Pathogenesis of osteoporosis in children

Osteoporosis in childhood is a systemic skeletal disease characterized by decreased bone mineral density (BMD), abnormal bone microarchitecture, and an increased susceptibility to pathological fractures. Unlike in adults, osteoporosis in children occurs primarily due to abnormalities in osteogenesis and bone remodeling during the period of active growth and peak bone mass formation.

1. Features of bone tissue formation in childhood

The formation of bone mass in children is a complex biological process regulated by the interaction of cellular, humoral and mechanical factors:

• In the phase of intensive growth, bone formation processes predominate, which ensure linear growth of the skeleton and thickening of the cortical bone layer.
• Peak bone mass is reached by the age of 18–20, after which the processes of bone formation and resorption are leveled off. Disruption of these processes in childhood prevents the achievement of an adequate peak bone mass, creating the preconditions for osteoporosis.

2. Cellular and molecular mechanisms

Bone tissue undergoes constant remodeling, which is carried out by the interaction of two main types of cells:

• Osteoblasts are cells that synthesize an organic matrix (osteoid) rich in type I collagen and promote its mineralization.
• Osteoclasts are multinucleated cells responsible for the resorption of mineralized matrix.

The main pathogenetic mechanism in osteoporosis in children is a shift in balance towards increased osteoclast activity and/or inhibition of osteoblastogenesis.

2.1. RANK/RANKL/OPG system

• RANKL (Receptor Activator of Nuclear Factor κB Ligand), expressed by osteoblasts and osteocytes, stimulates the differentiation of osteoclast precursors into active osteoclasts.
• Osteoprotegerin (OPG), produced by osteoblasts, is a natural inhibitor of RANKL and blocks binding to the RANK receptor on osteoclasts.
• In osteoporosis, there is a decrease in OPG expression and/or overexpression of RANKL, which leads to increased osteoclastogenesis.

2.2. Wnt/β-catenin signaling pathway

• This pathway activates osteoblasts and stimulates bone formation.
• Wnt signaling inhibitors such as costeokerin and DKK-1 block osteogenesis, promoting the development of osteoporosis.

2.3. Glucocorticoid-induced mechanisms

• Glucocorticoids directly suppress the proliferation and differentiation of osteoblasts, induce their apoptosis and promote prolonged activation of osteoclasts.
• Children who receive GCS for a long time develop so-called secondary glucocorticoid osteoporosis.

3. Hormonal regulation of bone metabolism

In childhood, hormonal regulation plays a key role in the pathogenesis of osteoporosis:

• Estrogens and androgens stimulate bone formation, inhibit osteoblast apoptosis, and suppress osteoclast activity. Their deficiency in hypogonadism or delayed puberty leads to a decrease in BMD.
• Parathyroid hormone (PTH) in physiological concentrations stimulates osteogenesis (anabolic effect), but in hyperparathyroidism it increases bone resorption.
• Vitamin D and calcium ensure adequate mineralization of osteoid; their deficiency leads to disruption of calcium homeostasis and osteomalacia.

4. Etiopathogenetic classification of osteoporosis in children

• Primary (idiopathic) osteoporosis:
  • Juvenile idiopathic osteoporosis is a rare disease of unknown etiology that manifests itself in the prepubertal period.
  • Osteogenesis imperfecta is a genetic disorder of type I collagen.
• Secondary osteoporosis:
  • Endocrinopathies (hypogonadism, hyperthyroidism, hypercorticism).
  • Chronic immobilization (cerebral palsy, spinal injury).
  • Medicinal (glucocorticoids, anticonvulsants).
  • Chronic inflammatory diseases (juvenile idiopathic arthritis, celiac disease).

5. Microarchitectural changes in bone tissue

With osteoporosis in children the following occurs:

• Thin cortical bone with multiple porous areas.
• Trabecular bone reduction: trabeculae become thin and scattered, their number and connectivity decrease, which leads to a loss of mechanical strength of the bone.

Conclusion

The pathogenesis of osteoporosis in children is multicomponent and includes disruption of cellular interactions (osteoblasts and osteoclasts), hormonal regulation and molecular signaling pathways. The key point is disruption of bone tissue formation and remodeling processes during the period of active growth, which prevents the achievement of peak bone mass. This condition requires early diagnosis and timely correction, since osteoporosis in childhood significantly increases the risk of osteopenic fractures and predisposes to the development of osteoporosis in adulthood.

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