5. osteogenesis & osteolysis of alveolar bone in health & disease 18-11-09

Osteogenesis & OsteolysisOf Alveolar Bone In

Health & DiseaseDr. Sandip Ladani

Guided by,

Dr. Mihir N. ShahDr. Archita Kikani

Dr. Hiral ParikhDr. Niraj Motwani

Guided by,

Dr. Mihir N. ShahDr. Archita Kikani

Dr. Hiral ParikhDr. Niraj Motwani

• Introduction• Development• Bone formation• Regulation of bone formation• Bone resorption• Regulation of bone resorption• Bone Modeling Vs Bone Remodeling• Ageing & Bone• Bone’s Role in Calcium Homeostasis• Alveolar Bone in Disease• Clinical Implication

Contents

Introduction• BONE:

– Bone is a mineralized connective tissue that performs the function of support, protection and locomotion.

• ALVEOLAR PROCESS :

- It is defined as the parts of the maxilla and mandible that support the sockets of the teeth.

Development of Alveolar Process

• Tooth-dependent bony structures.- Schroeder HE, 1991.

• The alveolar process consists of bone which is formed both by cells from – the dental follicle (alveolar bone proper) and – cells which are independent of tooth

development.

Development of the alveolar bone proper

• Late bell stage:– Bony septa and bony bridge start to form.

• Dental Follicle surrounds each tooth germ.• Continued bodily movement.• Major changes in alveolar process.• Height• Cell differentiation from dental follicle

– Fibroblast, cementoblast, osteoblast.• Osteoblast: Alveolar bone proper –Ten Cate, Hoffman

• Size & Shape : Alveolar Bone proper• Rest of bony structure: periosteal bone formation - Schroeder

Remodeling of the alveolar processes during tooth eruption

• The alveolar processes - already grown over the occlusal plane of the developing tooth.

• Gubernacular canal must be widened by osteoclastic bone resorption.• New bone formation at the base of the bony crypt – outward eruption force• Dental Follicle – Key structural component responsible for regulating eruption -

Eskici, Larson EK.• Monocytes containing tartrate-resistant acid phosphatase, an indicator of

lysosyme activity – Osteoclast precursors.• Recent: Factors: - Wise GE

– Colony stimulating factor-1 : recruitment & differentiation of preosteoclasts– Epidermal growth factor : upregulates the production of CSF-1 via its ability to stimulate

the cells of the reduced enamel organ to make interleukin – 1 α

BONE FORMATION

BONE FORMATION

Cellular DifferentiationCellular Differentiation

Stromal stem cellStromal stem cell OsteoblastOsteoblastOsteogenic PathwayOsteogenic Pathway

Controlled by cascade of events involving genetic programming and gene regulation by various hormones, cytokines and growth factors.

Controlled by cascade of events involving genetic programming and gene regulation by various hormones, cytokines and growth factors.

• Collagen type I and Alkaline Phosphatase – characteristic of osteogenic lineage.

• Type II collagen – Lost• Type III collagen – Diminishes progressively.

BONE FORMATION

Osteogenic Master Gene

α2 β

1

Receptor

BONE FORMATION

BONE FORMATION

in vivo

indu

ces

expr

essi

on

subsequent emergence

BONE FORMATION

• Various developmentally regulated genes:• Homeobox genes – hoxa-2, hoxd-13 and hoxa-13, dlx-5, msx-1

and msx-2

• Various developmentally regulated genes:• Homeobox genes – hoxa-2, hoxd-13 and hoxa-13, dlx-5, msx-1

and msx-2

BONE FORMATION

Cbfa1Cbfa1

Functional role in the differentiation of all mineralizing tissue cells. For eg. Odontoblasts, Cementoblasts, Ameloblasts

Complete absence of ossified tissues.

- Komori T et al, 1997

BONE FORMATION

Osteogenic Master Gene

• BMP-2– Upregulates Cbfa1 & Msx-2 leading to osteogenic

differentiation.

• TGF-ß– Increases Cbfa1 – No osteogenic differentiation

Therefore, other factors induced by BMP are necessary for complete expression of the osteoblastic phenotype.

BONE FORMATION

BMP-4InducesInduces

RegulatesRegulates

Potential

factorPotential

factor

BONE FORMATION

REGULATION OF BONE FORMATION

Production of Osteoblastic cells

Activity of Osteoblastic cells


• Parathyroid Hormone:– Regulates serum calcium levels– Stimulates bone resorption– But also – anabolic effects mediated through

TGF-β and Insulin like Growth Factor-I.

Thus affects Bone remodelingThus affects Bone remodeling


• Vitamin D3:– Stimulates bone resorption.– Essential for normal bone growth and

mineralization.– Calcium absorption from the intestine.– Strongly stimulates the synthesis of osteocalcin

and osteopontin by osteoblasts.– Suppresses collagen production.


• Insulin: (Anabolic effect)– Targets osteoblasts directly.– Stimulates bone matrix formation and

mineralization.– Indirectly affects bone formation by a

stimulation of IGF-I produced in the liver.


• Growth Hormone: (Anabolic effect)– Required for attaining normal bone mass– Anabolic effect through IGF-I production.


• Glucocorticoids: (in vitro)– promotes differentiation of osteoblasts and

stimulate bone matrix formation.


• Glucocorticoids: (in vivo)


• Bone Morphogenetic Proteins:– Belong to TGF-β family.– Can induce chondrogenic and osteogenic

differentiation in undifferentiated mesenchymal cells.– Stimulating differentiation of more mature

osteoblasts.– Stimulate collagen production.– No marked effects on bone matrix formation.


• TGF-β:– Can act as a potent inhibitor of osteogenic

induction by BMP.– Strongly stimulates expression of matrix

proteins by osteoblastic cells.


• TGF-β:


• IGF-I and II: (Potent Anabolic Agents)– Similar effects like TGF-β on matrix proteins

and matrix metalloproteinases.– Also stimulates proliferation of Osteoblastic

cell precursors.


• Fibroblast growth factors : (Basic)– Increased proliferation of osteoprogenitors.– Promote osteogenic differentiation.

• PDGF:– Promotes osteogenesis as Fibroblast growth

Factors.– Also influences the expression of other

cytokines.

31


BONE RESORPTION

• Specialized cell : Osteoclast• Produced by the monocyte/macrophage

lineage of hematopoietic cells.

BONE RESORPTION

Receptor Activator of Nuclear Factor κB / Ligand

Osteoprotegerin Ligand

Hyaluronan

receptor

CD44

Fusion of monocytic precursors occurs at the site of bone resorption to form osteoclasts.

Fusion of monocytic precursors occurs at the site of bone resorption to form osteoclasts.

αvß 3 integrin with CD44

Highly expressed in

osteoclasts and osteoclasts precursors

Signaling cell attachment and also possibly for

osteoclast chemotaxis

(haptotaxis) & migration

BONE RESORPTION

1. Demineralization Phase

2. Degradation of matrix

BONE RESORPTION


BONE RESORPTION

2. Degradation of matrix


Lysosomal enzymesLysosomal enzymesMatrix metalloproteinases

activated under acidic conditions observed in

resorption lacunae

Matrix metalloproteinases activated under acidic conditions observed in

resorption lacunae

Can degrade matrix macromolecules, including collagen

BONE RESORPTION

Mechanism for limiting

resorptive activity.

Mechanism for limiting

resorptive activity.

BONE RESORPTION

REGULATION OF BONE RESORPTION

Calcitonin: Causes cytoplasmic contraction of the cell membrane in mature osteoclasts and their dissociation into monocytic cells

Regulate Osteoclast development through the OPG/OPGL/RANK pathway

REGULATION OF BONE RESORPTION

Stimulates proliferation of precursor cells.Indirectly via PGE2

BONE MODELING

VsBONE

REMODELING

• Modeling is the process used by bone to shape itself, rating an organ with maximal compressive strength, which is associated with the formation and growth of bones in childhood and adolescence.

BONE MODELING

Periodontology 2000, Vol. 14, 1997

BONE REMODELING

• Remodeling represents a change that occurs within the mineralized bone without a concomitant alteration of the architecture of the tissue.

Why Remodel Bone ???• Allows bone to respond to loads (stresses)• Allows repair of microdamage• Participates in serum Ca2+ regulation• Replacement of old bone with new bone

BONE REMODELING

– Forst HM-1964

IN NORMAL ADULTS

COUPLING

OsteoblastsOsteoblasts OsteoclastsOsteoclasts

BONE REMODELING HYPOTHESIS

• The number of sites entering the bone formation phase, called the activation frequency, together with the individual rates of the two processes, determines the rate of tissue turnover.

• Significance:– Resorption depth and mean wall thickness may vary by on 10-20%

of normal in different diseases– Activation frequency may vary by upto 50-100%.

• Thus, in most diseases, the activation frequency is the most important regulator of bone turnover and changes in the bone mass.

- Ericksen Ef, 1986

ACTIVATION FREQUENCY

BONE MULTICELLULAR UNITS (BMUs)A BMU is comprised of

(1) a front osteoclast residing on a surface of newly resorbed bone (the resorption front), (2) a compartment containing vessels and pericytes, and (3) a layer of osteoblasts present on a newly formed organic matrix (the deposition front).

Osteoclast (OC)Osteoblasts (OB) Osteoid (OS)Vascular structures (V)RL = reversal lineLB = lamellar bone

•Becomes “machinery” that remodels bone.•Forms in response to molecular signaling.•Functions over a period of weeks to months (10 m/day).

AGING & BONE

•Starts at the age of approximately 25-30 years, when maximal bone formation is achieve.

•From that age, a steady decline in bone mass begins for both men and women. (more severe in females)

•The decrease in bone mass leads to:•Thinning of cortical bone due to tunneling or trabeculation of the endosteal cortical envelope, with expansion of the marrow cavity accompanied by some gain in diameter.

Bone’s Role in Calcium Homeostasis

Bone’s Role in Calcium HomeostasisSome

stimulus causes blood calcium level to decrease

Some stimulus

causes blood calcium level to decrease

Increase production of cAMP in

Parathyroid Gland

Increase production of cAMP in

Parathyroid GlandMore PTH

is secreted

More PTH is

secreted

Stimulates osteoblast to release IL-1 & IL-6

Stimulates osteoblast to release IL-1 & IL-6

Migration of monocyte to bone areas

Migration of monocyte to bone areas

LIF secreted by osteoblast

coalesces monocytes to

form osteoclast

LIF secreted by osteoblast

coalesces monocytes to

form osteoclast

Causes bone resorption &

release of calcium in

blood.

Negative fe

edback

Negative fe

edback

Turns Off

Turns Off

Alveolar Bone in Disease

Clinical Implications

• Alveolar bone is dependent upon the presence of teeth for its preservation.

• Maintenance is also compromised by trauma and inflammatory episodes associated with periodontal disease.

• Rapid remodeling – important for movement of teeth in response to occlusive and orthodontic forces.


Site specific remodeling in the absence of inflammation.


Potential Therapeutic Strategies To Treat Bone Resorption

Potential Therapeutic Strategies To Treat Bone Resorption

Increases apoptosis of osteoclasts thus

reducing life spanFlurbiprofen & Ibuprofen Promotes apoptosisCurrent therapeutic agents

for osteoporosis.Also is used for coating

implant surface.

Block the initial osteoclast adhesion to

the matrix.

Reduce the protease degradation of the

organic matrix.

Conclusion

Conclusion

•Alveolar bone has interdependence with dentition.

•Constant state of Flux.

•Rate of remodeling is unique to alveolar bone and is important for its adaptability.

•Many of the factors that regulate bone remodeling like, Cbfa1 & Osteoprotegrin, appear to exert their effects either directly or indirectly through these genes, which have become important targets for developing pharmacological and clinical strategies to regulate the rate of bone formation and resorption that will be important for maintenance of a healthy periodontium.

• Carranza’s Clinical Periodontology, 10th edition.• Periodontology 2000 Vol. 3, 1993• Periodontology 2000 Vol. 13, 1997• Periodontology 2000 Vol. 14, 1997• Periodontology 2000 Vol. 24, 2000• Periodontology 2000 Vol. 41, 2006• Principles of Anatomy & Physiology, 11th edition, by

Tortora & Derrickson.• Clinical Periodontology & Implant Dentistry, 5th edition,

Jan Lindhe

References

Thank You

5. osteogenesis & osteolysis of alveolar bone in health & disease 18-11-09

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