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10/18/14 Bone Development 6 • Osteogenesis (_____________________) — bone Dssue formaDon • Stages – Bone formaDon—begins in the 2nd month of development – Postnatal bone growth—unDl early adulthood – Bone remodeling and repair—________________ Bones and Skeletal Tissues: Part B Two Types of OssificaDon Mesenchymal cell Collagen fiber Ossification center 1. ___________________________ ossificaDon – Membrane bone develops from fibrous membrane – Forms flat bones, e.g. clavicles and cranial bones 2. ___________________________ ossificaDon – CarDlage (endochondral) bone forms by replacing hyaline carDlage – Forms most of the rest of the skeleton Osteoid Osteoblast Ossification centers appear in the fibrous connective tissue membrane. • Selected centrally located mesenchymal cells cluster and differentiate into osteoblasts, forming an ossification center. 1 Figure 6.8, (1 of 4) 1 10/18/14 Osteoblast Osteoid Osteocyte Newly calcified bone matrix 2 Bone matrix (osteoid) is secreted within the fibrous membrane and calcifies. • Osteoblasts begin to secrete osteoid, which is calcified within a few days. • Trapped osteoblasts become osteocytes. Mesenchyme condensing to form the periosteum Trabeculae of woven bone Blood vessel 3 Woven bone and periosteum form. • Accumulating osteoid is laid down between embryonic blood vessels in a random manner. The result is a network (instead of lamellae) of trabeculae called woven bone. • Vascularized mesenchyme condenses on the external face of the woven bone and becomes the periosteum. Figure 6.8, (2 of 4) Figure 6.8, (3 of 4) Endochondral OssificaDon Fibrous periosteum Osteoblast Plate of compact bone Diploë (spongy bone) cavities contain red marrow • Uses __________________ carDlage models • Requires breakdown of hyaline carDlage prior to ossificaDon 4 Lamellar bone replaces woven bone, just deep to the periosteum. Red marrow appears. • Trabeculae just deep to the periosteum thicken, and are later replaced with mature lamellar bone, forming compact bone plates. • Spongy bone (diploë), consisting of distinct trabeculae, persists internally and its vascular tissue becomes red marrow. Figure 6.8, (4 of 4) 2 10/18/14 Month 3 Week 9 Birth Childhood to adolescence Articular cartilage Secondary ossification center Epiphyseal blood vessel Area of deteriorating cartilage matrix Hyaline cartilage Spongy bone formation Bone collar Primary ossification center Spongy bone • _________________ growth: – ↑ length of long bones Epiphyseal plate cartilage • _________________ growth: Medullary cavity – ↑ thickness and remodeling of all bones by osteoblasts and osteoclasts on bone surfaces Blood vessel of periosteal bud 1 Bone collar 2 Cartilage in the forms around center of the hyaline cartilage diaphysis calcifies model. and then develops cavities. 3 The periosteal bud inavades the internal cavities and spongy bone begins to form. 4 The diaphysis elongates and a medullary cavity forms as ossification continues. Secondary ossification centers appear in the epiphyses in preparation for stage 5. Postnatal Bone Growth 5 The epiphyses ossify. When completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages. Figure 6.9 Growth in Length of Long Bones Resting zone • Epiphyseal plate carDlage organizes into four important _______________ __________: – ProliferaDon (growth) – Hypertrophic – CalcificaDon – OssificaDon (osteogenic) 1 Proliferation zone Cartilage cells undergo mitosis. 2 Hypertrophic zone Older cartilage cells enlarge. Calcified cartilage spicule Osteoblast depositing bone matrix Osseous tissue (bone) covering cartilage spicules 3 Calcification zone Matrix becomes calcified; cartilage cells die; matrix begins deteriorating. 4 Ossification zone New bone formation is occurring. Figure 6.10 3 10/18/14 Hormonal RegulaDon of Bone Growth • Growth hormone sDmulates ________________ ___________ acDvity • Thyroid hormone modulates acDvity of growth hormone • Testosterone and estrogens (at ________________) – Promote adolescent growth spurts – End growth by inducing epiphyseal plate closure Bone growth Cartilage grows here. Cartilage is replaced by bone here. Cartilage grows here. Cartilage is replaced by bone here. Bone remodeling Articular cartilage Epiphyseal plate Bone is resorbed here. Bone is added by appositional growth here. Bone is resorbed here. Figure 6.11 Bone Deposit • Occurs where bone is ________________ or added strength is needed • Requires a diet rich in protein; vitamins C, D, and A; calcium; phosphorus; magnesium; and manganese Bone Deposit • Sites of new matrix deposit are revealed by the – _________________________ • Unmineralized band of matrix – _________________________ • The abrupt transiDon zone between the osteoid seam and the older mineralized bone 4 10/18/14 Bone ResorpDon • _________________________ secrete – Lysosomal enzymes (digest organic matrix) – Acids (convert calcium salts into soluble forms) • Dissolved matrix is transcytosed across osteoclast, enters intersDDal fluid and then _________________ Hormonal Control of Blood Ca2+ • _________________ is necessary for – Transmission of nerve impulses – _________________ contracDon – _________________ coagulaDon – SecreDon by glands and _________________ – Cell division Control of Remodeling • What controls conDnual _________________ of bone? – Hormonal mechanisms that maintain calcium homeostasis in the blood – Mechanical and _________________ forces Hormonal Control of Blood Ca2+ • Primarily controlled by parathyroid hormone (PTH) ↓ Blood Ca2+ levels ↓ Parathyroid glands release PTH ↓ PTH sDmulates osteoclasts to degrade bone matrix and release Ca2+ ↓ ↑ Blood Ca2+ levels 5 10/18/14 Hormonal Control of Blood Ca2+ Calcium homeostasis of blood: 9–11 mg/100 ml BALANCE BALANCE Stimulus Falling blood Ca2+ levels Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood. Parathyroid glands PTH Parathyroid glands release parathyroid hormone (PTH). • May be affected to a lesser extent by calcitonin ↑ Blood Ca2+ levels ↓ Parafollicular cells of thyroid release calcitonin ↓ Osteoblasts deposit calcium salts ↓ ↓ Blood Ca2+ levels • LepDn has also been shown to influence bone density by inhibiDng _________________ Figure 6.12 Load here (body weight) Response to Mechanical Stress • _________________: A bone grows or remodels in response to forces or demands placed upon it • ObservaDons supporDng Wolff’s law: – _________________ (right or lec handed) results in bone of one upper limb being thicker and stronger – Curved bones are thickest where they are most likely to buckle – Trabeculae form along _________________ – Large, bony projecDons occur where heavy, acDve _________________ aeach Head of femur Tension here Compression here Point of no stress Figure 6.13 6 10/18/14 • ClassificaDon of Bone Fractures ClassificaDon of Bone Fractures Bone _________________ may be classified by four “either/or” classificaDons: 3. _________________ of the break to the long axis of the bone: • Linear—parallel to long axis of the bone • Transverse—perpendicular to long axis of the bone 4. Whether or not the bone ends _________________ the skin: • _________________ (open)—bone ends penetrate the skin • _________________ (closed)—bone ends do not penetrate the skin 1. PosiDon of bone ends acer fracture: • Nondisplaced—ends retain normal posiDon • Displaced—ends out of normal alignment 2. Completeness of the break • _________________—broken all the way through • _________________—not broken all the way through Common Types of Fractures • All fractures can be described in terms of – _________________ – _________________ – _________________ Table 6.2 7 10/18/14 Table 6.2 Stages in the Healing of a Bone Fracture Table 6.2 Hematoma 1. _________________ forms – Torn blood vessels hemorrhage – Clot (hematoma) forms – Site becomes swollen, painful, and _________________ 1 A hematoma forms. Figure 6.15, step 1 8 10/18/14 Stages in the Healing of a Bone Fracture External callus 2. _________________ callus forms – PhagocyDc cells clear debris – Osteoblasts begin forming spongy bone within 1 week – Fibroblasts secrete _________________ to connect bone ends – Mass of repair Dssue now called fibrocarDlaginous callus Internal callus (fibrous tissue and cartilage) New blood vessels Spongy bone trabecula 2 Fibrocartilaginous callus forms. Figure 6.15, step 2 Stages in the Healing of a Bone Fracture 3. ________ _________formaDon – New trabeculae form a bony (hard) callus – Bony callus formaDon conDnues unDl firm union is formed in ~2 months Bony callus of spongy bone 3 Bony callus forms. Figure 6.15, step 3 9 10/18/14 Stages in the Healing of a Bone Fracture 4. Bone _________________ – In response to mechanical stressors over several months – Final structure resembles _________________ Healed fracture 4 Bone remodeling occurs. Figure 6.15, step 4 HomeostaDc Imbalances • _________________ and rickets Hematoma Internal callus (fibrous tissue and cartilage) External callus New blood vessels Bony callus of spongy bone Healed fracture Spongy bone trabecula 1 A hematoma forms. 2 Fibrocartilaginous 3 Bony callus forms. callus forms. 4 Bone remodeling occurs. – Calcium salts not deposited – Rickets (childhood disease) causes bowed legs and other bone deformiDes – Cause: _________________deficiency or insufficient dietary calcium Figure 6.15 10 10/18/14 HomeostaDc Imbalances • _________________ – Loss of bone mass—bone resorpDon outpaces deposit – Spongy bone of spine and neck of femur become most suscepDble to fracture – _________________ • Lack of estrogen, calcium or vitamin D; peDte body form; immobility; low levels of TSH; diabetes mellitus Figure 6.16 Osteoporosis: Treatment and PrevenDon • Calcium, vitamin D, and fluoride supplements • ↑ Weight-‐bearing exercise throughout life • Hormone (_________________) replacement therapy (HRT) slows bone loss • Some _________________ (Fosamax, SERMs, staDns) increase bone mineral density Paget’s Disease • Excessive and haphazard bone formaDon and breakdown, usually in spine, pelvis, femur, or skull • PageDc bone has very high raDo of _________________ to _________________ bone and reduced mineralizaDon • Unknown cause (possibly ______________) • _________________ includes calcitonin and biphosphonates 11 10/18/14 Developmental Aspects of Bones Parietal bone Occipital bone • _________________ skeleton ossifies predictably so fetal age easily determined from X rays or sonograms • At birth, most ___________ __________ are well ossified (except _________________) Mandible Frontal bone of skull Clavicle Scapula Radius Ulna Ribs Humerus Vertebra Ilium Tibia Femur Figure 6.17 Developmental Aspects of Bones • Nearly all bones completely _________________ by age 25 • Bone mass decreases with age beginning in 4th decade • Rate of loss determined by _________________ and environmental factors • In old age, bone _________________ predominates 12