{"entity":{"id":"bone-modifying-agents","kind":"technology","name":"Bone-modifying agents (bisphosphonates, denosumab)","aka":[],"tldr":"Zoledronic acid and denosumab reduce fractures, spinal cord compression and bone pain from bone metastases and myeloma, prevent treatment-induced bone loss, and in postmenopausal breast cancer modestly reduce recurrence in bone.","summary":"Pamidronate (1995, myeloma) and zoledronic acid (2002) reduce skeletal-related events by ~30-40%; denosumab (anti-RANKL, 2010) is superior to zoledronic acid for delaying SREs in solid tumours and non-inferior in myeloma, without renal dosing. Adjuvant bisphosphonates reduce bone recurrence and breast cancer mortality in postmenopausal women (EBCTCG 2015 meta-analysis: 3.3% absolute mortality reduction) and are guideline-recommended; denosumab did not improve disease outcomes adjuvantly (D-CARE). De-escalated dosing (12-weekly zoledronic acid, CALGB 70604) is standard. Osteonecrosis of the jaw (1-2%; dental review), hypocalcaemia, atypical femoral fractures and rebound vertebral fractures after stopping denosumab are the key harms. Also used for hypercalcaemia of malignancy and cancer-treatment-induced bone loss (aromatase inhibitors, ADT).","status":"standard-of-care","asOf":"2026-09-08","wikipedia":"https://en.wikipedia.org/wiki/Bisphosphonate","links":[{"label":"EBCTCG adjuvant bisphosphonates (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(15)60908-4"},{"label":"ASCO bone-modifying agents guideline","url":"https://doi.org/10.1200/JCO.2017.75.4614"}],"tags":["gap-fill","supportive"],"related":[],"cancers":["multiple-myeloma","breast-hr-positive","prostate","nsclc","rcc"],"sections":["supportive-care","rejuvenation"],"technologies":["pain-management","palliative-radiotherapy","survivorship-care-plan","cancer-treatment-bone-loss"],"targets":[],"drugs":["radium-223"],"companies":["outperform-cancer"],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":["paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet","paper-van-poznak-j-clin-oncol"],"journals":[],"dependsOn":[],"notes":[],"principle":"Inhibit osteoclast-mediated bone resorption (bisphosphonates via farnesyl pyrophosphate synthase in osteoclasts; denosumab by neutralising RANKL) to reduce the vicious cycle between tumour cells and bone turnover.","strengths":["Large reductions in fractures and cord compression","Adjuvant survival benefit in postmenopausal breast cancer","Generic zoledronic acid is cheap; 12-weekly dosing"],"limitations":["Osteonecrosis of the jaw","Denosumab discontinuation rebound","Optimal duration unknown"],"since":1995},"route":"/technologies/bone-modifying-agents/","neighbours":{"cancer":[{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"metastatic-cancer","kind":"cancer","name":"Metastatic cancer (cancer that has spread)","route":"/cancers/metastatic-cancer/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"nsclc","kind":"cancer","name":"Non-small-cell lung cancer","route":"/cancers/nsclc/"},{"id":"parathyroid-carcinoma","kind":"cancer","name":"Parathyroid carcinoma","route":"/cancers/parathyroid-carcinoma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"},{"id":"rcc","kind":"cancer","name":"Renal cell carcinoma","route":"/cancers/rcc/"}],"section":[{"id":"rejuvenation","kind":"section","name":"Recovery & Rejuvenation","route":"/fronts/rejuvenation/"},{"id":"supportive-care","kind":"section","name":"Supportive Care & Survivorship","route":"/fronts/supportive-care/"}],"technology":[{"id":"rejuv-paed-bone","kind":"technology","name":"Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds","route":"/technologies/rejuv-paed-bone/"},{"id":"cancer-treatment-bone-loss","kind":"technology","name":"Bone loss caused by cancer treatment, and what rebuilds it","route":"/technologies/cancer-treatment-bone-loss/"},{"id":"pain-management","kind":"technology","name":"Cancer pain management","route":"/technologies/pain-management/"},{"id":"palliative-radiotherapy","kind":"technology","name":"Palliative radiotherapy","route":"/technologies/palliative-radiotherapy/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"}],"drug":[{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},{"id":"ibandronic-acid","kind":"drug","name":"Ibandronic acid","route":"/drugs/ibandronic-acid/"},{"id":"pamidronate","kind":"drug","name":"Pamidronate","route":"/drugs/pamidronate/"},{"id":"radium-223","kind":"drug","name":"Radium-223 dichloride","route":"/drugs/radium-223/"},{"id":"zoledronic-acid","kind":"drug","name":"Zoledronic acid","route":"/drugs/zoledronic-acid/"}],"company":[{"id":"outperform-cancer","kind":"company","name":"Outperform Cancer","route":"/companies/outperform-cancer/"}],"paper":[{"id":"paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet","kind":"paper","name":"Adjuvant bisphosphonate treatment in early breast cancer: meta-analyses of individual patient data from randomised trials","route":"/key-papers/paper-early-breast-cancer-trialists-collaborative-group-ebctcg-lancet/"},{"id":"paper-van-poznak-j-clin-oncol","kind":"paper","name":"Role of Bone-Modifying Agents in Metastatic Breast Cancer: An American Society of Clinical Oncology-Cancer Care Ontario Focused Guideline Update","route":"/key-papers/paper-van-poznak-j-clin-oncol/"}],"term":[{"id":"bone-metastases","kind":"term","name":"Bone metastases and skeletal-related events","route":"/terms/bone-metastases/"}],"pathway":[{"id":"organ-tropism-seed-soil","kind":"pathway","name":"Organ tropism: seed and soil","route":"/pathways/organ-tropism-seed-soil/"}],"target":[{"id":"rankl","kind":"target","name":"RANK ligand (RANKL)","route":"/targets/rankl/"}],"trial":[{"id":"nct07028268","kind":"trial","name":"A Trial of SHR-2017 Injection in Patients With Bone Metastases From Solid Tumors","route":"/trials/nct07028268/"}]}}