Rickets is characterized by impaired mineralization of cartilage matrix (chondroid) and a resultant arrest in the formation of primary spongiosa. Osteomalacia is the corresponding disorder in skeletally mature individuals.
This is a fat soluble steroid hormone. It acts to increase calcium resorption from the gut and the kidneys.
The two main sources of Vitamin D are the diet (fatty fish, cod liver oil, fortified cereals, bread, milk) and endogenous production following exposure to sunlight.
The underlying defect may be vitamin D deficiency, or vitamin D resistance. Vitamin D resistance is a form of phosphate deficiency.
The commonest cause of vitamin D deficiency is nutritional deficiency.
Malabsorption can prevent intestinal absorption of vitamin D, e.g. from coeliac disease or primary biliary cirrhosis.
Phenytoin or rifampicin can interfere with liver conversion of D3 to 25-hydroxyvitamin D.
There are four types of vitamin D resistance. These are:
- Failure of production of 1,25 dihydroxyvitamin D. This results in type I vitamin D dependant rickets. Inheritance is AR.
- End organ insensitivity to Vitamin D. This results in type II vitamin D dependent rickets.
- Phosphate diabetes (hypophosphataemic rickets)
- This is an X-linked dominant disorder characterized by phosphate wasting and a normal calcium level, decreased phosphate level and an elevated alkaline phosphate level.
- Due to a defect in the PHEX gene
- Unlike other forms of rickets the bones appear radiodense because of a defect in osteoblast control of mineralization.
- Renal tubular acidosis.
Other causes of phosphate deficiency include Fanconi syndrome and nutritional phosphate deficiency which can occur in neonates on TPN.
Oncogenic osteomalacia can develop with vascular tumours, and has the features of hypophosphataemic rickets. Ifosfamide may cause hypophosphataemic rickets.
Osteomalacia is caused by failure to maintain a serum calcium-phosphate product sufficient to promote mineralization of newly formed osteoid.
Von Kossa’s stain shows an increased amount of pink staining osteoid compared with the black staining mineralized bone. The normal amount of osteoid should be only 2% of the total volume and occupy only 20% of the surface area.
There can be a decreased, normal or increased amount of bone. Osteomalacia can coexist with osteoporosis, in which case there will be fewer and thinner trabeculae and increased osteoid fronts.
Paediatric patients with rickets are short and have bowing of their legs which mirrors the physiologic tendency at the time; that is, bow legged when very young and knock kneed from age 3. The wrist, knees and ankles are prominent from the enlarged growth plates.
The child may develop scoliosis, coxa vara and long bone fractures.
They may have a rickety rosary (prominence of the costochondral junctions).
Hypocalcaemia may lead to tetany, convulsions, failure to thrive, listlessness and muscular flaccidity.
In adults vertebral compression fractures may lead to biconcave codfish vertebrae. Patients may have a generalized ache.
The only pathognomonic sign is Looser’s fracture, where a pathological fracture through a seam of unmineralized osteoid occurs. Looser’s fracture is found in the pelvis and scapula and on the compression side of bones but is rare.
Rickets causes splaying of the metaphyses, such that they become flared and irregular – aka cupping of the metaphyses. The physes are widened and the bones are bowed.
The pelvis can develop protrusio, and the hips develop coxa vara.
May require an iliac crest biopsy.
Lab results show low levels of phosphate, calcium and vitamin D metabolites, and elevated levels of alkaline phosphatase. A calcium-phosphate product less than 2.4 is virtually diagnostic.
Hypophosphataemic rickets: phosphate