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Bones  and  Skeletal  Tissues:  Part  B  

Bone  Development  

•  Osteogenesis  (_____________________)  —bone  Dssue  formaDon  

•  Stages  – Bone  formaDon—begins  in  the  2nd  month  of  development  

– Postnatal  bone  growth—unDl  early  adulthood  – Bone  remodeling  and  repair—________________  

Two  Types  of  OssificaDon  

1.  ___________________________  ossificaDon  –  Membrane  bone  develops  from  fibrous  

membrane  –  Forms  flat  bones,  e.g.  clavicles  and  cranial  bones  

2.  ___________________________  ossificaDon  –  CarDlage  (endochondral)  bone  forms  by  replacing  

hyaline  carDlage  –  Forms  most  of  the  rest  of  the  skeleton  

Figure 6.8, (1 of 4)

Mesenchymal cell Collagen fiber Ossification center

Osteoid

Osteoblast

Ossification centers appear in the fibrous connective tissue membrane. • Selected centrally located mesenchymal cells cluster and differentiate into osteoblasts, forming an ossification center.

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Figure 6.8, (2 of 4)

Osteoid

Osteocyte

Newly calcified bone matrix

Osteoblast

Bone matrix (osteoid) is secreted within the fibrous membrane and calcifies. • Osteoblasts begin to secrete osteoid, which is calcified within a few days.

• Trapped osteoblasts become osteocytes.

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Figure 6.8, (3 of 4)

Mesenchyme condensing to form the periosteum

Blood vessel

Trabeculae of woven bone

Woven bone and periosteum form. • Accumulating osteoid is laid down between embryonic blood vessels in a random manner. The result is a network (instead of lamellae) of trabeculae called woven bone.

• Vascularized mesenchyme condenses on the external face of the woven bone and becomes the periosteum.

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Figure 6.8, (4 of 4)

Fibrous periosteum

Osteoblast

Plate of compact bone

Diploë (spongy bone) cavities contain red marrow

Lamellar bone replaces woven bone, just deep to the periosteum. Red marrow appears. • Trabeculae just deep to the periosteum thicken, and are later replaced with mature lamellar bone, forming compact bone plates.

• Spongy bone (diploë), consisting of distinct trabeculae, per- sists internally and its vascular tissue becomes red marrow.

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Endochondral  OssificaDon  

•  Uses  __________________  carDlage  models    •  Requires  breakdown  of  hyaline  carDlage  prior  to  ossificaDon  

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Figure 6.9

Bone collar forms around hyaline cartilage model.

Cartilage in the center of the diaphysis calcifies and then develops cavities.

The periosteal bud inavades the internal cavities and spongy bone begins to form.

The diaphysis elongates and a medullary cavity forms as ossification continues. Secondary ossification centers appear in the epiphyses in preparation for stage 5.

The epiphyses ossify. When completed, hyaline cartilage remains only in the epiphyseal plates and articular cartilages.

Hyaline cartilage

Area of deteriorating cartilage matrix

Epiphyseal blood vessel

Spongy bone formation

Epiphyseal plate cartilage

Secondary ossification center

Blood vessel of periosteal bud

Medullary cavity

Articular cartilage

Childhood to adolescence

Birth Week 9 Month 3

Spongy bone

Bone collar Primary ossification center

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Postnatal  Bone  Growth  

•  _________________  growth:    – ↑  length  of  long  bones  

•  _________________  growth:    – ↑  thickness  and  remodeling  of  all  bones  by  osteoblasts  and  osteoclasts  on  bone  surfaces  

Growth  in  Length  of  Long  Bones    

•  Epiphyseal  plate  carDlage  organizes  into  four  important  _______________  __________:    – ProliferaDon  (growth)  – Hypertrophic  – CalcificaDon  – OssificaDon  (osteogenic)  

Figure 6.10

Calcified cartilage spicule

Osseous tissue (bone) covering cartilage spicules

Resting zone

Osteoblast depositing bone matrix

Proliferation zone Cartilage cells undergo mitosis.

Hypertrophic zone Older cartilage cells enlarge.

Ossification zone New bone formation is occurring.

Calcification zone Matrix becomes calcified; cartilage cells die; matrix begins deteriorating.

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Hormonal  RegulaDon  of  Bone  Growth  

•  Growth  hormone  sDmulates  ________________  ___________  acDvity  

•  Thyroid  hormone  modulates  acDvity  of  growth  hormone  

•  Testosterone  and  estrogens    (at  ________________)  – Promote  adolescent  growth  spurts  – End  growth  by  inducing  epiphyseal  plate  closure  

Figure 6.11

Bone growth Bone remodeling

Articular cartilage

Epiphyseal plate

Cartilage grows here.

Cartilage is replaced by bone here. Cartilage grows here.

Bone is resorbed here.

Bone is resorbed here.

Bone is added by appositional growth here. Cartilage

is replaced by bone here.

Bone  Deposit  •  Occurs  where  bone  is  ________________  or  added  strength  is  needed  

•  Requires  a  diet  rich  in  protein;  vitamins  C,  D,  and  A;  calcium;  phosphorus;  magnesium;  and  manganese  

Bone  Deposit  

•  Sites  of  new  matrix  deposit  are  revealed  by  the  – _________________________  

•  Unmineralized  band  of  matrix  

– _________________________  •  The  abrupt  transiDon  zone  between  the  osteoid  seam  and  the  older  mineralized  bone  

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Bone  ResorpDon  

•  _________________________  secrete  – Lysosomal  enzymes  (digest  organic  matrix)  – Acids  (convert  calcium  salts  into  soluble  forms)  

•  Dissolved  matrix  is  transcytosed  across  osteoclast,  enters  intersDDal  fluid  and  then  _________________  

Control  of  Remodeling  

•  What  controls  conDnual  _________________  of  bone?  – Hormonal  mechanisms  that  maintain  calcium  homeostasis  in  the  blood  

– Mechanical  and  _________________  forces    

Hormonal  Control  of  Blood  Ca2+  

•  _________________  is  necessary  for  – Transmission  of  nerve  impulses  – _________________  contracDon  – _________________  coagulaDon  – SecreDon  by  glands  and  _________________  – Cell  division  

Hormonal  Control  of  Blood  Ca2+  

•  Primarily  controlled  by  parathyroid  hormone  (PTH)  ↓  Blood  Ca2+  levels    

↓  Parathyroid  glands  release  PTH  

↓  PTH  sDmulates  osteoclasts  to  degrade  bone  matrix  and  

release  Ca2+    ↓  

↑  Blood  Ca2+  levels    

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Figure 6.12

Osteoclasts degrade bone matrix and release Ca2+ into blood.

Parathyroid glands

Thyroid gland

Parathyroid glands release parathyroid hormone (PTH).

Stimulus Falling blood Ca2+ levels

PTH

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

Hormonal  Control  of  Blood  Ca2+  

•  May  be  affected  to  a  lesser  extent  by  calcitonin  ↑  Blood  Ca2+  levels  

↓  Parafollicular  cells  of  thyroid  release  calcitonin  

↓  Osteoblasts  deposit  calcium  salts      

↓  ↓  Blood  Ca2+  levels  

•  LepDn  has  also  been  shown  to  influence  bone  density  by  inhibiDng  _________________  

Response  to  Mechanical  Stress  •  _________________:  A  bone  grows  or  remodels  in  

response  to  forces  or  demands  placed  upon  it  •  ObservaDons  supporDng  Wolff’s  law:  

–  _________________  (right  or  lec  handed)  results  in  bone  of  one  upper  limb  being  thicker  and  stronger  

–  Curved  bones  are  thickest  where  they  are  most  likely  to  buckle  

–  Trabeculae  form  along  _________________  –  Large,  bony  projecDons  occur  where  heavy,  acDve  _________________  aeach  

Figure 6.13

Load here (body weight)

Head of femur

Compression here

Point of no stress

Tension here

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ClassificaDon  of  Bone  Fractures    

•  Bone  _________________  may  be  classified  by  four  “either/or”  classificaDons:  

1.  PosiDon  of  bone  ends  acer  fracture:  •  Nondisplaced—ends  retain  normal  posiDon  •  Displaced—ends  out  of  normal  alignment  

2.  Completeness  of  the  break  •  _________________—broken  all  the  way  through  •  _________________—not  broken  all  the  way  through  

ClassificaDon  of  Bone  Fractures  3.  _________________  of  the  break  to  the  long  axis  of  the  

bone:  •  Linear—parallel  to  long  axis  of  the  bone  •  Transverse—perpendicular  to  long  axis  of  the  bone  

4.  Whether  or  not  the  bone  ends  _________________  the  skin:  

•  _________________  (open)—bone  ends  penetrate  the  skin  

•  _________________  (closed)—bone  ends  do  not  penetrate  the  skin  

Common  Types  of  Fractures  

•  All  fractures  can  be  described  in  terms  of  – _________________  – _________________  – _________________  

Table 6.2

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Table 6.2 Table 6.2

Stages  in  the  Healing  of  a  Bone  Fracture  

1.  _________________  forms  –  Torn  blood  vessels  hemorrhage  –  Clot  (hematoma)  forms    –  Site  becomes  swollen,  painful,  and  

_________________    

Figure 6.15, step 1

A hematoma forms. 1

Hematoma

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Stages  in  the  Healing  of  a  Bone  Fracture  

2.  _________________  callus  forms  –  PhagocyDc  cells  clear  debris  –  Osteoblasts  begin  forming  spongy  bone  within  1  

week  –  Fibroblasts  secrete  _________________  to  

connect  bone  ends  –  Mass  of  repair  Dssue  now  called  

fibrocarDlaginous  callus  

Figure 6.15, step 2

Fibrocartilaginous callus forms. 2

External callus

New blood vessels

Spongy bone trabecula

Internal callus (fibrous tissue and cartilage)

Stages  in  the  Healing  of  a  Bone  Fracture  

3.  ________  _________formaDon  –  New  trabeculae  form  a  bony  (hard)  callus  –  Bony  callus  formaDon  conDnues  unDl  firm  union  

is  formed  in  ~2  months  

Figure 6.15, step 3

Bony callus forms. 3

Bony callus of spongy bone

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Stages  in  the  Healing  of  a  Bone  Fracture  

4.  Bone  _________________  –  In  response  to  mechanical  stressors  over  several  

months  –  Final  structure  resembles  _________________  

Figure 6.15, step 4

Bone remodeling occurs. 4

Healed fracture

Figure 6.15

Hematoma External callus

Bony callus of spongy bone Healed fracture

New blood vessels

Spongy bone trabecula

Internal callus (fibrous tissue and cartilage)

A hematoma forms. Fibrocartilaginous callus forms.

Bony callus forms. Bone remodeling occurs.

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HomeostaDc  Imbalances  

•  _________________  and  rickets  – Calcium  salts  not  deposited  – Rickets  (childhood  disease)  causes  bowed  legs  and  other  bone  deformiDes  

– Cause:  _________________deficiency  or  insufficient  dietary  calcium  

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HomeostaDc  Imbalances  

•  _________________  – Loss  of  bone  mass—bone  resorpDon  outpaces  deposit  

– Spongy  bone  of  spine  and  neck  of  femur  become  most  suscepDble  to  fracture  

– _________________  •  Lack  of  estrogen,  calcium  or  vitamin  D;  peDte  body  form;  immobility;  low  levels  of  TSH;  diabetes  mellitus  

Figure 6.16

Osteoporosis:  Treatment  and  PrevenDon  

•  Calcium,  vitamin  D,  and  fluoride  supplements  •  ↑  Weight-­‐bearing  exercise  throughout  life  •  Hormone  (_________________)  replacement  therapy  (HRT)  slows  bone  loss    

•  Some  _________________  (Fosamax,  SERMs,  staDns)  increase  bone  mineral  density  

Paget’s  Disease  

•  Excessive  and  haphazard  bone  formaDon  and  breakdown,  usually  in  spine,  pelvis,  femur,  or  skull  

•  PageDc  bone  has  very  high  raDo  of  _________________  to  _________________  bone  and  reduced  mineralizaDon  

•  Unknown  cause  (possibly  ______________)  •  _________________  includes  calcitonin  and  biphosphonates  

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Developmental  Aspects  of  Bones  

•  _________________  skeleton  ossifies  predictably  so  fetal  age  easily  determined  from  X  rays  or  sonograms  

•  At  birth,  most  ___________  __________  are  well  ossified  (except  _________________)  

Figure 6.17

Parietal bone

Radius Ulna

Humerus

Femur

Occipital bone

Clavicle Scapula

Ribs

Vertebra Ilium

Tibia

Frontal bone of skull Mandible

Developmental  Aspects  of  Bones  

•  Nearly  all  bones  completely  _________________  by  age  25  

•  Bone  mass  decreases  with  age  beginning  in  4th  decade  

•  Rate  of  loss  determined  by  _________________  and  environmental  factors    

•  In  old  age,  bone  _________________  predominates