ISSN 1662-4009 (online)

ESPE Yearbook of Paediatric Endocrinology (2023) 20 7.8 | DOI: 10.1530/ey.20.7.8

D.T.C.deWinter-2@prinsesmaximacentrum.nl Lancet Diabetes Endocrinol. 2023 Jan;11(1):21–32.


Brief summary: This Dutch cross-sectional study aimed to assess risk factors for impaired bone mineral density (BMD) and fractures (particularly vertebral fractures) in adult survivors of childhood cancer. The relationships between low BMD (Z-score ≤–1), very low BMD (Z-score ≤–2), fractures, vertebral fractures, and demographic, treatment-related, endocrine, and lifestyle-related factors was analyzed by logistic regression.

BMD was assessed by dual-energy x-ray absorptiometry (DXA). Fractures that occurred at least 5 years after cancer diagnosis were self-reported and further defined using available medical history. Fracture history was compared to population data from the Swedish national registry.

Low BMD was found in 559/1548 patients (36.1%) and very low BMD in 149/1548 (9.6%). Factors associated with low BMD were: male sex, underweight, high carboplatin dose, any cranial radiotherapy, hypogonadism, hyperthyroidism, low physical activity, and severe vitamin D deficiency. Factors associated with very low BMD were: male sex, underweight, cranial radiotherapy, growth hormone deficiency, and severe vitamin D deficiency. The standardized incidence ratio of any first fracture was 3.53 for men, and 5.35 for women, and 33/249 (13.3%) participants had vertebral fractures. Factors specifically associated with vertebral fractures were: older age at follow-up, previous treatment with platinum compounds, growth hormone deficiency, and low physical activity.

It is well known that childhood cancer survivors are prone to skeletal comorbidities in adulthood. In this study, reduced BMD (particularly very low lumbar spine BMD) was found to be a strong indicator for increased fracture risk. However, the cross-sectional design could only assess associations between current risk factors and history of fractures, and not their effects on future fracture risk. Moreover, fragility fractures resulting from low-energy trauma could not be differentiated from high-energy fractures, and vertebral fracture assessment was performed only in a subgroup of patients.

Interestingly, high-dose carboplatin therapy was identified as a new and independent treatment-related risk factor for low BMD. On the contrary, it is noteworthy that treatment with high doses of glucocorticoids (expressed as prednisone-equivalent dose) was not associated with either low or very low BMD or fracture risk. Adult survivors of childhood cancer are confirmed to be at increased risk of vertebral and non-vertebral fractures compared to the general population. Survivors treated with cranial, craniospinal, or total body irradiation show the highest risk and need intensive long-term follow-up of bone health. Surveillance is also recommended for cancer survivors with endocrine disorders as growth hormone deficiency, hyperthyroidism, and hypogonadism. Lifestyle changes, such as increased physical activity and an adequate vitamin intake, could contribute to improved bone health.

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