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.

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

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

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

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

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

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

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)

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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

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.

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

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.

Fracture Repair Assigned Reading Section 6.6 Table 6.1