Trial reportThe New England journal of medicine2009
Giant osteoclast formation and long-term oral bisphosphonate therapy.
Trial report in The New England journal of medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 163 papers, 2 of them syntheses that pooled it.
What it found
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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
163 citing papers in PubMed, 2 syntheses or guidelines pooled it, 385 citations in OpenAlex.
- Clinical Data for Parametrization ofFrontiers in bioengineering and biotechnology · 2022Pooled it
- Osteoporosis drug therapy strategies in the setting of disease-modifying agents for autoimmune disease.Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA · 2013Pooled it
- Identification of osteoclast-osteoblast coupling factors in humans reveals links between bone and energy metabolism.Nature communications · 2020Trial
- Markers of inflammation after zoledronic acid redosing.Journal of bone and mineral metabolism · 2014Trial
- Decreased circulating dopamine β-hydroxylase is associated with medication-related osteonecrosis of the jaw and implicates sympathetic dysregulation.Experimental & molecular medicine · 2026Article
- The Early Effect of Alendronate, Hop Extract and Their Combination on Bone Structural Properties in a Rat Model of Osteoporosis.Medical sciences (Basel, Switzerland) · 2026Article
- Graphene-Based 3D Scaffolds in Bone Regeneration: Emerging Opportunities for MRONJ Treatment.Pharmaceutics · 2026Review
- In silico exploration of osteoclast precursor inhibition for preventing rapid bone loss after denosumab discontinuation.NPJ systems biology and applications · 2026Article
- Effects of Zoledronate on Alveolar Bone and Teeth in Rats: Relationship Between Root Resorption and Occlusion.International journal of dentistry · 2026Article
- Peri-implant inflammation increases the risk of osteonecrosis in mice treated with bisphosphonate.Journal of periodontology · 2025Article
- Comparing incomplete atypical femur fractures in patients with or without bisphosphonate treatment: radiography and bone morphology in a retrospective study of 19 cases.Acta orthopaedica · 2025Article
- Mild antiresorptive activity of an anti-vascular endothelial growth factor A antibody and sunitinib in a rat model of bone resorption.Bone reports · 2025Article
- Bisphosphonate-Conjugated Sitafloxacin for Treatment ofPharmaceuticals (Basel, Switzerland) · 2025Article
- Chinese expert consensus on the diagnosis and clinical management of medication-related osteonecrosis of the jaw.Journal of bone oncology · 2024Review
- Generation of BT-Amide, a Bone-Targeted Pyk2 Inhibitor, EffectiveJournal of medicinal chemistry · 2024Article
- Increased bone mass but delayed mineralization: in vivo and in vitro study for zoledronate in bone regeneration.BMC oral health · 2024Article
- Article
- Discovering Potential in Non-Cancer Medications: A Promising Breakthrough for Multiple Myeloma Patients.Cancers · 2024Review
- Article
- Hydroxychloroquine and a low activity bisphosphonate conjugate prevent and reverse ovariectomy-induced bone loss in mice through dual antiresorptive and anabolic effects.Research square · 2024Article
103 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundBisphosphonates decrease bone resorption and are commonly used to treat or prevent osteoporosis. However, the effect of bisphosphonates on their target cells remains enigmatic, since in patients benefiting from therapy, little change, if any, has been observed in the number of osteoclasts, which are the cells responsible for bone resorption.
methodsWe examined 51 bone-biopsy specimens obtained after a 3-year, double-blind, randomized, placebo-controlled, dose-ranging trial of oral alendronate to prevent bone resorption among healthy postmenopausal women 40 through 59 years of age. The patients were assigned to one of five groups: those receiving placebo for 3 years; alendronate at a dose of 1, 5, or 10 mg per day for 3 years; or alendronate at a dose of 20 mg per day for 2 years, followed by placebo for 1 year. Formalin-fixed, undecalcified planar sections were assessed by bone histomorphometric methods.
resultsThe number of osteoclasts was increased by a factor of 2.6 in patients receiving 10 mg of alendronate per day for 3 years as compared with the placebo group (P<0.01). Moreover, the number of osteoclasts increased as the cumulative dose of the drug increased (r=0.50, P<0.001). Twenty-seven percent of these osteoclasts were giant cells with pyknotic nuclei that were adjacent to superficial resorption cavities. Furthermore, giant, hypernucleated, detached osteoclasts with 20 to 40 nuclei were found after alendronate treatment had been discontinued for 1 year. Of these large cells, 20 to 37% were apoptotic, according to both their morphologic features and positive findings from in situ end labeling.
conclusionsLong-term alendronate treatment is associated with an increase in the number of osteoclasts, which include distinctive giant, hypernucleated, detached osteoclasts that are undergoing protracted apoptosis.
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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.