Attributable risk and consequences of bone mineral density deficits in childhood cancer survivors

Goodenough CG; Baedke JL; Delaney AM; Wilson CL; Brinkman TM; Im C; Ware ME; Inaba H; Clark KL; Armstrong GT; Mulrooney DA; Pui CH; Green DM; Merchant TE; Srivastava DK; asui Y; Hudson MM; Robison LL; Kaste SC; Ness KK; Chemaitilly W

doi:10.1530/ey.22.9.8

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ESPE Yearbook of Paediatric Endocrinology (2025) 22 9.8 | DOI: 10.1530/ey.22.9.8

ESPEYB25 9. Oncology and Chronic Disease Bone Health after Childhood Cancer (1 abstracts)

9.8. Attributable risk and consequences of bone mineral density deficits in childhood cancer survivors

Goodenough CG , Baedke JL , Delaney AM , Wilson CL , Brinkman TM , Im C , Ware ME , Inaba H , Clark KL , Armstrong GT , Mulrooney DA , Pui CH , Green DM , Merchant TE , Srivastava DK , Yasui Y , Hudson MM , Robison LL , Kaste SC , Ness KK & Chemaitilly W

JAMA Netw Open. 2025 Jan 2;8(1):e2454069. PMID: 39792384. doi: 10.1001/jamanetworkopen.2024.54069. [email protected]

Brief summary: This study analysed cross-sectional and longitudinal data from a cohort of 3,919 adult survivors of childhood cancer (median age 32, 53% males) to determine the risk of moderate (≤1 SD) and severe (≤2 SD) bone mineral density (BMD) impairment, evaluated by lumbar quantitative computed tomography (QCT).

The prevalence of moderate or severe BMD deficits was 22% and 7%, respectively, and was higher in males (P<0.001). Severe deficits were associated with young age 5–9 years at cancer diagnosis, high dose of cranial radiotherapy ≥30 Gy, testicular or pelvic radiation, underweight, sedentary lifestyle, and smoking. BMD impairment was also associated with hypogonadism and growth hormone deficiency (GHD), which were untreated in 56% and 95% of patients, respectively. Survivors with moderate or severe BMD deficits were less likely to live independently and more likely to require personal assistance, report depressive symptoms, and experience poor quality of life.

Comment: This large study confirms previous findings and reinforces current recommendations that support long-term bone mineral density surveillance for survivors treated with cranial or craniospinal radiotherapy and total body irradiation¹. Modifiable risk factors (such as hypogonadism, growth hormone deficiency, smoking, and sedentary behaviour) represent important targets for intervention. In particular, the prevalence of untreated hormonal deficiencies should be carefully addressed, especially given the challenges these patients often face in maintaining regular physical activity. Limitations of the study include: (1) the exclusion of some eligible patients; (2) the absence of data on fractures and spinal X-rays; and (3) the lack of information on factors negatively impacting BMD, such as history of trauma, prevalent scoliosis, prolonged immobilization, or previous traumatic fractures. Finally, the high radiation exposure due to QCT should be avoided, particularly in this patient population. Indeed, even the most recent guidelines clearly recommend DXA as the preferred screening method^1-2.

References: 1. van Atteveld JE, Mulder RL, van den Heuvel-Eibrink MM, Hudson MM, Kremer LCM, Skinner R, Wallace WH, Constine LS, Higham CE, Kaste SC, Niinimäki R, Mostoufi-Moab S, Alos N, Fintini D, Templeton KJ, Ward LM, Frey E, Franceschi R, Pavasovic V, Karol SE, Amin NL, Vrooman LM, Harila-Saari A, Demoor-Goldschmidt C, Murray RD, Bardi E, Lequin MH, Faienza MF, Zaikova O, Berger C, Mora S, Ness KK, Neggers SJCMM, Pluijm SMF, Simmons JH, Di Iorgi N. Bone mineral density surveillance for childhood, adolescent, and young adult cancer survivors: evidence-based recommendations from the International Late Effects of Childhood Cancer Guideline Harmonization Group. Lancet Diabetes Endocrinol. 2021 Sep;9(9):622-637. doi: 10.1016/S2213-8587(21)00173-X. PMID: 34339631.2. Açikgöz G, Bora A, Nur S. Comparison of QCT and DEXA findings for lumbar vertebra in young adults and the elderly. Acta Radiol. 2024 Jul;65(7):759-764. doi: 10.1177/02841851241257524. PMID: 39087833.