A Systematic Review of Selected Musculoskeletal Late Effects in Survivors of Childhood Cancer

Abstract

Survivors of childhood cancer are at risk for treatment-related musculoskeletal late effects. Early detection and orthopedic intervention can help ameliorate musculoskeletal late effects and prevent subsequent complications. This systematic review summarizes the literature describing associations between cancer, its treatment, and musculoskeletal late effects. We searched PubMed and Web of Science for English language articles published between January 1970 and December 2012. The search was limited to investigations with at least 15 participants and conducted at least 2 years after completion of therapy for childhood, adolescent, or young adult cancer. Some late skeletal effects, including low bone mineral density, osteonecrosis, slipped capital femoral epiphyses, oncogenic rickets, and hormone-related growth disturbances have been previously reviewed and were excluded, as were outcomes following amputation and limb-salvage procedures. Of 2347 references identified, 30 met inclusion criteria and were retained. An additional 54 studies that met inclusion criteria were found in reference lists of retained studies. Of 84 studies, 60 focused on associations between radiotherapy, six between chemotherapy, and 18 between surgery and musculoskeletal late effects. We found that younger age, higher radiation dosage, and asymmetric or partial bone radiation volume influences the effects of radiation on the musculoskeletal system. Methotrexate and vincristine are associated with long-term muscular strength and flexibility deficits. Laminectomy and chest wall resection are associated with spinal malalignment, and enucleation is associated with orbital deformities among survivors. Radiotherapy, chemotherapy, and surgery are associated with musculoskeletal late effects independently and additively. Associations are additionally influenced by host and treatment characteristics.

Self-reported endocrine late effects in adults treated for brain tumours, Hodgkin and non-Hodgkin lymphoma: a registry based study in Northern Germany

“…These observations fit to previously published studies from UK where the evaluation of a General Practitioner database revealed a comparably increased risk of osteoporosis and diabetes, particularly in patients with non-Hodgkin disease. Interestingly, despite our expectations that children and adolescents would be more prone to develop late effects, especially of the bone, the frequencies of adult late effects observed in this study appear to be largely similar (5,27,28,29,30,31,32,33). There are a number of potential underlying mechanisms, which due to the nature of the study must remain speculative.…”

Musculoskeletal complications following total body irradiation in hematopoietic stem cell transplant patients

“…Though TBI and HSCT allow for reduced early mortality and improved long‐term survivorship, they are associated with several acute and late‐onset toxicities . Important musculoskeletal complications are summarized in Supplementary Table S1 and include short stature, physeal damage, angular deformities, reduced bone mineral density (BMD), vertebral fractures and deformity, osteonecrosis, SCFE, and the development of benign or malignant tumors …”

“…The effect of irradiation on the spine is multifactorial and related to both direct effects on the bone itself as well as endocrine derangements . Though loss of standing height is better documented, sitting height is affected to a greater extent .…”

“…This number is expected to more than double by 2020 (242,000 patients) and to increase more than fivefold by 2030 (502,000 patients) . Unfortunately, increased survival is accompanied by a high burden of late effects as a result of childhood cancer treatment …”

“…In this review, we hope to bring attention to these important late effects. An improved understanding and awareness of these complications is necessary, as early detection and orthopaedic interventions can ameliorate musculoskeletal late effects and prevent subsequent complications …”