Bone Structure and Cellular Composition
Anatomically, bone consists of two layers. The outer compact bone layer is formed by osteons—structural units of concentric lamellae containing blood vessels and nerves. The inner spongy (cancellous) bone layer is a network of interlacing trabeculae forming spaces for the red bone marrow.
The dry weight of the bone matrix is divided equally: 50% inorganic minerals (hydroxyapatite crystals) and 50% organic proteins and water. The unmineralized matrix secreted by cells is called osteoid.
Three main cell types are responsible for tissue remodeling:
- Osteoblasts: Synthesize collagen and matrix proteins (e.g., osteonectin), regulate mineralization, and control the activity of resorbing cells.
- Osteocytes: Mature mononuclear cells trapped in lacunae. Their function is to maintain matrix structure.
- Osteoclasts: Multinucleated macrophages responsible for bone resorption.
Bone Dysplasias
Dysplasias are genetically determined cartilage and bone disorders leading to skeletal growth and structural defects.
Osteopetrosis (marble bone disease) is linked to impaired osteoclast function. Because resorption is lost, bone synthesis becomes excessive. Medullary cavities narrow, crowding out bone marrow and causing severe anemia. A characteristic radiographic feature is the "bone-within-a-bone" appearance.
Achondroplasia is a form of congenital dwarfism. A mutation in the FGFR3 gene causes the receptor to continuously suppress chondrocyte proliferation. Cartilage cells fail to be replaced by bone tissue, sharply inhibiting endochondral ossification (longitudinal growth). Intelligence in these patients remains completely normal.
Osteogenesis imperfecta ("brittle bone disease") is caused by mutations in type I collagen genes. The primary problem is bone mass deficiency and extreme fragility. Several types exist, ranging from lethal perinatal forms to milder variants featuring multiple fractures, blue sclerae, and hearing loss.
Paget's Disease and Fibrous Dysplasia
Paget's disease (osteitis deformans) typically manifests after age 40. A viral theory is widely accepted: a paramyxovirus infects osteoblasts, prompting them to release interleukin-6, which hyperactivates osteoclasts. The disease progresses through three stages:
- Osteolytic stage: Rapid destruction of the cortical plate.
- Osteoblastic stage: Chaotic formation of bone trabeculae, creating a characteristic coarse-fibered mosaic structure.
- Osteosclerotic stage: Decrease in osteoclast number, with bone marrow spaces replaced by adipose tissue.
The end result is thickening, deformation, and roughness of the affected bones. Complications include pathological fractures, kidney stones due to calcium release into the bloodstream, and, rarely, sarcoma.
In fibrous dysplasia, normal bone tissue is locally replaced by fibrous connective tissue containing primitive bone trabeculae, also leading to deformities.
Metabolic Diseases: Osteoporosis
These conditions involve metabolic disturbances. The primary pathology in this group is osteoporosis, characterized by a reduction in bone mass per unit volume. The pathogenesis centers on resorption exceeding synthesis.
Primary generalized osteoporosis makes bones fragile throughout the skeleton. The most common variant is postmenopausal (Type I). As estrogen levels drop in women, osteoblasts (which express estrogen receptors) begin to secrete cytokines. This powerfully stimulates osteoclast activity, accelerating skeletal destruction.