Introduction Bone formation (osteogenesis) can occur via two distinct processes that convert mesenchymal tissue to bone endochondral ossification mesenchymal tissue → cartilage intermediate → bone intramembranous ossification mesenchymal tissue → bone Bone remodeling requires a dynamic balance of formation and resorption that depends on multiple cell types osteoblasts osteocytes osteoclasts Endochondral Ossification Overview converts mesenchymal tissue to a cartilage intermediate and eventually to bone occurs in several different osteogenic processes embryonic long bone formation longitudinal physis (growth plate) growth non-rigid fracture healing Steps mesenchymal precursor cells commit to becoming cartilage cells (chondrocytes) occurs via paracrine signaling committed mesenchymal cells differentiate into chondrocytes chondrocytes rapidly proliferate and secrete cartilage-specific extracellular matrix to form a cartilage model chondrocytes die via apoptosis as the matrix calcifies surrounding cells differentiate into osteoblasts to begin replacing degraded cartilage with bone matrix (osteoid) blood vessels penetrate the diaphyseal cartilage core and osteoblasts form a primary ossification center diaphyseal bone thickens and epiphyseal cartilage becomes calcified blood vessels penetrate the epiphyseal cartilage core and osteoblasts form secondary ossification centers initial bone is immature woven bone with irregular random collagen fibers bone remodeling eventually converts immature woven bone to mature lamellar bone with parallel arranged collagen fibers Intramembranous Ossification Overview converts mesenchymal tissue directly to bone no cartilage intermediate also known as Haversian remodeling occurs in several different osteogenic processes embryonic flat bone formation skull facial bones clavicle rigid fracture healing Steps mesenchymal cells proliferate and differentiate directly into osteoblasts osteoblasts produce bone matrix (osteoid) initial bone is immature woven bone with irregular random collagen fibers bone remodeling eventually converts immature woven bone to mature lamellar bone with parallel arranged collagen fibers Bone Remodeling Multiple cell types are required for healthy bone remodeling osteoblasts function bone-forming cells produce a collagen-proteoglycan matrix that can bind calcium salts for osteoid calcification origin derived from fibroblasts osteocytes function bone cells transmit signals through bone secrete growth factors to regulate activity of osteoblasts and osteoclasts origin derived from osteoblasts that become embedded in bone matrix osteoclasts function bone-resorbing cells mobilize matrix minerals via acidification, then degrade matrix material via proteases origin derived from monocytes clinical relevance involved in correction of displacement and angulation in pediatric fractures requires the coordinated activity of osteoclasts in reabsorbing the convex side of the deformity osteoblasts in filling the concave side of the deformity inadequate osteoblastic activity will lead to impaired bone mineralization rickets/osteomalacia excess osteoclastic activity will lead to increased bone resorption osteoporosis Paget disease of bone osteitis fibrosa cystica inadequate osteoclastic activity will lead to insufficient bone resorption osteopetrosis