eMedicine Specialties > Radiology > Pediatrics

Rickets

Author: Rick R van Rijn, MD, PhD, Pediatric Radiologist, Department of Radiology, Academic Medical Center Amsterdam
Coauthor(s): Kieran McHugh, MBBCh, Honorary Lecturer, The Institute of Child Health; Consultant Pediatric Radiologist, Department of Radiology, Great Ormond Street Hospital for Children, London, UK
Contributor Information and Disclosures

Updated: Mar 18, 2009

Introduction

Background

Rickets is an entity in which mineralization is decreased at the level of the growth plates, resulting in growth retardation and delayed skeletal development. Osteomalacia is found within the same spectrum, affects trabecular bone, and results in undermineralization of osteoid bone. By definition, rickets is found only in children prior to the closure of the growth plates, while osteomalacia occurs in persons of any age. Any child with rickets also has osteomalacia, while the reverse is not necessarily true.^1,2,3

Pathophysiology

Rickets results from a vitamin D deficiency, the abnormal metabolism of vitamin D, or the abnormal metabolism or excretion of inorganic phosphate. Histologic changes are seen at the level of the growth plates or, more specifically, at the level of the hypertrophic zone, where an increased number of disorganized cells is found. The increased number of cells results in increased width and thickness of the hypertrophic zone.

Understanding of the pathophysiology of vitamin D–deficiency rickets requires knowledge of the biochemistry of vitamin D (cholecalciferol). What generally is termed vitamin D is actually a prohormone, which requires activation. In the human body, vitamin D can be either exogenous (vitamin D₂, acquired through food supplements) or endogenous (vitamin D₃, resulting from exposure of the body to sunlight). Activation is accomplished by hydroxylation of vitamin D at 2 sites. The first hydroxylation, at the 25 site on the vitamin D molecule, occurs mainly in the liver, although this process may also occur in the kidneys and intestine. This step in the vitamin D pathway is a self-limiting feedback system, which is necessary because 25-hydroxyvitamin D persists only for several days in the human body, while vitamin D itself can be stored in the liver for months.

The second hydroxylation, at the 1 site on the vitamin D molecule, always takes place in the kidneys; this process is regulated by the enzyme 25-hydroxyvitamin D₁ a-hydroxylase. Only after the second hydroxylation occurs does vitamin D become active (1,25-dihydroxyvitamin D). Activation is regulated by parathyroid hormone (PTH), a potent inhibitor of 25-hydroxyvitamin D₁ a-hydroxylase. When PTH is suppressed, 25-hydroxyvitamin D is converted into the much less potent 24,25-dihydroxyvitamin D. The action of 1,25-dihydroxyvitamin D is 2-fold; first, it regulates and enhances absorption of calcium from the intestines, and second, it may stimulate differentiation of stem cells into osteoclasts.

Metabolic bone disease of prematurity, seen in infants with very low birthweight (VLBW), can occur in as many as 55% of infants weighing less than 1000 g at birth.⁴ In the third trimester of pregnancy, bone mineral density shows the highest rate of increase. In this stage, the requirement for calcium and phosphorus is at its maximum level. If the amount of dietary calcium is too low, renal a-1-hydroxylase is activated and 1,25-dihydroxyvitamin D is generated. This in turn increases the uptake of calcium and phosphorus in the gastrointestinal tract and inhibits the release of PTH.

Although PTH reduces the output of phosphorus in urine and decreases bone absorption, the potent bone-absorbing capacities of 1,25-dihydroxyvitamin D leads to a net decrease in bone mass. Therefore, it is of the utmost importance that nutrition be especially adapted in infants with VLBW. In utero, the fetus receives approximately 120-140 mg/kg of calcium and 70-80 mg/kg of phosphorus, but breast milk contains only 60 mg/kg of calcium and 30 mg/kg of phosphorus. It is easy to see that these levels are inadequate and that infants with VLBW need special formula to gain bone mass.

(For further discussion, see Backstrom,⁴ as well as Disorders of Bone Mineralization, Hypophosphatemic Rickets, and Osteomalacia and Renal Osteodystrophy.)

Because rickets results from a metabolic disturbance, the underlying disease should be diagnosed. The causes of rickets can be classified into 11 main categories:

• Vitamin D deficiency
  • Dietary deficiency
  • Deficient endogenous synthesis
• Gastrointestinal tract disorders
  • Small intestine diseases with malabsorption
  • Partial or total gastrectomy
  • Hepatobiliary disease
  • Chronic pancreatic insufficiency
• Disorders of vitamin D metabolism
  • Hereditary - Pseudovitamin D deficiency or vitamin D dependency (types I and II)
  • Acquired
    • Use of anticonvulsants
    • Chronic renal failure
• Acidosis
  • Distal renal tubular acidosis (classic or type I)
  • Secondary forms of renal acidosis
  • Ureterosigmoidostomy
  • Drug-induced disease
    • Chronic acetazolamine ingestion
    • Chronic ammonium chloride ingestion
• Chronic renal failure
• Phosphate depletion
  • Dietary - Low phosphate intake plus ingestion of nonabsorbable antacids
    • Hereditary - X-linked hypophosphatemic rickets or adult-onset vitamin D–resistant hypophosphatemic osteomalacia
    • Acquired - Sporadic hypophosphatemic osteomalacia (phosphate diabetes), tumor-associated (oncogenous) rickets, osteomalacia, neurofibromatosis, and fibrous dysplasia
• Generalized renal tube disorders
  • Primary renal tube disorders
  • Renal tube disorders associated with systemic metabolic abnormality
    • Cystinosis
    • Glycogenosis
    • Lowe syndrome
  • Systemic disorder with associated renal disease
    • Hereditary - Inborn errors (Wilson disease, tyrosinemia) and neurofibromatosis
    • Acquired - Multiple myeloma, nephrotic syndrome, and kidney transplantation
    • Intoxication-related - Cadmium, lead, outdated tetracycline
• Primary mineralization defects
  • Hereditary
  • Acquired
    • Diphosphonate treatment
    • Fluoride treatment
• States of rapid bone formation with or without a relative defect in bone resorption
  • Postoperative hyperparathyroidism with osteitis fibrosa cystica
  • Osteopetrosis
• Defective matrix synthesis - Fibrogenesis imperfecta ossium
• Miscellaneous
  • Magnesium-dependent conditions
  • Axial osteomalacia
  • Parenteral alimentation
  • Aluminum intoxication
  • Isofosfamide treatment

Frequency

United States

In the Western world, exact data on the prevalence of rickets are hard to find; however, Welch and colleagues stated that around the year 1900, finding children younger than 2 years who were not affected would have been difficult in urban areas.⁵ In the following 50 years, with the introduction of dietary supplements for children, rickets was eradicated almost completely.

In the last few years, reports have indicated that the prevalence of rickets has increased. A recent study described 5 cases of vitamin D–deficient rickets in Georgia; in all cases, the child was a black male who was breastfed for more than 6 months without additional vitamin D supplementation.⁶

When the mother has a low vitamin D level, the child can be born with a relative vitamin D deficiency as a result of decreased maternal transfer. In these cases, vitamin D supplementation during pregnancy can increase birthweight and growth. Additionally, the breast milk of a mother with a low vitamin D level will contain less vitamin D than normal, adding to the risk of development of rickets. However, even in mothers with a normal vitamin D level, breastfeeding can cause rickets because the recommended daily vitamin D intake for infants is 200 IU, while breast milk contains only 12-60 IU/L. This has led to the advice to supplement vitamin D when breastfeeding.

International

In most developing countries, rickets is seldom seen, supposedly as a result of high exposure to sunlight. An exception occurs in groups of women who are rarely allowed to leave the house (largely for religious reasons) or who must wear veils (chadors) when they do. Because these women may have low vitamin D levels, their babies are at a higher risk of developing rickets.^7,8

Premature babies: This group is at a relatively high risk of developing rickets. Dabezies and Warren described a 39% incidence of rickets and an associated 10% fracture incidence in premature infants with VLBW.⁹

Mortality/Morbidity

• When patients receive adequate treatment, no mortality is associated with rickets; however concomitant diseases, such as pneumonia, tuberculosis, and enteritis, occur with a higher frequency in individuals with the disorder and may cause death.
• Morbidity is nonexistent in patients who are diagnosed and treated in a timely fashion. Even in more advanced cases, bowed limbs may return to normal over a period of years. Only in patients with advanced rickets may permanent skeletal deformities occur. Sequelae consist of bowed legs or arms, knock-knees, deformities of the thoracic cage and spine, and skeletal dysplasia.

Race

• In the Western world, blacks develop rickets more often than whites. This is probably a result of darkly pigmented skin, which may reduce the penetration of ultraviolet light.
• In a Dutch article reporting on rickets in adults, Muslim women in the Netherlands wearing a chador were shown to be at high risk for developing vitamin D deficiency, resulting in osteomalacia. The deficiency resulted from underexposure to sunlight. If these women breastfeed their infants, the children also are at high risk of developing vitamin D deficiency. This issue has also been addressed by other authors, from different countries.¹⁰

Sex

Boys and girls are affected equally with rickets. There is a form of genetic rickets, called X-linked hypophosphatemic rickets, in which some children, often girls, may be only moderately affected. However, girls with this disorder can have rickets symptoms that are just as severe as those in boys.

Age

• By definition, rickets occurs only in children whose growth plates have not closed. The growth plates close at the end of puberty, at approximately age 17 years in females and age 19 years in males.
• Premature neonates are especially at risk because their requirements for vitamin D, calcium, and phosphate are higher than those in full-term neonates.

Anatomy

The most affected skeletal sites are the anterior costochondral junctions of the middle ribs, the proximal humerus, the distal radius and ulna, the distal femur, and the proximal and distal tibia.

Presentation

Clinical findings are related to the involved skeletal site.

• Head
  • Skull - Craniotabes may occur, in which the bones of the skull soften and flattening of the posterior skull can be seen. These effects may be transient or permanent. Another feature is the prominence of the frontal bones and the major foramen, resulting in frontal bossing or a prominent, sometimes square, forehead (caput quadratum).
  • Teeth - Teeth may erupt later than normal because of undermineralization. Enamel can be of poor quality, resulting in caries.
• Thorax
  • Rachitic rosary - The enlarged ends of the ribs, resembling beads, can be palpable and visible at the costochondral junction. As a result, the sternum can become more prominent, leading to a pigeon breast or pectus carinatum appearance.
  • Harrison groove - The groove is a semicoronal impression over the abdomen at the level of the insertion of the diaphragm, which can be seen in rickets.
• Spine - A mild to more pronounced scoliosis may be seen as a result of rickets.
• Pelvis - A prominent promontory can be found, and the anteroposterior (AP) diameter of the pelvis can shrink as a result of scoliosis. If this persists in girls, it can cause complications later in life during childbirth.
• Extremities
  • Arms
    • Bowing of the long bones, as a reaction to greenstick fractures, results from concurrent osteomalacia.
    • Thickening of the wrist at the level of the epiphysis is not visible radiographically, since the lesion consists of cartilage, although fraying and cupping of the metaphysis is evident.
  • Legs
    • Bowing of the long bones (genu varum)as a result of weight bearing is typical.
    • Anterior bowing of the tibia (saber shin deformity) may occur.
    • Development of knock-knees (genu valgum) may occur because of displacement of the growth plates during active disease.
    • Thickening at the level of the ankle may occur, identical to the process in the wrist.
• Ligaments and muscles - Laxity in the ligaments is increased, and muscle tone is decreased. This combination leads to a delay in motor development.

Preferred Examination

Plain radiography of the affected bones is the preferred examination. The distal radius and ulna typically demonstrate rachitic lesions early on radiographs. In preterm neonates and young infants, radiographs of the knee may be more reliable than those of the wrist.

Limitations of Techniques

In the early stage of rickets, radiographs depict no pathology; however, chemical changes in blood serum can already be found at this time.

Differential Diagnoses

Bone Metastases

Other Problems to Be Considered

Metaphyseal chondroplasia (type, Schmid)

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