Introduction
Background
Rickets is a disease of growing bone that is unique to children and adolescents. It is caused by a failure of osteoid to calcify in a growing person. Failure of osteoid to calcify in adults is called osteomalacia. Vitamin D deficiency rickets occurs when the metabolites of vitamin D are deficient. Less commonly, a dietary deficiency of calcium or phosphorus may also produce rickets. Vitamin D-3 (cholecalciferol) is formed in the skin from a derivative of cholesterol under the stimulus of ultraviolet-B light. Ultraviolet light or cod liver oil was the only significant source of vitamin D until early in the 20th century when ergosterol (vitamin D-2) was synthesized from irradiated plant steroids.
During the Industrial Revolution, rickets appeared in epidemic form in temperate zones where the pollution from factories blocked the sun’s ultraviolet rays. Thus, rickets was probably the first childhood disease caused by environmental pollution.
Natural nutritional sources of vitamin D are limited primarily to fatty, ocean-going fish. In the United States, dairy milk is fortified with vitamin D (400 IU/L) Human milk contains little vitamin D, generally less than 20-40 IU/L. Therefore, infants who are breastfed are at risk for rickets, especially those who receive no oral supplementation and those who have darkly pigmented skin, which blocks penetration of ultraviolet light.
Anteroposterior and lateral radiographs of the wrist of an 8-year-old boy with rickets demonstrates cupping and fraying of the metaphyseal region.
Radiographs of the knee of a 3.6-year-old girl with hypophosphatemia depict severe fraying of the metaphysis.
Radiograph in a 4-year-old girl with rickets depicts bowing of the legs caused by loading.
Findings in patients with rickets.
Pathophysiology
Cholecalciferol (ie, vitamin D-3) is formed in the skin from 5-dihydrotachysterol. This steroid undergoes hydroxylation in 2 steps. The first hydroxylation occurs at position 25 in the liver, producing calcidiol (25-hydroxycholecalciferol), which circulates in the plasma as the most abundant of the vitamin D metabolites and is thought to be a good indicator of overall vitamin D status. The second hydroxylation step occurs in the kidney at the 1 position, where it undergoes hydroxylation to the active metabolite calcitriol (1,25-dihydroxycholecalciferol). This cholecalciferol is not technically a vitamin but a hormone.
Calcitriol acts at 3 known sites to tightly regulate calcium metabolism. Calcitriol promotes absorption of calcium and phosphorus from the intestine, increases reabsorption of phosphate in the kidney, and acts on bone to release calcium and phosphate. Calcitriol may also directly facilitate calcification. These actions increase the concentrations of calcium and phosphorus in extracellular fluid. The increase of calcium and phosphorus in extracellular fluid, in turn, leads to the calcification of osteoid, primarily at the metaphyseal growing ends of bones but also throughout all osteoid in the skeleton. Parathyroid hormone facilitates the 1-hydroxylation step in vitamin D metabolism.
In the vitamin D deficiency state, hypocalcemia develops, which stimulates excess parathyroid hormone, which stimulates renal phosphorus loss, further reducing deposition of calcium in the bone. Excess parathyroid hormone also produces changes in the bone similar to those occurring in hyperparathyroidism. Early in the course of rickets, the calcium concentration in the serum decreases. After the parathyroid response, the calcium concentration usually returns to the reference range, though phosphorus levels remain low. Alkaline phosphatase, which is produced by overactive osteoblast cells, leaks to the extracellular fluids so that its concentration rises to anywhere from moderate elevation to very high levels.
Intestinal malabsorption of fat and diseases of the liver or kidney may produce the clinical and secondary biochemical picture of nutritional rickets. Anticonvulsant drugs (eg, phenobarbital, phenytoin) accelerate metabolism of calcidiol, which may lead to insufficiency and rickets, particularly in children who are kept indoors in institutions.
Calcium and vitamin D intakes are low in infants who are fed vegan diets, particularly lactovegans, and monitoring of their vitamin D status is essential.1
Recent studies have noted that disorders of increased fibroblast growth factor 23 (FGF-23)function are associated with rickets.2
Frequency
United States
In the United States, vitamin D deficiency rickets does not occur in formula-fed infants because formula and milk sold in the United States contains 400 IU of vitamin D per liter. Except in pediatric patients with chronic malabsorption syndromes or end-stage renal disease, nearly all cases of rickets occur in breastfed infants who have dark skin and receive no vitamin D supplementation.
International
Incidence in Europe is similar to that in the United States. In sunny areas, such as in the Middle East, rickets may occur when infants are bundled in clothing and are not exposed to sunlight. In some parts of Africa, deficiency of calcium, phosphorus, or both in the diet may also lead to rickets, especially in societies were corn is predominant in the diet.
Mortality/Morbidity
Skeletal deformity and short stature may occur. Severe rickets has been associated with respiratory failure in children, and resulting pelvic distortion in females may lead to problems with vaginal delivery later in life.
Race
Individuals with dark skin are at increased risk for vitamin D deficiency rickets.
Sex
No sexual predilection is noted.
Age
By definition, rickets is observed only in growing children, although the effects may be observed later in life.
Clinical
History
- Generalized muscular hypotonia of an unknown mechanism is observed in most patients with clinical (as opposed to biochemical and radiographic) signs of rickets.
- Craniotabes manifests early in infants with vitamin D deficiency, although this feature may be normal in infants, especially for those born prematurely.
- If rickets occurs at a later age, thickening of the skull develops. This produces frontal bossing and delays the closure of the anterior fontanelle. In the long bones, laying down of uncalcified osteoid at the metaphases leads to spreading of those areas, producing knobby deformity, which is visualized on radiography as cupping and flaring of the metaphyses.
- Weight bearing produces deformities such as bowlegs and knock-knees.
- In the chest, knobby deformities results in the rachitic rosary along the costochondral junctions. The weakened ribs pulled by muscles also produce flaring over the diaphragm, which is known as Harrison groove. The sternum may be pulled into a pigeon-breast deformity.
- In more severe instances in children older than 2 years, vertebral softening leads to kyphoscoliosis. The ends of the long bones demonstrate that same knobby thickening. At the ankle, palpation of the tibial malleolus gives the impression of a double epiphysis (Marfan sign). Because the softened long bones may bend, they may fracture one side of the cortex (ie, greenstick fracture).
More on Rickets |
 Overview: Rickets |
| Differential Diagnoses & Workup: Rickets |
| Treatment & Medication: Rickets |
| Follow-up: Rickets |
| Multimedia: Rickets |
| References |
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References
Zmora E, Gorodischer R, Bar-Ziv J. Multiple nutritional deficiencies in infants from a strict vegetarian community. Am J Dis Child. Feb 1979;133(2):141-4. [Medline].
McKay CP, Portale A. Emerging topics in pediatric bone and mineral disorders 2008. Semin Nephrol. Jul 2009;29(4):370-8. [Medline].
Shah BR, Finberg L. Single-day therapy for nutritional vitamin D-deficiency rickets: a preferred method. J Pediatr. Sep 1994;125(3):487-90. [Medline].
Greer FR. Issues in establishing vitamin D recommendations for infants and children. Am J Clin Nutr. Dec 2004;80(6 Suppl):1759S-62S. [Medline].
[Guideline] Wagner CL, Greer FR. Prevention of rickets and vitamin D deficiency in infants, children, and adolescents. Pediatrics. Nov 2008;122(5):1142-52. [Medline].
Feldman D, Glorieux FH, Pike JW. Vitamin D. San Diego: Academic Press; 1997.
Harrison HE, Harrison HC. Disorders of calcium and phosphate metabolism in childhood and adolescence. Philadelphia: WB Saunders Co; 1979.
Price DI, Stanford LC Jr, Braden DS, Ebeid MR, Smith JC. Hypocalcemic rickets: an unusual cause of dilated cardiomyopathy. Pediatr Cardiol. Sep-Oct 2003;24(5):510-2. [Medline].
Further Reading
Keywords
rickets, infantile osteomalacia, juvenile osteomalacia, rachitis, vitamin D deficiency, skeletal deformity, growth disturbance, hypocalcemia, tetany, rickets, osteoid, nutritional rickets, craniotabes, familial hypophosphatemia rickets, environmental pollution, muscular hypotonia, frontal bossing, delayed closing of anterior fontanelle, knobby deformity, rachitic rosary, Harrison groove, pigeon-breast deformity, kyphoscoliosis, Marfan sign, greenstick fracture, bowlegs, knock-knees, tetany, dietary deficiency of calcium, dietary deficiency of phosphorus, vitamin D-2, ergosterol, chronic malabsorption syndromes, end-stage renal disease, short stature
