File 1

Question 1

1. What is hydroxypatite and where is it found in the body?

Answer 1

Hydroxypatite is a crystalline salt composed primarily of calcium and phosphate that is deposited in the organic matrix of bones and teeth.

Question 2

2. How does the calcium to phosphorus ratio vary in hydroxypatite under different nutritional conditions?

Answer 2

The calcium to phosphorus ratio in hydroxypatite can vary from 1.3 to 2.0 on a weight basis depending on nutritional conditions.

Question 3

3. What are the primary components of hydroxypatite crystals?

Answer 3

Hydroxypatite crystals are composed mainly of calcium and phosphate ions with the formula {Ca10(PO4)6(OH)2}.

Question 4

4. Describe the physical structure of hydroxypatite crystals.

Answer 4

Hydroxypatite crystals are shaped like platelets or rods with dimensions of 8-15Å in thickness 20-40Å in width and 200-400Å in length.

Question 5

5. Which ions other than calcium and phosphate are found in bone salts?

Answer 5

Magnesium sodium potassium and carbonate ions are also present in bone salts.

Question 6

6. Why do x-ray diffraction studies not show crystals formed by magnesium and other ions in bone?

Answer 6

These ions are believed to conjugate to the hydroxypatite crystals rather than form distinct crystals of their own.

Question 7

7. What is the significance of ions such as strontium and uranium conjugating with bone crystals?

Answer 7

Foreign ions like strontium and uranium can conjugate with bone crystals leading to prolonged irradiation of bone tissue potentially causing conditions like osteogenic sarcoma.

Question 8

8. What percentage of the bone matrix is made up of organic components?

Answer 8

The organic matrix of bone makes up 30% of the bone structure.

Question 9

9. What are the two major substances found in the extracellular matrix of bone?

Answer 9

The extracellular matrix of bone consists of ground substances (proteoglycans) and fibrous proteins (mainly collagen).

Question 10

10. What is the function of Type I collagen in bone?

Answer 10

Type I collagen provides tensile strength to bone helping it resist pulling forces.

Question 11

11. How does the structure of Type I collagen contribute to its strength?

Answer 11

Type I collagen is composed of a triple helix of three polypeptides bound tightly together giving it tensile strength comparable to steel.

Question 12

12. What role does the interaction between collagen fibers and calcium salts play in bone strength?

Answer 12

The interaction between collagen fibers and calcium salts gives bone both tensile strength and compressional strength making it a durable structure.

Question 13

13. What are glycosaminoglycans (GAGs) and what is their function in bone?

Answer 13

Glycosaminoglycans are components of proteoglycans that bind large amounts of water forming the gel-like matrix of the body’s ground substance.

Question 14

14. Why are bones more brittle than cartilage?

Answer 14

Bones contain less proteoglycan than cartilage leading to a reduced capacity to retain water and resulting in a more brittle structure.

Question 15

15. How do glycosaminoglycans protect hydroxyapatite molecules after death?

Answer 15

Glycosaminoglycans bind tightly to hydroxyapatite protecting the crystals from destructive effects of temperature and chemical agents.

Question 16

16. What is the role of proteoglycans in inhibiting bone calcification?

Answer 16

Proteoglycans inhibit calcification by masking collagen fibrils and occupying critical spaces reducing diffusion and sequestration of calcium ions.

Question 17

17. What are small leucine-rich proteoglycans (SLRPs) and where are they found in bone?

Answer 17

SLRPs are a family of proteins in bone that consist of core proteins with leucine-rich repeats and glycosaminoglycan side chains playing a role in bone structure.

Question 18

18. What is osteocalcin and where is it produced?

Answer 18

Osteocalcin is the most abundant non-collagenous protein in bone produced by osteoblasts.

Question 19

19. What is the primary function of osteocalcin?

Answer 19

Osteocalcin binds calcium and is involved in bone remodeling acting as a marker for osteoblast activity and bone turnover.

Question 20

20. How does vitamin K influence osteocalcin?

Answer 20

Osteocalcin is a vitamin K-dependent protein requiring it for proper function in calcium binding and bone regulation.

Question 21

21. What is matrix Gla protein (MGP) and what is its role in bone?

Answer 21

MGP is a γ-carboxylglutamic acid-containing protein that regulates extracellular matrix calcification in bone.

Question 22

22. How do osteopontin and osteonectin contribute to bone function?

Answer 22

Osteopontin aids in calcium binding and bone resorption while osteonectin supports bone remodeling and mass maintenance.

Question 23

23. What are the functions of fibronectin in bone tissue?

Answer 23

Fibronectin coordinates migration interaction and differentiation of osteoblast precursors contributing to bone formation.

Question 24

24. What is the significance of bone sialoprotein (BSP) in bone development?

Answer 24

BSP acts as a nucleus for hydroxyapatite crystal formation and provides cell attachment within the bone matrix.

Question 25

**25. What growth factors influence bone formation and remodeling?**

Answer 25

Transforming growth factor β (TGF-β) bone morphogenetic proteins (BMPs) and insulin-like growth factors (IGFs) are critical in bone formation and remodeling.

Question 26

**26. What role does IGF-I play in bone metabolism?**

Answer 26

IGF-I stimulates mitogenesis collagen synthesis and bone remodeling contributing to bone growth.

Question 27

**27. How do osteoblasts contribute to bone growth?**

Answer 27

Osteoblasts secrete collagen and other matrix proteins forming new bone matrix (osteoid) and regulating mineralization.

Question 28

**28. What is the origin of osteoclasts and what is their primary function?**

Answer 28

Osteoclasts are derived from monocytes and are responsible for bone resorption breaking down bone tissue to regulate calcium levels.

Question 29

**29. How does the balance of bone resorption and deposition maintain bone health?**

Answer 29

Bone health is maintained by a balance between osteoclast-mediated resorption and osteoblast-mediated deposition known as bone remodeling.

Question 30

**30. What is Paget’s disease and how does it affect bone remodeling?**

Answer 30

In Paget’s disease osteoclasts are overactive leading to excessive bone resorption followed by disorganized and excessive bone formation by osteoblasts.

Question 31

**31. What are the components of the receptor activator of nuclear factor kappa B ligand (RANKL) pathway?**

Answer 31

The RANKL pathway involves osteoblasts producing RANKL which binds to RANK receptors on osteoclast precursors stimulating osteoclast differentiation.

Question 32

**32. How is osteoclast activity inhibited?**

Answer 32

Osteoclast activity is inhibited by osteoprotegerin (OPG) which binds to RANKL blocking its interaction with RANK on osteoclast precursors.

Question 33

**33. What is the role of OPG in bone resorption therapy?**

Answer 33

OPG mimics the action of blocking RANKL helping to treat bone loss in conditions like osteoporosis by inhibiting osteoclast formation.

Question 34

**34. How do osteoclasts degrade bone?**

Answer 34

Osteoclasts degrade bone by secreting acids and enzymes such as cathepsin K and matrix metalloproteinases which dissolve bone minerals and organic matrix.

Question 35

**35. What is a resorption pit and how is it formed?**

Answer 35

A resorption pit is formed by osteoclasts during bone degradation where the ruffled border increases surface contact and dissolves bone matrix.

Question 36

**36. How does bone remodeling occur throughout life?**

Answer 36

Bone remodeling involves continuous cycles of resorption by osteoclasts and deposition by osteoblasts maintaining bone strength and mineral balance

Question 37

**37. What is the significance of haversian canals in bone structure?**

Answer 37

Haversian canals are channels that contain blood vessels and nerves allowing for nutrient delivery and waste removal within bone tissue.

Question 38

**38. How does osteoclast activity contribute to osteoporosis?**

Answer 38

Increased osteoclast activity leads to excessive bone resorption weakening bones and causing osteoporosis.

Question 39

**39. What role do proteoglycans play in bone tissue?**

Answer 39

Proteoglycans bind water help form the bone's gel-like matrix and inhibit excessive calcification maintaining bone flexibility and structure.

Question 40

**40. How do osteoblasts regulate mineralization in bone?**

Answer 40

Osteoblasts control mineral deposition by secreting matrix proteins and regulating calcium and phosphate levels to promote bone formation.

Question 41

**41. How does osteocalcin act as a chemoattractant for osteoclasts?**

Answer 41

Osteocalcin attracts osteoclasts to sites of bone resorption aiding in the regulation of bone remodeling and turnover.

Question 42

**42. Why is collagen so critical to bone strength?**

Answer 42

Collagen provides tensile strength to bones allowing them to resist stretching and bending forces essential for overall bone integrity.

Question 43

**43. How does the triple-helix structure of collagen affect its function?**

Answer 43

The triple-helix structure of collagen makes it extremely strong and resistant to stretching vital for ensuring that bones can withstand mechanical stress and maintain structural integrity.

Question 44

*44. How do phosphate and calcium combine to form hydroxyapatite crystals?**

Answer 44

Calcium and phosphate ions combine within the organic matrix of bones to form hydroxyapatite crystals. These crystals accumulate between collagen fibers contributing to the rigidity and hardness of bones.

Question 45

45. What is the relationship between osteoblasts and bone formation?**

Answer 45

Osteoblasts are responsible for the synthesis and deposition of new bone matrix. They produce collagen and facilitate

Question 46

1. **What is the role of osteoclasts in bone remodeling**

Answer 46

Osteoclasts are responsible for bone resorption by breaking down bone tissue which allows for the removal of old or damaged bone and is crucial for maintaining bone health.

Question 47

2. **How does an imbalance in bone remodeling lead to osteoporosis**

Answer 47

An imbalance occurs when there is excessive osteoclast activity leading to increased bone resorption which weakens bones and results in osteoporosis.

Question 48

3. **What happens in Paget’s disease of bone**

Answer 48

In Paget’s disease osteoclasts are more active than osteoblasts causing excessive bone resorption followed by disorganized bone formation leading to abnormally large and deformed bones.

Question 49

4. **Where are osteoblasts located in the bone**

Answer 49

Osteoblasts are found on the outer surfaces of bones and within bone cavities where they contribute to bone deposition.

Question 50

5. **What is the function of RANKL in osteoclast differentiation**

Answer 50

RANKL is a cytokine produced by osteoblasts that binds to receptors on osteoclast precursors stimulating their differentiation into mature osteoclasts necessary for bone resorption.

Question 51

6. **How is osteoclast activity inhibited**

Answer 51

Osteoclast activity is inhibited by osteoprotegerin (OPG) which binds to RANKL on osteoblasts preventing the interaction with osteoclast precursors and thus blocking their differentiation.

Question 52

7. **What is the significance of the OPG-RANKL pathway in treating bone diseases**

Answer 52

The OPG-RANKL pathway is important because drugs that mimic OPG’s action can block RANKL interactions and are used to treat bone loss conditions like osteoporosis and bone cancer.

Question 53

8. **How do osteoclasts degrade bone matrix**

Answer 53

Osteoclasts secrete hydrogen ions and enzymes such as cathepsin K and MMP-9 into the resorption pit which dissolve the bone salts and degrade the organic matrix.

Question 54

9. **What is an osteon and how does it form**

Answer 54

An osteon is a structural unit of bone that forms when new bone is deposited in concentric layers after osteoclasts have created a tunnel during bone resorption.

Question 55

10. **What are the two steps in bone deposition**

Answer 55

Bone deposition involves first the formation of osteoid which is the unmineralized bone matrix and second the mineralization of this osteoid where calcium hydroxyapatite crystals are deposited to harden the bone.

Question 56

11. **What factors promote bone mineralization**

Answer 56

Factors that promote bone mineralization include alkaline phosphatase and nucleating substances which initiate the crystallization of calcium salts into the bone matrix.

Question 57

12. **What factors inhibit bone mineralization**

Answer 57

Bone mineralization is inhibited by substances such as magnesium ions pyrophosphates nucleotides and citrates which prevent spontaneous precipitation of minerals in tissue fluids.

Question 58

13. **What is the role of cathepsin K in bone resorption**

Answer 58

Cathepsin K is an acid protease secreted by osteoclasts that helps to degrade the organic components of bone matrix such as type 1 collagen during bone resorption.

Question 59

14. **How does carbonic anhydrase II contribute to bone resorption**

Answer 59

Carbonic anhydrase II generates hydrogen ions which are pumped into the resorption pit by osteoclasts to acidify the area and dissolve bone salts facilitating bone resorption.

Question 60

15. **What is the function of chloride channels (ClC-7) in osteoclasts**

Answer 60

Chloride channels (ClC-7) transport chloride ions into the resorption pit to maintain electrical neutrality during the process of hydrogen ion secretion in bone resorption.

Question 61

16. **What is the significance of the ruffled border in osteoclasts**

Answer 61

The ruffled border increases the surface area of the osteoclast in contact with the bone matrix creating a highly localized environment where bone resorption occurs more efficiently.

Question 62

17. **What happens in Howship’s lacunae during bone resorption**

Answer 62

Howship’s lacunae are depressions formed by osteoclasts on the bone surface where bone resorption takes place through the action of enzymes and acids.

Question 63

18. **How do osteoclasts form**

Answer 63

Osteoclasts form by the fusion of multiple mononuclear precursor cells derived from the bone marrow creating a large multinucleated cell specialized in bone resorption.

Question 64

19. **How do osteoblasts respond after osteoclasts complete bone resorption**

Answer 64

After osteoclasts finish resorbing bone osteoblasts invade the area and begin depositing new bone in successive layers eventually filling the resorption cavity.

Question 65

20. **What is the process of osteoclastogenesis**

Answer 65

Osteoclastogenesis refers to the differentiation and activation of osteoclasts from precursor cells driven by the interaction of RANKL with its receptor RANK on the surface of osteoclast precursors.

Question 66

21. **What are the initial calcium salts deposited during bone mineralization**

Answer 66

The initial calcium salts deposited during bone mineralization are amorphous compounds like CaHPO4 and Ca3(PO4)2 which later transform into hydroxyapatite crystals.

Question 67

22. **What is the role of alkaline phosphatase in bone mineralization**

Answer 67

Alkaline phosphatase promotes bone mineralization by breaking down inhibitors of mineralization and creating an environment favorable for the deposition of calcium salts.

Question 68

23. **What is heterogenous nucleation in bone mineralization**

Answer 68

Heterogenous nucleation occurs when the presence of a nucleating substance allows for the formation of calcium crystals in the bone matrix even in the absence of a locally increased concentration of minerals.

Question 69

24. **What is the function of the H+ATPase proton pump in osteoclasts**

Answer 69

The H+ATPase proton pump transports hydrogen ions into the resorption pit to acidify the environment enabling the dissolution of bone salts during bone resorption.

Question 70

25. **How does bone turnover differ between infants and adults**

Answer 70

Bone turnover is much higher in infants where calcium in bone is completely renewed at a rate of 100% per year while in adults the turnover rate is about 18% per year.

Question 71

1. **What is Robinson’s alkaline phosphatase theory of mineralization?**

Answer 71

It suggests that alkaline phosphatase hydrolyzes organic phosphates like pyrophosphates increasing local phosphate ion concentration which leads to spontaneous precipitation of calcium phosphate and the formation of hydroxyapatite crystals.

Question 72

2. **Why is the alkaline phosphatase theory considered the least acceptable?**

Answer 72

Because alkaline phosphatase is present in non-calcifying tissues and studies show that inorganic phosphate and calcium alone are insufficient for mineralization; other enzymes and energy barriers are involved.

Question 73

3. **How does collagen act in the nucleation theory of mineralization?**

Answer 73

Collagen serves as a template where apatite crystals can be laid down reducing the energy required for mineralization allowing crystal formation even without increased local ion concentration.

Question 74

4. **What are the main objections to the collagen seeding theory?**

Answer 74

It fails to explain mineralization in tissues like enamel and cartilage which don’t contain collagen and in soft tissues that contain collagen but do not mineralize.

Question 75

5. **What is the matrix vesicle theory of mineralization?**

Answer 75

It proposes that mineralization begins in small vesicles (matrix vesicles) that bud off from osteoblasts chondrocytes and odontoblasts. These vesicles accumulate calcium and phosphate leading to hydroxyapatite formation.

Question 76

6. **How is phosphate (Pi) derived in matrix vesicle mineralization?**

Answer 76

Phosphate is derived from membrane phospholipids which are hydrolyzed by phospholipase enzymes and through Na/Pi cotransporters that bring phosphate into matrix vesicles.

Question 77

7. **What role does calcium play in matrix vesicle mineralization?**

Answer 77

Calcium enters matrix vesicles through annexin channels and combines with phosphate to form hydroxyapatite crystals which later deposit in the extracellular matrix.

Question 78

8. **How do TNAP

Answer 78

NPP1

Question 79

9. **What happens if there is a deficiency in NPP1 or ANKH proteins?**

Answer 79

Deficiencies lead to reduced levels of pyrophosphate causing excessive calcification in bones and tissues such as in bone spurs or conditions like ankylosing spondylitis.

Question 80

10. **Why do hydroxyapatite crystals not form in normal tissues despite ion supersaturation?**

Answer 80

Inhibitors like pyrophosphate matrix Gla protein osteopontin and fetuin are present in tissues to prevent unwanted precipitation of calcium salts.

Question 81

11. **How do calcium salts precipitate in arterial walls during arteriosclerosis?**

Answer 81

Calcium salts precipitate in arterial walls causing them to become rigid and bone-like which is a characteristic of arteriosclerosis.

Question 82

12. **Why do calcium salts deposit in degenerating tissues?**

Answer 82

Degenerating tissues such as old fibrous tissue or blood clots can provide a site for calcium salt deposition as seen in conditions like tuberculosis.

Question 83

13. **What are the main functions of continual bone remodeling?**

Answer 83

Bone remodeling helps adjust bone strength in response to stress reshape bones for better support and replace old brittle bone with new tough organic matrix.

Question 84

14. **How does bone stress affect osteoblast activity?**

Answer 84

Bone subjected to stress or heavy loads triggers osteoblasts to deposit more bone increasing its thickness and strength to match the mechanical demands.

Question 85

15. **What happens to bone shape after a fracture heals at an angle?**

Answer 85

Increased deposition occurs on the compressed inner side of the bone while resorption occurs on the non-compressed outer side gradually reshaping the bone.

Question 86

16. **How does continual physical stress influence bone thickness in athletes?**

Answer 86

Athletes experience greater bone stress which stimulates more osteoblastic activity resulting in thicker and stronger bones compared to non-athletes.

Question 87

17. **Why is it important to replace old bone with new organic matrix?**

Answer 87

Old bone becomes brittle over time and replacing it with new organic matrix helps maintain bone strength and flexibility preventing fractures.

Question 88

18. **How does bone brittleness differ between children and the elderly?**

Answer 88

Children have higher rates of bone deposition and resorption making their bones less brittle while elderly individuals have slower rates leading to more brittle bones.

Question 89

19. **How does physical stress lead to bone shape changes over time?**

Answer 89

Bone deposition and resorption occur in response to stress patterns allowing the bone to adapt and reshape itself to better support mechanical forces.