Summary
Highlights
Bone development, or ossification, begins about four weeks after fertilization. Initially, skeletal elements are formed from cartilage or fibrous connective tissue, not bone. True bone formation starts around two months of fetal development. There are two primary types of ossification based on the tissue being converted into bone: endochondral ossification (from cartilage) and intramembranous ossification (from fibrous connective tissue).
Intramembranous ossification is the less common type, mainly forming flat bones of the skull and clavicles. It involves four stages: 1. Formation of the center of ossification where mesenchymal cells differentiate into osteoblasts. 2. Calcification, where the bone matrix hardens with calcium salts and osteoblasts become osteocytes. 3. Trabecula formation, where trabeculae fuse to create spongy bone. 4. Periosteal development, where mesenchyme forms a periosteum, and compact bone replaces superficial spongy bone. This process leaves soft spots (fontanels) in infants' skulls that close after birth.
Endochondral ossification, responsible for most bones, involves transforming hyaline cartilage into bone. The process starts at six weeks with mesenchymal cells aggregating to form a cartilage model. A bone collar forms around the shaft surface, and blood vessels invade, converting perichondrium cells into osteoblasts. A primary ossification center develops in the diaphysis, and later, secondary ossification centers form in the epiphyses. Cartilage remains at the epiphyseal plate (for growth) and articular cartilage (for shock absorption).
Bone growth in length occurs at the epiphyseal plate. This plate has four zones of cartilage cells: the zone of resting cartilage (inactive), the zone of proliferation (chondrocytes divide rapidly and push towards the diaphysis), the zone of hypertrophy (chondrocytes grow and mature), and the zone of calcification (cartilage matrix mineralizes). The continuous proliferation and subsequent calcification/ossification at the diaphyseal end push the epiphysis away from the diaphysis, lengthening the bone.
As bones lengthen, they must also thicken through appositional growth to maintain strength. Osteoblasts beneath the periosteum secrete new bone matrix on the bone's surface. This process involves the periosteum folding to enclose blood vessels, forming new Haversian systems (osteons) around them, thus increasing the bone's width.
Several factors influence bone growth. Vitamin A stimulates osteoblast activity; a deficiency impairs lamellar bone remodeling, especially in developing skulls. Vitamin C is crucial for converting osteoblasts to osteocytes and for collagen synthesis, strengthening the bone matrix. Vitamin D enhances calcium absorption in the digestive tract, essential for bone hardness and strength.
Hormones significantly regulate bone growth. Human Growth Hormone, from the pituitary gland, promotes general tissue growth; excessive levels lead to gigantism, while insufficient levels cause dwarfism. Thyroid hormone (thyroxin) controls metabolic rate; high levels hasten epiphyseal plate closure, resulting in a shorter stature, while low levels slow growth. Sex hormones (testosterone and estrogens) cause growth spurts during adolescence but ultimately lead to epiphyseal plate closure, stopping bone lengthening.