Osteogenesis And Bone Growth PDF

OSTEOGENESIS DR ATIKAH ABDUL LATIFF SENIOR LECTURER AND BONE ANATOMY DEPARTMENT GROWTH FACULTY OF MEDICINE  By the end of this lecture, you should be able to: 1. Describe the process of ossification and LEARNING ossification...

OSTEOGENESIS DR ATIKAH ABDUL LATIFF SENIOR LECTURER AND BONE ANATOMY DEPARTMENT GROWTH FACULTY OF MEDICINE  By the end of this lecture, you should be able to: 1. Describe the process of ossification and LEARNING ossification centres. 2. Describe the processes involved in the OBJECTIVES two types of ossification. 3. Describe the process of bone growth and remodelling. 4. Describe fracture healing.  Osteoprogenitor (osteogenic) cells -- undifferentiated cells – can divide to replace themselves & can become osteoblasts – found in inner layer of periosteum and endosteum Osteoblasts -- form matrix & collagen fibers but can’t divide FOUR TYPES OF BONE CELLS Osteocytes -- the principal cells of bone tissue. – mature cells that no longer secrete matrix Osteoclasts -- huge cells from fused monocytes (WBC) – serve to break down bone tissue – function in bone resorption at surfaces such as endosteum WHAT IS OSSIFICATION? ¡ All embryonic connective tissue begins as mesenchyme ¡ Bone formation is called osteogenesis or ossification ¡ Two types of ossification occur – Intramembranous ossification is the formation of bone directly from fibrous connective tissue membranes (dermis) – Endochondral ossification is the formation of bone from hyaline cartilage models  Intramembranous ossification begins in utero during fetal development and continues on into adolescence. At birth, the skull and clavicles are not fully ossified nor are the sutures of the skull closed. INTRAMEMBRANOUS This allows the skull and shoulders to deform OSSIFICATION during passage through the birth canal. The last bones to ossify via intramembranous ossification are the flat bones of the face, which reach their adult size at the end of the adolescent growth spurt. INTRAMEMBRANOUS OSSIFICATION During intramembranous ossification, compact and spongy bone develops directly from sheets of mesenchymal (undifferentiated) connective tissue. The flat bones of the face, most of the cranial bones, and the clavicles (collarbones) are formed via intramembranous ossification. The process begins when mesenchymal cells in the embryonic skeleton gather together and begin to differentiate into specialised cells. Some of these cells will differentiate into capillaries, while others will become osteogenic cells and then osteoblasts. Although they will ultimately be spread out by the formation of bone tissue, early osteoblasts appear in a cluster called an ossification center. The osteoblasts secrete osteoid, uncalcified matrix, which calcifies (hardens) within a few days as mineral salts are deposited on it, thereby entrapping the osteoblasts within. Once entrapped, the osteoblasts become osteocytes (Figure 1b). As osteoblasts transform into osteocytes, osteogenic cells in the surrounding connective tissue differentiate into new osteoblasts. Osteoid (unmineralized bone matrix) secreted around the trabecular matrix, while osteoblasts on the surface of the spongy bone become the periosteum (Figure 1c). The periosteum capillaries then creates a protective layer of compact bone superficial to the trabecular bone. The trabecular bone crowds nearby blood vessels, which eventually condense into red marrow ENDOCHONDRAL OSSIFICATION In endochondral ossification, bone develops by replacing hyaline cartilage. Cartilage does not become bone. Instead, cartilage serves as a template to be completely replaced by new bone. Endochondral ossification takes much longer than intramembranous ossification. Bones at the base of the skull and long bones form via endochondral ossification. In a long bone, for example, at about 6 to 8 weeks after conception, some of the mesenchymal cells differentiate into chondrocytes (cartilage cells) that form the cartilaginous skeletal precursor of the bones. Soon after, the perichondrium, a membrane that covers the cartilage, appears. ENDOCHONDRAL OSSIFICATION As more matrix is produced, the chondrocytes in the centre of the cartilaginous model grow in size. As the matrix calcifies, nutrients can no longer reach the chondrocytes. This results in their death and the disintegration of the surrounding cartilage. Blood vessels invade the resulting spaces, not only enlarging the cavities but also carrying osteogenic cells with them, many of which will become osteoblasts. These enlarging spaces eventually combine to become the medullary cavity. As the cartilage grows, capillaries penetrate it. This penetration initiates the transformation of the perichondrium into the bone-producing periosteum. Here, the osteoblasts form a periosteal collar of compact bone around the cartilage of the diaphysis. By the second or third month of fetal life, bone cell development and ossification ramps up and creates the primary ossification centre, a region deep in the periosteal collar where ossification begins ENDOCHONDRAL OSSIFICATION After birth, this same sequence of While these deep changes are By the time the fetal skeleton is fully events (matrix mineralization, death of occurring, chondrocytes and cartilage formed, cartilage only remains at the chondrocytes, invasion of blood vessels continue to grow at the ends of the joint surface as articular cartilage and from the periosteum, and seeding with bone (the future epiphyses), which between the diaphysis and epiphysis as osteogenic cells that become increases the bone’s length at the same the epiphyseal plate, the latter of which osteoblasts) occurs in the epiphyseal time bone is replacing cartilage in the is responsible for the longitudinal regions, and each of these centers of diaphyses. growth of bones. activity is referred to as a secondary ossification center. ENDOCHONDRAL OSSIFICATION ¡ Endochondral ossification involves replacement of cartilage by bone and forms most of the bones of the body BONE GROWTH IN LENGTH It is a layer of hyaline cartilage On the epiphyseal side of the The epiphyseal plate is the where ossification occurs in epiphyseal plate, cartilage is area of growth in a long bone. immature bones. formed. Between ages 18 to 25, epiphyseal plates close – On the diaphyseal side, The epiphyseal plate is cartilage cells stop dividing and cartilage is ossified, and the composed of four zones of bone replaces the cartilage diaphysis grows in length. cells and activity. (epiphyseal line) (Growth in length stops by age 25) ZONES OF THE EPIPHYSEAL PLATE The proliferative zone is the next layer toward the diaphysis and contains stacks of slightly larger chondrocytes. It makes new chondrocytes (via mitosis) to replace those that die at the diaphyseal end of the plate. Chondrocytes in the next layer, the zone of maturation and hypertrophy, are older and larger than those in the proliferative zone. The more mature cells are situated closer to the diaphyseal end of the plate. The longitudinal growth of bone is a result of cellular division in the proliferative zone and the maturation of cells in the zone of maturation and hypertrophy. Most of the chondrocytes in the zone of calcified matrix, the zone closest to the diaphysis, are dead because the matrix around them has calcified. Capillaries and osteoblasts from the diaphysis penetrate this zone, and the osteoblasts secrete bone tissue on the remaining calcified cartilage. Thus, the zone of calcified matrix connects the epiphyseal plate to the diaphysis. A bone grows in length when osseous tissue is added to the diaphysis. Bones continue to grow in length until early adulthood. The rate of growth is controlled by hormones, which will be discussed later. When the chondrocytes in the epiphyseal plate cease their proliferation and bone replaces the cartilage, longitudinal growth stops. All that remains of the epiphyseal plate is the epiphyseal line ZONES OF EPIPHYSEAL PLATE  While bones are increasing in length, they are also increasing in diameter; growth in diameter can continue even after longitudinal growth ceases. This is called appositional growth. BONE GROWTH Osteoclasts resorb old bone that lines the medullary cavity, while IN THICKNESS/ osteoblasts, via intramembranous ossification, produce new bone tissue beneath the periosteum. DIAMETER The erosion of old bone along the medullary cavity and the deposition of new bone beneath the periosteum not only increase the diameter of the diaphysis but also increase the diameter of the medullary cavity. This process is called modeling. BONE GROWTH IN THICKNESS  – Old bone is constantly Remodeling is the ongoing destroyed by osteoclasts, replacement of old bone whereas new bone is tissue by new bone tissue constructed by osteoblasts – Several hormones and calcitriol control bone growth Ongoing since osteoclasts carve out small tunnels and BONE and bone remodelling osteoblasts rebuild osteons. REMODELLING – osteoclasts form leak-proof seal around cell edges – Continual redistribution of secrete enzymes and acids bone matrix along lines of beneath themselves – release mechanical stress – distal calcium and phosphorus into femur is fully remodeled every interstitial fluid – osteoblasts 4 months take over bone rebuilding  ¡ Nutrition – adequate levels of minerals and vitamins o calcium and phosphorus for bone growth FACTORS o o vitamin C for collagen formation vitamins K and B12 for protein synthesis AFFECTING ¡ Sufficient levels of specific hormones – during childhood need insulin-like growth factor BONE o o promotes cell division at epiphyseal plate need hGH (growth), thyroid (T3 & T4) GROWTH – at puberty the sex hormones, estrogen and testosterone, stimulate sudden growth and modifications of the skeleton to create the male and female secondary characteristics GROWTH HORMONE Growth hormone (GH) secretion from anterior pituitary is regulated by the hypothalamus and the mediators of GH actions. Major regulatory factors include GH releasing hormone (GHRH), somatostatin (SRIF), GH releasing peptide (ghrerin) and insulin-like growth factor (IGF-I). The principal physiological regulation mechanisms of GH secretion are neural endogenous rhythm, sleep, stress, exercise, and nutritional and metabolic signals. GH deficiency results from various hereditary or acquired causes, which may be isolated or combined with other pituitary hormone deficiencies. GH deficiency can be treated with recombinant human GH, which results in accelerating growth in children and normalization of intermediary metabolism in adults. GH hypersecretion mostly results from a pituitary tumor and causes acromegaly or gigantism. Hypersecretion of GH can be treated by transsphenoidal surgery. Medical treatment with octreotide and analogs is also effective to reduce GH secretion in combination with or without the surgery. HORMONAL ABNORMALITIES AFFECTING BONE GROWTH Both men or women that Oversecretion of hGH Undersecretion of hGH lack oestrogen receptors (human growth hormone) or thyroid hormone on cells grow taller than during childhood during childhood normal – oestrogen is produces giantism produces dwarfism responsible for closure of growth plate GROWTH HORMONE HYPO AND HYPERSECRETION  Formation of fracture hematoma – damaged blood vessels produce clot in 6-8 hours, bone cells die – inflammation brings in phagocytic cells for clean-up duty – new capillaries grow into damaged area Formation of fibrocartilagenous (soft) callus – fibroblasts invade & lay down collagen fibers – chondroblasts produce fibrocartilage to span the broken ends of the bone REPAIR OF A Formation of bony (hard) callus – osteoblasts secrete spongy bone that joins 2 broken ends of bone – lasts 3-4 months FRACTURE Bone remodeling – compact bone replaces the spongy bone in the bony callus – surface is remodeled back to normal shape *callus: thickened and hardened part of skin or soft tissue BONE FRACTURE REPAIR THANK YOU!