An Overview of Rickets in Children

Abstract

Rickets is a common bone disease worldwide that is associated with disturbances in calcium and phosphate homeostasis and can lead to short stature and joint deformities. Rickets can be diagnosed based on history and physical examination, radiological features, and biochemical tests. It can be classified into 2 major groups based on phosphate or calcium levels: phosphopenic and calcipenic. Knowledge of categorization of the type of rickets is essential for prompt diagnosis and proper management. Nutritional rickets is a preventable disease through adequate intake of vitamin D through both dietary and sunlight exposure. There are other subtypes of rickets, such as vitamin D-dependent type 1 rickets and vitamin D-dependent type 2 rickets (due to defects in vitamin D metabolism), renal rickets (due to poor kidney function), and hypophosphatemic rickets (vitamin D-resistant rickets secondary to renal phosphate wasting wherein fibroblast growth factor-23 (FGF-23) often plays a major role), which requires closer monitoring and supplementation with activated vitamin D with or without phosphate supplements. An important development has been the introduction of burosumab, a human monoclonal antibody to FGF-23, which is approved for the treatment of X-linked hypophosphatemia among children 1 year and older.

Keywords: chronic kidney disease; hypocalcemia; hypophosphatemia; phosphorus; vitamin D.

Figure 1

Different types of rickets. ADHR, autosomal dominant hypophosphatemic rickets; ARHR, autosomal recessive hypophosphatemic rickets; CKD, chronic kidney disease; VDDR, vitamin D–dependent type 1 rickets; XLHR, X-linked hypophosphatemic rickets.

Figure 2

Sources and metabolism of vitamin D. PTH, parathyroid hormone.

Figure 3

Parathyroid/bone/kidney axis. 1. Parathyroid hormone (PTH) increases 1,25 dihydroxy vitamin (vit) D synthesis in the kidney. 2. Fibroblast growth factor 23 (FGF-23) is produced by bone and it acts on the kidney. 3. FGF-23 decreases PTH and 1,25 dihydroxy vitamin D. 4. Both PTH and 1,25 dihydroxy vitamin D increase FGF-23 syntheses.

Figure 4

Algorithmic approach to a child with rickets. CKD, chronic kidney disease; GFR, glomerular filtration rate; N, normal; PTH, parathyroid hormone; TMP, renal threshold phosphate concentration; TmPO4, renal tubular reabsorption of phosphate; VDDR, vitamin D–dependent type 1 rickets.