Bone Formation and Remodeling

Endochondrial ossification

• bones preformed in hyaline cartilage and cartilage is replaced by bone
• process occurs while maintaining supportive function of skeleton
• occurs in most bones, follows genetic template

Process

1. Mesenchymal cells cluster and differentiate into chondroblasts, which form a cartilaginous matrix. Cartilage is surrounded by perichondrium with chondroblasts.
2. Cartilage enlarges by interstitial and appositional growth
3. Osteoprogenitor cells in the perichondrium become osteoblasts and deposit a thin collar of compact bone around diaphysis; the perichondrium is now called periosteum..
4. Chondrocytes beneath the collar and in midshaft hypertrophy and lacunae expand, reducing the amount of matrix. Chemical changes cause the matrix to calcify, which limits diffusion and chondrocytes die. Empty lacunae merge to form small cavities within calcified matrix.
5. Vessels and osteoprogenitor cells grow into calcified cartilage of diaphysis forming an osteogenic bud, which forms osteoblasts that secrete bone matrix over the surfaces of calcified cartilage matrix producing trabecular bone.
6. In center of diaphysis osteoclasts resorb trabecular bone to form medullary cavity. Called Primary Ossification Center (POC)
7. Secondary Ossification Centers form in the epiphyses later by same sequence: hypertrophy, calcification, replacement, but there is no collar and bone remains trabecular. A band of articular cartilage and the epiphyseal plate of cartilage remains.

Epiphyseal plate is responsible for growth in diaphyseal length. Cartilage formation occurs at epiphyseal side and bone formation at diaphyseal side.

Zones:

1. Resting cartilage - anchors plate to bone
2. Proliferating cartilage - mitotic, chondrocytes form stacks of cells
3. Hypertrophic cartilage - cells and lacunae enlarge, matrix reduced
4. Calcified cartilage - matrix calcifies and chondrocytes die
5. Ossification - vessels and osteoprogenitor cells invade, form osteoblasts and deposit bone matrix on calcified cartilage

When activity of Zone 2 is less than Zone 5 growth stops and plate becomes epiphyseal line

Articular cartilage is responsible for growth of epiphyses. Functions like epiphyseal plates but zones are not as obvious and articular cartilage never ossifies.

Bone diameter and bony projections are formed by appositional bone growth in periosteum.

Intramembranous ossification

• occurs in collagenous connective tissue membrane, no cartilage involved
• forms flat bones of skull, part of mandible, and clavicular diaphysis

Process:

1. Area becomes highly vascularized with large number of osteoprogenitor cells
2. Osteoprogenitor cells cluster and differentiate into osteoblasts
3. Osteoblasts deposit organic matrix with collagen fibers followed by calcification
4. Osteoblasts surrounded by calcified matrix become osteocytes in lacunae
5. Clusters form calcified spicules, which continue to elongate and fuse together to form a trabecular latticework or are remodeled into compact bone around vessels
6. Periosteum forms on outside and endosteum on inside surfaces, non-ossified membrane between is called fontanel
7. Growth and remodeling of flat bones are result of bone resorption by osteoclasts and bone formation by osteoblasts in coordinated fashion.
   1. ex. deposition on outer surface and edges with resorption on inner surfaces of a bone

Bone Remodeling and Repair

Remodeling is a combination of osteoblasts building bone and osteoclasts breaking down bone. Normal bone maintenance requires balanced activity of both cell types. Increasing or decreasing the activity of one cell type will increase or decrease the amount of bone present.

1. Functional adaptation - bone tissue will remodel to resist mechanical stresses applied to the bone, ex. exercise increases osteoblast activity producing thicker bones and larger sites for muscle attachment
2. After a long bone fracture, an internal callus and an external callus largely of cartilage form, endochondrial ossification occurs and remodeling reforms the bone shape

Divisions of the skeletal system

1. Axial skeleton -  skull and hyoid, vertebral column, ribs, sternum
2. Appendicular skeleton - scapula and clavicle, arms, pelvis, legs