Chapter 6- Part II Bone Development Bone growth and hormonal regulation of bone growth Bone remodeling –Regulation of blood Ca2 + Bone Repair Osteomalacia,

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  • Chapter 6- Part II

    Bone DevelopmentBone growth and hormonal regulation of bone growthBone remodelingRegulation of blood Ca2+Bone RepairOsteomalacia, Rickets, OsteoporosisCauses and Treatments

  • Can you identify all of these parts of a bone?

  • What is the definition ofOssification


  • Formation of the Bony SkeletonBegins at week 8 of embryonic developmentOssificationIntramembranous ossification bone develops from a fibrous membraneEndochondral ossification bone forms by replacing hyaline cartilage

  • Endochondral and Intramembranous ossificationBoth processes are more similar than they are differentSame cells participate and do similar thingsAt biochemical and cellular level, many of the same events occurDifferences:Site of activityOrganization of activityNumbers of centers of ossificationWhat is replaced

  • Intramembranous ossification

    Also called dermal ossificationOccurs in fibrous membrane of mesenchymeFlat bones of the skull, mandible, and clavicleYou lucky ducks dont have to know the steps of this process!

  • The Birth of BoneWhen new bone is born, either during development or regeneration, it often starts out as spongy bone (even if it will later be remodeled into compact bone)

  • Endochondral OssificationNote: you DO have to know this oneBegins in the second month of developmentUses hyaline cartilage bones as models for bone construction then ossifies cartilage into bone Common, as most bones originate as hyaline cartilageThis is like a trick the body uses to allow long bones to grow in length when bones can only grow by appositional growth

  • Bone formation in a chick embryoStained to represent hardened bone (red) and cartilage (blue)

    : This image is the cover illustration from The Atlas of Chick Development by Ruth Bellairs and Mark Osmond, published by Academic Press (New York) in 1998

  • Bone formation in a human embryo

  • Endochondral OssificationBone replaces a cartilaginous model (hyaline)Occurs in most bones 1. Cells of the perichondrium differentiate to osteoblasts and form a bone collar around the outside (a periosteum)2. Chondrocytes at center of model grow large, cause calcification to happen all around themselves, and then they die, leaving behind big spaces (fancy term= cavitation)3. Spaces invaded by periosteal bud, (blood vessels, nerve, lymphatic vessel, osteoclasts, osteoblasts)Osteoclasts and -blasts arrive. Set up primary ossification center, and bone growth occurs (as spongy bone, trabeculae) spreads along shaft of bone, toward ends.4. Primary ossification center grows, and a medullary cavity is carved out. Cartilage continues to grow at the epiphyseal side of the shaft. 5. At or after birth, the centers of each epiphysis also begin to be replaced by bone, each end is a secondary ossification center At the epiphyseal plate (growth plate), as long as cartilage growth outpaces replacement by bone, bone length continues.

  • Stages of Endochondral Ossification

  • Endochondral Ossificationand the race is onWhen secondary ossification is complete, where would you find hyaline cartilage?

  • Endochondral Ossification: Step 5 (Elongation)Epiphyses fill with spongy bone but cartilage remains at two sites:ends of bones within the joint cavity = articular cartilagecartilage at the metaphysis = epiphyseal cartilage (plate)

    Figure 69 (Step 6)

  • What occurs at the epiphyseal plate, or growth plate? and the race is on

  • Postnatal Bone GrowthGrowth in length of long bonesCartilage on the side of the epiphyseal plate closest to the epiphysis is relatively inactiveCartilage abutting the shaft of the bone organizes into a pattern that allows fast, efficient growth Cells of the epiphyseal plate proximal to the resting cartilage form three functionally different zones: growth, transformation, and osteogenic

  • Functional Zones in Long Bone GrowthGrowth zone cartilage cells undergo mitosis, pushing the epiphysis away from the diaphysisTransformation zone older cells enlarge, the matrix becomes calcified, cartilage cells die, and the matrix begins to deteriorateOsteogenic zone new bone formation occurs

  • Growth in Length of Long BoneFigure 6.9

  • Growth Plate

  • Epiphyseal cartilages undergo ossification and become epiphyseal lines

  • More on Postnatal bone growthRemember that bone growth can only occur from the outside (appositional growth). So this type of endochondral growth is a way for bones to grow from the inside and lengthen because it is the cartilage that is growing, not the bone

  • Key ConceptAs epiphyseal cartilage grows through the division of chondrocytes it pushes the ends of the bone outward in length. At the inner (shaft) side of the epiphyseal plate, recently born cartilage gets turned into bone, but as long as the cartilage divides and extends as fast or faster than it gets turned into bone, the bone will grow longer

  • Long Bone Growth and RemodelingGrowth in length cartilage continually grows and is replaced by bone as shown Remodeling bone is resorbed and added by appositional growth as shown compact bone thickens and strengthens long bones with layers of circumferential lamellae

  • Long Bone Growth and RemodelingFigure 6.10

  • Appositional Growth

  • Epiphyseal LinesWhen long bone stops growing, between the ages of 18 25:epiphyseal cartilage disappears epiphyseal plate closesvisible on X-rays as an epiphyseal line

    At this point, bone has replaced all the cartilage and the bone can no longer grow in length

  • Bone growth during youthWhat is the most important hormone for bone growth during infancy and childhood? Where in the body does this hormone have its most critical effects?Thyroid hormone, and sex hormones also play a role in bone growthPrimary cause of gigantism? Dwarfism?

  • What do we need to grow healthy bones?Rickets

  • In the adult, bone remodeling occurs constantly and also when we break a boneWhat does bone remodeling involve?

    Bone remodeling is a continual, life-long process5% of our bone mass is recycled/weekSpongy bone is replaced every 3-4 yearsOld, not-remodeled bone becomes brittleIf removal is faster than deposition, bones get weaker!

  • Bone deposition & bone resorptionOsteoblasts build boneLay down osteoidOsteoid calcifies when calcium and phosphate reach specific concentrations and in the presence of alkaline phosphatase

    Osteoclasts dissolve boneRelease lysosomal enzymes and hydrocholric acidPhagocytose demineralized matrix, dead osteocytes

  • What regulates and controls bone remodeling?#1 BLOOD CALCIUM LEVELS! First, where/how does the body GET newcalcium?From birth to age 10, children need 400-800 mg/day From ages 11-24 need 1200-1500 mg/daySecond, why is it so critical that blood calcium levels are maintained? Or, what physiological processes are affected by changes in calcium?

    What hormones have the most important role in calcium regulation?

  • Parathyroid Hormone (PTH) is released in response to LOW blood Ca2+ levelsWhat does PTH do once released? What cells of the body have PTH receptors?Is this a negative or positive feedback loop?

    Osteoclastsdegrade bonematrix and release Ca2+into blood.ParathyroidglandsThyroidglandParathyroidglands releaseparathyroidhormone (PTH).StimulusFalling bloodCa2+ levelsPTHCalcium homeostasis of blood: 911 mg/100 ml

  • PTH increases blood calcium levelsvia VitDStimulates osteoclastsDecreases Ca2+ excretion at kidneysStimulates calcium absorption at gut, via calcitriol (Vit D)

  • Calcitonin and Ca2+ regulationCalcitonin is a hormone released by cells (parafollicular cells) of the thyroid At physiological levels, calcitonin does not have an important role in calcium regulation.Mixed results for calcitonin in treatment of osteoporosis or hypercalcemia


  • Bone remodeling

    #2- is also controlled by mechanical stressWhat causes stress on bones?Wolffs law holds that a bone grows or remodels in response to the demands placed on itExamples of Wolffs law in action? Inaction?

  • Bone remodeling is controlled by mechanical stress

    How does Wolffs law work?Deforming a bone (mechanical stress) produces a small electrical currentOsteocytes and/or collagen molecules act as biosensorsIn a frequently loaded or pulled region of a bone, growth is stimulatedCan magnets or applied voltage increase bone growth/healing?

  • Bone FracturesNondisplaced or displaced fractureIncomplete or complete fractureLinear or transverse fractureClosed (simple) or open (compound) fracture

    How is a fracture treated?

  • Bone RepairWhen bones are fractured, blood vessels are broken1. A large blood clot (hematoma) forms around the injured area2. Capillaries grow into hematoma and dead cells, pathogens and debris are cleaned up by immune cells. Fibroblasts, osteoblasts, -clasts migrate to area, start to rebuild. Some fibroblasts differentitate into chondrocytes. Fibrocartilage (soft) callus formed.3. Over time, the cartilage is replaced by bone.Bone callus- exists from 3-4 weeks after injury to 2-3 months later4. Remodeling of the affected area may continue for months to years.

  • How do fractures repair?HematomaExternalcallusBonycallus ofspongyboneHealedfractureNewbloodvesselsSpongybonetrabeculaInternalcallus(fibroustissue andcartilage)1A hematoma forms.2 Fibrocartilaginouscallus forms. 3Bony callus forms.4 Boneremodelingoccurs.

  • The first x-ray was taken right after a fracture. The second was 2 months later, showing some callus. Notice that the