1. Bone Formation D
Describe intramembranous and endochondral ossification in the embryo.
Describe epiphyseal and appositional bone growth in infants, children, and adolescents.
Describe bone remodeling.
Discuss factors that affect bone growth and remodeling.

2. Ossification
The process by which bone forms. Also called osteogenesis.
Occurs during:
Initial bone formation in embryo and fetus
Bone growth in infants, children, and adolescents
Bone remodeling throughout life
Fracture repair

3. At week 6 mesenchyme begins to ossify. Intramembranous ossification
Bone Formation
Before week 6 embryonic “skeleton” is composed of bone-shaped mesenchyme.
At week 6 mesenchyme begins to ossify.
Intramembranous ossification
Endochondral ossification
From hyaline cartilage

4. Intramembranous Ossification (simpler)
Occurs within mesenchyme
Only forms flatbones
skull bones – including facial
Clavicles
“soft spots”
Layers of spongy bone veneered with hard bone
Ossification of fibrous CT begins at ~6-8 weeks of development

5. Intramembranous Ossification (simpler)
Develop an ossification center
Chemical msgs  stem cells in mesechyme  osteogenic cells  osteoblasts  ECM
Calcify matrix
Secretion of ECM stops
Osteocytes extend processes
Calcification
Form trabeculae
Made while ECM forms
Fuse around vessels = spongy bone – RBM made
Develop periosteum
Mesenchyme condenses at periphery
Thin compact bone layer replaces spongy surface

6. Woven vs. Lamellar Bone Woven bone – weak Lamellar bone - strong
Haphazard organization of fibers
Osteoblasts produce osteoid rapidly
In all fetal bones – replaced later by lamellar bone
Also present after fractures – initially woven bone as healing occurs.
Lamellar bone - strong
Secondary bone created by remodeling of woven bone.
Highly organized alignment of collagen in sheets
Fibers run in opposite directions in cross-section
tensile strength
Less osteocytes

7. Figure 6.5 Intramembranous ossification.
Intramembranous ossification involves the formation of bone within mesenchyme arranged in sheet-like layers that resemble membranes.

8. Endochondral Ossification
Occurs in hyaline cartilage developed from mesenchyme
Replacement of cartilage “template” by bone
Forms skeleton below skull (except clavicles)
Best observed in a long bone (most bones are formed this way)

9. Endochondral Ossification
6 steps
Develop cartilage model
Grow cartilage model
Develop primary ossification center
Develop medullary cavity
Develop secondary ossification centers
Form articular cartilage and epiphyseal plate

10. Figure 6.6 Endochondral ossification.
During endochondral ossification, bone gradually replaces a cartilage model.

11. iClicker Question
Which of the following two minerals are needed in large quantities when bones are growing?
Calcium and chlorine
Magnesium and sulfur
Calcium and phosphorous
Manganese and sulfur
Potassium and phosphorous

12. Mehmet Ozyurek of Turkey
Bone Growth
Epiphyseal growth – longer
Appositional growth – thicker
Some bones never stop growing
Mehmet Ozyurek of Turkey

13. Bone Growth in thickness
Appositional growth
At surface – periosteal cells  osteoblasts  secrete ECM  become surrounded  osteocytes
Osteoblasts in endosteum deposit bone ECM forming new concentric lamellae  creating new osteons
As new osteons are made, osteoblasts continue to add new circumferential lamellae to outer surface  increase thickness
Usually less break down than build up
Unequal process = thicker, stronger bone, but not too heavy

14. Figure 6.8 Bone growth in thickness.
As new bone is deposited on the outer surface of bone by osteoblasts, the bone tissue lining the medullary cavity is destroyed by osteoclasts in the endosteum.
Turn to pg. 181 in your textbook and look at FIG 6.8

15. Bone Growth in Length Long Bones grow longer because:
Cartilage grows on the epiphyseal side of the plate
Cartilage ossifies on the diaphyseal side of the plate (endochondral ossification)
Radiograph of 12 year old child's leg showing growth plates

16. Bone Growth in Length – Zones of epiphyseal plate
Zone of resting cartilage – closest to epiphysis
Small scattered chondroctyes – no function in growth
Firmly attaches epiphyseal plate to epiphysis.
 Zone of proliferating cartilage – increase bone length
Larger chondroctyes stacked like coins
Cells divide – interstitial growth – push old cells into next layer
Zone of hypertrophic cartilage
Large columns of maturing chondrocytes
Begin to die – stimulating calcification
 Zone of calcified cartilage
Only a few cells thick – chondrocytes are dead due to calcified ECM
Calcified cartilage reorganized into woven bone (eventually remodelled)
Osteoclasts digest center – extends medullary cavity 
This zone becomes “new diaphysis” cemented to rest of diaphysis

17. Figure 6.7 Epiphyseal (growth) plate.
The epiphyseal plate allows the diaphysis of a bone to increase in length.

18. Bone Growth in Length
Ossification “chases” cartilage formation along length of diaphysis
Before the end of adolescence
Epiphyseal plate remains thick (constant) because:
Cartilage Growth = Cartilage Ossification
During the end of adolescence
Epiphyseal plate gets thinner because:
Cartilage Growth < Cartilage Ossification

19. Radiograph of adult’s leg showing epiphyseal lines
Bone Growth in Length
Epiphyseal plate closure occurs:
At about 18 years old in females
At about 21 years old in males
Epiphyseal plate  epiphyseal line
Radiograph of adult’s leg showing epiphyseal lines

20. iClicker Question
Which of the following correctly lists the order of the four zones of cartilage found within the growth plate starting at the ephiphysis and extending to the diaphysis?
calcified cartilage, resting cartilage, proliferating cartilage, hypertrophic cartilage
resting cartilage, proliferating cartilage, calcified cartilage, hypertrophic cartilage
proliferating cartilage, resting cartilage, hypertrophic cartilage, calcified cartilage
resting cartilage, proliferation cartilage, hypertrophic cartilage, calcified cartilage

21. Bone Remodeling Bone remodeling – the ongoing replacement of bone
Bone deposition
Bone resorption
Benefits
Removes injured bone
Triggered by lifestyle / diet changes
Strength of bone is related to exposed stresses, newly formed bone exposed to heavy loads will grow thicker and be stronger
New bone is more resistant to fracturing

22. Factors Affecting Bone Growth and Remodeling
Adequate dietary intake of minerals
Calcium and phosphorus
Adequate intake of vitamins
Vitamin C – synthesizes collagen
Vitamin D – increases absorption of calcium
Vitamin A – stimulates osteoblasts

23. Factors Affecting Bone Growth and Remodeling
Sufficient levels of hormones:
Growth hormone (hGH)
Pituitary gland  dwarfism / giantism
Insulinlike growth factors (IGFs)
Stimulate osteoblasts, cell division at plate, synthesize proteins to build new bone
Thyroid hormone
Stimulate osteoblasts
Insulin
Promotes bone growth – synthesis of proteins
Sex hormones – testosterone and estrogen
Increased osteoblast activity, synthesis of ECM and teenage “growth spurt”
Adults – slows resorption, increases deposition
Robert Wadlow 8ft 11in

24. Control of Bone Remodeling
Needs to be carefully regulated:
To resist forces acting on the skeleton.
Athlete’s more robust than couch potato’s
Regulatory mechanisms preserving skeletal strength are not well understood
Possibly electrical signals detect weak areas and “shore them up”
Sex hormones – stimulate deposition, slow resorption
Maintain Ca++ homeostasis in the blood.
Ionic calcium is essential for nerve impulse transmission, muscle contraction, blood coagulation, gland activity, and even cell division.
Maintenance of Ca++ homeostasis is better understood - primarily involves parathyroid hormone.

25. Bone’s Role in Ca2+ Homeostasis
Describe the importance of calcium in the body.
Explain how blood calcium level is regulated.

26. Figure 6.10 Negative feedback regulation of blood calcium.
Release of calcium from bone matrix and retention of calcium by the kidneys are the two main ways that blood calcium level can be increased.

27. Fracture Repair
Assigned Reading
Section 6.6
Table 6.1