Rickets has been around for centuries, but its roots as a symptom of vitamin D deficiency began only in the 17th century, when Francis Glisson published his findings on the disease and proposed that it was a disease of the rich rather than the poor. When the industrial revolution took place in the 1800’s, the number of children with rickets soared, only, this time, it affected more than half the children in the overcrowded and highly polluted industrialized areas.
As early as 1822 the researcher Sniadecki recognized its association with poor or reduced sunlight exposure, and in a few more decades, it was well known that cod liver oil was efficacious in treating this condition. Mellanby and McCollum pioneered the discovery of vitamin D as the effective agent in cod liver oil which prevented and treated rickets, which led to the addition of this vitamin to milk and other foods as a means of fortification against this disfiguring disease.
Vitamin D is a fat-soluble substance, and is therefore found in few foods of plant origin. It is therefore commonly ingested as a supplement or through the ingestion of fortified milk or milk products.
In most people, vitamin D is synthesized in the skin on exposure to a narrow wavelength band of ultraviolet radiation. This means that deficiency is more likely during winter in temperate regions, because outdoor exposure is limited, clothing is heavier and less skin is exposed, and the amount of sunshine is restricted. Moreover, the ultraviolet rays in this band are absorbed by the atmosphere during winter. Older people produce the vitamin less efficiently than younger people.
Vitamin D deficiency is likely when the serum level of 25-hydroxy cholecalciferol drops below 30 nmol/L. This is the inactive storage form of the vitamin. The following table shows the levels of the vitamin associated with health risks.
Table 1: Serum concentrations of 25-hydroxycholecalciferol in health and disease
|
Concentration (nmol/L)
|
Health status
|
|
<30
|
Vitamin D deficiency: rickets or osteomalacia, depending on age
|
|
30-50
|
Potential risk of deficiency, poor overall health
|
|
≥50
|
Adequate to maintain health
|
In order to avoid deficiency, recommended dietary allowances (RDAs) have been worked out, and range from 400 to 800 IU (10-20 mcg) based on the age. These RDAs do not allow for sunlight exposure, to prevent deficiency in case of limited outdoors activity. The table below details the RDA at various ages for diverse population groups:
Table 2: Recommended dietary allowances for vitamin D
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Age
|
RDA for vitamin D (IU)
|
|
<12 months
|
400
|
|
1-13 years
|
600
|
|
14-70 years
|
600
|
|
> 70 years
|
800
|
Reasons for vitamin D deficiency
The chief causes for low vitamin D levels include:
- poor dietary sources, such as in veganism, lactose intolerance or milk allergy, or vegetarianism
- poor absorption, as in malabsorption syndromes including steatorrhea and obstructive jaundice
- increased requirements as in adolescence
- increased excretion
- low intake over a prolonged duration
- poor sunlight exposure
- impaired conversion of 25-hydroxy cholecalciferol to 1,25-dihydroxy cholecalciferol by the kidney
- liver and kidney disease which interfere with vitamin d activation and renal phosphate absorption
Conditions caused by vitamin D deficiency
Rickets and osteomalacia are the classical deficiency diseases caused by inadequate vitamin D.
Rickets
Occurring in children with vitamin D deficiency, this is caused by failure of mineralization of bone, leading to soft, pliable and eventually deformed bones. This was because the unmineralized osteoid of the bone tissue could not support the body’s weight nor the strain caused by various body movements. Rickets is still found throughout the world.
The peak incidence of rickets is between 3 and 18 months of age. Subtle manifestations of vitamin D deficiency in childhood may occur before the actual bone signs, and include:
- lethargy
- irritability
- growth failure
- hypocalcemic seizures
- frequent respiratory symptoms
Rickets may manifest in one of two ways:
- Symptomatic hypocalcemia during periods of fast growth, or increased metabolic demands, before there are any physical or radiologic evidence of rickets
- Chronic rickets or impaired bone mineralization with normal or asymptomatic low calcium levels
Early rickets presents with symptoms such as bone pain, delay in milestones such as standing and walking, frequent falls, and delayed growth. Severe calcium deficiency due to low vitamin D intake may also occur in the period of infancy. Some common signs and symptoms of hypovitaminosis D include:
In the established stage, it is called florid rickets. Its manifestations include:
- deformed legs, leading to bow legs and knock knees
- ribcage deformities, leading to a pigeon chest
- Enlarged growth plates at the wrists, ankles and costochondral junctions, because of the difficulty in forming bone, leading to the persistence of growth cartilage, and symptoms such as the rachitic rosary and Harrison’s sulcus, extending from the costal cartilage transversely outward to the axilla. This is due to the pulling in of the lower ribs by the diaphragmatic attachment.
- skull bossing
- curvature of the spine, leading to kyphoscoliosis
- generalized muscular weakness
Breastfeeding may cause rickets under the following conditions:
- prolonged exclusive breastfeeding
- dark-skinned mothers and infants, which impairs vitamin D synthesis in skin
- mothers who are not deficient in vitamin D
Reasons for rickets in children
- Use of sunscreen
- Lack of outdoor activity or play by children, as in daycare programs
Diagnosis of rickets
- Rickets is diagnosed by X-rays of the long bones of the knees and the wrists. The characteristic finding is of wide growth plates due to poor mineralization, and a frayed appearance at the metaphyseal margin.
- Laboratory tests show low serum phosphate levels, with high alkaline phosphatase. Serum 25-hydroxy cholecalciferol concentrations are very low, below 5 ng/mL, in case of rickets due to vitamin D deficiency. Differential diagnoses include calcium deficiency, a not uncommon cause of rickets, in which case vitamin D levels may not be so low. In addition, with adequate solar exposure or if the child has received vitamin D supplementation, vitamin D levels may not be low.
Osteomalacia
This is the effect of vitamin D deficiency in adults, and means weak bones. It manifests with bone pain and muscular weakness, often subtle in the first stages. It is due to the failure of mineralization of organic osteoid because of low calcium and phosphate levels. Its characteristic manifestations include:
- bone pain, which may mimic that of fibromyalgia or arthritis, but usually affects the part of the bone between the joints, sparing the muscle and soft tissue.
- proximal muscle weakness and instability
- low back pain on both side of the spine
- muscle aches
- throbbing pain deep in the bone, on pressing the sternum or tibia
Diagnosis
- Radiographic features include pseudofractures of the pelvis or other bones, including the femurs, metatarsals or scapular lateral margins
- Laboratory findings include high serum alkaline phosphatase and parathyroid hormone (PTH) levels, with low calcium and phosphate. Vitamin D values may or may not be low.
Abnormalities of immune function
Vitamin D stimulates innate immunity and prevents chronic disease conditions due to failure of immunity
- predisposition to acute infections
- dysfunction of innate immunity
- Reduction of the threshold for chronic conditions such as cancers of the prostate, breast or colon, and leukemias, as well as diabetes mellitus, psoriasis and autoimmune conditions such as multiple sclerosis, systemic lupus erythematosus and rheumatoid arthritis.
- Vitamin D also reduces the likelihood of cancer by promoting cellular differentiation, reducing the growth of tumor cells, stimulating apoptosis of cancer cells and reducing angiogenesis in tumors.
Stages of vitamin D deficiency
- Reduction in 25-OH-D level, with low calcium but normal phosphate, and high or normal 1,25-diOH-D2.
- Reduction in 25-OH-D level with normal calcium and low phosphate, slightly high alkaline phosphatase, and low bone demineralization.
- Severe reduction in 25-OH-D along with reduced calcium, and phosphate levels, with high alkaline phosphatase, and signs of bone demineralization.
Clinical signs of vitamin D deficiency
- lowered absorption of calcium from the gut, from approximately 35% to 15%
- high PTH secretion due to low vitamin D levels
- calcium withdrawal from bone with reduced bone mass, leading to increased fracture risk
- rickets and osteomalacia
- abnormal immune function
- bone loss due to high parathyroid hormone secretion, leading to calcium mobilization from the bone
Risk groups for vitamin D deficiency
- Exclusively breastfed infants, unless mothers supplement with vitamin D in high doses, or the infant is exposed to sunlight for 30 minutes a week with just a nappy on. If the infant is fully clothed, 2 hours of exposure are required per week.
- Older adults because of reduced efficiency of conversion of vitamin D in the skin.
- People who are not adequately exposed to the sun whether because of being confined to the home, religious reasons for full body covering, or indoors occupations.
- Dark-skinned people, because melanin hinders the passage of ultraviolet radiation which effects the conversion of vitamin D in the skin.
- Inflammatory bowel disease or other fat malabsorption conditions, such as liver disease, cystic fibrosis or ulcerative colitis.
- Obese people, or following gastric bypass surgery – adipose tissue sequesters the vitamin in its inactive form, while gastric bypass hinders absorption from the duodenum.
- Adolescents or children whose calcium intake is minimal may suffer deficient vitamin D in winter due to the lack of sunlight exposure.
- Certain anticonvulsants also interfere with vitamin D metabolism .
References
Further Reading
Vitamin D supplementation shows promising impact on cardiometabolic health