- Clinical science
The musculoskeletal system is comprised of bones and connective tissue structures, such as cartilage, ligaments, and tendons. These structures are brought into motion by skeletal muscles. To withstand resultant forces, bone tissue resists pressure and tension and is minimally elastic. Bone tissue mainly consists of bone cells (osteoblasts, osteocytes, and osteoclasts) and a mineralized extracellular matrix that is primarily made up of collagen fibrils and hydroxyapatite crystals. Ossification, or bone formation, begins with a framework that consists of either mesenchymal connective tissue (intramembranous ossification) or cartilage (endochondral ossification). Woven bone is formed, which is replaced by the more solid and layered lamellar bone. The outer cortical layers can be macroscopically differentiated from the branched center of the trabeculae.
- Supportive function
- Protective function
- Storage (calcium and phosphorus reservoir)
Long bones: include the femur, humerus, ulna, radius, fibula, metacarpals, and phalanges
- Metaphysis: area between the epiphysis and the diaphysis
- Apophysis: large bony projections where ligaments and tendons attach
- Short bones: Include tarsal and carpal bones
- Flat bones
- Bones that develop within tendons (e.g., the patella)
- Function to reduce friction of the tendon and to reduce excessive wear
- Irregular bones
The exact composition or organization of individual bone components differs in the various bones types and maturation stages. All human bones are composed of the same basic elements:
- Bone cells: build and remodel bones
- Bone matrix: composed of organic and inorganic components
- Bone membranes: cover the inner and outer surface of the bone
- Bone marrow: either actively involved in hematopoiesis (red bone marrow) or primarily replaced by adipose cells (yellow bone marrow)
|Osteoprogenitor cells|| || |
Composed of organic and inorganic material
- Periosteum: membrane of connective tissue that covers the outer surface of the bone in two distinct layers
- Endosteum: membrane that lines the inner surface of the bone (e.g., trabecular bone or Haversian canal)
- Red bone marrow (hematopoietic): primarily in the short and flat bones and partly in the epiphyses of the long bones in adults
- Yellow bone marrow (fat storage): primarily fills the medullary cavities of the long bones in adults
For more details on bone marrow, see the article on .
- Bone is derived from mesoderm.
|Endochondral ossification||Intramembranous ossification|
|Process|| || |
The skull undergoes both processes: The viscerocranium (e.g., frontal bone) is derived from the neural crest and undergoes membranous ossification, whereas the chondrocranium (e.g., sphenoid, ethmoid bone) and neurocranium (e.g., occipital and parietal bones) are derived from paraxial mesoderm and undergo endochondral ossification!
Stages of bone maturity
Bones are arranged into woven bone (primary bone) during embryonic development or bone healing. The structure of woven bone is disorganized and transformed into organized tissue of lamellar bone (secondary bone) through continuous remodeling.
|Woven bone||Lamellar bone|
|Histology|| || |
|Characteristics|| || |
Vascularization of lamellar bones
Bone canals and associated vessels
- Haversian canal + Haversian vessel: canal in the center of the osteon, which contains Haversian vessels that supply the bone with blood
- Volkmann's canal (perforating channels) + Volkmann's vessels: canals radiating from the periosteum that are at a right angle to Haversian vessels and are supplied by Volkmann's vessels
Development of long bones
Primary ossification center: diaphysis
- Secondary ossification center: epiphysis
- Longitudinal growth of the long bones
- Chondrocyte proliferation at the epiphyseal plates → longitudinal growth with the epiphysis pushed away from the diaphysis
- Cartilage tissue degradation and remodeling in bone tissue from the medullary cavity
- The proliferation zone progresses with the same velocity as the ossification zone.
- Longitudinal growth ends when chondrocytes cease proliferating and bone replaces cartilage (ossification zone) in a process known as epiphyseal fusion.
- Zone of resting cartilage
Proliferation zone: mitosis of chondrocytes
- Proliferation process
- Vertical (from an isogenic neighbor): transverse septum
- Horizontal (from nonisogenic neighbors): longitudinal septum
- Zone of hypertrophy
Zone of calcification
- Effect: mineralized columns remain (ossified longitudinal septa)
- Approx. ⅓ of the longitudinal septa is retained with the remaining septa degraded by chondroclasts.
- Zone of ossification: colonization of the mineralized longitudinal septae by osteoblasts → osteoid formation → mineralization
Achondroplasia is a genetic disorder with impaired cartilage formation and results in a short stature. It especially affects the epiphyseal plates of the long bones, which close prematurely. The absence of longitudinal growth leads to a short stature with a disproportional body stature (e.g., normal trunk with a disproportional head and short, plump extremities).
During childhood or adolescence, a fracture near a joint may damage the unclosed epiphyseal plate, which can result in growth disorders (e.g., asymmetry, inhibition, acceleration) during healing.
The human skeleton is in a continuous dynamic state of remodeling. Not only does this apply to the replacement of immature woven bone by lamellar bone, but also for adaptation of adult bones to their individual load.
- Cells involved: osteoclasts (degrade) and osteoblasts (build)
- Duration: usually longer than the lifespan of cells involved → continual replacement of cells involved
Blasts build, clasts crumble!
- Osteoclasts are followed by osteoblasts → deposition of the first osteoid layer in the tunnel
- Additional osteoblasts follow and deposit osteoid onto the first osteoid layer → osteoblasts of the first layer are walled in → become osteocytes
- The deposition process is repeated until the tunnel is almost full → central remains open
- The innermost (i.e., last) generation of osteoblasts is no longer walled in → cells return to their resting state and form the endosteum
Mineralization: occurs successively
- Osteoblasts secrete collagen and vesicles into the extracellular matrix.
- Vesicles contain enzymes (e.g., alkaline phosphatase), which increase local phosphate levels by cleavage of, e.g., pyrophosphate.
- Calcium-binding molecules in the vesicles most likely serve as a focal point.
- Initial formation of hydroxyapatite crystals around the focal point in the vesicles
- Independent growth of the crystals until penetration of the vesicle membrane
- Release of crystals in the extracellular matrix
- Growth of crystals in the extracellular matrix and accumulation of collagen fibrils
- Osteoclasts organize in Howship lacunae (small depressions on the trabecular bone surface). They move to resorb trabecular bone and form a tight seal around the resorption area.
- Osteoclasts produce protons via the enzyme carbonic anhydrase.
- Secretion of chloride ions (passive) and protons (active, via ATPase) in Howship lacunae (→ HCl), with the formation of an acidic environment (∼ pH 4.5) → dissolution of inorganic bone elements
- Secretion of lysosomal enzymes (especially cathepsin K and matrix metalloproteinases) → degradation of organic bone elements
- Endocytosis/transcytosis of the bone elements
- Load on the bone leads to increased bone mass.
- Absence of load (e.g., due to being confined in bed) results in decreased bone mass.
- RANK (receptor activator of nuclear factor κB): receptor on osteoclasts and osteoclast precursors for interaction with osteoblasts
- RANKL (receptor activator of nuclear factor κB ligand)
- Osteoprotegerin (OPG): a regulatory protein secreted by osteoblasts that binds to RANKL and inhibits its effect (i.e., inhibits osteoclasts)
- M-CSF (= macrophage colony stimulating factor): secreted by osteoblasts → promotes proliferation of osteoclast precursor cells
- Negative feedback by osteoclasts: Growth factors are embedded in the bone matrix and are released during degradation by osteoclasts → stimulates osteoblasts.
Hormones: PTH, sex hormones (especially estrogen)
- PTH effects
- Estrogen effects
- Vitamin D
- Primary bone healing: occurs when the broken ends of the bone are very close together (interval < 1 mm), e.g., when surgically fixed
- Secondary bone healing: occurs when the distance of the fracture ends is larger
- fracture ends (e.g., through insufficient immobilization). can occur if the healing process is permanently disturbed by motion of the