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Pathogenesis of rickets
Last reviewed: 04.07.2025
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Vitamin D, which enters the body with food, combines with a 2 -globulin and enters the liver, where under the action of the enzyme 25-hydroxalase it is converted into a biologically active metabolite - 25-hydroxycholecalciferol (25-OH-D3), (calcidiol). This metabolite enters the kidneys from the liver, where under the influence of the enzyme 1 oc-hydroxylase 2 metabolites are synthesized from it:
- 1,25-dihydroxycholecalciferol [l,25-(OH) 2 -D3 (calcitriol), which is 5-10 times more active than vitamin D. It is a fast-acting active compound that plays a key role in regulating calcium absorption in the intestine and its delivery to organs and tissues.
- 24,25-dihydroxycholecalciferol [24,25- (OH) 2 -D3, which ensures the fixation of calcium and phosphates in bone tissue, suppresses the secretion of parathyroid hormone. This is a long-acting compound that controls bone mineralization with sufficient calcium delivery to the sites of its formation.
The concentration of calcium in the blood serum is a constant value and is 2.25-2.7 mmol/l. Normally, the concentrations of calcium and phosphorus are maintained in a ratio of 2:1, which is necessary for the correct formation of the skeleton. Calcium in the blood is in 2 forms - ionized and bound to protein.
Absorption of calcium ions is carried out by the epithelium of the small intestine with the participation of calcium-binding protein, the synthesis of which is stimulated by the active metabolite of vitamin D - l,25-(OH) 2 -D 3. It is necessary along with the hormones of the thyroid and parathyroid glands for normal ossification and growth of the skeleton. Vitamin D deficiency leads to a decrease in the level of the active metabolite in the blood serum, which disrupts the absorption of calcium ions in the intestine, their reabsorption by the renal tubules, and also reduces the activity of calcium and phosphorus resorption from bone, which can lead to hypocalcemia.
A decrease in the level of ionized calcium in the blood plasma leads to stimulation of the parathyroid gland receptors, which stimulates the production of parathyroid hormone. The main effect of parathyroid hormone is the activation of osteoclasts that dissolve bone tissue and the inhibition of collagen synthesis in osteoblasts. As a result, calcium is mobilized from bone tissue into the blood (compensation for hypocalcemia) and uncalcified bone is formed, which causes the development of osteoporosis and then osteomalacia. At the same time, parathyroid hormone reduces the reabsorption of phosphates in the renal tubules, as a result of which phosphorus is excreted in the urine, hyperphosphaturia and hypophosphatemia (an earlier sign than hypocalcemia) develop. A decrease in the phosphorus content in the blood plasma leads to a slowdown in oxidative processes in the body, which is accompanied by the accumulation of underoxidized metabolites and the development of acidosis. Acidosis also prevents calcification of bones by maintaining phosphorus-potassium salts in a dissolved state. The main pathological changes in rickets are noted in the metaepiphyseal zones of bones. They soften, become curved, and become thinner. Along with this, there is an overgrowth of defective (non-calcified) osteoid tissue.
Calcitonin is a powerful parathyroid hormone antagonist. It reduces the number and activity of osteoclasts, inhibits bone resorption, ensures the return of calcium to bone tissue, and suppresses the secretion of parathyroid hormone. Calcitonin secretion increases with an increase in the concentration of calcium in the blood and decreases with a decrease in it.
In the development of rickets, in addition to the disturbance of mineral metabolism, disturbances of fat and carbohydrate metabolism are important, in particular, a decrease in the formation of citrates from pyruvic acid, since a decrease in the concentration of citric acid disrupts the transport of calcium into the blood. In addition, with rickets, the reabsorption of amino acids in the kidneys decreases, aminoaciduria develops, and disturbances of protein metabolism worsen the absorption of calcium and phosphates.
The most significant links in the pathogenesis of rickets are considered to be:
- disruption of cholecalciferol formation in the skin;
- violation of phosphorus-calcium metabolism in the liver and kidneys;
- insufficient intake of vitamin D.
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