Evaluation of Multiple Fractures, Low Bone Mass, and Severe Osteomalacia in Children with Osteogenesis Imperfecta and Hypophosphatasia

Introduction: Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are examples of inherited bone disorders resulting in bones that fracture — crumble — and ruin. OI results from mutations in the COL1A1 or COL1A2 genes encoding type I collagen, whereas HPP is caused by gene defects affecting bone mineralization, specifically the ALPL gene. In cases of dual mutations, diagnosis and treatment varies between patients. Management is informed by genetic testing, bisphosphonates (for OI), and enzyme replacement therapy (for HPP). Aims and Objective: To analyze various parameters related to multiple fractures, low bone mass, and severe osteomalacia in paediatric patients diagnosed with osteogenesis imperfecta and hypophosphatasia. Method: This prospective observational study evaluated low bone mass, fracture prevalence, and osteomalacia severity in 64 children with Osteogenesis Imperfecta (OI) and Hypophosphatasia (HPP) compared to healthy controls. Bone biopsies were collected and analyzed using histomorphometry and light microscopy imaging after tetracycline labelling. Bone samples were prepared, stained, and evaluated. Result: The study revealed significantly lower height (p = 0.01) and BMD Z-scores (lumbar spine: p < 0.001) in patients with OI and HPP. Elevated serum ALP (p < 0.001), pyridoxal-5′-phosphate (p < 0.001), and changes in pyridoxal (p < 0.001) levels were observed post-treatment. Other findings included significant differences in serum phosphate (p = 0.05), 25-hydroxyvitamin D (p = 0.02), magnesium (p = 0.04), and urinary biomarkers between groups, indicating altered bone metabolism in patients. Conclusion: The study has concluded that there is a significant difference in bone density, metabolic parameters, and bone remodelling rates between patients and controls, indicating distinct bone metabolism profiles. These differences suggest a need for targeted therapeutic strategies for patients with OI and HPP.