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Effects of Deficiency of Vitamin D

In growing children a deficiency of vitamin D causes rickets while in adult (mostly women) osteomalacia results. Since bone abnormalities are the most important feature of rickets, a brief review of the bone physiology is given first

Brief Physiology of Bone: Bone can be considered to be a connective tissue made rigid by an orderly deposition of mineral crystals. Bone fibers consist mainly of the protein ossein (identical with collagen) encrusted with crystalline mineral, the fiber being set in an amorphous gel of mucopolysaccharide called ground substance. Two other proteins, osseomucoid and osseoalbuminoid, also occur in the bone butto lesser extent than ossein. It is important to realize that the bone is being continually destroyed and renewed. Thus the bony tissue is not inert and static but is quite dynamic. The chemical composition of fat-free bone is given below:

Water = 25 %
Inorganic matter (chiefly Ca and P in a ratio of  2.2 : 1) = 45 %
Organic matter (proteins and Mucopolysachharides) = 30%  (in which 95% is ossein)

The inorganic fraction is made of crystals forming hexagonal plates measuring 50x10 mu which are deposited in a regular way on and parallel to the axis of the collagen fibers. The small size and flat surface of these crystals give them a large surface area. Bone crystal consist of chiefly hydroxyapatite, 3Ca3(PO4).Ca(OH)2 but they also contain carbonate citrate and small amounts of Na, Mg, Cl and F. The crystals are surrounded by a hydration shell which permits the free exchange of ions between extracellular fluid and interior of the crystals. The total area of the Crystal of bone salt in man is 100 to 200 acres. Lead, strontium, and radium can replace Ca ios while Fluoride can replace hydroxyl ions in the crystal.

Bone development: At the end of long bones during normal growth the cartilage cell degenerate and disappear and are replaced by osteoblast. Capillaries grows into this site and the osteoblasts produce the organic matter consisting of proteins and mucopolysaccharides. The osteoblasts also bring about the seeding of crystal of some form of calcium phosphate. Mineral deposition takes place which is accompanied by glycolysis and production of organic phosphates in the osteoblasts. The osteoblasts generally contain the enzyme alkaline phosphate which is probably essential for splitting organic phosphate esters thus providing phosphates to be deposited in the bone. This takes place when the product, serum Ca x Pi, exceeds a critical value. The initial precipitate is unstable and changes later to hydroxyapatite. The bone is made dense by crystal growth and displacement of water in addition to other changes.

   Rickets

It is a disease primarily due to a deficiency of dietary intake of vitamin D but an inadequate supply of Ca, P and sunlight may also play a part. Rickets is associated with the following abnormalities:

  1. As compared to normal bone the rickety bone has less inorganic matter and this decreased mineral content of the bone is the primary defect in rickets. The cartilage cells at the ends of long bone do not generate but continue to proliferate. The activity of the osteoblasts is usually increased as shown by increased cells and osteoid. The epiphyseal line which normally is very thin line consisting of cartilage cells become greatly widened both laterally and in depth so that nodules develop at costochondral junctions (rickety rosary) and at wrists, ankles, and knees. The bones develop characteristic deformities. The tibia bends forwards (bow legs), the femur outwards and the spine shows kyphosis or scoliosis. There appears a transverse groove corresponding with the insertion of the diaphragm on either side of thorax (Harrison’s Sulcus). The sternum protrudes forward (pigeon breast). The chest deformities are the most dangerous manifestations of vitamin D deficiency because they impair pulmonary ventilation. The forehead protrudes due to heaping up of bosses of spongy bone in the frontal region. The parietal bones also show prominent bosses. The skull also shows craniotabes, i.e. softness of the skull with widening of sutures and fontanelles. The humerus and the bones of the forearm also become curved. There is a delayed closure of fontanelles, retarded eruption of teeth, etc. in addition to the bony lesions the child also shows general debility and has a protruding abdomen (pot belly) due to poor musculature.
    On chemical analysis, bones of rickety patients are found to contain much less inorganic matter i.e. Ca and P but water as compared to normal bones. 
  2. In rickets the serum Ca level is usually normal (or may be low) but inorganic P as a rules is decreased to 1 to 2 mg% against a normal level of 4 to 6 mg%. It has been shown that if the product of serum Ca and inorganic P levels (taken as mg/100 ml) is 40 or more, rickets will not occur. If this product is below 30, rickets occurs as a rule. Vitamin D administration raises this value to above 40. The parathyroid glands show hyperplasia.
  3. Serum alkaline phosphate activity is much increased in rickets and this finding is of help in diagnosis. This enzymes is probably concerned with the removal of phosphate from organic phosphates such as hexose and glycerol phosphates in bone which helps in ossification.
  4. There is a delay in dentition. There may be defective enamel production which predisposes teeth to decay or caries.

Rickets should be diagnosed at the earliest because once bony deformities are developed, it becomes difficult or even impossible to reverse them. Characteristics X-ray changes in bone occur before rickets becomes clinically manifest making it possible to diagnose rickets at an early stage.

   Osteomalacia or Adult Rickets

It occurs mostly in women who are economically poor and have undergone repeated cycles of pregnancy and lactation. Lactation puts relatively more burden on the mother than pregnancy. In osteomalacia bone minerals are mobilized. Ca mobilization is seen to be present in bone cortex and trabeculae. The bone becomes even softer than in rickets. As the bone soften weight causes bowing of long bones, vertical shortening of vertebrae and flattering of the pelvic bones which narrow the pelvic outlet. The contracted pelvis is an important cause of difficulty in child birth. There may occur a spontaneous fracture or collapse of vertebrae. Serum Ca level may be decreases to a level where tetany results.