Classification of Rickets
Rickets is classified into two major categories based on the underlying metabolic disturbance: calciopenic rickets (caused by defective intestinal calcium absorption) and phosphopenic rickets (caused by renal phosphate wasting). 1, 2
Primary Classification Framework
The fundamental distinction separates rickets based on which mineral deficiency drives the pathophysiology:
1. Calciopenic Rickets
This form results from inadequate calcium availability due to:
- Vitamin D deficiency (most common cause worldwide) 3
- Dietary calcium deficiency 3
- Vitamin D metabolism defects:
- 1-α-hydroxylase deficiency (Vitamin D-dependent rickets type 1)
- Vitamin D receptor defects (Vitamin D-dependent rickets type 2) 4
- Malabsorption states (fat malabsorption, liver disease) 3
The pathophysiology involves insufficient serum calcium, triggering PTH elevation, which then causes secondary hypophosphatemia through impaired renal phosphate conservation 3.
2. Phosphopenic Rickets
This form results from primary renal phosphate wasting and is subdivided into:
FGF23-dependent forms:
- X-linked hypophosphatemia (XLH) - most common hereditary form
- Autosomal dominant hypophosphatemic rickets (ADHR)
- Autosomal recessive hypophosphatemic rickets (ARHR)
- Tumor-induced osteomalacia (TIO) 5
FGF23-independent forms:
- Hereditary hypophosphatemic rickets with hypercalciuria (HHRH)
- Fanconi syndrome
- Renal tubular disorders 4, 5
Alternative Classification by Mechanism
A mechanistic classification based on the pathway to hypophosphatemia includes 6:
- High PTH activity (secondary to calcium deficiency)
- High FGF23 activity (primary phosphate wasting)
- Primary renal phosphaturia (tubular defects independent of PTH or FGF23)
Clinical Pitfall
The critical caveat is that hypophosphatemia is the final common pathway for ALL forms of rickets 6. Biochemical testing alone cannot definitively distinguish between calciopenic and phosphopenic rickets, as combined deficiencies are common 3. The distinction requires integrating clinical history, physical examination findings, radiographic changes, AND a comprehensive metabolic panel including serum calcium, phosphorus, 25OHD, PTH, alkaline phosphatase, and when indicated, 1,25(OH)2D and FGF23 levels 1, 7.
Nutritional rickets (vitamin D and/or calcium deficiency) must be excluded first before pursuing genetic testing for hereditary forms, as it remains the most prevalent cause globally and responds to simple supplementation 3, 8.