{"entity":{"id":"cancer-treatment-bone-loss","kind":"technology","name":"Bone loss caused by cancer treatment, and what rebuilds it","aka":[],"tldr":"Hormone treatments, chemotherapy that stops the ovaries and long courses of steroids all thin the bones, fast enough to measure within a year. Some of it comes back when the treatment stops, and the drugs that prevent fracture while it is going on are well proven.","summary":"Four cancer treatments take bone, and each has been measured.\n\nAndrogen deprivation for prostate cancer: in the trial that first quantified it, men on leuprolide alone lost 3.3 per cent of lumbar spine bone mineral density, 2.1 per cent at the trochanter and 1.8 per cent at the total hip over 48 weeks, with trabecular spine density falling 8.5 per cent (Smith, NEJM 2001).\n\nAromatase inhibitors: in the bone substudy of the ATAC trial, median bone mineral density over five years of anastrozole fell 6.08 per cent at the lumbar spine and 7.24 per cent at the total hip, while the tamoxifen group gained 2.77 and 0.74 per cent. The same substudy recorded the reassurance that is usually left out: \"No patients with normal BMD at baseline became osteoporotic at 5 years.\"\n\nChemotherapy that stops the ovaries: among 35 premenopausal women whose ovaries failed during adjuvant chemotherapy, median spine density fell 4.0 per cent in the first six months and a further 3.7 per cent in the next six, while the 14 who kept ovarian function had no significant loss (Shapiro, JCO 2001). The loss tracks the oestrogen, not the drug.\n\nSteroids: weeks to months of dexamethasone or prednisolone, standard in myeloma and lymphoma, cause glucocorticoid bone loss on top of any of the above.\n\nWhat to do about it. ASCO's 2019 guideline advises assessing fracture risk with an established tool first, obtaining a bone density scan for those at substantial risk, optimising nutrition, exercise and lifestyle for everyone, and, where a drug is indicated, using \"bisphosphonates or denosumab at osteoporosis-indicated dosages\". The randomised evidence behind that is strong: in ABCSG-18, denosumab 60 mg twice a year in 3,420 postmenopausal women on an aromatase inhibitor halved the risk of a first clinical fracture (hazard ratio 0.50, 92 fractures against 176), with no adjudicated osteonecrosis of the jaw. In men on androgen deprivation, the same dose raised lumbar spine density by 5.6 per cent at 24 months against a 1.0 per cent loss on placebo and cut new vertebral fractures at 36 months from 3.9 to 1.5 per cent.\n\nVitamin D and calcium are where the honest answer disappoints. Correcting a genuine deficiency is worth doing and guidelines advise adequate intake alongside any bone drug, but supplements are not a substitute for one: in VITAL, 2,000 international units of vitamin D3 daily in 25,871 generally healthy adults made no difference to total, non-vertebral or hip fractures over a median 5.3 years. Those people were not selected for low bone density or on bone-losing cancer treatment, so the trial does not say vitamin D is useless in this setting; it says it is not the treatment.\n\nWhat comes back, and when: partial, and slowly. After five years of anastrozole stops, lumbar spine density rose again by a median 2.35 per cent in the sixth year and 4.02 per cent in the seventh, so the aromatase-inhibitor loss is not permanent. Bone lost on androgen deprivation recovers if testosterone returns, and bone lost to chemotherapy-induced ovarian failure recovers if ovarian function returns, which is itself age-dependent. A fracture that has already happened does not reverse, which is the argument for measuring and treating early rather than waiting.","status":"standard-of-care","asOf":"2026-10-02","wikipedia":"https://en.wikipedia.org/wiki/Osteoporosis","links":[{"label":"Management of Osteoporosis in Survivors of Adult Cancers With Nonmetastatic Disease: ASCO guideline (JCO 2019)","url":"https://doi.org/10.1200/JCO.19.01696"},{"label":"Pamidronate to prevent bone loss during androgen-deprivation therapy for prostate cancer (NEJM 2001)","url":"https://doi.org/10.1056/NEJMoa010845"},{"label":"Effect of anastrozole on bone mineral density: 5-year results from the ATAC trial (JCO 2008)","url":"https://doi.org/10.1200/JCO.2007.11.0726"},{"label":"Long-term effects of anastrozole on bone mineral density: 7-year results from the ATAC trial (Ann Oncol 2011)","url":"https://doi.org/10.1093/annonc/mdq541"},{"label":"Ovarian failure after adjuvant chemotherapy is associated with rapid bone loss (JCO 2001)","url":"https://doi.org/10.1200/JCO.2001.19.14.3306"},{"label":"Adjuvant denosumab in breast cancer (ABCSG-18) (Lancet 2015)","url":"https://doi.org/10.1016/S0140-6736(15)60995-3"},{"label":"Denosumab in men receiving androgen-deprivation therapy for prostate cancer (NEJM 2009)","url":"https://doi.org/10.1056/NEJMoa0809003"},{"label":"Supplemental vitamin D and incident fractures in midlife and older adults (VITAL) (NEJM 2022)","url":"https://doi.org/10.1056/NEJMoa2202106"}],"tags":["rejuvenation","survivorship","evidence:strong"],"related":[],"cancers":["prostate","breast-hr-positive","multiple-myeloma","dlbcl"],"sections":["rejuvenation","supportive-care","hormonal"],"technologies":["bone-modifying-agents","survivorship-care-plan","exercise-prescription-after-cancer","vitamin-d-omega3-supplementation","androgen-deprivation","endocrine-therapy"],"targets":[],"drugs":["denosumab","zoledronic-acid","letrozole","anastrozole","exemestane","leuprolide","goserelin","tamoxifen"],"companies":[],"institutions":[],"pathways":[],"terms":["treatment-induced-bone-loss","late-effects","aromatase-inhibitor","ovarian-function-suppression"],"trials":[],"people":[],"bottlenecks":["b-survivorship"],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"principle":"Oestrogen and testosterone restrain osteoclasts. Removing either, by an aromatase inhibitor, androgen deprivation or chemotherapy-induced ovarian failure, raises bone resorption above formation and density falls fastest in trabecular bone, which is why the spine goes first. Bisphosphonates and the anti-RANKL antibody denosumab suppress the osteoclast side of the balance.","strengths":["The loss is measurable with a scan patients can be sent for in any hospital","Randomised fracture reduction with denosumab in both the breast and prostate settings","Much of the density returns when the treatment that caused it stops"],"limitations":["Risk assessment and scanning are inconsistently done, so the first sign is often a fracture","Stopping denosumab without a follow-on drug causes rebound vertebral fractures","Vitamin D alone does not prevent fractures"]},"route":"/technologies/cancer-treatment-bone-loss/","neighbours":{"cancer":[{"id":"dlbcl","kind":"cancer","name":"Diffuse large B-cell lymphoma","route":"/cancers/dlbcl/"},{"id":"breast-hr-positive","kind":"cancer","name":"HR-positive / HER2-negative breast cancer","route":"/cancers/breast-hr-positive/"},{"id":"multiple-myeloma","kind":"cancer","name":"Multiple myeloma","route":"/cancers/multiple-myeloma/"},{"id":"prostate","kind":"cancer","name":"Prostate cancer","route":"/cancers/prostate/"}],"section":[{"id":"hormonal","kind":"section","name":"Hormonal Therapy","route":"/fronts/hormonal/"},{"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":"androgen-deprivation","kind":"technology","name":"Androgen deprivation & AR pathway inhibitors","route":"/technologies/androgen-deprivation/"},{"id":"rejuv-paed-bone","kind":"technology","name":"Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds","route":"/technologies/rejuv-paed-bone/"},{"id":"bone-modifying-agents","kind":"technology","name":"Bone-modifying agents (bisphosphonates, denosumab)","route":"/technologies/bone-modifying-agents/"},{"id":"rejuv-tx-bone-eyes-kidneys-lungs","kind":"technology","name":"Bone, eyes, kidneys and lungs after transplant","route":"/technologies/rejuv-tx-bone-eyes-kidneys-lungs/"},{"id":"endocrine-therapy","kind":"technology","name":"Endocrine therapy (SERMs, AIs, SERDs)","route":"/technologies/endocrine-therapy/"},{"id":"menopause-after-cancer-treatment","kind":"technology","name":"Menopause brought on by cancer treatment, and the options for it","route":"/technologies/menopause-after-cancer-treatment/"},{"id":"ovarian-function-after-chemotherapy","kind":"technology","name":"Ovarian function after chemotherapy: who recovers, and when","route":"/technologies/ovarian-function-after-chemotherapy/"},{"id":"rejuv-mind-sleeping-tablets-after-cancer","kind":"technology","name":"Sleeping tablets after cancer: what they do and what they do not","route":"/technologies/rejuv-mind-sleeping-tablets-after-cancer/"},{"id":"survivorship-care-plan","kind":"technology","name":"Survivorship care and late-effects surveillance","route":"/technologies/survivorship-care-plan/"},{"id":"testosterone-after-cancer-treatment","kind":"technology","name":"Testosterone after cancer treatment in men","route":"/technologies/testosterone-after-cancer-treatment/"},{"id":"exercise-prescription-after-cancer","kind":"technology","name":"The exercise prescription after cancer: the dose the guidelines state","route":"/technologies/exercise-prescription-after-cancer/"},{"id":"vitamin-d-omega3-supplementation","kind":"technology","name":"Vitamin D and omega-3 supplementation","route":"/technologies/vitamin-d-omega3-supplementation/"}],"drug":[{"id":"anastrozole","kind":"drug","name":"Anastrozole","route":"/drugs/anastrozole/"},{"id":"denosumab","kind":"drug","name":"Denosumab","route":"/drugs/denosumab/"},{"id":"exemestane","kind":"drug","name":"Exemestane","route":"/drugs/exemestane/"},{"id":"goserelin","kind":"drug","name":"Goserelin / leuprolide (ovarian function suppression)","route":"/drugs/goserelin/"},{"id":"letrozole","kind":"drug","name":"Letrozole (and other aromatase inhibitors)","route":"/drugs/letrozole/"},{"id":"leuprolide","kind":"drug","name":"Leuprolide (leuprorelin) and GnRH agonists","route":"/drugs/leuprolide/"},{"id":"tamoxifen","kind":"drug","name":"Tamoxifen","route":"/drugs/tamoxifen/"},{"id":"zoledronic-acid","kind":"drug","name":"Zoledronic acid","route":"/drugs/zoledronic-acid/"}],"term":[{"id":"aromatase-inhibitor","kind":"term","name":"Aromatase inhibitor","route":"/terms/aromatase-inhibitor/"},{"id":"late-effects","kind":"term","name":"Late effects and survivorship toxicity","route":"/terms/late-effects/"},{"id":"ovarian-function-suppression","kind":"term","name":"Ovarian function suppression (OFS)","route":"/terms/ovarian-function-suppression/"},{"id":"treatment-induced-bone-loss","kind":"term","name":"Treatment-induced bone loss","route":"/terms/treatment-induced-bone-loss/"}],"bottleneck":[{"id":"b-survivorship","kind":"bottleneck","name":"Survivorship and late effects are neglected","route":"/bottlenecks/b-survivorship/"}]}}