GOOD MORNING

CALCIUM METABOLISM

CONTENTS
INTRODUCTION IMPORTANCE OF CALCIUM SOURCES OF CALCIUM DISTRIBUTION OF CALCIUM DIETARY REQUIREMENTS ABSORPTION OF CALCIUM

OVERALL CALCIUM HOMEOSTASIS

EXCRETION OF CALCIUM PARATHYROID GLANDS AND PARATHORMONE

1,25-DIHYDROXYVITAMIN D(CALCITRIOL)
CALCITONIN REFERENCE

INTRODUCTION
Minerals constitute a small proportion of the body weight. Calcium is a macro element. These are required in

amounts greater than 100mg/ day. Calcium is the most abundant among the minerals in the body. It is the main constituent of hard tissues and is an important inorganic ion for many physiologic functions. It is vital for us to have a complete understanding of the general metabolism of calcium and phosphorous as it is these minerals that help in the formation and maintenance of the teeth and their supporting bony structure.

IMPORTANCE OF CALCIUM
1. 2.

Development of bones and teeth. Unique binding ability--stabilize the 3 dimensional structure of many enzymes and other proteins.

3.

Muscle contraction.

4. Blood Coagulation
5.

Nerve transmission

6. Cell membrane integrity and permeability 7.

Activation of enzymes

SOURCES OF CALCIUM
MILK MILK PRODUCTS

BEST SOURCE

GOOD SOURCE

BEANS LEAFY VEGETABLE FISH EGG YOLK CABBAGE

DIETARY REQUIREMENTS
Adult men and women Women during pregnancy, 800mg/day 1.5 g /day

lactation and postmenopause

Children (1- 18 yrs)

0.8- 1.2 g/day

Infants ( 1 year)

300 500 mg/day

DISTRIBUTION OF CALCIUM IN PLASMA

PLASMA LEVEL
Normal level is 9.4 mg/dl = 2.4 mmol/liter. Range = 9-11 mg/dl

FACTORS AFFECTING CALCIUM ABSORPTION

Factors Favoring

Factors Decreasing
Oxalates, phylates, phytic

PTH Vitamin D High protein diet Acidic pH Bile salts Negative Ca balance Pregnancy, lactation and

acids
Excess of phosphates in diet Excess of intestinal lipids Alkaline pH High body stores of calcium Menopause Rapid Intestinal Transit Time

growth
Calcium Deficiency

OVERALL CALCIUM HOMEOSTASIS

Serum [Ca2+] is determined by the interplay of intestinal absorption, renal excretion

and bone remodeling (bone resorption and

formation). Each component is hormonally regulated.

To maintain Ca2+ balance, net intestinal

absorption must be exactly balanced by

urinary excretion:

1. Positive Ca2+ balance Seen in growing children, where intestinal Ca2+ absorption exceeds urinary excretion and the difference is deposited in the growing bones.
2. Negative Ca2+ balance Seen in women during pregnancy or lactation, where intestinal Ca2+ absorption is less than urinary excretion .

DECREASED BLOOD CALCIUM LEVEL

PARATHYROID
KIDNEY

INCREASED BLOOD CALCIUM LEVEL

THYROID

PARATHORMONE

1,25-DIHYDROXY CHOLECALCIFEROL

CALCITONIN

BONE: Increase in resorption and release of calcium

INTESTINE: Increase in absorption of calcium

BONE: Inhibition of bone resorption and deposition of calcium

NORMAL BLOOD CALCIUM LEVEL

EXCRETION OF CALCIUM AND PHOSPHATE

80% in Feaces
About 60% of plasma

Remaining Urine

calcium is filtered by the kidneys.

60% of reabsorption

occurs in the PCT and remaining 40% occurs in the loop of Henle and distal tubules.
DCT reabsorption is

regulated by parathormone.

PRECIPITATION OF CALCIUM IN BONEThe initial stage in bone formation is osteoid matrix formation by osteocytes. Within a few days after the osteoid is formed, calcium salts begin to precipitate on the surfaces of the collagen fibers. The precipitates first appear at intervals along each collagen fiber, forming minute nidi that rapidly multiply and grow over a period of time into hydroxyapatite crystals.

BONE REMODELLING:
Remodeling is the major pathway of bony changes in

shape, resistance to forces, repair of wounds, and calcium and phosphate homeostasis in the body. Indeed, the coupling of bone resorption with bone formation

constitutes one of the fundamental principles by which

bone is necessarily remodeled throughout its life.

 Bone contains 99% of the body's calcium ions. A decrease in

blood calcium is mediated by receptors on the chief cells of the parathyroid glands, which then release parathyroid hormone(PTH). PTH stimulates osteoblasts to release Il-1 and Il-6 which stimulate monocytes to migrate into the bone area.

Leukemia inhibiting factor (LIT), secreted by osteoblasts,

coalesces monocytes into multinucleated osteoclasts, which then resorb bone, releasing calcium ions from hydroxyapatite into the blood.

 A feedback mechanism of normal blood levels of calcium

turns off the secretion of PTH. Meanwhile, osteoclasts have resorbed organic matrix along with hydroxyapatite. The breakdown of collagen from the organic matrix releases various osteogenic substrates, which are covalently bound to

collagen, and this in turn stimulates the differentiation of

osteoblasts, which ultimately deposit bone. This interdependency of osteoblasts and osteoclasts in remodeling is called coupling.

 When osteoclasts are active rather than resting, they

possess an elaborately developed ruffled border from

which hydrolytic enzymes are believed to be secreted.

These enzymes digest the organic portion of bone. The activity of osteoclasts and morphology of the ruffled border can be modified and regulated by hormones such as PTH (indirectly) and calcitonin, which has receptors on

the osteoclast membrane.

BONE REMODELLING CYCLE:

HARMONAL CONTROL OF CALCIUM AND PHOSPHORUS

VITAMIN D PTH

CALCITONIN

PARATHORMONE
Secreted by chief cells of parathyroid gland. The major hormone for regulation of the serum [Ca2+]. PTH can be referred to as the bodys defense against

hypocalcemia. The main function is to increase the level of calcium in plasma Target sites Bone Kidney Intestine

Activity of PTH
BONE
PTH promotes the resorption of bones by activating the

osteoclasts and also, by the formation of new osteoclasts, followed by their activation. Releases calcium & phosphate into blood. PTH acts on osteoblastic cells to express RANKL ( Receptor Activator of Nuclear Factor B Ligand), an inducer of osteocalstic bone resorption.

KIDNEY
PTH increases reabsorption of calcium & reduces reabsorption

of phosphate. Net effect of its action is increased calcium & reduced phosphate in plasma.

INTESTINE
Increases calcium reabsorption via vitamin D.

REGULATION OF PTH SECRETION

Controlled by the serum [Ca2+] by negative feedback. Decreased serum [Ca2+] increases PTH secretion. Mild decrease in serum [Mg2+] also stimulate PTH secretion.

HYPERPARATHYROIDISM
Parathyroid hypersecretion produces generalized

demineralization of the skeleton, increased osteoclasis

with proliferation of the connective tissue in the enlarged marrow spaces, and formation of bone cysts and giant cell tumors. The disease is called osteitis fibrosra cystica, or von Recklinghausen's bone disease.

ORAL CHANGES Malocclusion and tooth mobility, Radiographic evidence of alveolar osteoporosis with closely

meshed trabeculae, Widening of the periodontal ligament space, Absence of the lamina dura, and Radiolucent cystlike spaces. Bone cysts become filled with fibrous tissue with abundant hemosiderin laden macrophages and giant cells. These cysts have been called brown tumors, although they are not really tumors but Reparative giant cell granulomas. In some cases these lesions appear in the periapical region of teeth and can lead to a misdiagnosis of a lesion ot endodontic origin.

 Loss of the lamina dura and giant cell tumors in the jaws

are late signs of hyperparathyroid bone disease, which in itself is uncommon. Complete loss of the lamina dura does not occur often.
Loss of lamina dura may also occur in Paget's disease,

fibrous dysplasia, and osteomalacia.

 Acccording to the studies done by rosenberg and

Guralnick(1962), silverman et al(1962) and strock

MS(1945), 25%, 45%, and 50% of patients with

hyperparathyroidism have associated oral changes.
A relationship has been suggested between periodontal

disease in dogs and hyperparathyroidism secondary to calcium deficiency in the diet, (Henrikson 1962), but this

has not been confirmed by other studies (Svanberg,

Lindhe, Hugosonm et al 1973).

METASTATIC CALCIFICATION
Ectopic calcification in soft tissue is the most common feature

of hyperparathyroidism.
A reported 45% to 80% of the patients have nephrolithiasis and

/or nephrocalcinosis.
Other soft tissues involved are the subcutaneous tissues, walls

of blood vessels, articular cartilages, and joint capsules.

The pancreas and the salivary glands frequently develop

lithiasis.

HYPOCALCEMIA
Hypocalcemia is often asymptomatic. This leads to muscular and mental manifestations that

include paresthesia of hands, feet and circumoral muscles, anxiety, confusion and depression.
Spasm of the laryngeal muscles can lead to asphyxia and

death.

 Painful muscular spasms affect oral and laryngeal muscles.

If hypoparathyroidism is part of an autoimmune

polyendocrinopathy syndrome, oral mucocutaneous candidiasis

may be present in an acute or chronic form.

If hypoparathyroidism occur when teeth are still developing,

there will be abnormalities in the appearance and eruption

pattern.

 Malformed, anodontia, short blunt root apices, elongated

pulp chambers (some occluded by pulp stones, even in the

primary dentition), impacted teeth and mandibular

exostoses.

There may be enamel hypoplasia, single or parallel

horizontal bands on the enamel, and poorly mineralized

dentin.

Laboratory Findings
Hypocalcemia is characterized by the following:
serum [Ca2+] and tetany serum [phosphate] urinary phosphate excretion

 1,25- dihydroxycholecalciferol the active form of vitamin

VITAMIN D

VITAMIN D

D.
It behaves like a true harmone. Vitamin D containing food includes liver, eggs, milk and

other food of animal origin.

The sources of vitamin D in the body are dietary intake,

and more importantly, cutaneous synthesis of vitamin D (

cholecalciferol).

ACTION
The intestine, kidney and the bone are the chief target organs.

Increasing the synthesis of calcium channels and a carrier protein

for ca2+ called CALCIUM BINDING PROTEIN (CaBP) or CALBINDIN in many tissues, particularly the intestine.
It promotes the reabsorption of calcium and phosphate from the

renal tubules.
The active pump which transfers calcium ions out of the

osteocytic membrane into the ECF is vitamin D mediated.

VITAMIN D Deficiency
Embrace a group of disorders characterized by failure in the

mineralization of bones.

Rickets is failure of mineralization of endochondral new bone

formed at the growth plates in children, whereas osteomalacia is

failure of mineralization of newly formed organic bone matrix at site of bone turnover.

CAUSES
Dermal synthesis of vitamin D can be impaired by inadequate

sunlight in geographic regions of extreme latitude or in cultural

regions that wear extensive clothing to cover the whole body.

Calcium-deficient diets, as well as malabsorption states such as

those encountered after gastric resection .

Biliary obstruction may also produce a calcium deficiency by

preventing bile salts from reaching the intestine.

 Prolonged administration of anticonvulsant drugs ( eg:

phenobarbitol, primidone) can result in calcium deficiency because these drugs enhance liver enzyme activity, which leads to an increased breakdown of vitamin D to biologically inert products.

A variety of renal diseases, which may be congenital or may

result from a chronic nephritis.

RICKETS

DENTAL FINDINGS IN RICKETS

Developmental anomalies

of enamel and dentin

Delayed eruption Misalignment of teeth Increase caries index Wide predentin zone and

more interglobular dentin

 Vitamin D, or calcilerol, is essential for the absorption of

calcium from the gastrointestinal tract and the maintenance of the calcium-phosphorus balance.
Deficiency in vitamin D and imbalance in calcium-

phosphorus intake result in rickets in young children and

osteomalacia in adults.
No studies demonstrate a relationship between vitamin D

deficiency and periodontal disease.

 The effect of vitamin D deficiency or imbalance on the

periodontal tissues of young dogs results in osteoporosis of alveolar bone; osteoid that forms at a normal rate but remains uncalcified; failure of osteoid to resorb, which leads to its excessive accumulation; reduction in the width

of the periodontal ligament space; a normal rate of

cementum formation, but defective calcification and some cementum resorption; and distortion of the growth pattern of alveolar bone. - Becks et al 1946 and Weinmann and Schour 1945

 In osteomalacic animals, there is rapid, generalized, severe

osteoclastic resorption of alveolar bone; proliferation of fibroblasts that replace bone and marrow; and new bone formation around the remnants of unresorbed bony trabeculae.(Dreizen et al 1967) Radiographically, there is generalized partial to complete disappearance of the lamina dura and reduced density of the supporting bone, loss of trabeculae, increased radiolucency of the trabecular interstices, and increased prominence of the remaining trabeculae. Microscopic and radiographic changes in the periodontium are almost identical with those seen in experimentally induced hyperparathyroidism.

OSTEOPOROSIS:
Seen in old age Results from diminished organic bone matrix rather than

abnormal bone calcification.

With the increased rate of remodelling in older age, there is

uncoupling of the remodeling cycle, that is, rate of resorption exceeds the rate of formation. This results in a remodeling imbalance with net bone loss, lower bone mass, and ultimately increased risk for fractures.

CALCITONIN
Calcitonin is a peptide hormone

secreted by the parafollicular or C cells of the thyroid gland.

Also called as thyrocalcitonin. It is released in response to high

plasma calcium.
Calcitonin acts on bone

osteoclasts to reduce bone resorption.

ACTION OF CALCITONIN
Net result of its action is a decline in plasma calcium & phosphate .
Calcitonin is a physiological antagonist to PTH with respect to

Calcium. With respect to phosphate it has the same effect as PTH i.e. plasma phosphate level.
Osteoclast cells
Lose their ruffled borders Undergo cytoskeletal rearrangement

mobility
Detach from bone

Other Hormones Regulating Calcium

GROWTH HORMONE INSULIN TESTOSTERONE & OTHER HORMONES OESTROGENS STEROIDS THYROID HORMONES

GROWTH HORMONE
Increases the intestinal absorption of calcium and decreases

its excretion from urine.

Stimulates production of insulin like growth factor in bone

which stimulates protein synthesis in bone.

TESTOSTERONE
Acts on cartilage & increase the bone growth.

INSULIN
It is an anabolic hormone which favors bone formation.

GLUCOCORTICOSTEROIDS
Anti vitamin D action, decrease absorption of calcium in

intestine.
Inhibit protein synthesis and so decrease in bone

formation.
Inhibit new osteoclast formation & decrease the activity of

old osteoclasts.

 Exogenous cortisone may have an adverse effect on bone

quality and physiology. The systemic administration of

cortisone in experimental animals results in osteoporosis

of alveolar bone; capillary dilation and engorgement, with haemorrhage in the periodontal ligament and gingival

connective tissue; degeneration and reduction in the

number of collagen fibres of the periodontal ligament; and increased destruction of the periodontal tissues, associated with inflammation. Glickman et al 1953

 Stress increases circulating cortisol levels through

stimulation of the adrenal glands (hypothalamic-pituitary adrenal axis). This increased exposure to endogenous cortisol may have adverse effects on the periodontium by

diminishing the immune response to periodontal bacteria.

Drugs affecting calcium metabolism:

Steroids Antiepileptics (phenytoin) Anticoagulants Proton pump inhibitors

REFERENCE
Guyton and hall- textbook of medical physiology.

Davidsons Principles and practice of Medicine.

Sembulingam and sembulingam- Essentials of Medical

Physiology. Satyanarayan- Essentials of Biochemistry. Shafers- Oral Pathology. Rose- Periodontal Medicine.

GOOD MORNING!!!

 INTRODUCTION

CONTENTS

IMPORTANCE OF CALCIUM SOURCES OF CALCIUM DISTRIBUTION OF CALCIUM DIETARY REQUIREMENTS ABSORPTION OF CALCIUM OVERALL CALCIUM HOMEOSTASIS EXCRETION OF CALCIUM PARATHYROID GLANDS AND PARATHORMONE 1,25-DIHYDROXYVITAMIN D(CALCITRIOL)

CALCITONIN
PERIODONTIUM AND CALCIUM REFERENCE

PERIODONTIUM AND CALCIUM

DECREASED BLOOD CALCIUM LEVEL

PARATHYROID
KIDNEY

INCREASED BLOOD CALCIUM LEVEL

THYROID

PARATHORMONE

1,25-DIHYDROXY CHOLECALCIFEROL

CALCITONIN

BONE: Increase in resorption and release of calcium

INTESTINE: Increase in absorption of calcium

BONE: Inhibition of bone resorption and deposition of calcium

NORMAL BLOOD CALCIUM LEVEL

BONE REMODELLING:
Remodeling is the major pathway of bony changes in

shape, resistance to forces, repair of wounds, and calcium and phosphate homeostasis in the body. Indeed, the coupling of bone resorption with bone formation

constitutes one of the fundamental principles by which

bone is necessarily remodeled throughout its life.

 Bone contains 99% of the body's calcium ions. A decrease in

blood calcium is mediated by receptors on the chief cells of the parathyroid glands, which then release parathyroid hormone(PTH). PTH stimulates osteoblasts to release Il-1 and Il-6 which stimulate monocytes to migrate into the bone area.

Leukemia inhibiting factor (LIF), secreted by osteoblasts,

coalesces monocytes into multinucleated osteoclasts, which then resorb bone, releasing calcium ions from hydroxyapatite into the blood.

 A feedback mechanism of normal blood levels of calcium

turns off the secretion of PTH. Meanwhile, osteoclasts have resorbed organic matrix along with hydroxyapatite. The breakdown of collagen from the organic matrix releases various osteogenic substrates, which are covalently bound to

collagen, and this in turn stimulates the differentiation of

osteoblasts, which ultimately deposit bone. This interdependency of osteoblasts and osteoclasts in remodeling is called coupling.

 When osteoclasts are active rather than resting, they

possess an elaborately developed ruffled border from

which hydrolytic enzymes are believed to be secreted.

These enzymes digest the organic portion of bone. The activity of osteoclasts and morphology of the ruffled border can be modified and regulated by hormones such as PTH (indirectly) and calcitonin, which has receptors on

the osteoclast membrane.

BONE REMODELLING CYCLE:

HYPERPARATHYROIDISM
Parathyroid hypersecretion produces generalized

demineralization of the skeleton, increased osteoclasis

with proliferation of the connective tissue in the enlarged marrow spaces, and formation of bone cysts and giant cell tumors. The disease is called osteitis fibrosra cystica, or von Recklinghausen's bone disease.

 Loss of the lamina dura and giant cell tumors in the jaws

are late signs of hyperparathyroid bone disease, which in itself is uncommon. Complete loss of the lamina dura does not occur often.
Loss of lamina dura may also occur in Paget's disease,

fibrous dysplasia, and osteomalacia.

 Acccording to the studies done by rosenberg and

Guralnick(1962), silverman et al(1962) and strock

MS(1945), 25%, 45%, and 50% of patients with

hyperparathyroidism have associated oral changes.
A relationship has been suggested between periodontal

disease in dogs and hyperparathyroidism secondary to calcium deficiency in the diet, (Henrikson 1962), but this

has not been confirmed by other studies (Svanberg,

Lindhe, Hugosonm et al 1973).

VITAMIN D Deficiency
Embrace a group of disorders characterized by failure in the

mineralization of bones.

Rickets is failure of mineralization of endochondral new bone

formed at the growth plates in children, whereas osteomalacia is

failure of mineralization of newly formed organic bone matrix at site of bone turnover.

 The effect of vitamin D deficiency or imbalance on the

periodontal tissues of young dogs results in osteoporosis of alveolar bone; osteoid that forms at a normal rate but remains uncalcified; failure of osteoid to resorb, which leads to its excessive accumulation; reduction in the width

of the periodontal ligament space; a normal rate of

cementum formation, but defective calcification and some cementum resorption; and distortion of the growth pattern of alveolar bone. - Becks et al 1946 and Weinmann and Schour 1945

 In osteomalacic animals, there is rapid, generalized, severe

osteoclastic resorption of alveolar bone; proliferation of fibroblasts that replace bone and marrow; and new bone formation around the remnants of unresorbed bony trabeculae.(Dreizen et al 1967) Radiographically, there is generalized partial to complete disappearance of the lamina dura and reduced density of the supporting bone, loss of trabeculae, increased radiolucency of the trabecular interstices, and increased prominence of the remaining trabeculae. Microscopic and radiographic changes in the periodontium are almost identical with those seen in experimentally induced hyperparathyroidism.

 Periodontitis can be considered an abnormal inammatory

response to periodontal ora, in which hard and soft tissues are destroyed by auto-degradative mechanisms. (Birkedal-Hansen H. 1993, Graves DT, Cochran D 2003.)
As part of this process, monocytes respond to bacterial

invasion and secrete cytokines, which in turn cause lymphocytic infiltration, bone resorption, and dissolution of the extracellular matrix.

 Cytokines (cell proteins) regulate the bodys inammatory

response by transmitting signals between cells. Cytokines such as IL-1, IL-6, and TNF- are potent osteoclastogenic signaling agents, which result in the resorption of alveolar bone. (Birkedal-Hansen H. 1993, Salvi GE. 1997)
IL-1 also stimulates the release of metalloproteinases

(MMP), which degrade the extracellular matrix and prostaglandin E2 (PGE2), which causes vasodilation, edema, and bone resorption.

 Hypertension, diabetes mellitus, cardiovascular diseases,

and periodontal diseases are associated with obesity and, because vitamin D and 25(OH)D are stored in adipose tissue, obese subjects have low serum levels of 25(OH)D. (Ralston SH, 2004, Nishimura F 2003)

Moreover, specic vitamin D-receptor genotypes have

been shown to be associated with localized aggressive periodontal disease, with oral bone loss, clinical attachment loss, and tooth loss. (Hennig BJ et al 1999, Inagaki K et al 2003)

 In a study (Krook L et al 1972), 10 subjects with

periodontal disease received 1,000 mg/day of calcium supplementation and were followed for 6 months. The investigators reported that at the end of 6 months of treatment, gingival inammation was improved, probing depth and tooth mobility decreased, and new bone appeared to have formed as observed radiographically.

 A more recent 3-year hormone replacement study (Civitelli R,

2002) in which 67 periodontally healthy post-menopausal women received only 1,000 mg of calcium and 400 IU of vitamin D per day. Over a 3-year period, there were signicant increases in both alveolar bone mass and alveolar crest height. The apparent increase in crestal bone height was attributed to a reduction or complete relling of the remodeling space. After 3 years, this increase in crestal density (decrease in crestal porosity) would have been most pronounced in subjects with vitamin D deciency and radiographically would appear as an increase in alveolar crest height.

 In an examination of data on 12,000 adults who took part in

the Third National Health and Nutrition Examination Survey (NHANES III), (Nishida M et al, 2000). it was found that lower dietary intake of calcium increased attachment loss in a dose-dependent fashion. The investigators suggested that the increased risk of periodontal disease could be related to decreased alveolar bone density associated with inadequate calcium intake. The major limitations of the study are that it was cross-sectional and lacked exact data on calcium supplementation.

References:
Carranza 10 th edition Charles F. Hildebolt, Effect of Vitamin D and Calcium on

Periodontitis. J Periodontol 2005;76:1576-1587. Nishida M, Sara G, et al Calcium and the risk for periodontal disease J Periodontol 2000;71:1057-1066 Guyton and hall- textbook of medical physiology. Davidsons Principles and practice of Medicine. Sembulingam and sembulingam- Essentials of Medical Physiology. Satyanarayan- Essentials of Biochemistry. Shafers- Oral Pathology. Rose- Periodontal Medicine.

REFERENCE
Guyton and hall- textbook of medical physiology.

Davidsons Principles and practice of Medicine.

Sembulingam and sembulingam- Essentials of Medical

Physiology. Satyanarayan- Essentials of Biochemistry. Shafers- Oral Pathology. Rose- Periodontal Medicine.

THANK YOU!

OSTEOPOROSIS
Meaning- Porous Bone. Too little bone to provide mechanical support. Osteopenia- reuction in bone mineral density (BMD) below a predefined level. Osteoporosis is characterised by a reduction in BMD to a level below what is required for mechanical support.

 Definition:
a systemic skeletal disease characterized by low bone

mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture.
A World Health Organization panel has operationally

defined osteoporosis as a BMD that is 2.5 SD below the mean peak value in young adults.

 The pathophysiology of osteoporosis is poorly understood.

Bone mass at any given time is related to peak bone mass and bone loss that has occurred since peak mass was attained. Bone is continuously remodelled throughout the life of an individual, and the rate of remodelling is

increased in older adults. With the increased rate of

remodelling in older age, there is uncoupling of the remodelling cycle, that is, the rate of resorption exceeds the rate of formation.

 This results in a remodelling imbalance with net bone loss,

lower bone mass, and ultimately increased risk for

fractures. Such an imbalance would be even greater if the

rate of initiation of new bone remodelling cycles were to increase. Therefore, genetically determined bone mass and age constitute the major determinants of risk of osteoporosis and osteoporotic fractures.

 It has long been postulated that mandibular bone density

may be indicative of systemic bone mineral density. In a classic series of studies, done by Kribbs and colleagues they addressed this relationship in both normal and osteoporotic women. In a study, (Kribs PJ 1983), total body calcium as assessed by neutron activation analysis, was found to be associated with mandibular density as measured by quantitative analysis of intraoral radiographs. In another study (Kribs PJ 1990), done in normal, nonosteoporotic women, revealed that bone mass was not affected by age but was significantly associated with skeletal bone mass at the spine and wrist.

Tooth Loss and Osteoporosis

Several studies have demonstrated a relationship between

tooth loss and systemic osteoporosis in both dentate and edentulous individuals.
Daniell and colleagues (1983) suggested that systemic

bone loss was a risk factor for edentulism. Women with severe osteoporosis, were three times more likely (44% versus 15%) to have no teeth compared with healthy, agematched controls.

 In a 7-year longitudinal study, rate of systemic bone loss

was a predictor of tooth loss in postmenopausal women.

(Krall EA et al 1996).. For each 1% per year decrease in

whole body BMD, the risk for tooth loss more than quadrupled. Decreases in BMD at the femoral neck and spine resulted in a 50% and 45% increased risk of tooth loss respectively.

 Collectively, evidences indicate that osteoporotic women

have lost significantly more teeth, and more are edentulous compared with nonosteoporotic women. (daniell HW 1983, Taguchi A 1995, Krall EA 1994, 1996)
Thus, women that are at risk for or suffer from

osteoporosis are also at risk for tooth loss.

Periodontal Disease and Osteopenia/ Osteoporosis

Unlike the clear relationship between osteoporosis and

tooth loss, controversy still exists concerning the

association between osteopenia/osteoporosis and

periodontal disease. Different studies have given conflicting results accounting for much of the controversy.

 In a study done by Wactawski-Wende and colleagues,45

including 70 postmenopausal women, a significant relationship was found between alveolar crestal bone height as a measure of periodontitis and skeletal osteopenia (femur and lumbar spine) measured by DXA. This relationship was seen after controlling for possible confounders such as dental plaque, years of menopause, and smoking. In addition, there was a relationship between osteopenia at the hip and probing attachment loss in this same group.

 The relationship between osteopenia and severity of

periodontal disease was also examined in a sample from the Third National Health and Nutrition Examination Survey (NHANES III) of 11,247 individuals 20 to 90 years of age.46 Osteopenia of the hip was significantly associated with severity of periodontal disease (mean attachment loss > 1.5 mm) in females and males alike, independently of the confounding effects of age, gender, smoking, or intake of dietary calcium.
This association was increased even further in

postmenopausal females. Hence, though limited, the evidence suggests an association between osteopenia, osteoporosis, and periodontal disease.

CORISK FACTORS FOR OSTEOPOROSIS AND PERIODONTAL DISEASE

Osteoporosis and periodontal disease are chronic,

multifactorial diseases. Therefore, both diseases share

common risk factors.

Risk factors common to both osteoporosis and periodontal

disease are listed under the categories of genetic, dietary,

environmental, and systemic factors.

Estrogen Deficiency
Estrogen deficiency is the factor most closely associated

with postmenopausal osteoporosis.

Estrogen regulates bone remodeling by modulating the

production of cytokines and growth factors, especially IL1b, TNF-a, GM-CSF, and M-CSF from bone cells.
IL-1, TNF-a, and GM-CSF contribute to bone resorption

by promoting osteoclast recruitment and differentiation from bone marrow precursors. Osteoblast precursors respond to the loss of estrogen by secreting IL-6, which then induces osteoclastogenesis.

 Three studies have directly examined the relationship of

estrogen status/deficiency and periodontal disease.

Norderyd and colleagues (1993) reported lower, although

not statistically significant, levels of clinical attachment loss in postmenopausal women receiving estrogen supplementation compared with estrogen-deficient postmenopausal women. In addition, gingival bleeding was statistically significantly reduced in the estrogentreated postmenopausal women compared with the estrogen-deficient group, after controlling for levels of supragingival plaque and frequency of dental treatment.

 In a 5-year longitudinal study (Jacobs et al 1996) of 69 women

with surgical or natural menopause receiving hormone

replacement therapy compared lumbar spine BMD, measured by

dual photon absorptiometry, with mandibular bone mass assessed by quantitative measures of standardized intraoral

radiographs. A statistically significant but moderate correlation

was observed between mandibular and lumbar spine bone mass and that estrogen replacement therapy after surgical or natural menopause had a positive effect on bone mass not only of the lumbar spine but the mandible as well.

 In a 1-year longitudinal study of 24 postmenopausal

women,(Payne and colleagues (1997)) it was seen that estrogen-deficient women displayed a mean net loss in alveolar bone density compared with estrogen sufficient women, who displayed a mean net gain in alveolar bone density. The authors proposed estrogen deficiency as a risk factor for alveolar bone density loss. Thus, in the estrogen deficient state, the governor controlling cytokines and bone remodelling is lost, resulting in increased bone resorption and net skeletal and alveolar bone loss.

Vitamin D Genotypes
Activated form of vit D molecules bind to the vitamin D

receptor (VDR), a nuclear receptor that is highly expressed in the target organs of calcium metabolism.
Activated form of vit. D exhibits its physiologic and

pharmacologic effects by activating the vitamin D receptor.

 VDR belongs to nuclear recptor super family of

transcription factor.
VDR responds to endocrine signal (vit D3) and

metabolites (lithocholic acid)

 VDR is localised in both cytosol and nucleus and

accumulates in the nucleus in response to 1,25(OH)2 D3 binding.

DR3 VDR binding elements.. In regulatory regions of

many target genes, including 25-hydroxyvitamin D 24hydroxylase (CYP24A1), calbindin D9k. Cathelicidin antimicrobial peptide (CAMP) and transient receptor potential vanilloid type 6 (TRPV6).

 Nuclear receptors including VDR undergo a

confirmational change in the cofactor binding site and

activation function AF2 domain upon ligand binding, a

structural rearrangement that results in the dynamic exchange of cofactor complexes.

Dynamic and co-ordinated interaction of co factor

complexes and VDR is required for efficient regulation of

transcription.

 VDR mutations have been identified in HVDRR

.(Malloy PJ 1999).
Ligand activated VDR induces the expression of

genes involved in calcium metabolism, such as calbindin D9k, TRPV6, and TRPV5.

Activation of VDR by pharmacological doses of vit D regulates osteoblasts by inducing the bone remodelling proteins osteocalcin and osteopontin and upregulates the RANKL, a paracrine signal for osteoclastogenesis.

 VDR mediated induction of osteoblast RANKL may

account for enhanced bone resorption. Chondrocyte specific VDR- ablated mice have reduced RANKL

expression and reduced osteoclastogenesis.

VDR regulates bone homeostasis through actions in

osteoblasts and chondrocytes.

 Vitamin D deficiency is a risk factor for osteoporotic

fractures, and treatment of osteoporotic women with 1,25(OH)2D3 increases BMD and decreases the incident

of vertebral compression fractures. Vitamin D supresses

pro inflammatory responses and enhances innate immunity. Therefore VDR ligands can be clinically useful in the treatment of osteoporosis associated periodontal disease.

 Along with the loss of function VDR

mutations responsible for HVDRR, associations of several VDR restriction fragment length polymorphisms with several diseases including DM, cancer, osteoporosis and periodontal disease have been reported.
The RFLPs Bsml, Tru91, Taq1, EcoRV and

Apal may infulence mRNA stability.

Insufficient clearence of periodontopathic bacteria and subsequent bone destruction are suggested to cause aggressive periodontitis. VDR ligands stimulate innate immunity by inducing antimicrobial peptides and have bone anabolic suggesting that VDR ligands can be applied for prevention of aggressive periodontitis .

 A dysregulated release of proinflammatory

cytokines by the monocye/macrophages and lymphocytes is considered to induce chronic periodontitis.

Since Vit D has potent immunomodulatory effects that is by inhibiting the proinflammatory cytokine release VDR ligands may be effective in the treatment.

REFERENCES
Periodontal Medicine- Rose LF and Genco RJ. Amano Y, et al. Vitamin D and periodontal

disease. J Oral Sci 2009;51:11-20.

THANK YOU!!!