Bone Tissue Chapter 7 By Abdul Fellah, Ph.D. Copyright (c) The McGraw-Hill Companies, Inc. Permission required for reproduction or display.

Bone Tissue Tissues and organs of the skeletal system Histology of osseous tissue Bone development Physiology of osseous tissue Bone disorders

Bone as a Tissue Connective tissue with a matrix hardened by minerals (calcium phosphate) Individual bones consist of bone tissue, marrow, blood, cartilage and periosteum Continually remodels itself Functions of the skeletal system support, protection, movement, electrolyte balances, acid-base balance and blood formation

Shapes of Bones Long bones – levers acted upon by muscles Short bones – glide across one another in multiple directions Flat bones – protect soft organs Irregular bones

General Features of Bones Shaft (diaphysis) = cylinder of compact bone marrow cavity (medullary cavity) lined with endosteum (osteogenic cells and reticular connective tissue) Enlarged ends (epiphyses) spongy bone covered by compact bone enlarged to strengthen joint and attach ligaments Joint surface covered with articular cartilage Shaft covered with periosteum outer fibrous layer of collagen inner osteogenic layer of bone forming cells Epiphyseal plate (growth plate)

Structure of a Long Bone Compact and spongy bone Marrow cavity Articular cartilage Periosteum

Structure of a Flat Bone External and internal surfaces composed of compact bone Middle layer is spongy bone and bone marrow Skull fracture may leave inner layer of compact bone unharmed

Cells of Osseous Tissue (1) Osteogenic cells in endosteum, periosteum or central canals give rise to new osteoblasts arise from embryonic fibroblasts multiply continuously Osteoblasts mineralize organic matter of matrix Osteocytes are osteoblasts trapped in the matrix they formed cells in lacunae connected by gap junctions inside canaliculi

Cells of Osseous Tissue (2) Osteoclasts develop in bone marrow by fusion of 3-50 stem cells Reside in pits that they ate into the bone

Matrix of Osseous Tissue Dry weight = 1/3 organic and 2/3 inorganic matter Organic matter collagen, glycosaminoglycans, proteoglycans and glycoproteins Inorganic matter 85% hydroxyapatite 10% calcium carbonate other minerals (fluoride, potassium, magnesium) Combination provides for strength and resilience minerals resist compression; collagen resists tension bone adapts by varying proportions

Histology of Compact Bone

Compact Bone Osteon = basic structural unit cylinders formed from layers (lamellae) of matrix around central canal (osteonic canal) collagen fibers alternate between right- and left-handed helices from lamella to lamella osteocytes connected to each other and their blood supply by tiny cell processes in canaliculi Perforating canals or Volkmann canals vascular canals perpendicularly joining central canals

Blood Vessels of Bone

Spongy Bone Spongelike appearance formed by plates of bone called trabeculae spaces filled with red bone marrow Trabeculae have few osteons or central canals no osteocyte is far from blood of bone marrow Provides strength with little weight trabeculae develop along bone’s lines of stress

Spongy Bone Structure and Stress

Bone Marrow In medullary cavity (long bone) and among trabeculae (spongy bone) Red marrow like thick blood reticular fibers and immature cells Hemopoietic (produces blood cells) in vertebrae, ribs, sternum, pelvic girdle and proximal heads of femur and humerus in adults Yellow marrow fatty marrow of long bones in adults Gelatinous marrow of old age yellow marrow replaced with reddish jelly

Intramembranous Ossification Condensation of mesenchyme into trabeculae Osteoblasts on trabeculae lay down osteoid tissue (uncalcified bone) Calcium phosphate is deposited in the matrix forming bony trabeculae of spongy bone Osteoclasts create marrow cavity Osteoblasts form compact bone at surface Surface mesenchyme produces periosteum

Intramembranous Ossification 1 Produces flat bones of skull and clavicle.

Intramembranous Ossification 2 Note the periosteum and osteoblasts.

Stages of Endochondral Ossification

Endochondral Ossification 1 Bone develops from pre-existing model perichondrium and hyaline cartilage Most bones develop this process Formation of primary ossification center and marrow cavity in shaft of model bony collar developed by osteoblasts chondrocytes swell and die stem cells give rise to osteoblasts and clasts bone laid down and marrow cavity created

Primary Ossification Center and Primary Marrow Cavity

Endochondral Ossification 2 Secondary ossification centers and marrow cavities form in ends of bone same process Cartilage remains as articular cartilage and epiphyseal (growth) plates growth plates provide for increase in length of bone during childhood and adolescence by early twenties, growth plates are gone and primary and secondary marrow cavities united

Secondary Ossification Centers and Secondary Marrow Cavities

Fetal Skeleton at 12 Weeks

The Metaphysis Zone of reserve cartilage = hyaline cartilage Zone of proliferation chondrocytes multiply forming columns of flat lacunae Zone of hypertrophy = cell enlargement Zone of calcification mineralization of matrix Zone of bone deposition chondrocytes die and columns fill with osteoblasts osteons formed and spongy bone is created

Reserve Cart. Endrochondral Ossification: TRANSITIONAL ZONE

Bone Growth and Remodeling Bones increase in length interstitial growth of epiphyseal plate epiphyseal line is left behind when cartilage gone Bones increase in width = appositional growth osteoblasts lay down matrix in layers on outer surface and osteoclasts dissolve bone on inner surface Bones remodeled throughout life Wolff’s law of bone = architecture of bone determined by mechanical stresses action of osteoblasts and osteoclasts greater density and mass of bone in athletes or manual worker is an adaptation to stress

Bone Growth: in Length (childhood) Zone of ‘Resting’ Cartilage (i.e., not functioning in bone growth, but mitotic) Nearest epiphysis Small, scattered chondrocytes doing normal work; anchor E. plate to bone Zone of Proliferating Cartilage: Slightly larger chondrocytes arranged in columns Chondrocytes mitose to replace cells dying at diaphyseal side Zone of Hypertrophic Cartilage: Chondrocytes hypertrophy (grow in size), accumulate glycogen (carbohydrate), Matrix between cells narrows (lacunae getting larger, walls thinner forming hollow columns)

Bone Growth: in Length (childhood) Zone of Calcified Cartilage: Dead chondrocytes (matrix has calcified; can’t get food/oxygen) Zone of Bone Deposition Bone/marrow invades spaces Chondroclasts invade, disolve calcified cartilage Osteoblasts lay down osteoid to replace cartilage Bone eventually is remodeled (layers deposted toward center, so old lamellae are on periphery of osteon) Epiphyseal plates close (~ 18 - 25 years old); process stops; plate  line

Dwarfism Achondroplastic Pituitary long bones stop growing in childhood normal torso, short limbs spontaneous mutation during DNA replication failure of cartilage growth Pituitary lack of growth hormone normal proportions with short stature

Bone Growth: in Width - Appositional Growth (forever) Only way mature bones can grow Process ~ to intramembranous ossification Osteogenic cells in periosteum differentiate into osteoblasts which Secrete osteoid which Calcifies (osteoblasts become osteocytes) Ridges form around BV Ridges fold together & fuse; groove becomes a tunnel that encloses the BV

Bone Growth: in Width - Appositional Growth (forever) Periosteum now is endosteum (note: this is a similar process to forming neural tube in early embryonic development) Osteoblasts form lamellae (process moves inward) Results in creation of new osteon Osteoblasts deep to periosteum simultaneously form circumferential lamellae, so more thickness Process is dependent on presence of Ca, P, other ions, Vit C (synthesis of collagen etc.), Vit. K, B12 (needed for protein synthesis), Vit A (stimulates osteoblasts)

Mineral Deposition Mineralization is crystallization process osteoblasts produce collagen fibers spiraled the length of the osteon minerals cover the fibers and harden the matrix ions (calcium and phosphate and from blood plasma) are deposited along the fibers ion concentration must reach the solubility product for crystal formation to occur Abnormal calcification (ectopic) may occur in lungs, brain, eyes, muscles, tendons or arteries (arteriosclerosis)

Mineral Resorption from Bone Bone dissolved and minerals released into blood performed by osteoclasts “ruffled border” hydrogen pumps in membrane secrete hydrogen into space between the osteoclast and bone surface chloride ions follow by electrical attraction hydrochloric acid (pH 4) dissolves bone minerals enzyme (acid phosphatase) digests the collagen Dental braces reposition teeth and remodel bone create more pressure on one side of the tooth stimulates osteoclasts to remove bone decreased pressure stimulates osteoblasts

Calcium and Phosphate Phosphate is component of DNA, RNA, ATP, phospholipids, and pH buffers ~750 g in adult skeleton plasma concentration is ~ 4.0 mg/dL 2 plasma forms: HPO4 -2 and H2PO4- Calcium needed in neurons, muscle contraction, blood clotting and exocytosis ~1100g in adult skeleton plasma concentration is ~ 10 mg/dL

Ion Imbalances Changes in phosphate levels = little effect Changes in calcium can be serious hypocalcemia is deficiency of blood calcium causes excitability of nervous system if too low muscle spasms, tremors or tetany ~6 mg/dL laryngospasm and suffocation ~4 mg/dL with less calcium, sodium channels open more easily, sodium enters cell and excites neuron hypercalcemia is excess of blood calcium binding to cell surface makes sodium channels less likely to open, depressing nervous system muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL Calcium phosphate homeostasis depends on calcitriol, calcitonin and PTH hormone regulation

Carpopedal Spasm Hypocalcemia demonstrated by muscle spasm of hands and feet.

Hormonal Control of Calcium Balance Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.

Calcitriol (Activated Vitamin D) Produced by the following process UV radiation and epidermal keratinocytes convert steroid derivative to cholecalciferol - D3 liver converts it to calcidiol kidney converts that to calcitriol (vitamin D) Calcitriol behaves as a hormone that raises blood calcium concentration increases intestinal absorption and absorption from the skeleton increases stem cell differentiation into osteoclasts promotes urinary reabsorption of calcium ions Abnormal softness (rickets) in children and (osteomalacia) in adults without vitamin D

Calcitriol Synthesis and Action

Calcitonin Secreted (C cells of thyroid gland) when calcium concentration rises too high Functions reduces osteoclast activity as much as 70% increases the number and activity of osteoblasts Important in children, little effect in adults osteoclasts more active in children deficiency does not cause disease in adults Reduces bone loss in osteoporosis

Correction for Hypercalcemia

Parathyroid Hormone Glands on posterior surface of thyroid Released with low calcium blood levels Function = raise calcium blood level causes osteoblasts to release osteoclast-stimulating factor (RANKL) increasing osteoclast population promotes calcium resorption by the kidneys promotes calcitriol synthesis in the kidneys inhibits collagen synthesis and bone deposition by osteoblasts Sporatic injection of low levels of PTH causes bone deposition

Correction for Hypocalcemia

Other Factors Affecting Bone Hormones, vitamins and growth factors Growth rapid at puberty hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth plate girls grow faster than boys and reach full height earlier (estrogen stronger effect) males grow for a longer time and taller Growth stops (epiphyseal plate “closes”) teenage use of anabolic steroids = premature closure of growth plate and short adult stature

Fractures and Their Repair Stress fracture caused by trauma car accident, fall, athletics, etc Pathological fracture in bone weakened by disease bone cancer or osteoporosis Fractures classified by structural characteristics break in the skin multiple pieces

Types of Bone Fractures

Healing of Fractures 1 Normally 8 - 12 weeks (longer in elderly) Stages of healing fracture hematoma (1) - clot forms, then osteogenic cells form granulation tissue soft callus (2) fibroblasts produce fibers and fibrocartilage hard callus (3) osteoblasts produce a bony collar in 6 weeks remodeling (4) in 3 to 4 months spongy bone replaced by compact bone

Healing of Fractures 2

Treatment of Fractures Closed reduction fragments are aligned with manipulation and casted Open reduction surgical exposure and repair with plates and screws Traction risks long-term confinement to bed Electrical stimulation used on fractures if 2 months necessary for healing Orthopedics = prevention and correction of injuries and disorders of the bones, joints and muscles

Fractures and Their Repairs

Osteoporosis 1 Bones lose mass and become brittle (loss of organic matrix and minerals) risk of fracture of hip, wrist and vertebral column complications (pneumonia and blood clotting) Postmenopausal white women at greatest risk by age 70, average loss is 30% of bone mass black women rarely suffer symptoms

Osteoporosis 2 Estrogen maintains density in both sexes (inhibits resorption) testes and adrenals produce estrogen in men rapid loss after menopause, if body fat too low or with disuse during immobilizaton Treatment ERT slows bone resorption, but increases risk breast cancer, stroke and heart disease PTH slows bone loss if given daily injection Forteo increases density by 10% in 1 year may promote bone cancer best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40

Spinal Osteoporosis