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. 2022 Mar 10;14(6):1168. doi: 10.3390/nu14061168

Table 2.

Main etiologies of rickets.

Calcium Related
Calcium deficiency with normal or low-normal vitamin D status
Very low dietary calcium intake
Calcium malabsorption (similar causes as vitamin D malabsorption, see below)
Vitamin D-related
Severe vitamin D deficiency
Low sunshine exposure and low dietary intake
Malabsorption (e.g., after bariatric surgery, bowel resection, celiac disease, cholestatic liver disease, exocrine pancreatic insufficiency, inflammatory bowel disease)
Increased renal loss of vitamin D and 25OHD (nephrotic syndrome)
Increased catabolism: especially drug-induced or genetic mutations of CYP3A4
Impaired hepatic 25-hydroxylation: mostly due to genetic mutations of CYP2R1 (OMIM #600081)
Impaired renal 1α-hydroxylation: chronic kidney disease (renal osteomalacia), or genetic (=1α-hydroxylase (CYP27B1) deficiency (OMIM #264700)
Vitamin D resistant rickets
Hereditary vitamin D-resistant rickets (VDR mutations) (OMIM #277440)
Vitamin D-dependent rickets with normal VDR (hnRNP overexpression) (OMIM #600785)
Phosphate related rickets/osteomalacia or Hypophosphatemic rickets/osteomalacia
Gastrointestinal causes
Poor nutritional intake (e.g., breastfed very low birth weight infants),
Chronic diarrhea
Excessive phosphate binders
Renal phosphate wasting
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    Tumor-induced (oncogenic) osteomalacia

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    Fanconi syndrome (mostly HIV medications such as tenofovir)

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    X-linked dominant hypophosphatemic rickets (PHEX mutations) (OMIM #307800)

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    X-linked recessive hypophosphatemic rickets (CLCN5 mutations) (OMIM #300554)

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    Autosomal dominant hypophosphatemic rickets (FGF23 mutations) (OMIM #193100)

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    Autosomal recessive hypophosphatemic rickets type 1 (DMP1 mutations) (OMIM #241520), type 2 (ENPP1 mutations) (OMIM #613312)

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    Hereditary hypophosphatemic rickets with hypercalciuria (SLC34A3) (OMIM #241530)

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    Dent disease-1 (CLCN5 mutations) (OMIM #300009,)

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    Dent disease-2 (OCRL mutations) (OMIM #300555)

Rickets and osteomalacia related to inhibition of mineralization
Metabolic acidosis (genetic or acquired)
Metal related: aluminum toxicity (e.g., from antacids, dialysis fluid), fluorosis, iron, cadmium, strontium, etc.
Hypophosphatasia (inorganic pyrophosphate accumulation) (OMIM #146300)
Matrix abnormalities Type VI osteogenesis imperfecta (SERPINF1 mutations) (OMIM #613982)
Fibrogenesis imperfecta ossium
Axial osteomalacia