Metabolic bone disease of prematurity: current knowledge, controversies, and research priorities

Despite decades of research and significant improvements in neonatal nutrition, clinicians still struggle with fundamental questions about metabolic bone disease of prematurity diagnosis, treatment, and long-term consequences. This review examines what we know about metabolic bone disease of prematurity, the gaps in our understanding, and highlights the controversies in clinical practice. Typical practices include biochemical screening, which may begin at 3-4 weeks for at-risk infants, with alkaline phosphatase and phosphate levels serving as primary markers of disease. Nutritional optimization through adequate parenteral and enteral provisions, such as via fortified human milk or specialized preterm formulas, represents the main prevention and treatment approach. However, given the lack of consensus on diagnostic thresholds and definitions for metabolic bone disease of prematurity, there remain inconsistent prevention and treatment strategies. This review offers practical guidance based on current evidence, while identifying critical areas where additional research is needed to continue to improve outcomes.