Bone mineral density deficits in childhood cancer survivors: Pathophysiology, prevalence, screening, and management

Abstract

As chemotherapy and other sophisticated treatment strategies evolve and the number of survivors of long-term childhood cancer grows, the long-term complications of treatment and the cancer itself are becoming ever more important. One of the most important but often neglected complications is osteoporosis and increased risk of fracture during and after cancer treatment. Acquisition of optimal peak bone mass and strength during childhood and adolescence is critical to preventing osteoporosis later in life. However, most childhood cancer patients have multiple risk factors for bone mineral loss. Cancer itself, malnutrition, decreased physical activity during treatment, chemotherapeutic agents such as steroids, and radiotherapy cause bone mineral deficit. Furthermore, complications such as growth hormone deficiency and musculoskeletal deformity have negative effects on bone metabolism. Low bone mineral density is associated with fractures, skeletal deformity, pain, and substantial financial burden not only for childhood cancer survivors but also for public health care systems. Thus, it is important to monitor bone health in these patients and minimize their risk of developing osteoporosis and fragility fractures later in life.

Bone morbidity in pediatric acute lymphoblastic leukemia

“…52,53) Vincristine, a vinca alkaloid that disrupts microtubular formation, reduces type 1 collagen synthesis, induces neuropathy leading to poor balance, and increases the risk of falls. 54)…”

The bone–fat interface: basic and clinical implications of marrow adiposity

“…But the resulting osteopenia and increased skeletal fragility later in life, particularly for children treated early, is a major co-morbidity. (81) Many of these patients have persistent marrow adiposity on bone biopsy or by MRI, and their bone density is usually well below age-matched controls. Lifelong treatment with anti-osteoporosis drugs is not a palatable or cost effective option.…”

Poor bone health at the end of puberty in childhood cancer survivors

“…[9,10] Possible risk factors (RFs) for BMD deficits include diagnosis (brain tumor, lymphoma, or leukemia), chemotherapeutic agents (corticosteroids or methotrexate), radiation protocol (cranial or total body irradiation), and simultaneous endocrine dysfunctions (gonadal dysfunction, growth hormone [GH] dysfunction, or thyroid abnormalities). [9,10] Many follow-up guidelines indicate the use of BDM to evaluate childhood cancer survivors who are at risk for BMD deficits. [11] Pubertal development is important for peak bone mass formation and future bone health.…”