last.The Journal of clinical endocrinology and metabolism · 2023Article
- Long-term and sequential treatment for osteoporosis.Nature reviews. Endocrinology · 2023Review
- Phylobone: a comprehensive database of bone extracellular matrix proteins in human and model organisms.Bone research · 2023Article
- Management of bone loss due to endocrine therapy during cancer treatment.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2023Review
- Exercise for optimizing bone health after hormone-induced increases in bone stiffness.Frontiers in endocrinology · 2023Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bisphosphonates (BPs) are commonly used in the treatment of osteoporosis and are effective in the prevention of fragility fracture. Long-term use has been associated with the development of atypical femur fractures (AFFs) and osteonecrosis of the jaw (ONJ). Drug holidays seek to reduce the risk of insufficiency fractures (AFFs) while maintaining durable effects of long-term treatment in the prevention of fragility fracture. Guidelines suggest that BP drug holidays be considered after 3 to 5 years. However individual factors impacting this decision and outcomes are unclear. This review examines key factors in the planning of a safe BP drug holiday and surrogate markers of fracture risk in patients discontinuing treatment. Fifteen randomized control trials and 19 real-world studies were included, including nationwide prospective studies from several countries. Increases in bone turnover markers (BTMs) and reductions in bone mineral density (BMD) were generally observed during BP drug holidays. Resurgent bone turnover was problematic in high-risk patients in whom fractures recurred as early as 12 months following a drug holiday. Risk factors for holiday-related fractures included older age, low hip BMD, underweight, low medication adherence, and prevalent/incident fractures. Zoledronic acid conferred the most durable reduction in fractures, particularly after six annual infusions. Five years of alendronate was insufficient in preventing vertebral fractures in high-risk patients embarking on a drug holiday. Relatively faster offset of antiresorptive effect was seen in risedronate users with more frequent fractures than alendronate during a drug holiday. Studies directly counterbalancing effects of long-term treatment on AFF risk versus drug holiday outcomes in the same population were lacking. In the absence of persistently high fracture risk and following a specific treatment duration dependent on the BP used, drug holidays are safe and mitigate the risk of AFF. However, anti-resorptive effects diminish over time; ongoing monitoring and careful planning of BP resumption is necessary. © 2022 The Authors.
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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.