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

 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.INTRODUCTION  Minerals constitute a small proportion of the body weight. These are required in amounts greater than 100mg/ day. .  Calcium is a macro element.

Unique binding ability--stabilize the 3 dimensional structure of many enzymes and other proteins. 4. Activation of enzymes . Development of bones and teeth. 2. Muscle contraction. Blood Coagulation 5. Nerve transmission 6.IMPORTANCE OF CALCIUM 1. Cell membrane integrity and permeability 7. 3.

SOURCES OF CALCIUM • MILK • MILK PRODUCTS BEST SOURCE GOOD SOURCE • BEANS • LEAFY VEGETABLE • FISH • EGG YOLK • CABBAGE .

8.DIETARY REQUIREMENTS  Adult men and women  Women during pregnancy.5 g /day lactation and postmenopause  Children (1.  800mg/day  1.2 g/day  Infants ( 1 year) 300 – 500 mg/day .1.18 yrs) 0.

DISTRIBUTION OF CALCIUM IN PLASMA .

4 mmol/liter.4 mg/dl = 2.PLASMA LEVEL  Normal level is 9.  Range = 9-11 mg/dl .

phylates.FACTORS AFFECTING CALCIUM ABSORPTION  Factors Favoring  Factors Decreasing  Oxalates. 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 .

To maintain Ca2+ balance. Each component is hormonally regulated.OVERALL CALCIUM HOMEOSTASIS Serum [Ca2+] is determined by the interplay of intestinal absorption. net intestinal absorption must be exactly balanced by urinary excretion: . renal excretion and bone remodeling (bone resorption and formation).

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

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 .DECREASED BLOOD CALCIUM LEVEL PARATHYROID KIDNEY INCREASED BLOOD CALCIUM LEVEL THYROID PARATHORMONE 1.

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.

The precipitates first appear at intervals along each collagen fiber.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. forming minute nidi that rapidly multiply and grow over a period of time into hydroxyapatite crystals. calcium salts begin to precipitate on the surfaces of the collagen fibers.

BONE REMODELLING:  Remodeling is the major pathway of bony changes in shape. repair of wounds. the coupling of bone resorption with bone formation constitutes one of the fundamental principles by which bone is necessarily remodeled throughout its life. Indeed. . resistance to forces. and calcium and phosphate homeostasis in the body.

releasing calcium ions from hydroxyapatite into the blood. PTH stimulates osteoblasts to release Il-1 and Il-6 which stimulate monocytes to migrate into the bone area. which then release parathyroid hormone(PTH). A decrease in blood calcium is mediated by receptors on the chief cells of the parathyroid glands. . Bone contains 99% of the body's calcium ions. which then resorb bone. coalesces monocytes into multinucleated osteoclasts. Leukemia inhibiting factor (LIT). secreted by osteoblasts.

The breakdown of collagen from the organic matrix releases various osteogenic substrates. osteoclasts have resorbed organic matrix along with hydroxyapatite. which ultimately deposit bone. which are covalently bound to collagen. This interdependency of osteoblasts and osteoclasts in remodeling is called coupling. A feedback mechanism of normal blood levels of calcium turns off the secretion of PTH. . Meanwhile. and this in turn stimulates the differentiation of osteoblasts.

they possess an elaborately developed ruffled border from which hydrolytic enzymes are believed to be secreted. which has receptors on the osteoclast membrane. When osteoclasts are active rather than resting. The activity of osteoclasts and morphology of the ruffled border can be modified and regulated by hormones such as PTH (indirectly) and calcitonin. These enzymes digest the organic portion of bone. .

BONE REMODELLING CYCLE: .

HARMONAL CONTROL OF CALCIUM AND PHOSPHORUS VITAMIN D PTH CALCITONIN .

• PTH can be referred to as the body‟s defense against hypocalcemia.PARATHORMONE • Secreted by chief cells of parathyroid gland. • The main function is to increase the level of calcium in plasma • Target sites  Bone  Kidney  Intestine . • The major hormone for regulation of the serum [Ca2+].

by the formation of new osteoclasts.  INTESTINE  Increases calcium reabsorption via vitamin D.  Releases calcium & phosphate into blood.  Net effect of its action is increased calcium & reduced phosphate in plasma.  KIDNEY  PTH increases reabsorption of calcium & reduces reabsorption of phosphate.Activity of PTH  BONE  PTH promotes the resorption of bones by activating the osteoclasts and also.  PTH acts on osteoblastic cells to express RANKL ( Receptor Activator of Nuclear Factor КB Ligand). . an inducer of osteocalstic bone resorption. followed by their activation.

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

and formation of bone cysts and giant cell tumors. The disease is called osteitis fibrosra cystica. . or von Recklinghausen's bone disease. increased osteoclasis with proliferation of the connective tissue in the enlarged marrow spaces.HYPERPARATHYROIDISM  Parathyroid hypersecretion produces generalized demineralization of the skeleton.

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

fibrous dysplasia. and osteomalacia.  Loss of lamina dura may also occur in Paget's 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.

 A relationship has been suggested between periodontal disease in dogs and hyperparathyroidism secondary to calcium deficiency in the diet. but this has not been confirmed by other studies (Svanberg. Lindhe. (Henrikson 1962). silverman et al(1962) and strock MS(1945). Hugosonm et al 1973). and 50% of patients with hyperparathyroidism have associated oral changes. 25%. Acccording to the studies done by rosenberg and Guralnick(1962). 45%. .

walls of blood vessels.  The pancreas and the salivary glands frequently develop lithiasis.  A reported 45% to 80% of the patient‟s have nephrolithiasis and /or nephrocalcinosis. articular cartilages. and joint capsules.  Other soft tissues involved are the subcutaneous tissues.METASTATIC CALCIFICATION  Ectopic calcification in soft tissue is the most common feature of hyperparathyroidism. .

. anxiety. feet and circumoral muscles.  This leads to muscular and mental manifestations that include paresthesia of hands.HYPOCALCEMIA  Hypocalcemia is often asymptomatic. confusion and depression.  Spasm of the laryngeal muscles can lead to asphyxia and death.

.  If hypoparathyroidism is part of an autoimmune polyendocrinopathy syndrome. Painful muscular spasms affect oral and laryngeal muscles. 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.

short blunt root apices.  There may be enamel hypoplasia. impacted teeth and mandibular exostoses. and poorly mineralized dentin. single or parallel horizontal bands on the enamel. elongated pulp chambers (some occluded by pulp stones. Malformed. even in the primary dentition). . anodontia.

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

 It behaves like a true harmone. eggs. 1. cutaneous synthesis of vitamin D ( cholecalciferol).  Vitamin D containing food includes liver. and more importantly. milk and other food of animal origin.dihydroxycholecalciferol the active form of vitamin VITAMIN D VITAMIN D D.25. .  The sources of vitamin D in the body are dietary intake.

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 It promotes the reabsorption of calcium and phosphate from the renal tubules.  Increasing the synthesis of calcium channels and a carrier protein for ca2+ called “CALCIUM BINDING PROTEIN” (CaBP) or CALBINDIN in many tissues.  The active pump which transfers calcium ions out of the osteocytic membrane into the ECF is vitamin D mediated. particularly the intestine. kidney and the bone are the chief target organs.ACTION  The intestine. .

.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.

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.  Calcium-deficient diets.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. .

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. . Prolonged administration of anticonvulsant drugs ( eg: phenobarbitol.  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 .

is essential for the absorption of calcium from the gastrointestinal tract and the maintenance of the calcium-phosphorus balance. . Vitamin D.  Deficiency in vitamin D and imbalance in calcium- phosphorus intake result in rickets in young children and osteomalacia in adults. or calcilerol.  No studies demonstrate a relationship between vitamin D deficiency and periodontal disease.

failure of osteoid to resorb. and distortion of the growth pattern of alveolar bone. which leads to its excessive accumulation. reduction in the width of the periodontal ligament space.Becks et al 1946 and Weinmann and Schour 1945 . but defective calcification and some cementum resorption. osteoid that forms at a normal rate but remains uncalcified. a normal rate of cementum formation. The effect of vitamin D deficiency or imbalance on the periodontal tissues of young dogs results in osteoporosis of alveolar bone. .

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

that is. there is uncoupling of the remodeling cycle. and ultimately increased risk for fractures. lower bone mass. This results in a remodeling imbalance with net bone loss.  With the increased rate of remodelling in older age. .OSTEOPOROSIS:  Seen in old age  Results from diminished organic bone matrix rather than abnormal bone calcification. rate of resorption exceeds the rate of formation.

 Also called as thyrocalcitonin.  Calcitonin acts on bone osteoclasts to reduce bone resorption.CALCITONIN  Calcitonin is a peptide hormone secreted by the parafollicular or “C” cells of the thyroid gland. .  It is released in response to high plasma calcium.

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.

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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.

degeneration and reduction in the number of collagen fibres of the periodontal ligament. capillary dilation and engorgement. –Glickman et al 1953 . associated with inflammation. 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. and increased destruction of the periodontal tissues. with haemorrhage in the periodontal ligament and gingival connective tissue.

 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 .

textbook of medical physiology.  Davidson’s Principles and practice of Medicine.  Shafers.Oral Pathology.Essentials of Biochemistry. .  Satyanarayan.Periodontal Medicine.REFERENCE  Guyton and hall.Essentials of Medical Physiology.  Sembulingam and sembulingam.  Rose.

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 .

Indeed. . repair of wounds. resistance to forces.BONE REMODELLING:  Remodeling is the major pathway of bony changes in shape. the coupling of bone resorption with bone formation constitutes one of the fundamental principles by which bone is necessarily remodeled throughout its life. and calcium and phosphate homeostasis in the body.

which then release parathyroid hormone(PTH). which then resorb bone. coalesces monocytes into multinucleated osteoclasts. A decrease in blood calcium is mediated by receptors on the chief cells of the parathyroid glands. secreted by osteoblasts. . Bone contains 99% of the body's calcium ions. Leukemia inhibiting factor (LIF). releasing calcium ions from hydroxyapatite into the blood. PTH stimulates osteoblasts to release Il-1 and Il-6 which stimulate monocytes to migrate into the bone area.

Meanwhile. and this in turn stimulates the differentiation of osteoblasts. The breakdown of collagen from the organic matrix releases various osteogenic substrates. osteoclasts have resorbed organic matrix along with hydroxyapatite. This interdependency of osteoblasts and osteoclasts in remodeling is called coupling. which are covalently bound to collagen. which ultimately deposit bone. A feedback mechanism of normal blood levels of calcium turns off the secretion of PTH. .

which has receptors on the osteoclast membrane. These enzymes digest the organic portion of bone. When osteoclasts are active rather than resting. they possess an elaborately developed ruffled border from which hydrolytic enzymes are believed to be secreted. The activity of osteoclasts and morphology of the ruffled border can be modified and regulated by hormones such as PTH (indirectly) and calcitonin. .

BONE REMODELLING CYCLE: .

The disease is called osteitis fibrosra cystica.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. or von Recklinghausen's bone disease.

fibrous dysplasia. Complete loss of the lamina dura does not occur often. Loss of the lamina dura and giant cell tumors in the jaws are late signs of hyperparathyroid bone disease. and osteomalacia. which in itself is uncommon. .  Loss of lamina dura may also occur in Paget's disease.

and 50% of patients with hyperparathyroidism have associated oral changes. 25%. 45%. (Henrikson 1962). . but this has not been confirmed by other studies (Svanberg. Hugosonm et al 1973). silverman et al(1962) and strock MS(1945). Acccording to the studies done by rosenberg and Guralnick(1962). Lindhe.  A relationship has been suggested between periodontal disease in dogs and hyperparathyroidism secondary to calcium deficiency in the diet.

VITAMIN D Deficiency  Embrace a group of disorders characterized by failure in the mineralization of bones. whereas osteomalacia is failure of mineralization of newly formed organic bone matrix at site of bone turnover. .  Rickets is failure of mineralization of endochondral new bone formed at the growth plates in children.

a normal rate of cementum formation. . which leads to its excessive accumulation. reduction in the width of the periodontal ligament space. but defective calcification and some cementum resorption. osteoid that forms at a normal rate but remains uncalcified. The effect of vitamin D deficiency or imbalance on the periodontal tissues of young dogs results in osteoporosis of alveolar bone. and distortion of the growth pattern of alveolar bone. failure of osteoid to resorb.Becks et al 1946 and Weinmann and Schour 1945 .

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

(Birkedal-Hansen H. 1993. Periodontitis can be considered an abnormal inflammatory response to periodontal flora. in which hard and soft tissues are destroyed by auto-degradative mechanisms.)  As part of this process. and dissolution of the extracellular matrix. which in turn cause lymphocytic infiltration. bone resorption. Graves DT. monocytes respond to bacterial invasion and secrete cytokines. Cochran D 2003. .

 Cytokines (cell proteins) regulate the body‟s inflammatory response by transmitting signals between cells. IL-6. which causes vasodilation. and bone resorption. and TNF-α are potent osteoclastogenic signaling agents. Cytokines such as IL-1. . (Birkedal-Hansen H. edema. which result in the resorption of alveolar bone. Salvi GE. which degrade the extracellular matrix and prostaglandin E2 (PGE2). 1997)  IL-1 also stimulates the release of metalloproteinases (MMP). 1993.

 Hypertension. (Hennig BJ et al 1999. clinical attachment loss. specific vitamin D-receptor genotypes have been shown to be associated with localized aggressive periodontal disease. cardiovascular diseases. because vitamin D and 25(OH)D are stored in adipose tissue. (Ralston SH. Nishimura F 2003)  Moreover. diabetes mellitus. and periodontal diseases are associated with obesity and. 2004. obese subjects have low serum levels of 25(OH)D. Inagaki K et al 2003) . with oral bone loss. and tooth loss.

probing depth and tooth mobility decreased.000 mg/day of calcium supplementation and were followed for 6 months. and new bone appeared to have formed as observed radiographically. . 10 subjects with periodontal disease received 1. In a study (Krook L et al 1972). gingival inflammation was improved. The investigators reported that at the end of 6 months of treatment.

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

The major limitations of the study are that it was cross-sectional and lacked exact data on calcium supplementation. . 2000). it was found that lower dietary intake of calcium increased attachment loss in a dose-dependent fashion.000 adults who took part in the Third National Health and Nutrition Examination Survey (NHANES III). (Nishida M et al. In an examination of data on 12. The investigators suggested that the increased risk of periodontal disease could be related to decreased alveolar bone density associated with inadequate calcium intake.

Oral Pathology. Rose.Essentials of Medical Physiology. Hildebolt. et al Calcium and the risk for periodontal disease J Periodontol 2000. Satyanarayan.Periodontal Medicine.textbook of medical physiology. Sembulingam and sembulingam. Davidson‟s Principles and practice of Medicine.76:1576-1587. Sara G.References:  Carranza 10 th edition  Charles F.71:1057-1066 Guyton and hall.Essentials of Biochemistry. . Shafers. Effect of Vitamin D and Calcium on        Periodontitis. J Periodontol 2005. Nishida M.

Oral Pathology.  Rose.  Sembulingam and sembulingam.textbook of medical physiology.  Shafers.Periodontal Medicine.  Satyanarayan.REFERENCE  Guyton and hall.  Davidson’s Principles and practice of Medicine.Essentials of Medical Physiology.Essentials of Biochemistry. .

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

”  A World Health Organization panel has operationally defined osteoporosis as a BMD that is 2. Definition:  “a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration with a consequent increase in bone fragility and susceptibility to fracture. .5 SD below the mean peak value in young adults.

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With the increased rate of remodelling in older age. Bone is continuously remodelled throughout the life of an individual. Bone mass at any given time is related to peak bone mass and bone loss that has occurred since peak mass was attained. that is. and the rate of remodelling is increased in older adults. . the rate of resorption exceeds the rate of formation. The pathophysiology of osteoporosis is poorly understood. there is uncoupling of the remodelling cycle.

Therefore. This results in a remodelling imbalance with net bone loss. genetically determined bone mass and age constitute the major determinants of risk of osteoporosis and osteoporotic fractures. 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. lower bone mass. .

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

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. .

(Krall EA et al 1996). Decreases in BMD at the femoral neck and spine resulted in a 50% and 45% increased risk of tooth loss respectively. . In a 7-year longitudinal study.. rate of systemic bone loss was a predictor of tooth loss in postmenopausal women. For each 1% per year decrease in whole body BMD. the risk for tooth loss more than quadrupled.

 Collectively. . and more are edentulous compared with nonosteoporotic women. women that are at risk for or suffer from osteoporosis are also at risk for tooth loss. Krall EA 1994. 1996)  Thus. Taguchi A 1995. (daniell HW 1983. evidences indicate that osteoporotic women have lost significantly more teeth.

. controversy still exists concerning the association between osteopenia/osteoporosis and periodontal disease. Different studies have given conflicting results accounting for much of the controversy.Periodontal Disease and Osteopenia/ Osteoporosis  Unlike the clear relationship between osteoporosis and tooth loss.

years of menopause. there was a relationship between osteopenia at the hip and probing attachment loss in this same group. In addition. In a study done by Wactawski-Wende and colleagues.  This relationship was seen after controlling for possible confounders such as dental plaque. and smoking. 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. .45 including 70 postmenopausal women.

the evidence suggests an association between osteopenia. osteoporosis.5 mm) in females and males alike. smoking.247 individuals 20 to 90 years of age. independently of the confounding effects of age. or intake of dietary calcium. though limited. . Hence. and periodontal disease.46 Osteopenia of the hip was significantly associated with severity of periodontal disease (mean attachment loss > 1.  This association was increased even further in postmenopausal females. gender. 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.

environmental. multifactorial diseases.  Risk factors common to both osteoporosis and periodontal disease are listed under the categories of genetic.CO–RISK FACTORS FOR OSTEOPOROSIS AND PERIODONTAL DISEASE  Osteoporosis and periodontal disease are chronic. . dietary. and systemic factors. Therefore. both diseases share common risk factors.

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TNF-a. TNF-a. Osteoblast precursors respond to the loss of estrogen by secreting IL-6. GM-CSF. .  Estrogen regulates bone remodeling by modulating the production of cytokines and growth factors.  IL-1. which then induces osteoclastogenesis.Estrogen Deficiency  Estrogen deficiency is the factor most closely associated with postmenopausal osteoporosis. and GM-CSF contribute to bone resorption by promoting osteoclast recruitment and differentiation from bone marrow precursors. especially IL1b. and M-CSF from bone cells.

 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. Three studies have directly examined the relationship of estrogen status/deficiency and periodontal disease. . after controlling for levels of supragingival plaque and frequency of dental treatment. In addition. gingival bleeding was statistically significantly reduced in the estrogentreated postmenopausal women compared with the estrogen-deficient group.

 In a 5-year longitudinal study (Jacob‟s 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 the estrogen deficient state.(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. In a 1-year longitudinal study of 24 postmenopausal women. The authors proposed estrogen deficiency as a risk factor for alveolar bone density loss. the governor controlling cytokines and bone remodelling is lost. Thus. resulting in increased bone resorption and net skeletal and alveolar bone loss. .

a nuclear receptor that is highly expressed in the target organs of calcium metabolism. D exhibits its physiologic and pharmacologic effects by activating the vitamin D receptor.Vitamin D Genotypes  Activated form of vit D molecules bind to the vitamin D receptor (VDR). .  Activated form of vit.

 VDR responds to endocrine signal (vit D3) and metabolites (lithocholic acid) . VDR belongs to nuclear recptor super family of transcription factor.

In regulatory regions of many target genes. VDR is localised in both cytosol and nucleus and accumulates in the nucleus in response to 1. Cathelicidin antimicrobial peptide (CAMP) and transient receptor potential vanilloid type 6 (TRPV6).  DR3 VDR binding elements…. calbindin D9k.25(OH)2 D3 binding.. . including 25-hydroxyvitamin D 24hydroxylase (CYP24A1).

a structural rearrangement that results in the dynamic exchange of cofactor complexes. Nuclear receptors including VDR undergo a confirmational change in the cofactor binding site and activation function AF2 domain upon ligand binding. .  Dynamic and co-ordinated interaction of co factor complexes and VDR is required for efficient regulation of transcription.

. and TRPV5.(Malloy PJ 1999). VDR mutations have been identified in HVDRR . TRPV6.  Ligand activated VDR induces the expression of genes involved in calcium metabolism. such as calbindin D9k.

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

 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 RFLP’s 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.

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Rose LF and Genco RJ.  Amano Y. J Oral Sci 2009. .51:11-20. et al. Vitamin D and periodontal disease.REFERENCES  Periodontal Medicine.

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