Chemotherapy-induced osteoporosis in pediatric oncology: pathophysiology and treatment

Juvenile osteoporosis is an increasingly recognized long-term complication in pediatric oncology. While advances in cancer therapy have improved survival, aggressive treatment protocols – chemotherapy, glucocorticoids, radiotherapy, surgery – often disrupt skeletal development during key phases of bone accrual. This review outlines the multifactorial pathophysiology of therapy-induced bone loss in children with cancer. The imbalance between bone formation and resorption is driven by inflammation, oxidative stress, hormonal deficits and direct drug toxicity. Agents such as methotrexate and glucocorticoids impair osteoblast function and enhance osteoclastogenesis. Endocrinopathies – particularly hypogonadism and growth hormone deficiency – further compromise peak bone mass acquisition. Compounding these effects are post-treatment nutritional deficits, physical inactivity, and psychological fatigue. Many survivors consume high-fat, low-nutrient diets and avoid exercise, worsening musculoskeletal health. These behaviors often stem from insufficient rehabilitation support and emotional exhaustion, perpetuating deconditioning and elevating fracture risk. Genetic factors are also implicated. Mutations in low-density lipoprotein receptor-related protein 5 (LRP5) and estrogen receptor 1 (ESR1) are associated with reduced bone mineral density in pediatric patients. Diagnosis is complicated by evolving pediatric criteria for bone density and growth-related variability in biomarkers. Nonetheless, early identification and continuous monitoring are essential. Interventions such as individualized physical activity programs, nutritional repletion, endocrine evaluation, and bisphosphonate therapy may counteract skeletal decline. In conclusion, secondary osteoporosis in pediatric cancer survivors reflects a convergence of oncologic, metabolic, behavioral, and genetic factors. Effective management requires early, multidisciplinary strategies targeting modifiable risks and predictive markers to preserve bone integrity and improve long-term quality of life.