Pathogenesis of rickets and vitamin D deficiency

Physiological effects of vitamin D metabolites

Active forms of vitamin D have a complex effect on phosphorus-calcium metabolism. Their influence is exerted through three main sites of action:

• Intestine. Here, metabolites stimulate the absorption of calcium and phosphorus ions. The basic mechanism of this process involves the potent activation of the synthesis of a specific calcium-binding protein by enterocytes.
• Renal system. At the renal level, vitamin D promotes a significant increase in the tubular reabsorption of phosphates, preventing their excessive loss in the urine.
• Bone tissue. During ossification, active forms of vitamin D stimulate the production of glycosaminoglycans. These compounds have the ability to bind calcium ions, which manifoldly potentiates and accelerates the full mineralization of the forming bone.

Cascade of disorders in vitamin D hypovitaminosis

Vitamin D deficiency inevitably triggers a chain of sequential biochemical and structural failures:

1. Decreased absorption. Due to vitamin deficiency, the production of calcium-binding protein and citrate (necessary for transport) drops. This leads to a sharp decrease in the absorption of calcium salts in the intestine.
2. Structural defects. The organic matrix of bone tissue loses its natural ability to adequately bind calcium and phosphorus.
3. Collagen damage. Excretion of amino acids in the urine increases (aminoaciduria develops). The loss of amino acids leads to a gross disruption of the spatial structure of bone collagen.
4. Secondary hyperparathyroidism. The drop in intestinal absorption provokes transient hypocalcemia. The body responds to it with a compensatory release of parathyroid hormone (PTH). PTH, striving to equalize the calcium level, begins to actively stimulate the formation of remaining vitamin D metabolites.

Role of parathyroid hormone and biochemical markers

The action of parathyroid hormone in rickets is aimed at emergency relief of hypocalcemia. PTH stimulates calcium resorption directly from bone tissue, sacrificing the bone to maintain blood calcium levels. Concurrently, this hormone inhibits citrate synthesis and sharply reduces renal phosphate reabsorption.

Dynamics of laboratory parameters:

• Hypophosphatemia acts as the earliest and most sensitive biochemical marker of developing rickets.
• Hypocalcemia is not an early symptom, contrary to common misconceptions. A persistent decrease in calcium is recorded predominantly in severe, advanced cases.
• Alkaline phosphatase (ALP) — its concentration in the blood increases predictably. This is a direct consequence of accelerated yet defective bone formation and overactive differentiation of osteoblasts, which heavily synthesize this enzyme.

Extraskeletal effects and metabolic imbalance

Vitamin D receptors are expressed in almost all organs, ensuring its systemic action. The deficiency of this nutrient strongly correlates with the development of a wide range of extraskeletal pathologies:

• Cardiovascular system: coronary heart disease (CHD), atherosclerotic vascular disease.
• Neurology: cognitive disorders, impaired neuroplasticity processes.
• Endocrine system: diabetes mellitus, obesity.
• Immune system: autoimmune, atopic, and oncological diseases, high susceptibility to infectious agents.

It is worth emphasizing that rickets should be considered a global mineral-deficient state. The disease can manifest even against the background of absolutely normal vitamin D levels. In this case, concomitant protein metabolism disorders, trace element deficiencies (magnesium, copper, iron), general multivitamin deficiency, and pathological activation of lipid peroxidation (LPO) processes predominate in the pathogenesis.

Class and exam questions

What else to study on this topic

• Mechanism of activation of calcium-binding protein synthesis in enterocytes
• The role of citrates in the transport and assimilation of calcium salts
• Pathophysiology of aminoaciduria and its effect on bone collagen
• The relationship between vitamin D and neuroplasticity processes and cognitive functions
• The effect of lipid peroxidation on the development of mineral-deficient conditions

Other topics in "Chapter 3. Adaptation, Early Childhood Nutrition, Rickets"

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