Osteopenia in children who have undergone posterior fossa or craniospinal irradiation for brain tumors

Objectives: To determine lumbar spine and total body bone mineral density (BMD) in pediatric patients who have undergone cranial or craniospinal irradiation for posterior fossa tumors, specifically medulloblastoma and ependymoma and to analyze the association between degree of osteopenia and factors that may affect BMD. Methods: Retrospective and prospective data collection included medical record review and examination, including pubertal, dietary, and activity assessment. Lumbar spine and total body BMD were measured by means of dual energy x-ray absorptiometry. Patients were routinely observed by the endocrinology department, and hormone deficiencies were corrected promptly. A subset of patients received calcium and vitamin D supplementation and underwent repeat BMD measurement I year later. Results: Of 24 patients aged 4 to 20 years, 11 of whom were mate, recruited from 1996 through 1999, 19 had medulloblastoma. All 19 underwent craniospinal radiotherapy plus a boost to the posterior fossa (mean +/- SD of 5410 +/- 130 rad [54.1 +/- 1.3 Gy] to the posterior fossa, mean +/- SD of 3470 +/- 460 rad [34.7 +/- 4.6 Gy] to the whole brain and spinal axis), and 8 of 19 under-went chemotherapy. The remaining 5 patients had ependymoma and underwent irradiation to the posterior fossa only (mean SD of 5680 +/- 720 rad [ 56.8 +/- 7.2 Gy]). Therefore, there were 3 treatment groups: craniospinal irradiation and chemotherapy, only craniospinal irradiation, and only posterior fossa irradiation. Bone mineral studies were performed a mean +/- SD of 5.42 +/- 3.23 years after therapy. Our patients had lower total body BMD (mean z score, -0.47; 95% confidence interval, -0.85 to -0.09) and lumbar spine BMD (mean z score, -1.27; 95% confidence interval, -1.81 to -0.73) as compared with those of the the general population. There was no significant difference in mean lumbar spine BMD between patients in the 3 groups. Our patients consumed a diet deficient in vitamin D and calcium (mean +/- SD 53.6% +/- 24.1% and 70.0% +/- 37.4% of the amount recommended, respectively). Of 7 patients who underwent measurements 1 year later, 5 had in increase in BMD that was parallel to normal curves, with no compensatory increase. Four patients were hypothyroid, 6 were growth hormone deficient, and 6 were both. All hormones were replaced, with the exception of growth hormone in 1 patient. By using regression analysis, the factors that affected lumbar spine BMD, protectively in both cases, were calcium intake (beta = 0.015, 95% confidence interval, 0.001-0.029) and female sex (beta = 1.422, 95% confidence interval, 0.456-2.388). Conclusions: Children who have undergone irradiation for posterior fossa tumors have diminished total body and lumbar spine BMD, as compared with those of the general population. This reduction was similar within all 3 treatment groups, which suggests that chemotherapy did not play a major role and that localized irradiation may have systemic effects. This population often has balance and gait problems, so the risk of falling, coupled with osteopenia, may place them at considerably increased risk of fractures.