stages of intramembranous ossification

Stages of Intramembranous Stages of Intramembranous OssificationOssification

An ossification center appears in the fibrous An ossification center appears in the fibrous connective tissue membraneconnective tissue membrane

Bone matrix is secreted within the fibrous Bone matrix is secreted within the fibrous membranemembrane

Woven bone and periosteum form Woven bone and periosteum form Bone collar of compact bone forms, and red Bone collar of compact bone forms, and red

marrow appearsmarrow appears


Figure 6.7.1


Figure 6.7.2


Figure 6.7.3


Figure 6.7.4

Endochondral OssificationEndochondral Ossification

Begins in the second month of developmentBegins in the second month of development Uses hyaline cartilage “bones” as models for Uses hyaline cartilage “bones” as models for

bone constructionbone construction Requires breakdown of hyaline cartilage prior Requires breakdown of hyaline cartilage prior

to ossificationto ossification

Stages of Endochondral Stages of Endochondral OssificationOssification

Formation of bone collarFormation of bone collar Cavitation of the hyaline cartilageCavitation of the hyaline cartilage Invasion of internal cavities by the periosteal bud, Invasion of internal cavities by the periosteal bud,

and spongy bone formationand spongy bone formation Formation of the medullary cavity; appearance of Formation of the medullary cavity; appearance of

secondary ossification centers in the epiphysessecondary ossification centers in the epiphyses Ossification of the epiphyses, with hyaline Ossification of the epiphyses, with hyaline

cartilage remaining only in the epiphyseal platescartilage remaining only in the epiphyseal plates

Stages of Endochondral OssificationStages of Endochondral Ossification

Figure 6.8

Formation ofbone collararound hyalinecartilage model.

Hyalinecartilage

Cavitation ofthe hyaline carti-lage within thecartilage model.

Invasion ofinternal cavitiesby the periostealbud and spongybone formation.

Formation of themedullary cavity asossification continues;appearance of sec-ondary ossificationcenters in the epiphy-ses in preparationfor stage 5.

Ossification of theepiphyses; whencompleted, hyalinecartilage remains onlyin the epiphyseal platesand articular cartilages.

Deterioratingcartilagematrix

Epiphysealblood vessel

Spongyboneformation

Epiphysealplatecartilage

Secondaryossificatoncenter

Bloodvessel ofperiostealbud

Medullarycavity

Articularcartilage

Spongybone

Primaryossificationcenter

Bone collar

1

2

34

5

Postnatal Bone GrowthPostnatal Bone Growth

Growth in length of long bonesGrowth in length of long bones Cartilage on the side of the epiphyseal plate closest Cartilage on the side of the epiphyseal plate closest

to the epiphysis is relatively inactiveto the epiphysis is relatively inactive Cartilage abutting the shaft of the bone organizes Cartilage abutting the shaft of the bone organizes

into a pattern that allows fast, efficient growth into a pattern that allows fast, efficient growth Cells of the epiphyseal plate proximal to the Cells of the epiphyseal plate proximal to the

resting cartilage form three functionally different resting cartilage form three functionally different zones: growth, transformation, and osteogenic zones: growth, transformation, and osteogenic

Functional Zones in Long Bone Functional Zones in Long Bone GrowthGrowth

Growth zone – cartilage cells undergo mitosis, Growth zone – cartilage cells undergo mitosis, pushing the epiphysis away from the diaphysispushing the epiphysis away from the diaphysis

Transformation zone – older cells enlarge, the Transformation zone – older cells enlarge, the matrix becomes calcified, cartilage cells die, matrix becomes calcified, cartilage cells die, and the matrix begins to deteriorateand the matrix begins to deteriorate

Osteogenic zone – new bone formation occursOsteogenic zone – new bone formation occurs

Growth in Length of Long BoneGrowth in Length of Long Bone

Figure 6.9

Long Bone Growth and Long Bone Growth and RemodelingRemodeling

Growth in length – cartilage continually grows Growth in length – cartilage continually grows and is replaced by bone as shown and is replaced by bone as shown

Remodeling – bone is resorbed and added by Remodeling – bone is resorbed and added by appositional growth as shown appositional growth as shown

Long Bone Growth and Long Bone Growth and RemodelingRemodeling

Figure 6.10

During infancy and childhood, epiphyseal During infancy and childhood, epiphyseal plate activity is stimulated by growth hormoneplate activity is stimulated by growth hormone

During puberty, testosterone and estrogens: During puberty, testosterone and estrogens: Initially promote adolescent growth spurtsInitially promote adolescent growth spurts Cause masculinization and feminization of specific Cause masculinization and feminization of specific

parts of the skeletonparts of the skeleton Later induce epiphyseal plate closure, ending Later induce epiphyseal plate closure, ending

longitudinal bone growth longitudinal bone growth

Hormonal Regulation of Bone Hormonal Regulation of Bone Growth During YouthGrowth During Youth

Bone RemodelingBone Remodeling

Remodeling units – adjacent osteoblasts and Remodeling units – adjacent osteoblasts and osteoclasts deposit and resorb bone at osteoclasts deposit and resorb bone at periosteal and endosteal surfacesperiosteal and endosteal surfaces

Bone DepositionBone Deposition

Occurs where bone is injured or added Occurs where bone is injured or added strength is neededstrength is needed

Requires a diet rich in protein, vitamins C, D, Requires a diet rich in protein, vitamins C, D, and A, calcium, phosphorus, magnesium, and and A, calcium, phosphorus, magnesium, and manganesemanganese

Alkaline phosphatase is essential for Alkaline phosphatase is essential for mineralization of bonemineralization of bone

Bone DepositionBone Deposition

Sites of new matrix deposition are revealed by Sites of new matrix deposition are revealed by the:the: Osteoid seam – unmineralized band of bone matrixOsteoid seam – unmineralized band of bone matrix Calcification front – abrupt transition zone Calcification front – abrupt transition zone

between the osteoid seam and the older between the osteoid seam and the older mineralized bonemineralized bone

Bone ResorptionBone Resorption

Accomplished by osteoclastsAccomplished by osteoclasts Resorption bays – grooves formed by Resorption bays – grooves formed by

osteoclasts as they break down bone matrixosteoclasts as they break down bone matrix Resorption involves osteoclast secretion of:Resorption involves osteoclast secretion of:

Lysosomal enzymes that digest organic matrixLysosomal enzymes that digest organic matrix Acids that convert calcium salts into soluble formsAcids that convert calcium salts into soluble forms

Bone ResorptionBone Resorption

Dissolved matrix is transcytosed across the Dissolved matrix is transcytosed across the osteoclast’s cell where it is secreted into the osteoclast’s cell where it is secreted into the interstitial fluid and then into the bloodinterstitial fluid and then into the blood

Importance of Ionic Calcium in Importance of Ionic Calcium in the Bodythe Body

Calcium is necessary for:Calcium is necessary for: Transmission of nerve impulsesTransmission of nerve impulses Muscle contractionMuscle contraction Blood coagulationBlood coagulation Secretion by glands and nerve cellsSecretion by glands and nerve cells Cell divisionCell division

Control of RemodelingControl of Remodeling

Two control loops regulate bone remodelingTwo control loops regulate bone remodeling Hormonal mechanism maintains calcium Hormonal mechanism maintains calcium

homeostasis in the bloodhomeostasis in the blood Mechanical and gravitational forces acting on the Mechanical and gravitational forces acting on the

skeletonskeleton

Hormonal MechanismHormonal Mechanism

Rising blood CaRising blood Ca2+2+ levels trigger the thyroid to levels trigger the thyroid to release calcitoninrelease calcitonin

Calcitonin stimulates calcium salt deposit in Calcitonin stimulates calcium salt deposit in bonebone

Falling blood CaFalling blood Ca2+2+ levels signal the parathyroid levels signal the parathyroid glands to release PTHglands to release PTH

PTH signals osteoclasts to degrade bone PTH signals osteoclasts to degrade bone matrix and release Camatrix and release Ca2+2+ into the blood into the blood

Hormonal Control of Blood CaHormonal Control of Blood Ca

Figure 6.11

PTH;calcitoninsecreted

Calcitoninstimulatescalcium saltdepositin bone

Parathyroidglands releaseparathyroidhormone (PTH)

Thyroidgland

Thyroidgland

Parathyroidglands

Osteoclastsdegrade bonematrix and releaseCa2+ into blood

Falling bloodCa2+ levels

Rising bloodCa2+ levels

Calcium homeostasis of blood: 9–11 mg/100 ml

PTH

Imbalance

Imbalance

Response to Mechanical StressResponse to Mechanical Stress

Wolff’s law – a bone grows or remodels in Wolff’s law – a bone grows or remodels in response to the forces or demands placed upon response to the forces or demands placed upon itit

Observations supporting Wolff’s law includeObservations supporting Wolff’s law include Long bones are thickest midway along the shaft Long bones are thickest midway along the shaft

(where bending stress is greatest)(where bending stress is greatest) Curved bones are thickest where they are most Curved bones are thickest where they are most

likely to bucklelikely to buckle

Response to Mechanical StressResponse to Mechanical Stress

Trabeculae form along lines of stressTrabeculae form along lines of stress Large, bony projections occur where heavy, Large, bony projections occur where heavy,

active muscles attachactive muscles attach

Bone Fractures (Breaks)Bone Fractures (Breaks)

Bone fractures are classified by:Bone fractures are classified by: The position of the bone ends after fractureThe position of the bone ends after fracture The completeness of the breakThe completeness of the break The orientation of the bone to the long axisThe orientation of the bone to the long axis Whether or not the bones ends penetrate the skinWhether or not the bones ends penetrate the skin

Types of Bone FracturesTypes of Bone Fractures

Nondisplaced – bone ends retain their normal Nondisplaced – bone ends retain their normal positionposition

Displaced – bone ends are out of normal Displaced – bone ends are out of normal alignmentalignment


Complete – bone is broken all the way throughComplete – bone is broken all the way through Incomplete – bone is not broken all the way Incomplete – bone is not broken all the way

throughthrough Linear – the fracture is parallel to the long axis Linear – the fracture is parallel to the long axis

of the boneof the bone


Transverse – the fracture is perpendicular to Transverse – the fracture is perpendicular to the long axis of the bonethe long axis of the bone

Compound (open) – bone ends penetrate the Compound (open) – bone ends penetrate the skinskin

Simple (closed) – bone ends do not penetrate Simple (closed) – bone ends do not penetrate the skinthe skin

Common Types of FracturesCommon Types of Fractures

Comminuted – bone fragments into three or Comminuted – bone fragments into three or more pieces; common in the elderlymore pieces; common in the elderly

Spiral – ragged break when bone is Spiral – ragged break when bone is excessively twisted; common sports injuryexcessively twisted; common sports injury

Depressed – broken bone portion pressed Depressed – broken bone portion pressed inward; typical skull fractureinward; typical skull fracture


Compression – bone is crushed; common in Compression – bone is crushed; common in porous bonesporous bones

Epiphyseal – epiphysis separates from Epiphyseal – epiphysis separates from diaphysis along epiphyseal line; occurs where diaphysis along epiphyseal line; occurs where cartilage cells are dyingcartilage cells are dying

Greenstick – incomplete fracture where one Greenstick – incomplete fracture where one side of the bone breaks and the other side side of the bone breaks and the other side bends; common in childrenbends; common in children


Table 6.2.1


Table 6.2.2


Table 6.2.3

Stages in the Healing of a Bone Stages in the Healing of a Bone FractureFracture

Hematoma formationHematoma formation Torn blood vessels Torn blood vessels

hemorrhagehemorrhage A mass of clotted A mass of clotted

blood (hematoma) blood (hematoma) forms at the fracture forms at the fracture sitesite

Site becomes swollen, Site becomes swollen, painful, and inflamedpainful, and inflamed

Figure 6.13.1


Fibrocartilaginous Fibrocartilaginous callus formscallus forms

Granulation tissue (soft Granulation tissue (soft callus) forms a few callus) forms a few days after the fracturedays after the fracture

Capillaries grow into Capillaries grow into the tissue and the tissue and phagocytic cells begin phagocytic cells begin cleaning debriscleaning debris

Figure 6.13.2


The fibrocartilaginous callus forms when:The fibrocartilaginous callus forms when: Osteoblasts and fibroblasts migrate to the fracture Osteoblasts and fibroblasts migrate to the fracture

and begin reconstructing the boneand begin reconstructing the bone Fibroblasts secrete collagen fibers that connect Fibroblasts secrete collagen fibers that connect

broken bone endsbroken bone ends Osteoblasts begin forming spongy boneOsteoblasts begin forming spongy bone Osteoblasts furthest from capillaries secrete an Osteoblasts furthest from capillaries secrete an

externally bulging cartilaginous matrix that later externally bulging cartilaginous matrix that later calcifiescalcifies


Bony callus formationBony callus formation New bone trabeculae New bone trabeculae

appear in the appear in the fibrocartilaginous callusfibrocartilaginous callus

Fibrocartilaginous callus Fibrocartilaginous callus converts into a bony (hard) converts into a bony (hard) calluscallus

Bone callus begins 3-4 Bone callus begins 3-4 weeks after injury, and weeks after injury, and continues until firm union continues until firm union is formed 2-3 months lateris formed 2-3 months later

Figure 6.13.3


Bone remodelingBone remodeling Excess material on the Excess material on the

bone shaft exterior and bone shaft exterior and in the medullary canal in the medullary canal is removedis removed

Compact bone is laid Compact bone is laid down to reconstruct down to reconstruct shaft wallsshaft walls

Figure 6.13.4

Homeostatic ImbalancesHomeostatic Imbalances

OsteomalaciaOsteomalacia Bones are inadequately mineralized causing Bones are inadequately mineralized causing

softened, weakened bonessoftened, weakened bones Main symptom is pain when weight is put on the Main symptom is pain when weight is put on the

affected boneaffected bone Caused by insufficient calcium in the diet, or by Caused by insufficient calcium in the diet, or by

vitamin D deficiencyvitamin D deficiency


RicketsRickets Bones of children are inadequately mineralized Bones of children are inadequately mineralized

causing softened, weakened bonescausing softened, weakened bones Bowed legs and deformities of the pelvis, skull, Bowed legs and deformities of the pelvis, skull,

and rib cage are commonand rib cage are common Caused by insufficient calcium in the diet, or by Caused by insufficient calcium in the diet, or by

vitamin D deficiencyvitamin D deficiency

Isolated Cases of RicketsIsolated Cases of Rickets

Rickets has been essentially eliminated in the Rickets has been essentially eliminated in the USUS

Only isolated cases appearOnly isolated cases appear Example: Infants of breastfeeding mothers Example: Infants of breastfeeding mothers

deficient in Vitamin D will also be Vitamin D deficient in Vitamin D will also be Vitamin D deficient and develop ricketsdeficient and develop rickets


OsteoporosisOsteoporosis Group of diseases in which bone reabsorption Group of diseases in which bone reabsorption

outpaces bone depositoutpaces bone deposit Spongy bone of the spine is most vulnerableSpongy bone of the spine is most vulnerable Occurs most often in postmenopausal womenOccurs most often in postmenopausal women Bones become so fragile that sneezing or stepping Bones become so fragile that sneezing or stepping

off a curb can cause fracturesoff a curb can cause fractures

Osteoporosis: TreatmentOsteoporosis: Treatment

Calcium and vitamin D supplementsCalcium and vitamin D supplements Increased weight-bearing exerciseIncreased weight-bearing exercise Hormone (estrogen) replacement therapy Hormone (estrogen) replacement therapy

(HRT) slows bone loss(HRT) slows bone loss Natural progesterone cream prompts new bone Natural progesterone cream prompts new bone

growthgrowth Statins increase bone mineral densityStatins increase bone mineral density

Thought to kill off osteoclasts and/or promote Thought to kill off osteoclasts and/or promote growth and development of osteoblastsgrowth and development of osteoblasts

Paget’s DiseasePaget’s Disease

Characterized by excessive bone formation and Characterized by excessive bone formation and breakdownbreakdown

Pagetic bone with an excessively high ratio of Pagetic bone with an excessively high ratio of woven to compact bone is formedwoven to compact bone is formed

Pagetic bone, along with reduced Pagetic bone, along with reduced mineralization, causes spotty weakening of bonemineralization, causes spotty weakening of bone

Osteoclast activity wanes, but osteoblast activity Osteoclast activity wanes, but osteoblast activity continues to workcontinues to work

Paget’s DiseasePaget’s Disease

Usually localized in the spine, pelvis, femur, Usually localized in the spine, pelvis, femur, and skulland skull

Unknown cause (possibly viral)Unknown cause (possibly viral) Treatment includes the drugs Didronate and Treatment includes the drugs Didronate and

FosamaxFosamax

Fetal Primary Ossification CentersFetal Primary Ossification Centers

Figure 6.15

Developmental Aspects of BonesDevelopmental Aspects of Bones

Mesoderm gives rise to embryonic Mesoderm gives rise to embryonic mesenchymal cells, which produce membranes mesenchymal cells, which produce membranes and cartilages that form the embryonic and cartilages that form the embryonic skeletonskeleton

The embryonic skeleton ossifies in a The embryonic skeleton ossifies in a predictable timetable that allows fetal age to predictable timetable that allows fetal age to be easily determined from sonogramsbe easily determined from sonograms

At birth, most long bones are well ossified At birth, most long bones are well ossified (except for their epiphyses)(except for their epiphyses)

Developmental Aspects of BonesDevelopmental Aspects of Bones

By age 25, nearly all bones are completely By age 25, nearly all bones are completely ossifiedossified

In old age, bone resorption predominatesIn old age, bone resorption predominates A single gene that codes for vitamin D A single gene that codes for vitamin D

docking determines both the tendency to docking determines both the tendency to accumulate bone mass early in life, and the accumulate bone mass early in life, and the risk for osteoporosis later in liferisk for osteoporosis later in life

stages of intramembranous ossification

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