Skeletal Morbidity in Children and Adolescents during and following Cancer Therapy

Abstract

Skeletal abnormalities are common in children and adolescents diagnosed and treated for a malignancy. The spectrum ranges from mild pain to debilitating osteonecrosis and fractures. In this review, we summarize the impact of cancer therapy on the developing skeleton, provide an update on therapeutic strategies for prevention and treatment, and discuss the most recent advances in musculoskeletal research. Early recognition of skeletal abnormalities and strategies to optimize bone health are essential to prevent long-term skeletal sequelae and diminished quality of life in childhood cancer survivors.

Keywords: Acute lymphoblastic leukemia; Chemotherapy; Fractures; Hematopoietic stem cell transplantation; Osteochondroma; Osteonecrosis; Radiotherapy; Retinoids.

Figure 1

The baseline prevalence and annual incidence proportions of vertebral and non-vertebral fractures in the 6-years following leukemia diagnosis. Reproduced with permission.¹¹ Copyright © 2018 Journal of Bone and Mineral Research.

Figure 2

Lateral spine radiographs from children with ALL and vertebral fractures. While clinically significant increases in spine BMD Z-scores were observed in all three patients, vertebral body reshaping was incomplete or absent in two of the three patients, as follows. (A) Complete vertebral body reshaping: lateral lumbar spine radiographs from a 5-year-old boy with pre-B cell ALL who presented at diagnosis with multiple vertebral fractures (I). Subsequent films showed progressive vertebral body reshaping (II, III), with complete reshaping at 5 years after diagnosis (IV). (B) Incomplete vertebral body reshaping: lateral lumbar spine radiographs from a 9-yearold girl with pre-B cell ALL who presented with a severe vertebral fracture at L₂ at baseline (I), incident vertebral fractures at 12 months at T₁₂ through L₄ (II), and incomplete vertebral body reshaping despite improvements in BMD Z-scores at 12 and 15 years of age (III and IV). (C) Absent vertebral body reshaping: lateral lumbar spine radiographs from a 17-year-old boy with pre-Bcell ALL who presented with a moderate vertebral fracture at L₂ at baseline (I), and absent vertebral body reshaping at subsequent time points (II to IV). LS BMD = lumbar spine bone mineral density; SDI = spinal deformity index from T₄ to L₄. Reproduced with permission.¹¹ Copyright © 2018 Journal of Bone and Mineral Research.

Figure 3

Bilateral distal femoral and bilateral proximal tibial valgus deformities noted in this patient following total body irradiation for hematopoietic stem cell transplantation. Diffuse, bony demineralization is present due to chronic glucocorticoid treatment. The leg length discrepancy required correction with a bilateral distal femoral and bilateral proximal tibial medial epiphysiodesis.

Figure 4

(A) Frontal and frog leg lateral views of the hip demonstrate widening of the left proximal femoral physis. (B) The epiphysis is slipped laterally and posteriorly consistent with left valgus SCFE. (C) Bilateral hip pinning of proximal femurs as surgical correction for the SCFE. Hip joint spaces post-surgical pinning are now symmetric with no evidence of avascular necrosis.

Figure 5

(A-B) X-ray imaging demonstrates an osteochondroma of the proximal fibula, a 5 × 3.1 cm, sessile lesion arising from the proximal fibular metadiaphysis that is continuous with the underlying bone cortex. This osteochondroma presented with clinical symptoms of pain with strenuous physical activity in a 12 year-old female with history of total body irradiation exposure for treatment of childhood leukemia and bone marrow transplantation. Notable growth of this lesion was appreciated on patient’s physical examination while on growth hormone therapy for underlying diagnosis of irradiation-induced growth hormone deficiency.