Chapter 10 Page 1
CHAPTER 10. RICKETS
1.Introduction
Rickets in the strict sense of the term is a disease caused by any interference with the process of enchondral[1] bone formation, the cascade of events normally taking place in the epiphyseal growth plates and resulting in gain in length of long bones. However, this is not the only calcifying structure in the growing individual. Bone remodelling and increase in thickness by periostal bone apposition are also active in growth and an alteration at those levels will result in osteomalacia[2], leading to excessive accumulation of osteoid tissue throughout the skeleton. The skeleton will thus be affected in its two main functions as the mechanical support for the other organs and the major reservoir of calcium to serve a large array of physiologic functions.
The calcium homeostasis (maintaining concentrations at a constant level) is important to maintain a normal neurological function, muscular contractility and bone mass. In the extracellular compartment calcium is always in equilibrium with phosphate. Their product has to remain constant, otherwise the calcium-phosphate complexes will precipitate. If calcium increases, phosphate will decrease. The biggest reservoir of those two minerals is the bone. Calcium concentrations are maintained in essence by three mechanism; 1) regulating the excretion through the kidney, 2) regulating the absorption through the intestine and 3) dissolving or depositing bone minerals.
The bone is affected in many ways by nutritional factors:
Clinical nutrition and bone diseaseNutritional / Vitamin D / Rickets/Osteomalacia
deficiency / Vitamin C / Scurvy
Copper / Fractures (premature
infants; parenteral
nutrition)
Nutrition / Calcium / Osteoporosis
related
In the present document only the pathological changes related to vitamin D deficiency will be discusses as well as epidemiological and other aspects.
2.Clinical picture
The clinical picture is one of bone deformities ranging from mild signs to very distinctive bone deformities. Clinical and radiological bone lesions predominate in the areas of rapid bone growth, namely the long bone epiphyses and the costochondral junctions. Thus the clinical manifestations are most striking at the time of greatest velocity. The maximum frequency of signs is usual found between 4-12 months with most of the signs seen in children below 18 months.
Palpable and visible knobbly enlargement of the long bones. Predominant sign when children cannot stand up. Correspond to the expanded epiphyses. Mostly observed at ankles and wrists.
Knobbly appearance of the costochondral junctions. Anterior axillary line “rachitic rosary”.
Skeletal deformations: tibial and femoral bowing. Weight bearing and muscle pull. Sometimes also forearms. Muscle traction on rib case can cause deformity.
Craniotables: delayed closure of the sutures and the fontanel with deformity of the skull (occipital and parietal flattening.
Deformities of the spine and pelvis (rare nowadays).
Delayed dental development, enamel hypoplasia, numerous caries.
Extraskeletal manifestations
Various clinical signs of hypocalcemia: seizures, tetany, laryngospasm, hypocalcemic myocardiopathy.
Hypotonia of the abdominal muscles, with protruding abdomen and umbilica hernia.
Defective ventilation: muscle weakness and thoracic cage deformities; pulmonary infections.
In older children and adolescents signs similar to those found in adults can be found: bone pain, waddling gait and fatigue.
Radiological findings
When present, the skeletal radiological signs reflect an already severe mineralisation defect. Although signs can be found in most bones, only an X-ray of the wrists and /or a frontal film of the knees is sufficient to make the diagnosis.
There is widening of the radiolucent space between the end of the bone shafts (the metaphysical lines) and the epiphyses which reflect the increase of uncalcified cartilage.
The end of the ossified long bones (what is normally a sharp line) are hazy and distorted: irregular, stipped, fuzzy, frayed or fringed. They are frequently hollowed with loss of their flat or convex configuration (so called cupping). Can spread laterally (cortical spurs).
At the costochodral junctions of the thorax, the same alterations are observed where cupping develops rapidly giving the so-called “champagne cork” aspect.
As a result of insufficient mineralisation, the centres of ossification are pale and irregular and their appearance might be delayed. The shafts of the long bones usually show diminished density with thinning of the cortices.
Besides poor mineralisation, bones may show deformities such as bowing of the tibia and femur, unrecognised fractures followed by callus formation, particularly in the ribs and fibula.
3.Vitamin D
3.1Physiology
The unique feature of vitamin D is that it is mainly produced in the human body by transformation of cholesterol metabolites to vitamin D3 in the skin under the influence of ultra violet light. The 7-dehydrocholesterol (also called pro-vitamin D3) is transformed to Pre-vitamin D3 by UV waves. Once formed, this pre-vitamin D3 begins to thermally equilibrate with vitamin D3 (or cholecalciferol). Pre-vitamin D3 is further metabolised in two metabolites that can revert to pre-vitamin D3. It is thought that this process is a way to both protect against toxicity (high dosages of vitamin D are toxic) and that these metabolites constitute in fact a reservoir of precursors which can revert to pre-vitamin D3 by UV light.
Vitamin D3 is bound to a vitamin D binding Protein (DBP) to be metabolised in the liver to 25 hydroxy D3 (25.OH cholecalciferol). The half-life of RBP-25OHD3 complex is 15-45 days and constitutes a factual reservoir of the vitamin. The final conversion happens in the kidney where 25.OH cholecalciferol is transformed to 1,25 dihydroxy cholecalciferol. It is this last metabolite which is metabolically active.
3.2 Regulation and biological actions of 1,25(OH)2D
When the calcium concentration drops, the parathyroid glands[3] secrete the parathyroid hormone PTH. This stimulates the production of 1,25(OH)2D. As a result of this (1) the active absorption of calcium in the intestine is stimulated, (2) the loss of calcium through the kidneys is decreased (resorption is stimulated) with increase in phosphate excretion and (3) bone cells (osteoclasts) are stimulated to resorp bone minerals and release calcium in the extra-cellular compartment. As a result of this the calcium concentration will rise and the secretion of PTH decrease.
3.3Vitamin D production
There is no doubt that the main source of vitamin D for humans is the production in the skin through the conversion of precursors under the influence of ultraviolet light. It is estimated that a one erythema producing dose of UV is equivalent to a dose of 10.000 IU of vitamin D.
The angle of incidence of the sun determines how much of the UV range needed for the transformation is present in sunlight. The lower the inclination of the sun, the lesser the amount. There is therefore, a large variation in vitamin D production according to the season. In the northern latitudes, vitamin D production is low in winter and spring.
Glass and particles in the atmosphere also reflect UV. Air pollution, such as seen in large cities, considerable decreases the UV content and hence the production of vitamin D. Dust in the air, such as can be found in desert countries, have the same effects.
Direct contact with the sun is essential for the production of vitamin D. Cultural habits of covering the children and keeping them indoors, is one major cause of the deficiency. In Europe the major cause was people living is densely populated cities with small alleys between houses where very little sunlight penetrated. In some countries living indoors in an air-conditioned environment behind glass is now a major cause.
In some countries like Egypt, Iran, India, Greece, Saudi Arabia, Libya and Nigeria where rickets is still reported the calcium intake from milk is low. The diet, largely cereal based, contains large amount of phytates which decrease considerably the bioavailability of Calcium. This in turn stimulates the PTH secretion and the production of 1,25(OH)2D. It has been demonstrated that high doses of 1,25(OH)2D enhance the biological inactivation of 25 OHD. Over time this will lead to a decrease in vitamin D and produce rickets. Thus an adequate supply of calcium may be as important for maintaining vitamin D status as is it for calcium homeostasis.
4.Food sources of vitamin D
Vitamin D content of food (µg/100 g)
Cereals
Grain, flours, starches0
Milk & milk products
Cow’s milk0.01-0.03
Human milk 0.04
Dried milk0.21
Cream0.1-0.28
Cheese0.03-0.5
YoghurtTrace-0.04
Eggs
Whole1.75
Yolk4.94
Fats and oils
Butter0.76
Cod liver oil210
Margarines and spreads5.8-8.00
Meat & meat products
Beef, lamb, pork, vealTrace
Poultry, gameTrace
Liver0.2-1.1
Fish and fish products
White fishTrace
Fatty fishTrace-25
Crustacea & molluscsTrace
Vegetables0
Added during production (Vitamin D2).
Source : Holland et al 1991
Although vitamin D is present in a number of foods such as egg yolk, oily fish, and to some extend milk, the natural diet can only be considered as a trivial source of vitamin D.
5.Treatment and prevention of common Rickets
5.1Nutritional requirements
With the major source of vitamin D derived from the skin, establishing requirement or allowance for vitamin D is difficult. Vitamin D toxicity can also occur when levels are around five times normal. In northern countries where the sunlight contains during the winter months less UV, there is more scope for adding vitamin D to food items. In the USA for instance, margarine and cow’s milk are fortified. In Australia no fortification is allowed.
Full term infant: 400-500 IU/day. Infants are entirely dependent of their mother for supply. Pregnant and lactating women should be encouraged to expose themselves to the sun.
Pre-term infant 500-1000 IU/day
Adults: 500 IU/day
5.2Treatment of common rickets
Vitamin D administration is usually the only treatment for rickets. Although metabolites of vitamin D exist, they have no advantage. There is, however, no agreement on the treatment schedule to use. Several therapeutic schedules are advocated in the literature: low oral daily doses for several weeks or months (2000 IU = 50 g per day for 6 months, 5000 IU per day for 2 months), or one oral, single large dose (200,000, 600,000 IU) that may be repeated one to two months mater.
A faster response in normalisation of biochemical parameters is usually seen in single large doses. A single large dose seems therefore, advisable. 200,000 IU seems the most appropriate.
It is important to make sure that the children are receiving enough calcium. A daily intake of 800 mg in infants and children, and 1 g in adults, is the required minimum during the first month of treatment. Milk and dairy products can easily supply this, but when this does not seem possible, calcium supplementation must be provided.
The first radiological signs of healing will appear after 2-4 months.
5.3Prevention
Exposure to sunlight is the best prevention. In high latitude countries, however, supplements may be needed.
Breastfed children should receive 400IU per day. Large doses of 200.000 IU (5 mg) can also be given every 3 months. This dose is not always well absorbed. The safest is to give daily small doses. Bottle feeds have already adjusted levels of vitamin D.
Food fortification has eradicated rickets in Europe.
The elderly are a particular group at risk. Many older people stay indoors most of the time and get very little exposed to sunlight. The can develop demineralisation of the bone with bone pains and fractures. Daily supplements can be necessary.
[1]Refers to the type of mineralisation where calciumphospate is deposited in cartilaginous bone.
[2]Osteomalacia refers to a disorder in which there is abnormal bone mineralisation and the ratio of mineral to matrix is diminished due to an excess of unmineralised osteoid. This in contrast to osteoporosis where there is a reduction in quantity of bone mass per unit of volume.
[3] These are glands situated in the upper lobes of the thyroid gland