1. BONE PHYSIOLOGY Chris van ZylKHC

2. Physical Structure: Composed of cells and predominantly collagenous extracellular matrix (type I collagen) called osteoid which become mineralized giving bone rigidity and strength  Compact (cortical) bone  Dense rigid outer shell  Minimal gaps and spaces  Accounts for 80% of the total bone mass of an adult skeleton

3. Physical Structure:  Trabecular (cancellous) bone  Central zone of interconnecting trabeculae  Network of rod- and plate-like elements  Make the overall organ lighter  Allow room for blood vessels and marrow

4. Microscopic Structure:  Haphazard organization of collagen fibers  Mechanically weak  Produced when osteoblasts produce osteoid rapidly  E.g. Fetal bones, fractures, Paget’s Woven:

5. Microscopic Structure:  Regular parallel alignment of collagen into sheets  Mechanically strong  Fibers run in opposite directions in alternating layers  Replaces woven bone after fracture Lamellar:

6. Cellular Structure:  Derived from osteoprogenitor cells  The bone-forming cells  Synthesize osteoid, mediates its mineralization  Found lined up along bone surfaces Osteoblasts

7. Osteoblast Stimulation  Stimulated to increase bone mass through increased secretion of osteoid  Stimulated by the secretion of:  Growth Hormone  Thyroid Hormone  Sex Hormones (oestrogens + androgens)  These hormones also promote increased secretion of osteoprotegerin  Inhibits osteoclast stimulation

8. Osteoblast Stimulation  Vit D + PTH + Osteocytes stimulates osteoblasts to secrete cytokines:  Stimulate bone resorption via osteoclasts  Differentiation of progenitor cells to osteoclasts  Decrease Osteoprotegerin

9. Cellular Structure:  Derived from macrophage monocyte cell-line  Phagocytic cells  Responsible for bone resorption  Important along with osteoblasts in the constant turnover and refashioning of bone Osteoclasts

10. Osteoclast Inhibition  Rate of bone resorption inhibited by:  Calcitionin (C cells of thyroid)  Osteoprotegerin (osteoblasts)

11. Cellular Structure:  Mature bone cells  Inactive osteoblasts, trapped and surrounded by bone matrix  Function:  Formation of bone  Matrix maintenance  Calcium homeostasis Osteocytes

12. Bone matrix  Type I Collagen  Ground substance proteoglycans  Non-collagen molecules involved in mineralization regulation 70% inorganic salts, 30% organic matrix Organic matrix:

13. Bone matrix  Polymer of numerous elongated overlapping tropocollagen subunits  Hole zones initial site of mineral deposition  Controls water content in bone  Regulating formation of collagen fibers in a form appropriate for mineralization Type I collagen:Ground substance proteoglycans:

14.  Calcium and phosphate in form of hydroxyapatite Bone matrix Non-collagen molecules:Inorganic component:  Osteocalcin:  Binds calcium  Osteonectin:  bridging function between collagen and mineral component

15. How is bone formed?  Collagen synthesized by osteoblasts  Secreted as osteoid  After maturation phase  Amorphous calcium phosphate precipitates in hole zones  Mineralization foci expand + coalesce into hydroxyapatite crystals  20% remains amorphous for readily available calcium buffer

16. How is bone formed?  Concentration of calcium + phosphate in extracellular fluid greater than required for spontaneous calcium deposition Inhibited by pyrophosphate  Deposition of calcium controlled by osteoblasts which secretes alkaline phosphatase vesicles Neutralizes pyrophosphate

17. Bone development and growth  Develops in 2 ways (2 types of ossification)  Both involve replacement of primitive collagenous supporting tissue by bone  Resultant woven bone is then extensively remodelled by resorption and appositional growth to form mature adult lamellar bone  Thereafter the process occurs at much reduced rate to accommodate functional stresses and to effect calcium homeostatis

18.  Two types of occification:  Endochondral ossification  Intramembranous ossification Bone development and growth

19. Endochondral ossification  E.g. long bones, vertebra, pelvis, base of skull  Hyaline cartilage is first formed in a shape corresponding closely to future bone  Cartilage model is covered - perichondrium  Bone matrix deposition - replacing the existing cartilage

20. Intramembranous ossification  E.g. vault of skull, maxilla, mandible  Deposition of bone in primitive mesenchymal tissue  Direct replacement of mesenchyme by bone  Cell differentiation into osteogenic tissue  These become impregnated with calcium salts

21. Remodeling/Bone turnover  Process of resorption followed by replacement of bone, with little change in shape  Occurs throughout a person's life  Purpose:  To regulate calcium homeostasis  Repair micro-damaged bones  To shape and sculpture the skeleton during growth

22. The role of bone in calcium homeostasis  Bone contains 99% of total body calcium  Bone resorption releases calcium into systemic circulation  Bone formation actively binds calcium, removing it from blood stream  Ca 2+ homeostasis controlled by:  Parathyroid hormone (parathyroid glands)  Calcitonin (Thyroid)  Calcitriol (Vit D 3 )

23.  Increases serum Ca 2+  Increases bone resorption by osteoclasts indirectly  Mediated by paracrines e.g. osteoprotegerin  Enhances renal reabsorption of calcium  Increases intestinal absorption of calciam  Via effects on Vit D The role of bone in calcium homeostasis Parathyroid hormone:

24.  Released when plasma Ca 2+ increases  Decreases bone resorption  Increases renal calcium excretion  Enhances intestinal absorption of calcium  Facilitates renal reabsorption  Helps mobilize Ca 2+ out of bone The role of bone in calcium homeostasis Calcitonin Calcitriol

25. References:  Human Physiology an Integrated Approach  Dee Unglaub Silverthorn  Wheater’s Functional Histology  B. Young, J.W. Heath  en.wikipedia.org/wiki/Bone  July 2012