Rickets

Definition and classification

The rickets is a skeletal pathology (osteopathy) with infantile onset, caused by a defect in the mineralization of the bone matrix and potentially responsible, in an advanced stage, for deformity and bone fractures. Based on the etiopathogenesis of rickets it is possible to classify it as:

1. Rickitism due to altered intake of vit D (calciferol):
• lack of rickets
• rickets due to chronic intestinal malabsorption
2. Rickets with altered hepatic metabolism of vit D:
   • rickets in hepato-biliary diseases (hepatic osteodystrophy)
   • chronic treatment rickets with anticonvulsant drugs (barbiturates)
3. Rickets due to altered renal metabolism of vit D:
   • familial hypophosphatemic rickets
   • type 1 vitamin D-dependent rickets
   • renal osteodystrophy
   • rickets from tubulopathies
   • oncogenetic rickets
4. Rickets with reduced action of vit D:
   • type 2 vitamin D-dependent rickets.

The reduced sun exposure, vomiting and prolonged diarrhea, together with the dietary deficiencies of calcium, magnesium and phosphorus, can favor the appearance of rickets. Not surprisingly, this is a rather common disease in developing countries, where poor hygiene conditions are added to malnutrition.

Symptoms

The symptomatology is characterized by skeletal and dental alterations, by muscular hypotonia and, sometimes, by laryngospasm and convulsions. The first clinical signs are manifested by the weakening of the occipital bone and the cranial parietal (craniotabe), accentuation of the frontal bumps, rachitic rosary (increased chondrocostal junctions), carinated chest (chest projected forward) and Harrison's groove (horizontal depression of the last coasts); with age, swollen metaphyses of long bones (wrists and ankles) appear, and with increasing stresses on the lower limbs, accentuated varism occurs (curvature of the diaphyses of femurs, shins and fibulae).

Synthesis of vitamin D

To better understand the etiology of the various forms of rickets, it is necessary to know the metabolism of vitamin D within the human body:

• Vitamin D3 or Colecalciferol is 90% produced by skin from cholesterol, through the action of solar UVA rays, and only 10% is introduced with the diet.
• Vitamin D3 synthesized in the skin must undergo some transformations before being active. The first occurs at the hepatic level, where it undergoes a first hydroxylation in position 25 by a hepatic 25-hydroxylase. The product of this hydroxylation is therefore a 25-OH-D3.
• 25-OH-vitamin D3 is still lacking in biological activity; to acquire it it must be further hydroxylated in position 1 at the renal level, where an renal alpha hydroxylase intervenes which turns it into 1, 25- (OH) ₂ -D3 or calcitriol, the active metabolite of vitamin D. Calcitriol determines an increased intestinal absorption of calcium and the mobilization of calcium and phosphates in the bone. The result is an increase in serum calcium (concentration of calcium in the blood).

Types of rickets

1. The most frequent lack of rickets is that of vit D; the insufficiency of calciferol induces the reduction of the intestinal absorption of calcium, consequently the hypocalcemia stimulates the production of parathormone, which reduces the renal excretion of the same mineral and stimulates its mobilization from the bones, reducing its mineralization.

With regard to rickets due to chronic intestinal malabsorption, this is a secondary complication to other conditions such as celiac disease, cystic fibrosis and intestinal resections; these are responsible for both calcium malabsorption and vitamin D.

In both cases there are low levels of both 25-OH-D3 and 1, 25- (OH) ₂ -D3.
2. Hepatic osteodystrophy is, as the term itself says, a skeletal alteration induced by a disease that compromises the liver; among these, the most common are biliary cirrhosis and biliary tract arthritis. Since hepatic activity is impaired, there are low levels of both 25-OH-D3 and 1, 25- (OH) ₂ -D3.

   The rickets due to anticonvulsant therapy, on the other hand, are due to the use of drugs such as barbiturates which, in 10-30% of cases, generates problems linked to skeletal deformation.

3. Familial hypophosphatemic rickets is a genetically autosomal dominant disease; the incidence is estimated between 1 / 10, 000 and 1 / 1, 000, 000 but the most likely ratio appears to be 1 / 20, 000.

   Type 1 vitamin D-dependent rickets is induced by a mutation of the gene that codes for renal alpha-hydroxylase, and consequently low levels of 1, 25- (OH) ₂ -D3 are recorded.

   Renal osteodystrophy is due to the reduction in renal function typical of chronic renal failure which often causes the onset of secondary hyperparathyroidism [hypocalcemia due to hyperphosphataemia and reduced synthesis of 1, 25- (OH) ₂ -D3 present in low concentrations due to of poor renal activity].

   Tubulopathic rickets is due to diseases such as Fanconi's syndrome, type 1 tyrosinemia and tubular acidosis.

   Oncogenetic rickets, on the other hand, are related to some forms of neoplasm (usually benign) of mesenchymal origin that generate hypophosphatemia due to reduced intestinal phosphate reabsorption added to low levels of 1, 25 (OH) ₂ .

4. Type 2 rickets is caused by the tissue resistance of the target organs to 1, 25- (OH) ₂ -D3; unlike type 1 rickets, where its levels are particularly low, in patients with type 2 rickets, 1, 25- (OH) ₂ -D3 is very high

The therapy useful for the remission of rickets is closely linked to the etiopathogenetic cause; the first goal is always to rebalance the levels of:

• vit. D [both 25 (OH) and 1, 25 (OH) ₂ ]
• serum calcium
• phosphorus

but to do so, in the forms of secondary rickets it is necessary to undertake a therapy useful for the resolution of the primitive disease. Genetic alterations do not fall into this category and, to reduce complications, it is necessary to increase the intake of vit. D above the normal recommended doses.

Bibliography:

• Manual of pediatrics - MA Castello - Piccin - cap5 - pag 152: 158.