Rickets, Vitamin D, and Ca/P Metabolism.

Area of Science:

• Endocrinology and Nutritional Science
• Historical Medical Research
• Genetics and Molecular Biology

Background:

• Rickets has been a significant public health issue since Roman times, with early treatments involving sunlight and cod liver oil.
• The 20th century saw major advancements, including the discovery of vitamin D's role and its active form, calcitriol.
• Research into parathyroid hormone (PTH) and its function in calcium and phosphate metabolism also progressed significantly.

Purpose of the Study:

• To provide a historical overview of rickets research and treatment.
• To trace the discovery and characterization of vitamin D and parathyroid hormone.
• To highlight key genetic discoveries related to hypophosphatemic rickets and phosphorus metabolism.

Main Methods:

• Historical literature review of medical descriptions and treatment advancements for rickets.
• Biochemical identification of active compounds like vitamin D and parathyroid hormone fragments.
• Genetic linkage analysis and gene cloning to identify causative mutations in rickets and related disorders.

Main Results:

• Sunlight and cod liver oil were early effective treatments for rickets.
• Vitamin D (D2, D3) and its active form, calcitriol, were identified, with their synthesis pathways elucidated.
• Genetic defects in PHEX and FGF23 were identified as causes of hypophosphatemic rickets, transforming understanding of phosphorus regulation.

Conclusions:

• The understanding of rickets has evolved from empirical treatments to detailed molecular and genetic insights.
• Vitamin D and PTH pathways are crucial for calcium and phosphate homeostasis.
• Genetic discoveries have revolutionized the diagnosis and understanding of various forms of rickets and metabolic bone diseases.