ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2015
OPG-Fc but Not Zoledronic Acid Discontinuation Reverses Osteonecrosis of the Jaws (ONJ) in Mice.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 70 citations in OpenAlex.
- The effects of sodium alendronate on socket healing after tooth extraction: a systematic review of animal studies.Brazilian oral research · 2024Pooled it
- Early bone-formation response to sclerostin antibody is altered by prior antiresorptive treatment in ovariectomized rats.JBMR plus · 2026Article
- The therapeutic window: timing dentoalveolar surgery to minimize MRONJ risk in denosumab-treated osteoporotic patients.JBMR plus · 2026Article
- Inflammatory bone loss and signaling pathways in periodontitis: mechanistic insights and emerging therapeutic strategies.Bone research · 2026Review
- Targeted drug repurposing in medication-related osteonecrosis of the jaw: a review of teriparatide and pentoxifylline/α-tocopherol protocols.Frontiers in medicine · 2026Review
- Peri-implant inflammation increases the risk of osteonecrosis in mice treated with bisphosphonate.Journal of periodontology · 2025Article
- Article
- Effect of Long-Term Treatment with Alendronate on Bone Repair and Mineralization Around Implants in Rats.Brazilian dental journal · 2024Article
- Review
- The effect of drug holiday on preventing medication-related osteonecrosis of the jaw in osteoporotic rat model.Journal of orthopaedic translation · 2023Article
- Management of bisphosphonate preparation-treated children in the field of pediatric dentistry.The Japanese dental science review · 2022Review
- Inhibition of HMGB1/RAGE Signaling Reduces the Incidence of Medication-Related Osteonecrosis of the Jaw (MRONJ) in Mice.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Radiographic changes of mandibular cortical bone in bisphosphonate drug holiday.Journal of the Korean Association of Oral and Maxillofacial Surgeons · 2022Article
- Strontium ranelate improves post-extraction socket healing in rats submitted to the administration of bisphosphonates.Odontology · 2022Article
- Osteonecrosis development by tooth extraction in zoledronate treated mice is inhibited by active vitamin D analogues, anti-inflammatory agents or antibiotics.Scientific reports · 2022Article
- Pharmacological Therapies for the Management of Inflammatory Bone Resorption in Periodontal Disease: A Review of Preclinical Studies.BioMed research international · 2022Review
- Review
- Review and Update of the Risk Factors and Prevention of Antiresorptive-Related Osteonecrosis of the Jaw.Endocrinology and metabolism (Seoul, Korea) · 2021Review
- Medication-Related Osteonecrosis of the Jaw: A Critical Narrative Review.Journal of clinical medicine · 2021Review
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 2 countries.
Funding
Abstract
Osteonecrosis of the jaws (ONJ) is a significant complication of antiresorptive medications, such as bisphosphonates and denosumab. Antiresorptive discontinuation to promote healing of ONJ lesions remains highly controversial and understudied. Here, we investigated whether antiresorptive discontinuation alters ONJ features in mice, employing the potent bisphosphonate zoledronic acid (ZA) or the receptor activator of NF-κB ligand (RANKL) inhibitor OPG-Fc, utilizing previously published ONJ animal models. Mice were treated with vehicle (veh), ZA, or OPG-Fc for 11 weeks to induce ONJ, and antiresorptives were discontinued for 6 or 10 weeks. Maxillae and mandibles were examined by μCT imaging and histologically. ONJ features in ZA and OPG-Fc groups included periosteal bone deposition, empty osteocyte lacunae, osteonecrotic areas, and bone exposure, each of which substantially resolved 10 weeks after discontinuing OPG-Fc but not ZA. Full recovery of tartrate-resistant acid phosphatase-positive (TRAP+) osteoclast numbers occurred after discontinuing OPG-Fc but not ZA. Our data provide the first experimental evidence demonstrating that discontinuation of a RANKL inhibitor, but not a bisphosphonate, reverses features of osteonecrosis in mice. It remains unclear whether antiresorptive discontinuation increases the risk of skeletal-related events in patients with bone metastases or fracture risk in osteoporosis patients, but these preclinical data may nonetheless help to inform discussions on the rationale for a "drug holiday" in managing the ONJ patient.
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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.