Bone Development & Skeleton Formation Osteogenesis and ossification: Synonyms of the process of bone tissue formation. Before 8 weeks the fetal skeleton is made of: Fibrous membranes Hyaline cartilage Ossification begins at week 8 of fetal development Bone formation (fetal/embryonic) is followed by: Bone growth (toward adulthood) Bone remodeling & repair (throughout life)

Bone Development & Skeleton Formation Fetal skeleton is cartilage & fibrous membranes There are two processes of bone formation: Intramembranous ossification: Development of bones from the fibrous membrane Resulting bone is called membrane bone Endochondral ossification: Formation of bones by replacing hyaline cartilage Resulting bone is called cartilage or endochondrial bone

Intramembranous Ossification Results in the formation of: The cranial bones of the skull & the clavicles Most of the flat bones Mesenchymal cells: They form the fibrous connective tissue membranes Fibrous connective tissue membranes: Become the supporting structures Ossification begins on these membranes at 8 wk of development

Four Main Stages of Intramembranous Ossification Step 1: Clustering of centrally located mesenchymal cells Differentiation of these cells into osteoblatsts Formation of ossification center Figure 6.7.1

Stages of Intramembranous Ossification Step 2: Secretion of osteoid (organic matrix) by osteoblasts Mineralization of osteoid (inorganic matrix) within few days Trapping of osteoblasts turns them into osteocytes Figure 6.7.2

Stages of Intramembranous Ossification Step 3: Formation of woven bone: Accumulating osteoid deposits between embryonic blood vessels randomely This forms a random network of trabeculae Vascularized mesenchyme condenses on the external surface of the formed bone & become the periosteum Figure 6.7.3

Stages of Intramembranous Ossification Step 4: Thickening of trabeculae next to the periosteum Formation of bone collar (future lamellar bone) Spongy bone become distinct internally vascular tissue of spongy bone becomes red bone marrow Figure 6.7.4

Endochondral Ossification Most bones are made by endochondral ossification Begins: In the second month of development Uses: Hyaline cartilage as models for bone construction Requires: Breakdown of hyaline cartilage prior to ossification

Endochondral Ossification (lnitiation) Begins in a central region of the hyaline cartilage shaft called: The primary ossification center Blood vessel infiltrate the perichondrium of cartilage converting it into: Vascularized periosteum Resulting change in nutrition causes: Underlying mesenchymal cells differentaite into osteoblasts Initiation of the ossification process

Stages of Endochondral Ossification (long bones): Formation of periosteal bone collar: Osteoblasts secrete osteoid around cartilage diaphysis A bony collar forms around the cartilage diaphysis Hyaline cartilage Primary ossification center Bone collar Formation of bone collar around hyaline cartilage model. 1

Stages of Endochondral Ossification Calcification and cavitation: Shaft chondrocytes hypertrophy Send calcification signal to surrounding matrix Impermeable calcified matrix causes: Chondrocytes death Matrix deterioration Formation of central cavities Figure 6.8

Stages of Endochondral Ossification Deteriorating cartilage matrix Cavitation of the hyaline carti- lage within the cartilage model. 2 Formation of bone collar around hyaline 1 Figure 6.8

Stages of Endochondral Ossification (long bones): Invasion of internal cavities by periosteal bud elements The periosteal bud contains: Arteries, veins, & lymphatic vessels Nerve fibers Red marrow elements Osteoblasts Osteoclasts Formation of the early version of Spongy bone: Osteoclasts partially erode calcified matrix Osteoblasts secrete osteoid around fragmented cartilage Bone-covered cartilage trabeculae form (early spongy bone)

Stages of Endochondral Ossification Spongy bone formation Blood vessel of periosteal bud Formation of bone collar around hyaline cartilage model. Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. 1 2 3 Figure 6.8

Stages of Endochondral Ossification (long bones): Formation of: The medullary cavity Appearance of: Secondary ossification centers in the epiphysis Continuation and completion of: Epiphysis ossification

Stages of Endochondral Ossification Epiphyseal blood vessel Secondary ossificaton center Medullary cavity Formation of bone collar around hyaline cartilage model. Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. Formation of the medullary cavity as ossification continues; appearance of sec- ondary ossification centers in the epiphy- ses in preparation for stage 5. 1 2 3 4 Figure 6.8

Stages of Endochondral Ossification (long bones): When secondary ossification is complete hyaline cartilage remains only in two locations: Epiphyseal plates: At the epiphysis-diaphysis junction Articular cartilages: At the epiphyseal surfaces

Stages of Endochondral Ossification Formation of bone collar around hyaline cartilage model. Hyaline cartilage Cavitation of the hyaline carti- lage within the Invasion of internal cavities by the periosteal bud and spongy bone formation. Formation of the medullary cavity as ossification continues; appearance of sec- ondary ossification centers in the epiphy- ses in preparation for stage 5. Ossification of the epiphyses; when completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages. Deteriorating matrix Epiphyseal blood vessel Spongy bone formation plate Secondary ossificaton center Blood vessel of periosteal bud Medullary cavity Articular Primary ossification Bone collar 1 2 3 4 5 Figure 6.8

Bone Development and Growth (infants & youth) Most bones stop growing during adolescence Some bones (facial) continue to grow ex. (nose & lower jaw) Growth in length is entirely by: Interstitial (from inside) growth of epiphyseal plates Growth in thickness (all bones) by: Appositional (from outside) growth Thickness of epiphyseal plates is maintained by a balance between : Cartilage growth at epiphysis side Bone replacement of cartilage at diaphysis side

Bone Development and Growth Toward puberty the plates become thinner due to: Less chondroblast division More bone replacement Longitudinal growth ends (epiphyseal closure) when: The bone of the epiphysis and diaphysis fuses Epiphyseal closures occurs at: 18 yr of age in females 21 yr of age in males

Hormonal Regulation of Bone Growth During infancy and childhood: Anterior pituitary growth hormone (GH): Stimulates epiphyseal plate activity Thyroid hormones: Modulate GH activity Maintain bone proportions

Hormonal Regulation of Bone Growth During puberty: Male & female hormones (testosterone & estrogens): Are released in increased amounts Initially, they: Promote growth spurts (adolescence associated) Masculinize & feminiz specific skeleton parts Later, they: Induce epiphyseal plate closure End longitudinal bone growth

Bone Remodeling: Bone Deposition & Resorption Occurs in adult skeleton Involves two processes: Bone deposition Bone resorption (removal) The processes are coupled & coordinated by: Osteoblasts (deposition) Osteoclasts (resorption) Occurs at both: Periosteum surface Endosteum surface

Bone Resorption Accomplished by osteoclasts Osteoclasts are: Multinucleated giant cells Arise from hematopoietic stem cells (same as macrophages) They move along bone surfaces digging grooves in matrix Bone resorption by osteoclasts involves secretion of: Lysosomal enzymes: Digest organic matrix Hydrochloric acid: Converts calcium salts into soluble forms

Long Bone Growth and Remodeling Figure 6.10

Break Slide Biol2401.____ Wed, Feb ___, ’13

Importance of Ionic Calcium in the Body Calcium is necessary for: Transmission of nerve impulses Muscle contraction Blood coagulation Glands & nerve cells secretion Cell division

Two control loops regulate bone remodeling Control of Remodeling Two control loops regulate bone remodeling Hormonal mechanism: Maintains calcium homeostasis in the blood Not to preserve the skeleton strength or well being Bones serve as a storehouse for ionic calcium Mechanical and gravitational forces : Forces acting on the skeleton

Hormonal Mechanism: Falling blood Ca2+ levels signal: PTH signals: The parathyroid glands Parathyroid releases parathyroid hormone (PTH) PTH signals: Osteoclasts Osteoclasts degrade bone matrix Ca2+ is releases into the blood

Hormonal Mechanism (cont’d): Rising blood Ca2+ level triggers: Thyroid parafollicular cells (C cells) Parafollicular cells release calcitonin Calcitonin: Inhibits bone resorption stimulates calcium salt deposition in bone matrix Most effective in children

Hormonal Control of Blood Ca PTH; calcitonin secreted Calcitonin stimulates calcium salt deposit in bone Thyroid gland Rising blood Ca2+ levels Imbalance Calcium homeostasis of blood: 9–11 mg/100 ml Falling blood Ca2+ levels Imbalance Thyroid gland Osteoclasts degrade bone matrix and release Ca2+ into blood Parathyroid glands Parathyroid glands release parathyroid hormone (PTH) PTH Figure 6.11

Reading Assignment (The folllowing Slides) Bone fractures Common types of bone fracture Homeostatic Imbalances Osteomalacia (adult) Rickets Osteoporosis

Bone Fractures Bone fractures are classified by: The position of the bone ends after fracture: Nondisplaced: bone ends retain their normal position Displaced: bone ends are out of normal alignment The completeness of the break Complete: bone is broken all the way through Incomplete: bone is not broken all the way through

Bone Fractures (Breaks) The orientation of the bone to the long axis Linear: the fracture is parallel to the long axis of the bone Transverse: the fracture is perpendicular to the long axis of the bone Whether or not the bones ends penetrate the skin Compound (open): bone ends penetrate the skin Simple (closed): bone ends do not penetrate the skin

Common Types of Fractures Comminuted: bone fragments into three or more pieces common in the elderly Compression: bone is crushed common in porous bones

Common Types of Fractures Table 6.2.1

Common Types of Fractures Spiral: ragged break when bone is excessively twisted common sports injury Epiphyseal: epiphysis separates from diaphysis along epiphyseal line occurs where cartilage cells are dying

Common Types of Fractures Table 6.2.2

Common Types of Fractures Depressed: broken bone portion pressed inward typical skull fracture Greenstick: incomplete fracture (one bone side breaks and the other bends) common in children

Common Types of Fractures Table 6.2.3

Homeostatic Imbalances Osteomalacia (adult) Soft and weak bones due to inadequate mineralization Main symptom is pain when weight is put on the affected bone Caused by: Insufficient dietary calcium Vitamin D deficiency

Homeostatic Imbalances Rickets Soft and weak bones of children (inadequately mineralized) Bowed legs and deformed pelvis, skull, and rib cage Caused by: Insufficient dietary calcium Vitamin D deficiency

Homeostatic Imbalances Osteoporosis Group of diseases Bone resorption outpaces bone deposit Matrix composition is normal; bone mass is reduced Spongy bone of the spine is most vulnerable Femur neck also susceptible Most often in postmenopausal women Bones become so fragile (sneezing or stepping off a curb can cause fractures)