Bone formation, resorption and factors affecting it.pptx

The balance between bone formation and resorption is essential for maintaining bone density and strength. Disruptions in this balance can lead to conditions such as osteoporosis. Understanding the factors that influence these processes can help in developing strategies to promote bone health and prevent bone-related diseases

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2. Bone Formation, Resorption, and factors affecting it GUIDED BY: Prof. Dr. Rabindra Man Shrestha Asssoc . Prof. Dr. Jyoti Dhakal PRESENTED BY : Dr. Kajal Mehta PG Resident D epartment of orthodontics 2

3. CONTENTS Introduction Classification of bone Composition of bone Bone cells Bone formation Bone Resorption Bone remodeling Factors affecting bone formation and resorption Clinical importance Reference Conclusion 3

4. INTRODUCTION Is a mineralized living tissue. provides site of attachment for tendons and muscles serves as a storage site for minerals 4

5. Classification of bone Based on morphologic shape Based on mode of development Based on histologic appearance 5

6. Based on morphologic shape 6

7. Based ON mode of development A) Endochondral bones formed by replacement of hyaline cartilage with bony tissue occurs in bones of trunk and extremities, Long bones, vertebrae, ribs, articular extremity of the mandible, base of the skull B) Intramembranous bones formed by replacement of sheet-like connective tissue membranes with bony tissues occurs in the cranial and facial flat bones of the skull, mandible, and clavicles 7

8. Based on histologic appearance A) Mature bone Compact bone(cortical bone) (Lamellar bone) Cancellous bone(spongy bone) B) Immature bone (Woven bone) 8

9. Compact bone Tightly packed osteons or Haversian systems, forming a solid mass. Cells are organized in circular fashion that reflects the lamellar structure of the Haversian system 1) Osteons - outer border 2) Vascular canals - if oriented along long axis of bone: Haversian canals - if oriented transversely to long axis of bone: Volkmann canals 3) Interstitial lamellae 9

10. Cancellous Bone Honeycomb appearance, with large marrow cavities and sheets of trabeculae of bone in the form of bars and plates 30-90% of bone is porous and contains red bone marrow 10

11. Woven bone First formed bone Irregularly oriented collagen fibers of varying diameters 11

12. Woven bone (Cont..) Role in wound healing by : 1) Rapidly filling osseous defects 2) Providing initial continuity for fractures and osteotomy segments 3) Strengthening a bone weakened by surgery or trauma. 12

13. 13 Nanci A. Ten Cate’s oral histology: development, structure, and function. 8th ed. St. Louis: Mosby; 2012

14. COMPOSITION OF BONE 14

15. Glycosaminoglycan-Containing Molecules Glycoproteins Small Integrin-Binding Ligand, N-Glycosylated Protein RGD-Containing Glycoproteins Gamma-Carboxy Glutamic Acid- Containing Proteins Serum Proteins COMPOSITION OF BONE(Contd..) 15

16. Bone cells Osteoprogenitor cells Lining cells Osteocytes cells Osteoblasts cells Osteoclasts cells 16

17. Osteoprogenitor cells Undifferentiated pluripotent mesenchymal stem cells Osteoprogenitor cells Determined (DOPCs) Inducible(IOPCs) Osteoblast Bone forming cells Growth factors Stimulated Express transcription factors- Cbfa1/Runx-2 Osterix 17

18. Osteoblast Mononucleated cells responsible for synthesis and secretion of macromolecules organic constituents of bone matrix Derived from Osteoprogenitor cells ( undifferentiated pluripotent mesenchymal stem cells) Basophilic, plump cuboidal elongated cells Found on the forming surface of growing or remodeling bone 18

19. Function of osteoblast Formation of new bone via synthesis of various proteins and polysaccharides Regulation of bone remodeling and mineral metabolism Mineralization of osteoid Secrete: Type I collagen Also: Small amount of Type V collagen, osteonectin, osteopontin , RANKL, osteoprotegerin, proteoglycans, 19

20. High level of alkaline phosphatase on outer surface of plasma membrane, which is used as a cytochemical marker to distinguish preosteoblasts from fibroblasts. Express receptors for various hormones: PTH, vit D3, estrogen and glucocorticoids Recognize resorptive signal and transmit to osteoclast via RANKL. 20

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22. Bone lining cells Flat in shape Few synthetic organelles, suggesting that they are less implicated in the production of matrix proteins 22

23. Osteocytes Compromise 90-95% of total bone cells Entrapped Osteoblasts within bone Number of osteoblast that become osteocytes depends on rapidity of bone formation 23

24. Within the bone matrix osteocytes reduces in size OSTEOCYTIC LACUNAE Canaliculi Penetrate bone matrix and permit diffusion of nutrients, gases and waste products between osteocytes and blood vessels Osteocytic processes are present within these canaliculi These processes of osteocytes contain bundles of microfilaments and some smooth endoplasmic reticulum. 24

25. Transformation of osteoblast into osteocytes Become embedded in bone as osteocytes Transform into inactive osteoblasts and become bone lining cells Undergo apoptosis Transdifferentiate into cells that deposit chondroid bone. 25

26. This transformation involves 3 cells: Preosteoblast Osteoblast Osteocyte Less cuboidal in shape Located distance from bone surface Do not deposit bone matrix but can still divide Cuboidal in shape Secretes bone matrix Embedded in secretory product (osteoid) 26

27. Osteoclast Bone cell that removes bone tissue by removing the mineralized matrix of bone Lie in resorption bays called Howship’s lacunae. 40–100 µm in diameter with 15 to 20 closely packed nuclei 27

28. Osteoclast(contd..) The presence of acid phosphatase distinguishes the osteoclast from other multinucleated giant cells. Cathepsin containing vesicles and vacuoles are present close to the ruffled border indicating resorptive activity of these cells. Responsible for bone resorption during bone remodeling. Synthesize and release the lysosomal enzymes necessary for bone resorption. Functions 28

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30. Removal of mineral and organic components of extracellular matrix of bone under the action of osteolytic cells, of which the most important is the osteoclast. Demineralization Phase Matrix Degradation Apoptosis of Osteoclasts Phases of bone resorption 30 Bone resorption

31. Demineralization Phase On the bone surface, osteoclasts attach and become polarized, form a ruffled border beneath which bone resorption takes place Acidic environment- Adenosine triphosphate, proton pumps generated by carbonic anhydrase Demineralization exposes the organic matrix 31

32. Matrix degradation Exposed collagen is degraded by lysosomal enzymes into its constituent amino acids by –phagocytic degradation and release of enzymes – acid phosphatase and cathepsin Matrix metalloproteinases gets activated under the acidic conditions –resorption lacunae- matrix degradation 32

33. Apoptosis of osteoclasts Sequestration of mineral ions and amino acids takes place inside osteoclasts. Osteoclasts undergo apoptosis- mechanism for limiting resorption activity 33

34. BONE REMODELING Continuous physiological process by which overall shape and size of bone is established. Performed by clusters of osteoclast and osteoblast arranged within temporary anatomical structures known as basic multicellular units (BMUs). 34

35. Active BMU consists of a leading front of osteoclasts Cutting cone Osteoblasts occupy the tail portion of the BMU Closing cone The process of bone synthesis and bone breakdown go on simultaneously and status of bone represents the net balance between two process “Coupling” of bone resorption and formation 35

36. Sequence of events Activation stage Resorption stage Reversal stage Formation stage Resting stage 36

37. 1.Activation Stage Detection of signal in form of mechanical strain/hormonal action by osteocytes Translation of these signals into biological signals Recruitment of monocyte-macrophage osteoclast precursors Interaction of osteoclast and osteoblast precursor cells(RANKL on osteoblasts and RANK on osteoclasts) Differentiation, migration and fusion of large multinucleated osteoclast 37

38. 2.Resorption stage Recruitment of osteoclast precursors Osteoclasts dissolve minerals followed by release of TGF, PDGF, IGF-1& 2 Scalloped Howship’s lacunae formed(resorption tunnel or cutting cone) Mononuclear cells (macrophages remove collagen remnants) 38

39. 3.Reversal stage Differentiation of osteoblast precursors and discontinuation of bone resorption occurs with osteoclast apoptosis A mononuclear cell of osteoblastic lineage prepares the bone surface for subsequent osteoblast-mediated bone formation called Reversal Cell Non collagenous protein matrix gets deposited on resorbed surface is called Reversal Line 39

40. 4.Formation stage Approximately for 4 months duration Mesenchymal stem cells or early osteoblasts progenitors return to the resorption lacunae They differentiate and ultimately lead to the formation of replacement bone New bone replaces the resorbed bone 40

41. 5.Resting stage Osteoblasts undergo apoptosis Change into bone-lining cells or become entombed within the bone matrix and terminally differentiate into osteocytes. Osteocytes play a key role in signaling the end of remodeling via secretion of antagonists to osteogenesis. 41

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43. Regulatory Factors in bone remodelling Systemic Factors Local Factors HORMONES Decrease bone resorption Calcitonin Oestrogen b) Increase bone resorption PTH(Continuous dose) Vitamin D- High Doses c) Increase bone formation Growth hormone Vitamin D- physiological doses Insulin PTH(intermittent) Glucocorticoids (Physiological Doses) d) Decrease bone formation Glucocorticoids (High Doses) Growth factors IGF-1 & 2 BMPs FGF PDGF EGF b) Cytokines IL-1, IL-6, IL-11 PGE2 TNF- & 43

44. Granulocyte macrophage colony forming unit (CFU-GM) Committed precursor cells Pre- osteoclast (immature multinucleated giant cell) RANK Osteoblast secrete: RANKL Interaction of RANK and RANKL Osteoclast OPG RANK-RANKL OPG PATHWAY 44

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46. Factors affecting bone formation Receptors for parathyroid hormones are found in osteoblasts, lining cells and osteocytes. Directly act on osteoblasts to promote osteoblastogenesis , reduce osteoblast apoptosis, reactivates quiescent lining cells. Increases osteoblasts differentiation. Parathyroid hormones : 46

47. 47 A continue hypersecretion of PTH, as occurs in primary hyperparathyroidism, leads to bone resorption. When administered at a low dose and intermittently, this hormone seems to be able to exert positive effects on bone volume and microarchitecture.   PTH induces the synthesis of IGF-I and, due to its effects on osteoblasts, this could be a key mediator of PTH effect on osteoblasts.

48. 2.Vitamin C Stimulates the synthesis of osteocalcin and osteopontin. Promote expression of genes involved in differentiation of chondrocytes. Ascorbic acid is an important regulator for osteoblast fate determination as well as proliferation. 48

49. 49 Chin, Kok-Yong ;  Ima- Nirwana , Soelaiman  Cell studies showed that vitamin C was able to induce osteoblast and osteoclast formation. However, high-dose vitamin C might increase oxidative stress and subsequently lead to cell death.  Vitamin C-deficient animals showed impaired bone health due to increased osteoclast formation and decreased bone formation . Human studies generally showed a positive relationship between vitamin C and bone health, indicated by bone mineral density, fracture probability and bone turnover markers.

50. 3. Glucocorticoids Profound effects on bone cell replication, differentiation, and function. Increase bone resorption by stimulating osteoclastogenesis by increasing the expression of RANK ligand and decreasing the expression of its decoy receptor, osteoprotegerin. Effects on osteoblast gene expression, including down-regulation of type 1 collagen and osteocalcin, and up-regulation of interstitial collagenase. 50

51. 4. Transforming growth factor β (TGF-β) Induces osteogenic differentiation of mesenchymal cells. Decrease in matrix degradation activity through inhibition of Matrix metalloproteinases. Inhibits the formation of osteoclast precursors and bone resorption 51

52. 5. Insulin Stimulate osteoblast differentiation in order to produce more osteocalcin, which would then stimulate more insulin production by the pancreas and greater insulin sensitivity of skeletal muscle. Stimulates bone matrix formation and mineralization. 52

53. 6. Insulin like growth factors : Stimulates proliferation of osteoblast precursors. Inhibits matrix metalloproteinases. 7. Platelet derived growth factor (PDGF) AND Fibroblast Growth factor (FGF): Regulate the recruitment of osteoprogenitor cells and their proliferation and differentiation into mature osteoblasts 53

54. Role of Vitamins Vitamin A- Controls activity, distribution and co-ordination of osteoblast/osteoclast. Vitamin B12- May inhibit osteoblast activity. Vitamin C- Helps maintain bone matrix, deficiency leads to decreased collagen production which inhibits bone growth and repair Vitamin D- Helps build bone by increasing calcium absorption 54

55. The markers of bone formation are (Serum markers): Alkaline phosphatase Osteocalcin Procollagen I extension peptide β2 microglobulin Markers of bone turnover 55

56. The markers of bone resorption are (Urinary markers) Urine calcium Urinary hydroxy proline Urine N-telopeptide (N terminus of collagen fibrils) Urine C-telopeptide (C terminus of collagen fibrils) Urine total pyridinoline Markers of bone turnover 56

57. Osteoporosis A systemic skeletal disease characterized by low bone density and microarchitectural deterioration of bone tissue with a consequent increase in bone fragility. INCIDENCE: 1 in 3 women/ 1 in 8 men Three times more common in women than men CLINICAL SIGNIFICANCE 57

58. CLINICAL FEATURE: Persistent back pain Loss of height Kyphosis TREATMENT: Lifestyle modification Calcium, Vitamin D Drugs- Bisphosphonates, Alendronate, Ibandronate 58

59. A correlation between increased tooth movement and an increased number of osteoclasts. Orthodontic tooth movement may have a high tendency to relapse in patients with osteoporosis. Found more root resorption in an acute corticosteroid treatment group when compared with the control group. Orthodontic treatment might best be postponed until a time when the patient is taken off medication In patients undergoing bisphosphonate administration, orthodontic tooth movement took longer, and bodily movements were limited 59

60. CLINICAL SIGNIFICANCE Rickets 60

61. Paget's disease: A chronic form of osteitis, most commonly affecting older people, causing thickening and hypertrophy of the long bones and deformity of the flat bones. The bone is excessively broken down ( osteoclastic activity) and re-formed ( osteoblastic activity) CLINICAL SIGNIFICANCE 61

62. Osteopetrosis Condition caused by a genetic defect resulting in absence of osteoclastic bone resorption Overgrowth of bone- thick, dense and sclerotic CLINICAL SIGNIFICANCE 62

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64. Conclusion Bone formation and resorption are critical processes in maintaining bone health and strength. Bone Formation is the process involves the creation of new bone tissue by osteoblasts. Bone Resorption is the process where osteoclasts break down bone tissue, releasing minerals into the blood. Balance between bone formation and resorption is necessary and deviation result in pathologic condition 64

65. references Nahian A, Davis DD. Histology, osteoprogenitor cells. InStatPearls [Internet] 2022 Dec 29. StatPearls Publishing. Orban’s Oral Histology and Embrology – 13 th Edition. Tencate Oral Histology – 8 th Edition. Lombardi G, Di Somma C, Rubino M, Faggiano A, Vuolo L, Guerra E, Contaldi P, Savastano S, Colao A. The roles of parathyroid hormone in bone remodeling: prospects for novel therapeutics. Journal of endocrinological investigation. 2011 Jul 1;34(7 Suppl):18-22. Chin KY, Ima- Nirwana S. Vitamin C and bone health: evidence from cell, animal and human studies. Current drug targets. 2018 Apr 1;19(5):439-50. Chaudhary NK, Timilsena MN, Sunuwar DR, Pradhan PM, Sangroula RK. Association of lifestyle and food consumption with bone mineral density among people aged 50 years and above attending the hospitals of Kathmandu, Nepal. Journal of Osteoporosis. 2019 May 22;2019. Tarvade SM, Daokar SG. Osteoporosis and orthodontics: a review. Scientific Journal of Dentistry. 2014;1(1):26-9. 65

66. references 8. Mizoguchi T, Ono N. The diverse origin of bone-forming osteoblasts. J Bone Miner Res. 2021 Aug;36(8):1432-1447. doi : 10.1002/jbmr.4410. Epub 2021 Jul 12. PMID: 34213032; PMCID: PMC8338797. 9. Boyce BF, Yao Z, Xing L. Osteoclasts have multiple roles in bone in addition to bone resorption. Crit Rev Eukaryot Gene Expr. 2009;19(3):171-80. doi : 10.1615/critreveukargeneexpr.v19.i3.10. PMID: 19883363; PMCID: PMC2856465. 10. Kelk P, Fasth A, Holgerson P, Sjöström M. Successful complete oral rehabilitation of a patient with osteopetrosis with extensive pre-treatments, bone grafts, dental implants and fixed bridges: a multidisciplinary case report. BMC Oral Health. 2023 Nov 28;23(1):940. doi : 10.1186/s12903-023-03707-3. PMID: 38017429; PMCID: PMC10683162. 66

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