Bone formation and bone growth Claudia Stanescu, Ph.D. Office Hours in Gittings 108 Tue 10-11am and Thurs 1-2pm or by appointmentObjectives: 1. Differentiate between the processes of intramembranous and endochondral ossification. 2. Be able to determine the order of events involved in intramembranous and endochondral ossification. 3. List the bones formed by intramembranous and endochondral ossification. 4. Describe how the presence of an epiphyseal plate facilitates the lengthening of bones. 5. Describe the process of appositional growth.Bone formation • Bones of an infant can be soft in certain regions: – Fontanels (soft spots on skull) – Epiphysis of long bones made of cartilage in infant – Epiphyseal plates stay as cartilage until adulthood (end of puberty)Bone formation Bones of fetus (before birth) composed of 1) Loose connective tissue – mesenchyme 2) Hyaline cartilage Ossification = replacement of connective tissue by bone – begins during the second month of development2 Types of Ossification 1) Intramembranous ossification “within membrane” Mesenchyme  bone 2) Endochondral ossification “inside cartilage” Mesenchyme  cartilage  bone Fifteen-week fetus. The red areas represent bones that are forming (calcified). Dark gray areas represent cartilage (uncalcified).Intramembranous ossification Bones formed by this process: – Cranial bones (frontal, parietal…) – Mandible – Sternum – Clavicle Heterotropic bone formation – sesamoid bones – abnormal stresses can stimulate bone formation in areas where bone is not normally foundIntramembranous Ossification Summary of steps: 1) Development of ossification center • Mesenchymal cells differentiate into osteogenic cells, then into osteoblasts • Osteoblasts secrete bone matrix 2) Calcification – osteoblasts deposit calcium into the matrix – osteoblasts differentiate into osteocytes 3) Formation of trabecullae (spongy bone) 4) Development of periosteum – Remodeling of spongy bone to compact boneCalcification vs. Ossification • Calcification = deposition of calcium • Ossification = replacement of connective tissue by bone tissue • Calcification is an essential part of ossificationEndochondral ossification Bones formed by this process: – Most bones in the body Growth in length at the epiphyseal plate also by endochondral ossificationEndochondral ossification steps: • Formation of a cartilage model from mesenchyme• Cartilage model grows in length and width • Cartilage model begins to calcify Endochondral ossification steps:• Blood vessels penetrate model and stimulate differentiation of osteogenic cells into osteoblasts • Osteoblasts secrete bony matrix • Calcification occurs • Primary ossification center forms (spongy bone) Endochondral ossification steps:Endochondral ossification steps: • Osteoclasts invade the newly formed bone and carve a marrow cavity • Spongy bone is remodeled into compact bone at diaphysis • Initially epiphyses remain as cartilage• Around the time of birth blood vessels penetrate the epiphyses • Secondary ossification center forms Endochondral ossification steps:• Spongy bone replaces most of the cartilage (except epiphyseal plates and articular cartilage) Endochondral ossification steps:Endochondral Ossification Summary Steps: 1) Cartilage model forms 2) Growth of cartilage model 3) Blood vessels penetrate model and stimulate differentiation of osteogenic cells into osteoblasts 4) Osteoblasts form bone on the outer surface of the model 5) Osteoblasts create a primary ossification center (bone replaces cartilage) 6) Osteoclasts create a marrow cavity 7) Spongy bone remodeled to compact bone 8) Around birth, a secondary ossification center forms 9) Spongy bone replaces cartilage at the epiphyses with the exception of epiphyseal plates and articular cartilagePrimary Ossification - Marrow cavity formed - Replaces all cartilage with bone - Located in diaphysis - Occurs before birth Secondary Ossification - No marrow cavity - Some cartilage is left for epiphyseal plates (growth) and articular cartilage - Located in epiphyses - Occurs around the time of birthBone growth in the hand 2 year-old 7 year-old AdultInterstitial Growth (Endochondral Ossification) • Growth in length Resting cartilage Proliferating cartilage Calcified cartilage (will become bone) Diaphysis (bone) Epiphysis (bone) Hypertrophic cartilageInterstitial growthInterstitial growth • Diaphyseal osteoclasts break down calcified cartilage • Osteoblasts lay down spongy bone • Chondroblasts will continue to form cartilage matrix at the proliferating cartilage region • Growth in length stops when the osteoclasts/osteoblasts work faster than the chondroblasts  epiphyseal plate closes and becomes the epiphyseal lineModel of Bone GrowthAppositional growth • Growth in width • Periosteal osteoblasts build bone on outer surface of bone and endosteal osteoclasts increase the diameter of the marrow cavity • Bone diameter and cortical width increase Periosteal osteoblasts build bone here Endosteal osteoclasts break down bone here Cross section of bone diaphysis in a child Cross section of bone diaphysis in an adultAppositional growth Medullary cavity Bone formed by osteoblasts Bone destroyed by osteoclasts Infant Child Young adult Adult (b) Macroscopic changes • Bone diameter increases • Cortical width increasesAppositional growth • Osteons are added to the periosteal side of bone by the following