57Good morning

Effect of endocrine on periodontium

Presenter:

Shashwati Paul

Post Graduate Student

CONTENTS

• Introduction

• Central endocrine system

• Peripheral endocrine system

• Effect of endocrine hormones on periodontium

adrenal gland hormones

thyroid hormones

parathyroid hormones

sex hormones

pancreatic hormones

• Conclusion

INTRODUCTION • Periodontitis is a type of chronic inflammatory disease affecting people

worldwide, which is characterized by the loss of periodontal connective tissue and alveolar bone, eventually leading to tooth loss.

• Hormones secreted by endocrine system play an important role in periodontitis..

ENDOCRINE SYSTEM

• Hormones chemical messengers which

travel through the body

• Effects the target cells in other organ.

CENTRAL ENDOCRINE GLANDS

• Hypothalamus

• Pituitary gland

HYPOTHALAMUS

• Homeostasis

• Regulation

• Hormones

PITUITARY GLAND

• Regulation

• Hormones

PERIPHERAL ENDOCRINE GLANDS

• ADRENAL GLAND

• THYROID GLAND

• PARATHYROID GLAND

• GONADS

• PANCREAS

EFFECT OF CENTRAL ENDOCRINE GLAND HORMONES ON THE PERIODONTIUM

• Britto et al 2011….

• M. Partovi et al in 2002…. In vitro studies… effect of dopamine on human periodontal ligament cells…

• Pituitary hormones…two case control studies…

MECHANISM PROPOSED

L- DOPA

Stimulates

Dopaminergic systems in the anterior position of hypophysis

To release Growth hormone

  Promoter of healing process

EFFECT OF PERIPHERAL ENDOCRINE GLAND HORMONES ON THE PERIODONTIUM

The hormones produced by the adrenal cortex include

• Mineralo-corticoid hormones e.g., Aldosterone,

• Glucocorticoid hormones e. g., cortisol,

• Gonadal hormones e. g., dehydro-epi-androsterone

ADRENAL GLAND HORMONES

EFFECT OF ADRENAL GLAND HORMONES ON THE PERIODONTIUM

Association between elevated cortisol levels and periodontitis were demonstrated by clinical studies by Rosania et al and Rai et al in 2009 and 2011.

By

Potential psycho-neuro-immunologic mechanism

Potential behavioural mechanism

POTENTIAL PSYCHO-NEURO-IMMUNOLOGIC MECHANISM

Negative emotion

Hypothalamus releases corticotropin realeasing hormone..

….. releases Adreno corticotropic hormone from pituitary

Adrenal cortex release Cortisol

• Short term elevations of cortisol reduce inflammation and mobilize immune components

Glucocorticoids(cortisol) decreases immunocompetency by inhibition of IgA, IgG and neutrophil function.

• Leads to increased biofilm colonization and reduced ability to prevent connective tissue invasion.

• After periods of chronic elevation, cortisol loses its ability to inhibit inflammatory responses chronic periodontitis

POTENTIAL BEHAVIOURAL MECHANISM

The higher cortisol and β endorphin concentrations significantly up regulates expression of MMP-1,2,7,11 and TIMP-1 in human gingival fibroblasts

 

Increased periodontal breakdown

 

Periodontitis

Patricia et al 2007

• Various kinds of psychologic stress activate HPA(hypothalamus Pituitary

Adreno cortical) system and SM(sympathetic adrenal medullary) system and

consequently induce significant increases in salivary cortisol and

catecholamine levels respectively

Thyroid hormone

Effect of thyroid hormone on periodontium:

• Early investigators reported clinical observations of severe alveolar bone loss in patients with myxedema, but contemporary clinical studies evaluating the effects of thyroid hormone are lacking.

• Although thyroid hormones are critical factors for postnatal skeletal development and regulation of the rate of bone remodeling, the influence of thyroid hormones on alveolar bone and destructive periodontal diseases are largely unknown.

• Thyroid diseases may affect the status of periodontal diseases, especially in hypothyroid conditions.

• Uncontrolled thyroid disease may lead to destruction of periodontium.

• Limited evidence till now.

• Periodontal treatment is safe in controlled conditions(meta analysis by Wang and Cohen , 2011)

Parathyroid gland hormone

• Hormones- parathormone

Calcium regulation

The resorption of calcium from bones by PTH is by

• Rapid phase

• Slow phase

RAPID PHASE

After reaching bone

PTH gets activated to receptors on cell membrane of osteoblasts and osteoclasts

Hormone receptor complex

Increases permeability of membranes of these cells for ca-ions

Accelerates ca-pump mechanism

Ca-ions move from bone cells into blood at faster rate

SLOW PHASE

When Osteoclasts are activated by PTH

Lysosomes release enzymes and citric acid and lactic acid

These substances dissolve organic matrix of bone releasing ca ions

Ca ions release to plasma

EFFECT OF PARATHYROID GLAND HORMONE ON PERIODONTIUM

.• Primary hyperparathyroidism, resulting principally from adenomas, and secondary

hyperparathyroidism, resulting primarily from chronic renal failure, have been implicated in alveolar bone destruction as a consequence of elevated parathyroid hormone levels.

• In general, increased tooth loss and poor oral hygiene have been associated with hyperparathyroidism.

• Brown tumors (i.e. circumferential intrabony jaw tumors), typically diagnosed in primary hyperparathyroidism, can cause dislocation of teeth.

• Similarly, there are supporting data that secondary hyperparathyroidism in chronic renal failure has been associated with destructive periodontal disease.

• ( Frankenthal S,2002)

• In an effort to elucidate the relationship of parathyroid hormone with destructive periodontal disease, recent clinical studies have examined the effects of parathyroid hormone on the periodontium.

• More specifically, this research has shown decreased cortical bone density, increased incidence of tori, as well as a positive correlation between serum parathyroid hormone levels and periodontal ligament space width in patients suffering from primary hyperparathyroidism when compared with the control group.

• However, there were no alterations in clinical periodontal parameters in the parathyroid hormone group, suggesting that parathyroid hormone-reduced bone density does not predispose individuals to alterations in the soft tissue attachment apparatus.

• In spite of the absence of positive hormone-induced effects on the periodontium noted in hyperparathyroidism patients, the novel use of parathyroid hormone has been suggested as a therapeutic aid in the prevention of destructive periodontal diseases

• LPS produced by various periodontopathogens such as P. gingivalis and Actinobacillus actinomycetemcomitans induce a local inflammatory response that ultimately leads to periodontal bone resorption (Fletcher et al., 2001).

• In the periodontium, LPS may promote an inflammatory reaction through the induction of several cytokines (Kondo et al., 2001; Nagasawa et al., 2002), known to be produced by several cell types, including gingival fibroblasts and recruited leukocytes (Nagasawa et al., 2002).

• PTH administration neutralizes LPS-mediated inflammation. (S.P.Barros, Journal of Dental Research 2003)

SEX STEROID HORMONES

• Women’s life cycle changes present unique challenges to the oral health care profession.

• Hormonal influences associated with reproductive process alter periodontal and oral tissue responses to local factors.

• Different phases of female life cycle: puberty, menses, pregnancy and the effect of oral contraceptives

ACTION OF SEX STEROID HORMONES ON PERIODONTIUM

• Increased Sex hormones increased synthesis of prostaglandin

Increases the gingival permeability leads to the alteration of microvasculature increase in inflammation

Kalkwarf, 1972

PROPOSED MECHANISMS

• Sex steroid induced increase in specific microbiota

kumare et al in 2013

• Immune endocrine interactions exaggerate periodontal responses

Shiau, Reynolds in 2010

• Specific populations of fibroblasts and epithelial cells are modulated by sex steroid hormones:

Mariotti. In 1994

SEX STEROID HORMONES AND THE CELLS OF PERIODONTIUM

Hormone Fibroblasts Androgens (testosterone &

hydrotestosterone)Decrease proliferationDecrease IL-6 production

Progesterone Decrease proliferationDecrease protein synthesisDecrease cytokine production

Estradiol Increase proliferationIncrease cytokine production

Factors influencing sex hormones on periodontium

• Gender

• Age

• Hormone supplements

Gender

• Studies by Lau et al 2001 showed that gender plays an important role in

changes associated with bone density throughout the entire skeleton.

• It was showed that 80% of decreased bone density patients were females.

• Regarding periodontal anatomic differences:

Residual ridge height was lower in women compared to men +

decreased amount of estrogen in post menopausal women was associated

with decreased crestal bone density

Age

• With regard to age, females undergo more biologic changes (hormonal

imbalances) compared to males such as during puberty, menstrual cycle,

pregnancy, menopause

Hormone supplements

• These are common used drugs that stimulates a state of pregnancy to prevent ovulation.

• Hormone supplements has helped in overcoming bone loss in menopausal women, it also has been associated with side effects like cancer

PUBERTY • Increased production of sex hormones(estrogen and

progesterone)• Increased prevalence of gingivitis without an increase in

amount of plaque• P. intermedia uses ovarian hormone as a substitute for

vitamin K growth factor( Kornman and Loesche,1979)

Longitudinal studies have examined the transformation of subgingival flora from pre puberty to puberty and have

demonstrated a significant increase in

• Prevotella intermedia,

• Capnocytophaga species ,

• Prevotella nigrescens,

(Delancy and Kornman)

Clinical findings• Erythematous tissue• Nodular hyperplastic lesion with increased deposits• Bleeding on probing

PREGNANCY

….Old saying…

• In 1877, Pinard recorded the first case

• Characterised by erythema, hyperplasia and gingival bleeding.

• Periodontal status prior to pregnancy influences the progression or severity of disease.

• Increased pocket depth, increased mobility

• Mostly seen in anterior region of mouth.

• Pregnancy granuloma or granuloma gravidarum or pregnancy epulis

• Female sex hormones increased local synthesis of angiogenic factors

• Periodontal disease alters systemic health effects the well being of fetus

Risk of low birth weight, preterm infants• Periodontal infection.. Releases endotoxin.. Enters

circulation..

ETIOLOGY OF GINGIVAL RESPONSES TO ELEVATED ESTROGEN & PROGESTERONE DURING PREGNANCY

• Subgingival plaque composition

B.melaninigenicus

P.intermedia……

P.Gingivalis

Campylobacter rectus

• Maternal immuno-response.

Decreased neutrophil chemotaxis, depression of cell mediated immunity with increase in progesterone.(Raber-durlacher,1993)

Down regulation of IL-6 Production due to progesterone decreased resistance of gingiva

• Sex hormone concentration

Progesterone reaches 100 ng/ml

Estrogen regulates cellular proliferation, differentiation and keratinisation

Progesterone influences the permeability of microvasculature, alters rate of collagen production, increases metabolic breakdown of folate

ORAL CONTRACEPTIVES• These mimics the hormone levels of pregnancy… clinical

manifestations are similar..• Increased response to local irritants.• Increased prostaglandin synthesis with increase in sex

steroids results in inflammation• Gingival melanosis

PANCREATIC HORMONES

• Effect of pancreatic hormones on periodontium

The metabolic disturbances and the resulting disease of diabetes mellitus are ultimately the result of a complete or partial reduction in insulin secretion from the β cells, impaired insulin action OR the destruction of the cells.

1997, American Diabetis Association classified into:• Type 1 Diabetes• Type 2 Diabetes • Gestational Diabetes• Other types

COMPLICATIONS OF DIABETES MELLITUS

Five classic complications

• Retinopathy

• Nephropathy

• Neuropathy

• Macrovascular disease

• Altered wound healing and sixth one is

• Periodontal disease

ORAL MANIFESTATIONS

Oral changes described in diabetic patients including

• Cheilosis

• Mucosal drying

• Cracking

• Burning mouth and tongue

• Diminished salivary flow

• Altered oral cavity flora

• Diabetes – risk factor

• Diabetes – increased gingival inflammation – bacterial plaque(Gusberti 1983)

• This response-level of glycemic control

• Presence of poor glycemic control- risk of less favourable response

• Prevalence of attachment loss and bone loss greater in diabetic patients…

MECHANISMS OF DIABETIC INFLUENCE ON PERIODONTIUM

These are primarily related to changes in

GCF glucose level

Periodontal vasculature

Collagen metabolism.

The subgingival microbiota

Host response

• Increased thickness of capillary endothelial cell basement membrane and walls of small blood vessel may be seen in diabetes.

• This thickening Impairs oxygen diffusion and nutrient provision across membrane alters normal periodontal tissue homeostasis.

FORMATION OF AGEs

• AGEs Arterial smooth muscle cell proliferation increased thickness of vessel walls

• In capillaries increase in crosslinking of AGE modified collagen inhibits normal degradation of proteins increased thickness of basement membrane.

• Increased LDL….AGE modified collagen bind to LDL Narrows the lumen

• Periodontally diseased sites harbor similar species as in non diabetics

…..host response plays a major role..

• Defects in PMN Adherence, chemotaxis and phagocytosis observed in diabetics..due to hyper-responsiveness… Oliver and colleagues,1993

• Hyperresponsive monocyte/macrophage phenotype stimulation by bacterial lps increased cytokine production(offenbacher,1996)

In vitro studies – decreased chemotaxis of PDL fibroblasts to PDGF when placed in hyperglycemic environment compared to normoglycemic condition.

Increased GCF level adversely affects wound healing and local host response to microbial challenge

CONCLUSION

• The influence of endocrine hormones in health and in disease is colossal.

• Ironically, still there is limited evidence and our understanding of the effect of these hormones on periodontium is still incomplete.

Source Hormone Target tissue Principle function PeriodontiumHypothalamus Prolactin inhibiting hormone

(dopamine)Anterior pituitary gland Inhibits prolactin release Stimulates periodontal ligament

cell proliferation

Anterior pituitary Growth hormone (somatotropin) Bone, soft tissues and liver Promotes growth, affects lipids and carbohydrate metabolism

Presence of growth hormone associated with protective effect on periodontium

Thyroid Thyroid hormones (tri iodothyrosine, thyroxine)

Most cells of body Regulators of numerous tissues including cardiac and brain involved with growth and metabolism

Deficiency may be associated with destructive periodontal diseases

Adrenal Cortisol,Weak androgens and estrogensProgesterone

Most tissues of bodySex accessory tissues

Important for glucose, protein and lipid metabolismLow potency of secreted hormones diminishes effects on target tissues

Excess cortisol associated with destructive periodontal diseasesKnown effects on periodontal tissues including growth of microbiota as well as disease progression

Pancreas Insulin (β cells) Skeletal muscle, liver, adipose tissue

Lowers the blood glucose, fatty acid and amino acid levels

Decreased insulin production associated with destructive periodontal diseases

Parathyroid Parathyroid hormone Bone, kidneys, intestine Increases plasma calcium Decreased cortical bone density and increased PDL width no effect on periodontal parameters

References • Carranza’s clinical Periodontology: 10th Ed: Saunders

• Partovi et al. Mitogenic effect of L dopa on human periodontal ligament fibroblast cells: Jour of Endodontics. Vol 28(3): 193-196

• Periodontal Medicine..Rose Mealey Genco

• Perio 2000, vol 61,2013

• Patricia R Cury et al: hydrocortisone affects the expression of MMP-1,2,3,7,11 and tissue inhibitor of matrix metalloproteinases TIMP-1 in human gingival fibroblasts: J Periodontol 2007: 78: 1309-1315

• Peruzzo et al. Systemic review of stress and psychological factors as possible risk factors for periodontal disease. J Periodontol 2007: 78: 1491-1504

• Frankenthal S et al: the effect of the secondary hyperthyroidism and hemodialysis therapy on alveolar bone and periodontium: J Clin Periodontol 2002: 29: 479-483

• Barros et al: parathyroid hormone protects against periodontitis associated bone loss: J Dent Res 2003: 83: 791

• Marriotti A: Sex steroid hormones and cell dynamics in the periodontium. Crit Rev Oral Biol Med 1994:5:27-53

• Lindhe et al : influence of sex hormones on gingival exudation in dogs with chronic gingivitis: J Periodontol Res: 3 :279-283

• Kumare et al: sex and the subgingival microbiome: do female sex steroids effect periodontol bacteria Perio 2000: 2013: 103

• Shiau, Reynolds: sex differences in destructive periodontal disease: exploring the biologic basis. J Periodontol 2010: 81: 1505-1517

• Mariotti AJ. Estrogen and extracellular matrix influence human gingival fibroblast proliferation and protein production. J Periodontol 2005: 76: 1391-1397