Rickets

Rickets is a condition that results in weak or soft

Prevention for exclusively breastfed babies is vitamin D supplements.[5] Otherwise, treatment depends on the underlying cause.^[2] If due to a lack of vitamin D, treatment is usually with vitamin D and calcium.^[2] This generally results in improvements within a few weeks.^[2] Bone deformities may also improve over time.^[5] Occasionally surgery may be performed to correct bone deformities.^[7][3] Genetic forms of the disease typically require specialized treatment.^[5]

Rickets occurs relatively commonly in the Middle East, Africa, and Asia.^[4] It is generally uncommon in the United States and Europe, except among certain minority groups.^[3][4] It begins in childhood, typically between the ages of 3 and 18 months old.^[3][4] Rates of disease are equal in males and females.^[3] Cases of what is believed to have been rickets have been described since the 1st century,^[8] and the condition was widespread in the Roman Empire.^[9] The disease was common into the 20th century.^[8] Early treatments included the use of cod liver oil.^[8]

Signs and symptoms

Signs and symptoms of dietary deficiency rickets can include bone tenderness, and a susceptibility for bone fractures, particularly greenstick fractures.^[10] Early skeletal deformities can arise in infants such as soft, thinned skull bones – a condition known as craniotabes,^[11][12] which is the first sign of rickets; skull bossing may be present and a delayed closure of the fontanelles.

Young children may have

Hypocalcemia, a low level of calcium in the blood can result in tetany – uncontrolled muscle spasms. Dental problems can also arise.^[10]

An X-ray or radiograph of an advanced patient with rickets tends to present in a classic way: the bowed legs (outward curve of long bone of the legs) and a deformed chest. Changes in the skull also occur causing a distinctive "square headed" appearance known as "caput quadratum".^[14] These deformities persist into adult life if not treated. Long-term consequences include permanent curvatures or disfiguration of the long bones, and a curved back.^[15]

Cause

Maternal deficiencies may be the cause of overt bone disease from before birth and impairment of bone quality after birth.

Exclusively breast-fed infants may require rickets prevention by vitamin D supplementation or an increased exposure to sunlight.[20]

In sunny countries such as Nigeria, South Africa, and Bangladesh, there is sufficient endogenous vitamin D due to exposure to the sun. However, the disease occurs among older toddlers and children in these countries, which in these circumstances is attributed to low dietary calcium intakes due to a mainly cereal-based diet.^[21]

Those at higher risk for developing rickets include:

• Breast-fed infants whose mothers are not exposed to sunlight
• Breast-fed infants who are not exposed to sunlight
• Breast-fed babies who are exposed to little sunlight
• Adolescents, in particular when undergoing the pubertal growth spurt^[22]
• Any child whose diet does not contain enough vitamin D or calcium

Diseases causing soft bones in infants, like hypophosphatasia or hypophosphatemia, can also lead to rickets.^[23]

Strontium is allied with calcium uptake into bones; at excessive dietary levels strontium has a rachitogenic (rickets-producing) action.^[24]

Sunlight

Sunlight, especially ultraviolet light, lets human skin cells convert vitamin D from an inactive to active state. In the absence of vitamin D, dietary calcium is not properly absorbed, resulting in

Rickets had historically been a problem in London, especially during the Industrial Revolution. Persistent thick fog and heavy industrial smog permeating the city blocked out significant amounts of sunlight to such an extent that up to 80 percent of children at one time had varying degrees of rickets in one form or the other.^[29] It is sometimes known "the English Disease" in some foreign languages (e.g. German: Die englische Krankheit, Dutch: Engelse ziekte, Hungarian: angolkór, Swedish: engelska sjukan).^[30]

Skin color theory

Rickets is often a result of vitamin D3 deficiency. The correlation between human skin color and latitude is thought to be the result of positive selection to varying levels of solar ultraviolet radiation. Northern latitudes have selection for lighter skin that allows UV rays to produce vitamin D from 7-dehydrocholesterol. Conversely, latitudes near the equator have selection for darker skin that can block the majority of UV radiation to protect from toxic levels of vitamin D, as well as skin cancer.^[31]

An anecdote often cited to support this hypothesis is that Arctic populations whose skin is relatively darker for their latitude, such as the Inuit, have a diet that is historically rich in vitamin D. Since these people acquire vitamin D through their diet, there is not a positive selective force to synthesize vitamin D from sunlight.^[32]

Environment mismatch: vitamin D deficiency arises from a mismatch between an individual's previous and current environment. This risk of mismatch increases with advances in transportation methods and increases in urban population size at high latitudes.^[33]

Similar to the environmental mismatch when dark-skinned people live at high latitudes, Rickets can also occur in religious communities that require long garments with hoods and veils.^[34] These hoods and veils act as sunlight barriers that prevent individuals from synthesizing vitamin D naturally from the sun.^[35]

In a study by Mithal et al.,^[36] vitamin D insufficiency of various countries was measured by lower 25-hydroxyvitamin D. 25(OH) D is an indicator of vitamin D insufficiency that can be easily measured. These percentages should be regarded as relative vitamin D levels, and not as predicting evidence for development of rickets.^[37]

Asian immigrants living in Europe have an increased risk for vitamin D deficiency. Vitamin D insufficiency was found in 40% of non-Western immigrants in the Netherlands, and in more than 80% of Turkish and Moroccan immigrants.

The Middle East, despite high rates of sun-exposure, has the highest rates of rickets worldwide.^[38] This can be explained by limited sun exposure due to cultural practices and lack of vitamin D supplementation for breast-feeding women. Up to 70% and 80% of adolescent girls in Iran and Saudi Arabia, respectively, have vitamin D insufficiency. Socioeconomic factors that limit a vitamin D rich diet also plays a role. In the United States, vitamin D insufficiency varies dramatically by ethnicity. Among females aged 70 years and older, the prevalence of low serum 25(OH) D levels was 28.5% for non-Hispanic whites, 55% for Mexican Americans, and 68% for non-Hispanic blacks. Among males, the prevalence was 23%, 45%, and 58%, respectively.^{[citation needed]}

A systematic review published in the Cochrane Library looked at children up to three years old in Turkey and China and found there was a beneficial association between vitamin D and rickets. In Turkey children getting vitamin D had only a 4% chance of developing rickets compared to children who received no medical intervention. In China, a combination of vitamin D, calcium and nutritional counseling was linked to a decreased risk of rickets.^[39]

Parents can supplement their nutritional intake with vitamin D enhanced beverages if they feel their child is at risk for vitamin D deficiency.^[40]

A recent review links rickets disease to exclusive consumption of

Rickets may be diagnosed with the help of:

• Blood tests:^[42]
  • Serum calcium may show low levels of calcium, serum phosphorus may be low, and serum alkaline phosphatase may be high from bones or changes in the shape or structure of the bones. This can show enlarged limbs and joints.
• A
  scan may be undertaken.^[42]
• Radiography typically show widening of the zones of provisional calcification of the metaphyses secondary to unmineralized osteoid. Cupping, fraying, and splaying of metaphyses typically appears with growth and continued weight bearing.^[43] These changes are seen predominantly at sites of rapid growth, including the proximal humerus, distal radius, distal femur and both the proximal and the distal tibia. Therefore, a skeletal survey for rickets can be accomplished with anteroposterior radiographs of the knees, wrists, and ankles.^[43]

In veterinary practice, rickets, osteodystrophy and mineral metabolism disorders are diagnosed using an ultrasound echosteometer in the design М.М. Orlov and А.V. Savinkov.^[44][45][46]

Types

• Vitamin D-related rickets^[47]
  • Vitamin D deficiency
  • Vitamin D-dependent rickets (VDDR)^[48]
    • Type 1: insufficiency in activation
      • VDDR1A:
        25-Hydroxyvitamin D3 1-alpha-hydroxylase
        deficiency
      • VDDR1B: CYP2R1 deficiency
    • Type 2: resistance to calcitriol
      • VDDR2A:
        calcitriol receptor
        mutation
      • VDDR2B: unknown nuclear ribonucleoprotein interfering with signal transduction
    • Type 3: excessive inactivation (CYP3A4 mutation, dominant)
• Hypocalcemia-related rickets
  • Hypocalcemia
  • Chronic kidney failure
    (CKD-BMD)
• Hypophosphatemia-related rickets
  • Congenital
    • Vitamin D-resistant rickets^[47]
    • Autosomal dominant hypophosphatemic rickets (ADHR)
    • Autosomal recessive hypophosphatemic rickets (ARHR)^[49]
  • Hypophosphatemia (typically secondary to malabsorption)
  • Fanconi's syndrome
• Secondary to other diseases
  • Tumor-induced osteomalacia
  • McCune-Albright syndrome
  • Epidermal nevus syndrome
  • Dent's disease

Differential diagnosis

Treatment involves increasing dietary intake of calcium, phosphates and vitamin D. Exposure to ultraviolet B light (most easily obtained when the sun is highest in the sky), cod liver oil, halibut-liver oil, and viosterol are all sources of vitamin D.^[53]

A sufficient amount of ultraviolet B light in sunlight each day and adequate supplies of calcium and phosphorus in the diet can prevent rickets. Darker-skinned people need to be exposed longer to the ultraviolet rays. The replacement of vitamin D has been proven to correct rickets using these methods of ultraviolet light therapy and medicine.^[8]

Recommendations are for 400 international units (IU) of vitamin D a day for infants and children. Children who do not get adequate amounts of vitamin D are at increased risk of rickets. Vitamin D is essential for allowing the body to uptake calcium for use in proper bone calcification and maintenance.^[54]

Supplementation

Sufficient vitamin D levels can also be achieved through dietary supplementation and/or exposure to sunlight. Vitamin D₃ (cholecalciferol) is the preferred form since it is more readily absorbed than vitamin D₂. Most dermatologists recommend vitamin D supplementation as an alternative to unprotected ultraviolet exposure due to the increased risk of skin cancer associated with sun exposure. Endogenous production with full body exposure to sunlight is approximately 250 µg (10,000 IU) per day.^[55]

According to the American Academy of Pediatrics (AAP), all infants, including those who are exclusively breast-fed, may need vitamin D supplementation until they start drinking at least 17 US fluid ounces (500 ml) of vitamin D-fortified milk or formula a day.^[56]

Despite this recommendation, a recent Cochrane systematic review has found limited evidence that vitamin D plus calcium, or calcium alone compared to vitamin D improves healing in children with nutritional rickets.^[57]

Surgery

Occasionally surgery is needed to correct severe and persistent deformities of the lower limbs, especially around the knees namely genu varum and genu valgum. Surgical correction of rachitic deformities can be achieved through osteotomies or guided growth surgery. Guided growth surgery has almost replaced the use of corrective osteotomies. The functional results of guided growth surgery in children with rickets are satisfactory. While bone osteotomies work through acute/immediate correction of the limb deformity, guided growth works through gradual correction.^[7]

Epidemiology

In developed countries, rickets is a rare disease^[58] (incidence of less than 1 in 200,000). Recently, cases of rickets have been reported among children who are not fed enough vitamin D.^[59]

In 2013/2014 there were fewer than 700 cases in England.^[59] In 2019 the number of cases hospitalised was said to be the highest in 50 years.^[60]

Rickets occurs relatively commonly in the Middle East, Africa, and Asia.^[4]

History

Greek physician

The word rickets may be from the Old English word wrickken ('to twist'), although because this is conjectured, several major dictionaries simply say "origin unknown". The name rickets is plural in form but usually singular in construction. The Greek word rachitis (ῥαχίτης,^[68] meaning 'in or of the spine') was later adopted as the scientific term for rickets, due chiefly to the words' similarity in sound.

See also

• Hypervitaminosis D

References