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FACTORS GOVERNING ALVEOLAR BONE REMODELING

Article · March 2019

DOI: 10.24327/ijrsr.2019.1003.3213

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Vaishnavi Ratheesh Sangeetha Subramanian

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 Available Online at http://www.recentscientific.com
International Journal of
CODEN: IJRSFP (USA)
Recent Scientific
International Journal of Recent Scientific Research Research
Vol. 10, Issue, 03(A), pp. 31215-31218, March, 2019
ISSN: 0976-3031 DOI: 10.24327/IJRSR
Review Article
FACTORS GOVERNING ALVEOLAR BONE REMODELING

Vaishnavi Ratheesh, Sangeetha Subramanian,

PSG Prakash and Devapriya Appukuttan
SRM Dental College, Ramapuram, Chennai-89
DOI: http://dx.doi.org/10.24327/ijrsr.2019.1003.3213

ARTICLE INFO ABSTRACT

Article History: Bones are dynamic, viable, highly organised living tissue and is the main constituent of
Received 13th December, 2018 musculoskeletal system. Though the main function of bones is to protect the internal structures and
Received in revised form 11th to provide support to various soft tissues, additionally they also provide haematopoiesis in bone
January, 2019 marrow. Bone constantly responds to the varying functional demands through continuous
Accepted 8th February, 2019 adaptation. This process of adaptation is known as ‘remodeling’. Bone modeling is a result of a
Published online 28th March, 2019 balance between bone formation by osteoblasts and bone resorption by osteoclasts. It is a continuous
process and at any given time approximately 5-25% of bone surface undergoes remodeling. As
normal physiological bone remodeling is imperative for the maintenance of bone strength and
Key Words:
integrity, any imbalance, will either lead to increase or decrease in bone mass. Significant
Bone constantly responds to the varying understanding of the interplay between different factors governing bone remodelling will potentiate
functional demands through continuous better treatment options for pathologies involving the hard tissue.
adaptation.

Copyright © Vaishnavi Ratheesh et al, 2019, this is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution and reproduction in any medium, provided the
original work is properly cited.

INTRODUCTION and the pathophysiology of bone remodeling are further

discussed in this article.
Alveolar bone is constantly being remodelled to adapt to
changes in occlusal load. Alterations in resorption and repair The Bone Remodeling Process
and the interplay of these two phenomena are known as The process takes place within bone cavities that need to be
remodeling. 1 Bone remodeling is an active and dynamic remodeled. In these cavities, there is the formation of
process potentiated by the processes of bone deposition by temporary anatomical structures called basic multicellular units
osteoblasts and bone resorption by osteoclasts in correct (BMUs), which are comprised of a group of osteoclasts ahead
balance. There is constant remodeling in all the bones of the forming the cutting cone and a group of osteoblasts behind
body in response to various stimuli.2At a typical remodeling forming the closing cone, associated with blood vessels and the
site, termed basic multicellular unit (BMU), specialized peripheral innervations. It has been suggested that BMU is
osteoclasts first remove bone over a period of approximately covered by a canopy of cells (possibly bone lining cells) that
three weeks. The resulting resorption lacuna is subsequently form the bone remodeling compartment (BRC).4 The BRC
filled by osteoblasts, a process lasting about three months.3 seems to be connected to bone lining cells on bone surface,
The bone remodeling cycle maintains the integrity of the which in turn are in communication with osteocytes enclosed
skeleton through the balanced activities of its constituent cell within the bone matrix.
types. Harold Frost in his research has shown that tight control Phases of Bone Remodeling
of bone remodeling at the level of the BMU throughout the
skeleton is essential to maintain structural integrity. The Activation: The interaction between cells of the osteoblastic
various phases of bone remodeling, the cells involved in the and hematopoietic system leads to the initiation of osteoclastic
remodeling process, the various regulators of bone remodeling bone resorption. Fibroblasts secrete collagenase and other

*Corresponding author: Vaishnavi Ratheesh

SRM Dental College, Ramapuram, Chennai-89
 Vaishnavi Ratheesh et al., Factors Governing Alveolar Bone Remodeling

matrix-destroying enzymes, leading to altered tissue integrity. Growth Factors

Osteoblastic cells can activate hematopoietic cells to
These are polypeptides produced by the bone cells themselves
differentiate into bone resorbing osteoclasts through the
which act as modulators of the cellular functions,
production of macrophage colony stimulating factor (M-CSF)
fundamentally growth, differentiation, and proliferation.
and receptor activator of NFB ligand (RANKL). Lining cells of
IGF - I and II ( Insulin- Like Growth Factor I and II )
osteoblastic origin on the bone surface may also play a role by
secreting proteolytic enzymes that remove a protein layer These are polypeptides similar to insulin; they are synthesized
which normally covers the mineralized matrix. by the liver and osteoblasts and found in high concentrations in
the osteoid matrix.5 They increase the number and function of
Resorption: Osteoclasts bind to the mineralized matrix through
the osteoblasts, stimulating collagen synthesis. Growth
vitronectin receptors and then form their resorbing apparatus,
hormone, estrogens, and progesterone increase their
which secrete hydrogen ions and matrix degrading enzymes,
production, while the glucocort icoids inhibit it. They also
particularly Cathepsin K. This permits the establishment of a
participate in the osteoblast osteoclast interaction and actively
low pH and a high concentration of enzymes that can degrade
participate in bone remodeling.6
collagen quite effectively at that low pH. In addition to this
cellular compartmentalization there may be a Transforming growth factor - β ( TGF- β ) TGF- β is a potent
compartmentalization of the entire bone remodeling unit stimulator of bone formation, promoting osteoblastic
because the lining cells remain intact above the osteoclastic differentiation and the synthesis of the osteoid matrix and
resorption sites and osteoblastic formation sites. This might inhibiting the synthesis of the proteases, especially the matrix
allow for growth factors released from osteoclasts or matrix metalloproteinase (MMP), an enzyme which degrades it.7 TGF-
during resorption to be retained for longer periods and at more β inhibits resorption on reducing the formation and
effective concentrations during the next phase. differentiation of the osteoclasts, as well as mature osteoclast
activity, and stimulating their apoptosis.8
Reversal: After osteoclastic resorption is complete there is a
reversal phase during which mononuclear cells, which may be Bone morphogenetic proteins ( BMP) are included in the
either of the mesenchymal or hematopoietic lineages, complete TGF- β family and are considered osteoinductive.9 They
the removal of matrix and prepares the bone for formation by stimulate the differentiation of the stem cells toward different
laying down a “cement line” of non-collagen proteins. cell lines (adipose tissue, cartilage, and bone). They are highly
abundant in bone tissue and they strongly promote osteoblastic
Formation: In the formation phase osteoblasts lay down
differentiation and are believed to inhibit osteoclastogenesis in
matrix, which becomes gradually mineralized. As each layer of
addition to stimulating osteogenesis.10
osteoblasts form its assigned amount of matrix it either
undergoes apoptosis, or becomes buried in the matrix as an Platelet - derived growth factor (PDGF), stimulates protein
osteocyte. As this process of replacing the resorption cavity is synthesis brought about by the osteoblasts, and, on the other,
completed, some of the osteoblasts may remain on the surface favors bone resorption. Other effects are the proliferation of
as lining cells. fibroblasts and smooth muscle cells, neovascularization, and
collagen synthesis. 11
Regulators of Bone Remodeling
Fibroblastic growth factor (FGF) has an anabolic effect on
The regulation of bone remodeling is both systemic and local
bone, as it is a mitogen of osteoblasts, vascular endothelial
which maintains the balance between bone resorption and bone
cells, and fibroblasts.
formation.
Vascular endothelial growth factor (VEGF) induces
Table 1 The critical mediators of Bone Resorption are listed
angiogenesis and vascular endothelial proliferation. It produces
below
vasodilation and an increase in vascular permeability. It is
Stimulators Inhibitors
Interleukin – 1 (IL-1) Interferon gamma (IFN-Ɣ)
produced in hypoxia and is currently considered one of the key
Interleukin – 6 (IL-6) Osteoprotegerin (OPG) factors in the first phases of fracture repair and bone
Tumor Necrosis Factor regeneration, as well as in tumor growth.
Estrogens
(TNF)
Parathyroid Hormone Granulocyte / macrophage - colony stimulating factor (GM-
Androgens CSF) is important in osteoclastogenesis and may play a role in
(PTH)
PTH-related Protein
Calcitonin (CT)
the pathogenesis of osteopetrosis.
(PTHrP)
Prostaglandin E2 (PGE2) Cyclosporin Tumor Necrosis Factor (TNF) in vitro stimulates resorption
Macrophage Colony and has been related with bone loss in arthritis and periodontal
Stimulating Factor disease.
(M-CSF)
Receptor Activator of Matrix Proteins
NFκB (RANK)
RANK Ligand (RANKL) The matrix proteins act as potential growth factor modulators.12
1,25 Dihydroxy Vitamin These proteins participate in the regulation of the
D3 (Vitamin D) differentiation of the cells contained within the matrix.
Collagen I is one of the earliest markers which regulates the
osteoprogenitor cells, and alkaline phosphatase is a surface
protein that could participate in the regulation of the
proliferation, migration, and differentiation of the osteoblastic

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 International Journal of Recent Scientific Research Vol. 10, Issue, 03(A), pp. 30693-30696, March, 2019

cells. Osteonectin, fibronectin, and osteocalcin promote cell Table 4 Abnormalities of Bone Remodeling in Diseased
attachment, facilitate cell migration, and activate cells. Conditions:
Bone Resorption Bone formation
Cytokines Osteoporosis ↑↑ ±↑
Glucocorticoid ↑ ↓↓
The cytokines like Interleukin 1 (IL-1), IL-6, IL-11, Periodontitis ↑↑ ↓↓
prostaglandin E2, Leukotrienes are important in bone Hyperthyroidism ↑↑ ↑↑
remodelingdirectly stimulates osteoclastic resorption, Paget disease ↑↑ ↑↑
increasing the proliferation and differentiation of the Inflammation ↑↑ ±↓
preosteoblasts, as well as the osteoclastic activity, and Immobilization ↓↓
inhibiting the apoptosis of the osteoclasts.13
DISCUSSION
Matrix Metalloproteinases (MMPs)
Bone remodeling involves tight coupling and regulation of
Matrix metalloproteinases (MMPs) are members of a family of osteoclasts and osteoblasts and is modulated by a wide variety
zinc-dependent proteolytic enzymes. Several MMPs expressed of hormones and osteocyte products secreted in response to
in the skeleton appear to function in endochondral ossification mechanical stimulation and microdamage. This process is often
during embryonic development and in modeling and characterized by complex mechanical and biochemical
remodeling of bone post natally and later in life. MMP activity signaling pathways.
is increased in areas of inflammation, including periodontitis,
leading to unwanted amounts of tissue destruction. Initially, bone resorption is conducted via a resorptive stimulus
produced by cytokines or mediators such as interleukin-1 (IL-
Systemic Regulators of bone Remodeling 1), interleukin-6 (IL-6), parathyroid hormone (PTH), PTH-
Calcium and phosphate Balance related protein (PTHrP), prostaglandin E2 (PGE2), and tumor
necrosis factor-alpha (TNF-α). In response to a specific
Calcium (Ca2+) is one of the main components of our bones. stimulus, preosteoclasts are recruited from the hematopoietic
Ca2+ balance is basically maintained by two hormones: lineage into the area of bone resorption and differentiate into
parathyroid hormone (PTH) and calcitriol (1,25- active osteoclasts. Osteoclasts possess the ruffled membrane
dihydroxyvitamin D). Parathyroid hormone is secreted when and clear zone that ensure the resorption process remains
the level of calcium in the blood falls below the amount needed localized beneath the osteoclast, maintaining the pH-regulating
by the body's cells. It promotes the absorption of calcium by proton pump in the bone resorptive microenvironment.
the digestive system and slows the excretion of calcium into the Resorption gradually slows and eventually ceases as the active
urine. It also stimulates osteoclasts to break down bone to osteoclasts are replaced with transient mononuclear cells; this
release calcium into the blood. When the calcium level in the is the reversal phase.
blood is adequate, the production of parathyroid hormone falls.
A third Ca2+ regulating hormone, calcitonin, is of minor The formative phase then begins with recruitment of pre-
importance in humans. It is secreted by parafollicular C cells in osteoblasts (mesenchymal precursor cells) into the site. This is
the thyroid gland and lowers plasma Ca2+ levels for a short followed by differentiation of pre-osteoblasts into osteoblasts
time by directly inhibiting osteoclast activity, with the system via the action of bone morphogenetic proteins (BMPs). In this
quickly swinging back to a neutral position. stage, some osteoblasts are entrapped in the bone matrix and
become osteocytes. Through the coupled process of bone
Hormonal Factors resorption and formation, on average, an exchange of 10% of
Table 3 Hormonal Regulators of Bone Remodeling the skeleton occurs every year over an individual’s lifetime.
Inappropriate regulation of bone remodeling can also lead to
Bone resorption Bone formation the net bone loss seen in osteopenia and periodontitis.
(osteoclast activity) (osteoblast activity)
Parathyroid
↑ ↑* CONCLUSION
Hormone
Vitamin D ↑ ↑* With the advent of new technologies, the coupling process of
Calcitonin ↓ - bone remodeling that happens within the BMUs has been
Estrogen ↓ ↓# explored from various perspectives. A thorough understanding
Growth hormone ↑ ↑
of the basic biology of bone remodeling is critical for
Thyroid hormone ↑ ↑
elucidation of the molecular and cellular mechanisms
*PTH and Vitamin D decreases collagen synthesis in high underlying the pathogenesis of disorders of bone remodeling
doses. # Estrogen decreases bone formation by decreasing
remodeling, but formation is decreased less than resorption and and also helps to encounter the underlying pathophysiology of
bone mass increases. several bones diseases. This knowledge will also unravel the
opportunities in devising new therapeutic strategies to control
Pathophysiology of Bone Remodeling bone formation and resorption based upon these novel
Cooper reported that systemic conditions which may provoke regulatory mechanisms.
bone loss are currently regarded as one of the factors that affect
an individual’s susceptibility to periodontal disease. A few of
the pathological entities wherein there is deranged skeletal
metabolism/remodeling are addressed below.

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 Vaishnavi Ratheesh et al., Factors Governing Alveolar Bone Remodeling

References 7. Bonewald F,Dall as SL. Role of active and latent

transforming growth factor- beta in bone
1. Clarke B. Normal bone anatomy and physiology. formation.J.Cell.Biochem.1994;55:350–7.
Clin.J.Am.Soc.Nephrol.2008;3:S131–9 8. Baylink DJ, Finkelman RD, Mohan S.Growth factors to
2. Raisz LG. Physiology and pathophysiology of stimulate bone formation.J.Bone.Miner.Res.1993;
boneremodeling. Clin. Chem. 1999; 45:1353-8. 8:565–72.
3. Asagiri M, Takayanagi H.The molecular understanding 9. Sakou T.Bone morphogenetic proteins: from basic
of osteoclast differentiation. Bone.2007; 40:251–64. studies to clinical approaches.Bone.1998; 22:591–603.
4. Parfitt AM.The bone remodeling compartment: a 10. Canalis E, Economides AN, Gazzerro E. Bone
circulatory function for bone lining morphogenetic proteins, their antagonists, and the
cells.J.Bone.Miner.Res.2001;16:1583–5. skeleton.Endocr.Rev.2003;24:218–35.
5. Cohick WS, Clemmons DR. The insulin-like growth 11. Nash TJ, Howlett CR, Martin C et al. Effects of
factors. Annu. Rev. Physiol.1993; 55:131–53. platelet-derived growth factor on tibial osteotomies in
6. Cohen MM Jr.The new bone biology: pathologic, rabbits.Bone.1994;15:203–8.
molecular, clinical correlates.Am.J.Med.Genet.A.2006; 12. Young MF.Bone matrix proteins: more than markers.
140:2646–706. Calcif Tissue Int.2003;72:2–4
13. Compston JE. Sex steroids and
bone.Physiol.Rev.2001;81:419–47.

How to cite this article:

Vaishnavi Ratheesh et al.,2019, Factors Governing Alveolar Bone Remodeling. Int J Recent Sci Res.
10(03), pp. 31215-31218. DOI: http://dx.doi.org/10.24327/ijrsr.2019.1003.3213

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