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Bone TissueBone Tissue

Tissues and organs of the skeletal Tissues and organs of the skeletal systemsystem

Histology of osseous tissueHistology of osseous tissue Bone developmentBone development Physiology of osseous tissuePhysiology of osseous tissue Bone disordersBone disorders

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Bone as a TissueBone as a Tissue

Connective tissue with a matrix hardened by Connective tissue with a matrix hardened by minerals (calcium phosphate)minerals (calcium phosphate)

Individual bones consist of bone tissue, Individual bones consist of bone tissue, marrow, blood, cartilage and periosteummarrow, blood, cartilage and periosteum

Continually remodels itselfContinually remodels itself Functions of the skeletal systemFunctions of the skeletal system

support, protection, movement, electrolyte support, protection, movement, electrolyte balances, acid-base balance and blood balances, acid-base balance and blood formationformation

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Shapes of BonesShapes of Bones

Long bones – levers Long bones – levers acted upon by musclesacted upon by muscles

Short bones – glide Short bones – glide across one another in across one another in multiple directionsmultiple directions

Flat bones – protect soft Flat bones – protect soft organsorgans

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General Features of BonesGeneral Features of Bones

Shaft (diaphysis) = cylinder of compact boneShaft (diaphysis) = cylinder of compact bone marrow cavity (medullary cavity) lined with endosteum marrow cavity (medullary cavity) lined with endosteum

(osteogenic cells and reticular connective tissue)(osteogenic cells and reticular connective tissue) Enlarged ends (epiphyses) Enlarged ends (epiphyses)

spongy bone covered by compact bonespongy bone covered by compact bone enlarged to strengthen joint and attach ligamentsenlarged to strengthen joint and attach ligaments

Joint surface covered with articular cartilageJoint surface covered with articular cartilage Shaft covered with periosteumShaft covered with periosteum

outer fibrous layer of collagen outer fibrous layer of collagen inner osteogenic layer of bone forming cellsinner osteogenic layer of bone forming cells

Epiphyseal plate (growth plate)Epiphyseal plate (growth plate)

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Structure of a Long BoneStructure of a Long Bone

Compact and Compact and spongy bonespongy bone

Marrow cavityMarrow cavity Articular cartilageArticular cartilage PeriosteumPeriosteum

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Structure of a Flat BoneStructure of a Flat Bone

External and External and internal surfaces internal surfaces composed of composed of compact bonecompact bone

Middle layer is Middle layer is spongy bone and spongy bone and bone marrowbone marrow

Skull fracture may Skull fracture may leave inner layer of leave inner layer of compact bone compact bone unharmedunharmed

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Cells of Osseous Tissue (1)Cells of Osseous Tissue (1)

Osteogenic cells in endosteum, periosteum or central canals Osteogenic cells in endosteum, periosteum or central canals give rise to new osteoblastsgive rise to new osteoblasts

arise from embryonic fibroblasts arise from embryonic fibroblasts multiply continuously multiply continuously

Osteoblasts mineralize organic matter of matrix Osteoblasts mineralize organic matter of matrix Osteocytes are osteoblasts trapped in the matrix they formedOsteocytes are osteoblasts trapped in the matrix they formed

cells in lacunae connected by gap junctions inside canaliculicells in lacunae connected by gap junctions inside canaliculi

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Cells of Osseous Tissue (2)Cells of Osseous Tissue (2)

Osteoclasts develop in bone marrow by fusion of 3-Osteoclasts develop in bone marrow by fusion of 3-50 stem cells 50 stem cells

Reside in pits that they ate into the boneReside in pits that they ate into the bone

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Matrix of Osseous TissueMatrix of Osseous Tissue Dry weight = 1/3 organic and 2/3 inorganic matterDry weight = 1/3 organic and 2/3 inorganic matter Organic matterOrganic matter

collagen, glycosaminoglycans, proteoglycans and collagen, glycosaminoglycans, proteoglycans and glycoproteinsglycoproteins

Inorganic matterInorganic matter 85% hydroxyapatite 85% hydroxyapatite 10% calcium carbonate10% calcium carbonate other minerals (fluoride, potassium, magnesium)other minerals (fluoride, potassium, magnesium)

Combination provides for strength and resilienceCombination provides for strength and resilience minerals resist compression; collagen resists tensionminerals resist compression; collagen resists tension bone adapts by varying proportions bone adapts by varying proportions

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Histology of Compact BoneHistology of Compact Bone

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Compact BoneCompact Bone Osteon = basic structural unitOsteon = basic structural unit

cylinders formed from layers (lamellae) of matrix cylinders formed from layers (lamellae) of matrix around central canal (osteonic canal)around central canal (osteonic canal)• collagen fibers alternate between right- and left-collagen fibers alternate between right- and left-

handed helices from lamella to lamellahanded helices from lamella to lamella osteocytes connected to each other and their osteocytes connected to each other and their

blood supply by tiny cell processes in canaliculiblood supply by tiny cell processes in canaliculi Perforating canals or Volkmann canalsPerforating canals or Volkmann canals

vascular canals perpendicularly joining central vascular canals perpendicularly joining central canalscanals

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Blood Vessels of BoneBlood Vessels of Bone

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Spongy BoneSpongy Bone

Spongelike appearance formed by plates of Spongelike appearance formed by plates of bone called trabeculaebone called trabeculae spaces filled with red bone marrowspaces filled with red bone marrow

Trabeculae have few osteons or central Trabeculae have few osteons or central canalscanals no osteocyte is far from blood of bone marrowno osteocyte is far from blood of bone marrow

Provides strength with little weightProvides strength with little weight trabeculae develop along bone’s lines of stresstrabeculae develop along bone’s lines of stress

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Spongy Bone Structure and StressSpongy Bone Structure and Stress

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Bone MarrowBone Marrow

In medullary cavity (long bone) and among In medullary cavity (long bone) and among trabeculae (spongy bone)trabeculae (spongy bone)

Red marrow like thick bloodRed marrow like thick blood reticular fibers and immature cellsreticular fibers and immature cells Hemopoietic (produces blood cells)Hemopoietic (produces blood cells) in vertebrae, ribs, sternum, pelvic girdle in vertebrae, ribs, sternum, pelvic girdle

and proximal heads of femur and and proximal heads of femur and humerus in adults humerus in adults

Yellow marrowYellow marrow fatty marrow of long bones in adultsfatty marrow of long bones in adults

Gelatinous marrow of old ageGelatinous marrow of old age yellow marrow replaced with reddish jellyyellow marrow replaced with reddish jelly

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Intramembranous OssificationIntramembranous Ossification

Condensation of mesenchyme into trabeculaeCondensation of mesenchyme into trabeculae Osteoblasts on trabeculae lay down osteoid Osteoblasts on trabeculae lay down osteoid

tissue (uncalcified bone)tissue (uncalcified bone) Calcium phosphate is deposited in the matrix Calcium phosphate is deposited in the matrix

forming bony trabeculae of spongy boneforming bony trabeculae of spongy bone Osteoclasts create marrow cavityOsteoclasts create marrow cavity Osteoblasts form compact bone at surfaceOsteoblasts form compact bone at surface Surface mesenchyme produces periosteumSurface mesenchyme produces periosteum

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Intramembranous Ossification 1Intramembranous Ossification 1

Produces flat bones of skull and clavicle.Produces flat bones of skull and clavicle.

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Intramembranous Ossification 2Intramembranous Ossification 2

Note the periosteum and osteoblasts.Note the periosteum and osteoblasts.

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Stages of Endochondral Stages of Endochondral OssificationOssification

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Endochondral Ossification 1Endochondral Ossification 1

Bone develops from pre-existing modelBone develops from pre-existing model perichondrium and hyaline cartilageperichondrium and hyaline cartilage

Most bones develop this processMost bones develop this process Formation of primary ossification center and Formation of primary ossification center and

marrow cavity in shaft of modelmarrow cavity in shaft of model bony collar developed by osteoblastsbony collar developed by osteoblasts chondrocytes swell and diechondrocytes swell and die stem cells give rise to osteoblasts and clastsstem cells give rise to osteoblasts and clasts bone laid down and marrow cavity createdbone laid down and marrow cavity created

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Primary Ossification Center and Primary Ossification Center and Primary Marrow CavityPrimary Marrow Cavity

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Secondary ossification centers and Secondary ossification centers and marrow cavities form in ends of bonemarrow cavities form in ends of bone same processsame process

Cartilage remains as articular cartilage Cartilage remains as articular cartilage and epiphyseal (growth) platesand epiphyseal (growth) plates growth plates provide for increase in length of growth plates provide for increase in length of

bone during childhood and adolescencebone during childhood and adolescence by early twenties, growth plates are gone and by early twenties, growth plates are gone and

primary and secondary marrow cavities unitedprimary and secondary marrow cavities united

Endochondral Ossification 2Endochondral Ossification 2

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Secondary Ossification Centers Secondary Ossification Centers and Secondary Marrow Cavitiesand Secondary Marrow Cavities

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The MetaphysisThe Metaphysis

Zone of reserve cartilage = hyaline cartilageZone of reserve cartilage = hyaline cartilage Zone of proliferationZone of proliferation

• chondrocytes multiply forming columns of flat lacunaechondrocytes multiply forming columns of flat lacunae Zone of hypertrophy = cell enlargementZone of hypertrophy = cell enlargement Zone of calcificationZone of calcification

• mineralization of matrixmineralization of matrix Zone of bone depositionZone of bone deposition

• chondrocytes die and columns fill with osteoblastschondrocytes die and columns fill with osteoblasts• osteons formed and spongy bone is created osteons formed and spongy bone is created

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Fetal Skeleton at 12 WeeksFetal Skeleton at 12 Weeks

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Bone Growth and RemodelingBone Growth and Remodeling

Bones increase in lengthBones increase in length interstitial growth of epiphyseal plateinterstitial growth of epiphyseal plate epiphyseal line is left behind when cartilage goneepiphyseal line is left behind when cartilage gone

Bones increase in width = appositional growthBones increase in width = appositional growth osteoblasts lay down matrix in layers on outer surface osteoblasts lay down matrix in layers on outer surface

and osteoclasts dissolve bone on inner surfaceand osteoclasts dissolve bone on inner surface Bones remodeled throughout lifeBones remodeled throughout life

Wolff’s law of bone = architecture of bone determined by Wolff’s law of bone = architecture of bone determined by mechanical stressesmechanical stresses

• action of osteoblasts and osteoclastsaction of osteoblasts and osteoclasts greater density and mass of bone in athletes or manual greater density and mass of bone in athletes or manual

worker is an adaptation to stressworker is an adaptation to stress

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DwarfismDwarfism

AchondroplasticAchondroplastic long bones stop growing long bones stop growing

in childhoodin childhood• normal torso, short limbsnormal torso, short limbs

spontaneous mutation spontaneous mutation during DNA replicationduring DNA replication

failure of cartilage growthfailure of cartilage growth Pituitary Pituitary

lack of growth hormonelack of growth hormone normal proportions with normal proportions with

short statureshort stature

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Mineral DepositionMineral Deposition

Mineralization is crystallization processMineralization is crystallization process osteoblasts produce collagen fibers spiraled the osteoblasts produce collagen fibers spiraled the

length of the osteonlength of the osteon minerals cover the fibers and harden the matrixminerals cover the fibers and harden the matrix

• ions (calcium and phosphate and from blood plasma) ions (calcium and phosphate and from blood plasma) are deposited along the fibers are deposited along the fibers

• ion concentration must reach the solubility product for ion concentration must reach the solubility product for crystal formation to occurcrystal formation to occur

Abnormal calcification (ectopic)Abnormal calcification (ectopic) may occur in lungs, brain, eyes, muscles, tendons may occur in lungs, brain, eyes, muscles, tendons

or arteries (arteriosclerosis)or arteries (arteriosclerosis)

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Ion ImbalancesIon Imbalances Changes in phosphate levels = little effectChanges in phosphate levels = little effect Changes in calcium can be seriousChanges in calcium can be serious

hypocalcemia is deficiency of blood calciumhypocalcemia is deficiency of blood calcium• causes excitability of nervous system if too lowcauses excitability of nervous system if too low

muscle spasms, tremors or tetany ~6 mg/dLmuscle spasms, tremors or tetany ~6 mg/dL laryngospasm and suffocation ~4 mg/dLlaryngospasm and suffocation ~4 mg/dL

• with less calcium, sodium channels open more easily, sodium with less calcium, sodium channels open more easily, sodium enters cell and excites neuronenters cell and excites neuron

hypercalcemia is excess of blood calciumhypercalcemia is excess of blood calcium• binding to cell surface makes sodium channels less likely to binding to cell surface makes sodium channels less likely to

open, depressing nervous systemopen, depressing nervous system muscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dLmuscle weakness and sluggish reflexes, cardiac arrest ~12 mg/dL

Calcium phosphate homeostasis depends on Calcium phosphate homeostasis depends on calcitriol, calcitonin and PTH hormone regulationcalcitriol, calcitonin and PTH hormone regulation

3030

Hormonal Control of Calcium Hormonal Control of Calcium BalanceBalance

Calcitriol, PTH and calcitonin maintain Calcitriol, PTH and calcitonin maintain normal blood calcium concentration.normal blood calcium concentration.

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Calcitriol (Activated Vitamin D)Calcitriol (Activated Vitamin D)

Produced by the following processProduced by the following process UV radiation and epidermal keratinocytes convert UV radiation and epidermal keratinocytes convert

steroid derivative to cholecalciferol - D3steroid derivative to cholecalciferol - D3 liver converts it to calcidiolliver converts it to calcidiol kidney converts that to calcitriol (vitamin D)kidney converts that to calcitriol (vitamin D)

Calcitriol behaves as a hormone that raises blood Calcitriol behaves as a hormone that raises blood calcium concentrationcalcium concentration increases intestinal absorption and absorption from the increases intestinal absorption and absorption from the

skeletonskeleton increases stem cell differentiation into osteoclastsincreases stem cell differentiation into osteoclasts promotes urinary reabsorption of calcium ionspromotes urinary reabsorption of calcium ions

Abnormal softness (rickets) in children and Abnormal softness (rickets) in children and (osteomalacia) in adults without vitamin D(osteomalacia) in adults without vitamin D

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Calcitriol Synthesis and ActionCalcitriol Synthesis and Action

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CalcitoninCalcitonin

Secreted (C cells of thyroid gland) when Secreted (C cells of thyroid gland) when calcium concentration rises too highcalcium concentration rises too high

FunctionsFunctions reduces osteoclast activity as much as 70%reduces osteoclast activity as much as 70% increases the number and activity of osteoblastsincreases the number and activity of osteoblasts

Important in children, little effect in adultsImportant in children, little effect in adults osteoclasts more active in childrenosteoclasts more active in children deficiency does not cause disease in adultsdeficiency does not cause disease in adults

Reduces bone loss in osteoporosisReduces bone loss in osteoporosis

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Correction for HypercalcemiaCorrection for Hypercalcemia

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Parathyroid HormoneParathyroid Hormone

Glands on posterior surface of thyroidGlands on posterior surface of thyroid Released with low calcium blood levelsReleased with low calcium blood levels Function = raise calcium blood levelFunction = raise calcium blood level

causes osteoblasts to release osteoclast-stimulating causes osteoblasts to release osteoclast-stimulating factor (RANKL) increasing osteoclast populationfactor (RANKL) increasing osteoclast population

promotes calcium resorption by the kidneyspromotes calcium resorption by the kidneys promotes calcitriol synthesis in the kidneyspromotes calcitriol synthesis in the kidneys inhibits collagen synthesis and bone deposition by inhibits collagen synthesis and bone deposition by

osteoblastsosteoblasts

Sporatic injection of low levels of PTH causes bone Sporatic injection of low levels of PTH causes bone depositiondeposition

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Correction for HypocalcemiaCorrection for Hypocalcemia

3737

Other Factors Affecting BoneOther Factors Affecting Bone

Hormones, vitamins and growth factorsHormones, vitamins and growth factors Growth rapid at pubertyGrowth rapid at puberty

hormones stimulate osteogenic cells, chondrocytes and hormones stimulate osteogenic cells, chondrocytes and matrix deposition in growth platematrix deposition in growth plate

girls grow faster than boys and reach full height earlier girls grow faster than boys and reach full height earlier (estrogen stronger effect)(estrogen stronger effect)

males grow for a longer time and tallermales grow for a longer time and taller

Growth stops (epiphyseal plate “closes”)Growth stops (epiphyseal plate “closes”) teenage use of anabolic steroids = premature closure of teenage use of anabolic steroids = premature closure of

growth plate and short adult staturegrowth plate and short adult stature

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Fractures and Their RepairFractures and Their Repair

Stress fracture caused by traumaStress fracture caused by trauma car accident, fall, athletics, etccar accident, fall, athletics, etc

Pathological fracture in bone weakened by Pathological fracture in bone weakened by diseasedisease bone cancer or osteoporosisbone cancer or osteoporosis

Fractures classified by structural Fractures classified by structural characteristicscharacteristics break in the skinbreak in the skin multiple piecesmultiple pieces

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Types of Bone FracturesTypes of Bone Fractures

4040

Healing of Fractures 1Healing of Fractures 1 Normally 8 - 12 weeks (longer in elderly)Normally 8 - 12 weeks (longer in elderly) Stages of healingStages of healing

fracture hematoma (1) - clot forms, then osteogenic fracture hematoma (1) - clot forms, then osteogenic cells form granulation tissuecells form granulation tissue

soft callus (2)soft callus (2)• fibroblasts produce fibers and fibrocartilagefibroblasts produce fibers and fibrocartilage

hard callus (3)hard callus (3)• osteoblasts produce a bony collar in 6 weeksosteoblasts produce a bony collar in 6 weeks

remodeling (4) in 3 to 4 months remodeling (4) in 3 to 4 months • spongy bone replaced by compact bonespongy bone replaced by compact bone

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Healing of Fractures 2Healing of Fractures 2

4242

Treatment of FracturesTreatment of Fractures

Closed reductionClosed reduction fragments are aligned with manipulation and castedfragments are aligned with manipulation and casted

Open reductionOpen reduction surgical exposure and repair with plates and screwssurgical exposure and repair with plates and screws

Traction risks long-term confinement to bedTraction risks long-term confinement to bed Electrical stimulation used on fractures Electrical stimulation used on fractures

if 2 months necessary for healingif 2 months necessary for healing

Orthopedics = prevention and correction of injuries Orthopedics = prevention and correction of injuries and disorders of the bones, joints and musclesand disorders of the bones, joints and muscles

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Fractures and Their RepairsFractures and Their Repairs

4444

Osteoporosis 1Osteoporosis 1

Bones lose mass and become brittle (loss of Bones lose mass and become brittle (loss of organic matrix and minerals)organic matrix and minerals) risk of fracture of hip, wrist and vertebral columnrisk of fracture of hip, wrist and vertebral column complications (pneumonia and blood clotting)complications (pneumonia and blood clotting)

Postmenopausal white women at greatest Postmenopausal white women at greatest riskrisk by age 70, average loss is 30% of bone massby age 70, average loss is 30% of bone mass black women rarely suffer symptomsblack women rarely suffer symptoms

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Osteoporosis 2Osteoporosis 2 Estrogen maintains density in both sexes Estrogen maintains density in both sexes

(inhibits resorption)(inhibits resorption) testes and adrenals produce estrogen in mentestes and adrenals produce estrogen in men rapid loss after menopause, if body fat too low or with rapid loss after menopause, if body fat too low or with

disuse during immobilizatondisuse during immobilizaton TreatmentTreatment

ERT slows bone resorption, but increases risk breast ERT slows bone resorption, but increases risk breast cancer, stroke and heart diseasecancer, stroke and heart disease

PTH slows bone loss if given daily injectionPTH slows bone loss if given daily injection• Forteo increases density by 10% in 1 yearForteo increases density by 10% in 1 year• may promote bone cancermay promote bone cancer

best treatment is prevention -- exercise and calcium best treatment is prevention -- exercise and calcium intake (1000 mg/day) between ages 25 and 40intake (1000 mg/day) between ages 25 and 40

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Spinal OsteoporosisSpinal Osteoporosis