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A child treated during the years in which bone is laid down may never reach the peak bone mass they would have had, which is a different problem from an adult losing bone already built. Thirty per cent of adult survivors of childhood leukaemia had low bone density, most strongly associated with growth hormone deficiency and smoking, both treatable.
Bone mass is built through childhood and adolescence and peaks in the twenties. Treatment given in that window does not only remove bone, it prevents bone from being made, so the adult starts from a lower ceiling and reaches the fracture threshold earlier.
The measured prevalence. In 862 adult survivors of childhood acute lymphoblastic leukaemia in the St Jude Lifetime Cohort, median age 31.3 (range 18.4 to 59.7), bone density measured by quantitative computed tomography of the first and second lumbar vertebrae was low (an age- and sex-standardised z score below minus one) in 30 per cent, and 18.6 per cent met criteria for frailty or prefrailty. After adjustment for body mass index, low bone density was associated with growth hormone deficiency in men (odds ratio 1.59, 95 per cent confidence interval 1.02 to 2.13) and current smoking (1.71, 1.02 to 2.85), and in women with growth hormone deficiency (2.18, 1.26 to 3.78) and moderate alcohol consumption (2.09, 1.14 to 3.83). Frailty or prefrailty in men was associated with growth hormone deficiency (2.97, 1.56 to 5.67) and smoking (3.26, 1.65 to 6.43). The authors' conclusion is that survivors "should receive counseling regarding lifestyle and undergo screening for hormonal deficits to minimize the risk of low BMD and frailty", which is to say that the two largest associations found are both treatable. Across all diagnoses in the same cohort, osteoporosis by clinical criteria had a crude prevalence of 9.6 per cent.
Osteonecrosis is the other bone problem, and it is a treatment complication rather than a slow deficit. It follows the steroids given in leukaemia protocols, it hurts, and it can destroy a hip or a knee in a teenager. In a nationwide Austrian cohort of 1,127 children with newly diagnosed acute lymphoblastic leukaemia treated on AIEOP-BFM-ALL 2000 and 2009 protocols, 73 developed symptomatic osteonecrosis, a five-year cumulative incidence of 7 per cent plus or minus 1, with a median time to onset of 1.64 years. Age at diagnosis was the dominant risk factor and the only independent predictor in multivariable analysis: the five-year incidence was 22 per cent plus or minus 3 in patients aged 10 to 18 against 2 per cent plus or minus 0 in those aged 1 to 9.
What to do. The Children's Oncology Group long-term follow-up guidelines include bone mineral density surveillance based on exposure, and the International Guideline Harmonization Group has published harmonised bone mineral density recommendations; osteonecrosis is on the group's list of topics still in development. The practical measures are the ones that would be offered to anyone: enough calcium and vitamin D, weight-bearing and resistance exercise, not smoking, and correcting the hormone deficits above. Bisphosphonates in survivors of childhood cancer have no fracture-reduction trial behind them and are used case by case; the adult evidence for cancer treatment-induced bone loss is in the separate record in this front and does not transfer directly to a person whose peak bone mass was never reached.
What comes back, and when: density improves with treatment of the underlying hormone deficiency and with exercise and nutrition, over years rather than months, and that is a real recovery. The peak bone mass never achieved is not recovered, which is the argument for acting while the survivor is still in their twenties rather than when a fracture arrives. Osteonecrosis once established does not reverse, and the question becomes joint preservation or replacement.
Bone mineral accrues through childhood under growth hormone, sex steroid and mechanical loading signals, with peak mass reached in the third decade. Glucocorticoids suppress osteoblasts and raise resorption; methotrexate impairs osteoblast function; cranial radiotherapy removes the growth hormone and gonadotrophin signals that drive accrual; and prolonged inactivity removes the loading. Osteonecrosis is a separate, vascular event in which steroid-induced marrow adipocyte expansion and altered perfusion cause segmental bone death, which is why its risk peaks in adolescents with larger skeletal marrow spaces rather than in younger children.
Query for this technology: (TITLE:"Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds" OR ABSTRACT:"Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds") AND (cancer OR tumor OR tumour OR oncology OR carcinoma OR lymphoma OR leukemia OR leukaemia OR myeloma OR sarcoma OR melanoma OR glioma). Results are unfiltered search hits about Bone after childhood cancer: peak bone mass, osteonecrosis and what rebuilds, not a curated reading list.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, Frailty and late effects in survivors, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), Childhood cancers (all types), Methotrexate and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, The pituitary, puberty and the hypothalamic axis after cranial radiotherapy in childhood, The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.
Shares International Guideline Harmonization Group for late effects of childhood cancer, St Jude Lifetime Cohort Study (SJLIFE), The Children's Oncology Group Long-Term Follow-Up Guidelines, How much illness childhood cancer survivors carry, and at what age and the tags rejuvenation, survivorship, paediatric, late-effects.