Systemic disease in etiology of periodontitis. ENDOCRINE DISTURBANCE AND HORMONE FLUCTUATIONS Diabetes Hormonal fluctuations associated with Puberty, Menstruation, Pregnancy, Menopause, Oral Contraceptives Osteoporosis Hyperparathyroidism

3. INDEX
 ENDOCRINE DISTURBANCE AND HORMONE
FLUCTUATIONS
 Diabetes
 Hormonal fluctuations associated with Puberty, Menstruation,
Pregnancy, Menopause, Oral Contraceptives
 Osteoporosis
 Hyperparathyroidism

4. Need for assessment of systemic
factors
To identify high-risk individuals in prior
so that preventive and treatment
procedures can be tailored to these
individuals.

5. These disturbances affect the
periodontal tissues directly,
modify the tissue response to
local factors and produce
anatomic changes in the gingiva
that may favor plaque
accumulation and disease
progression

6. Various systemic factors that play role in etiology of
periodontal disease are as follows:
Nutritional
Influences
Endocrine
Influences
Hematologic
Disorders
Genetic
Disorders
Effect of
systemic drug
therapy
Collagen
Vascular
Diseases
Cardiovascular
Diseases
Psychosomatic
Disorders
Other Systemic
Conditions-
Metal
Intoxication

7. ENDOCRINEDISORDERS

8. Diabetes
Osteoporosis
Hyperparathyroidism
Hormonal
fluctuations
associated with
puberty,
pregnancy,
menopause,
menstruation
ENDOCRINE
DISTURBANCES
AND HORMONE
FLUCTUATIONS

9. DIABETES

10. DIABETES (INDEX)
 Clinical symptoms of Diabetes
 Pathogenesis
 Altered microbiota
 Effects of advanced glycation end products (AGEs)
 Oral features
 Treatment
 Precautions

11. 2-Way Relationship Between
Diabetes and Periodontal disease
Diabetic people are more
susceptible to periodontal
disease
Periodontitis complicates
glycaemic control and enhances
insulin resistance resulting in
hyperglycaemia
Hyperglycaemia, in turn, causes
increased susceptibility to re-
infection and more severe
periodontal disease
Diabetes
Periodontal
Disease

12. Type-I (IDDM)
Type-II (NIDDM)
Gestational
Diabetes
Hyperglycaemia
secondary to other
Diseases
DIABETES MELLITUS

13. Clinical symptoms of Diabetes
Polyuria, polydipsia,
polyphagia, pruritus,
weakness, and
fatigue
Features are more
pronounced in Type
1 than in Type 2 DM
Treatment is aimed
at reducing blood
glucose levels to
prevent such
complications

14. COMPLICATIONS
MACROVASCULAR
COMPLICATIONS
(Increased risk of Myocardial
Infarction, Stroke due to
atherosclerosis)
MICROVASCULAR
COMPLICATIONS
(Retinopathy, Neuropathy,
Nephropathy, Poor wound
healing, Periodontal disease)

15. Thus, Periodontitis is a
complication of
Diabetes

17. IN PERIODONTITIS
Periodontal
destruction is
due to
upregulation of
innate
immunity i.e.
by neutrophils
and monocytes
Increase
release
of IL-β,
TNF-⍺,
IL-6,
PGE2,
MMP’s

18. IN
DIABETES
Hyperglycemia
causes
upregulation of
innate
immunity i.e. of
neutrophils and
monocytes
Increase
release
of IL-β,
TNF-⍺,
IL-6,
PGE2,
MMP’s

19. Thus the mechanism of
destruction is same in
both the diseases

20. SYNERGESTIC
DESTRUCTION IN
PRESENCE OF BOTH
PERIODONTITIS
UNCONTROLLED
DIABETES

21. MECHANISM OF ACTION
1. Changes in subgingival environment
o Altered microbiota
2. Formation of advanced glycation end products
(AGEs)

22. AGEs LEAD TO
 ↓ PMNL chemotaxis,
adherance and
phagocytosis
 Increased pro-
inflammatory
cytokines response
from monocyte /
macrophage
• Altered tissue
homeostasis and
wound healing
1. ↓ collagen production-
alterations in wound
healing
2. Increased MMP’s
activity
3. Accumulation of AGE’s
in blood vessels
4. ↓ tissue turnover
Increased Oxidative
stress induced by
neutrophils and
macrophages

23. 1.
MICROBIOLOGY
• Capnocytophaga
species and anaerobic
Vibrios with few
pigmented Bacteroids,
Actinobacillus
actinomycetemcomitans
INCREASE
IN

24. 2. FORMATION OF AGEs
AGE-RAGE
INTERACTIONS
HYPERGLYCEMIA LEADS TO-
non-enzymatic glycosylation of
proteins, lipids, carbohydrates
resulting in formation of advanced
glycation end products (AGEs)

25. AGE-RAGE
INTERACTIONS
HYPERGLYCEMIA LEADS TO
Formation of AGEs upregulate toll like receptors
RAGE (Receptors of advanced glycation end
products) present on neutrophils, monocytes,
fibroblast, vascular endothelial cells leading to
destructive effects

26. • AGEs forms at
normal glucose
levels, but its
formation increases
many folds in
hyperglycemic stage
leading to
destructive effects
AGEs

28. 1. AGE- RAGE INTERACTION ON
NEUTROPHIL
Impaired chemotaxis, reduced migration to gingival sulcus
leading to decreased phagocytosis of microorganisms.
Activate protein kinase C-⍺ (PKC-⍺)
activity in cell membranes causing
oxidative stress, release of free radicals
leading to periodontal destruction
Release of increased matrix
metalloproteinases (MMP-8), β glucoronidase
enzymes causing periodontal destruction

29. 2. AGE- RAGE INTERACTION ON
MONOCYTES/MACROPHAGES
Activate protein kinase
C-β (PKC-β) activity,
transcription factor-𝛋β
(OXIDATIVE STRESS)
in Monocytes
Increase transcription
and release of IL-6,
IL-1β, TNF⍺,
MMP’s, Reactive
oxygen species
(Superoxide)
Increased
soft and
hard tissue
periodontal
destruction

30. 2. AGE- RAGE INTERACTION ON
MONOCYTES/MACROPHAGES
Phagocytic functions
are impaired
Hyper responsive
macrophages with
increased release of
cytokines, MMP’s
leading to periodontal
destruction

31. 3. AGE- RAGE INTERACTION ON
VASCULAR ENDOTHELIAL CELLS
Induce
vasoconstriction,
coagulation, micro
thrombus formation,
thickening of vessel
walls
Impaired
perfusion
of tissues
Poor
healing

32. 4. AGE- RAGE INTERACTION ON
FIBROBLAST
Reduced
deposition of
collagen
Affect
osteoblast
function with
decreased
bone
formation
Poor
healing and
impaired
bone
deposition

34. Decreased synthesis
of collagen by
fibroblasts.
Increased
degradation of
collagen by
collagenase (MMP-8
released by
neutrophils).
Glycosylation of
existing collagen at
wound margins.
Defective
remodelling and
rapid degradation of
newly synthesized,
poorly cross-linked
collagen.
IMPAIRED WOUND HEALING DUE TO-

36. In undiagnosed or poorly
controlled diabetes mellitus
Multiple or recurrent
periodontal abscesses
Unexplained oedematous
gingival enlargement
Rapid destruction of
alveolar bone
Delayed wound healing

37. Other features include
Cheilosis, drying and
cracking of mucosa
Decreased salivary flow
Burning mouth
Opportunistic fungal
infections by Candida
albicans

39. Response to Periodontal
treatment in patients with DM
In well controlled DM, similar
response to treatment is seen as that
of non DM patients
In poorly controlled DM, less favorable
response to treatment. In these
patients, initial response to scaling
and root planing is good, but chances
of recurrence within 12 months is
greater

40. Treatment of periodontitis
in uncontrolled diabetic
patients
ANTIMICROBIAL
THERAPY
(SCALING , ROOT
PLANING)
HOST MODULATORY
AGENTS
(TO REDUCE
INFLAMMATORY HOST
PRODUCTS)

41. 1. ANTIPROTEINASES
2. BONE SPARING DRUGS
3. ANTI INFLAMMATORY DRUGS
HOST MODULATORY AGENTS

42. 1. ANTIPROTEINASES
SUBANTIMICROBIAL
DOSE OF
DOXYCYCLINE

43. ONLY DRUG
APPROVED BY
FDA TO BE
USED AS
HOST
MODULATORY
AGENT

44. SUBANTIMICROBIAL DOSE OF
DOXYCYCLINE
Inhibit
mammalian
collagenase
(MMP-8)
activity with no
antibiotic
resistance
inhibit MMP-
13, so decrease
bone resorption
Stimulates
fibroblast
collagen
production
Downregulates
expression of key
inflammatory
cytokines
(interleukin-1,
interleukin-6 and
tumour necrosis
factor-∝) and
prostaglandin E2
Scavenges and
inhibits
production of
reactive oxygen
species produced
by neutrophils
and macrophages

45. Periostat
(20-mg doxycycline
hyclate, twice daily
for periods of 3–9
months as an
adjunct to scaling
and root planing)

46. 2. BONE SPARING
DRUGS
BISPHOSPHONATES

47. inhibit bone
resorption by
disrupting osteoclast
activity
increase
osteoblast
differentiation
bind to
hydroxyapatite
crystals and
prevent their
dissolution
BISPHOSPHONATES

48. Long term therapy
leads to
“bisphosphonate-
associated
osteonecrosis’’

50. Long term NSAIDS has
shown to cause
gastroduodenal problems,
renal toxicity due to COX-
1 suppression
Beneficial effects of Omega-
3 fatty acids, rh IL-11, TNF
antagonist on periodontitis
in diabetic patients have
been yet evaluated in
animal studies only.

51. OTHER TREATMENT
MODALITIES
Glitazone,
thiazolidinedione,
lowers the level of P.
gingivalis and
Fusobacterium
nucleatum LPS
induced IL-6
production in
adipocytes
Statins lower the
migration of
macrophage to
inflamed tissues
The action of both
these drugs to control
progression of
periodontitis is not
yet proved

52. PRECAUTIONS
Maintain
meticulous oral
hygiene,
Receive
supportive
periodontal
therapy,
Fluoride as caries
preventive
agents.
Diabetes mellitus
related
xerostomia –
Artificial saliva
substitutes
Natural salivary
stimulants-
sugarless gum,
chewing raw
carrots.
Plan treatment
either before or
after periods of
insulin peak
activity
If patient is on
insulin, dentist
should determine
exact type being
used, its activity,
onset and time of
peak activity
Stress reduction
and adequate
pain control is
required as they
increase
epinephrine and
cortisol secretion
that elevate blood
glucose levels.

53. PUBERTY

54. PUBERTY
 Increased testosterone (in males) and increased
estradiol (in females) is seen.
 Increased no. of Prevotella Intermedia sp. seen, as
they substitute Progesterone & estrogen for menadione
(Vitamin K) as an essential nutrient.
 Increase in no. of Capnocytophaga species is seen,
responsible for the increased bleeding tendency
observed during puberty .
Oral manifestations: Gingivitis,
Gingival enlargement, Recurrent
apthous ulcers, Aggressive
periodontitis (0.1% to 0.4%)

55.  Clinical Features Of Puberty Induced
Gingivitis
i) Marginal & interdental gingival enlargement found
primarily on the facial surfaces, with lingual
surfaces remaining relatively unaltered.
ii) Increased gingival bleeding tendency
iii) Increased inflammation with relative less amounts
of plaque
i) When puberty is passed, the inflammation tends to
subside but does not disappear until adequate
plaque control is achieved.

56.  TREATMENT
i) Scaling and root planing is the treatment
of choice as symptoms reduced when
puberty ends.
ii) If enlargement is more, Gingivectomy is
done

57. MENSTRUATION

58. MENSTRUATION
During
menstruation,
changes seen are
Gingivitis
Increase in
GCF flow
Enlarged
hemorrhagic gingiva
in days preceding
menstrual flow
Minor
increase in
Tooth
mobility

59. In addition to gingival inflammation
 intraoral recurrent apthous ulceration
 herpes labialis lesions
 infections with Candida Albicans
are seen in some women and seem to be associated with increased
Progesterone levels during reproductive cycle.

60. PREGNANCY

61. PREGNANCY GINGIVITIS (INDEX)
 Pathogenesis
 Effect on Microbiota
 Effect of Estrogen and Progesterone
 Effect on Immune system
 Clinical Features
 Treatment

63. During pregnancy there is increased
levels of sex steroid hormones
Main estrogen in plasma in
pregnancy is estradiol; and main
progesterone is progestin

64. By the end of 3rd trimester, plasma
peak levels of these hormones are
100 ng/ml and 6ng/ml which is 10-30
times more than menstrual levels

65. PREGNANCY GINGIVITIS
Gingival inflammation, initiated by plaque, and
exacerbated by these hormonal changes in 2nd
and 3rd trimester of pregnancy, is referred as
Pregnancy Gingivitis. (seen in 30-100% cases)
First described in 1877
Gingival inflammatory changes usually begin in 2nd
month of pregnancy, and  in severity to 8th month,
after which there is abrupt decrease related to
reduction of sex steroid hormone secretion.

68.  .
There is 55 fold increase in P.
Intermedia in subgingival
plaque
Gestational hormones act as
growth factors for P. Intermedia
by satisfying the napthoquinone
requirement for bacteria

69.  .
Campylobacter level is directly
related to estradiol level
Bacteroides melaninogenicus sp.
also increases in pregnancy (55 fold)
and in those taking contraceptives
(16 fold)

71. Effect of Estrogen
Estrogen stimulates proliferation of gingival fibroblasts, synthesis and
maturation of the gingival CT.
Cause increase in leakage of leukocytes and plasma proteins from
post capillary venules by affecting the endothelial lining, contributing
to enhanced gingival inflammation
↓ Keratinization along with increase in epithelial glycogen results in
decreased effectiveness of the epithelial barrier

72. Effect of Progesterone
Increased Circulatory levels of Progesterone
enhances capillary permeability and dilatation by
forming gaps in endothelial lining of vessels,
resulting in increased gingival exudate
This increased gingival exudate effect caused by
progesterone is of long duration as compared to
same effect produced by histamine that is of short
duration.

73. Effect of Progesterone
It inhibits collagenase activity thus resulting in
accumulation of excess collagen in connective
tissue, causing enlargement.
Increased Progesterone levels ↓ the degree of
keratinization of gingival epithelium

74. • These hormones also  rate of folate metabolism in
oral mucosa.
• Since folate is required for tissue maintenance (DNA
formation), increased metabolism could deplete folate
stores and inhibit tissue repair.
• Thus folic acid tablet is always recommended in
pregnancy

76.  .
↓ Neutrophil chemotaxis and phagocytosis, alongwith T-cell responses further
causes the suppression of immune system to plaque
Progesterone in particular stimulates the production of inflammatory
mediator PGE2 & increased accumulation of PMNLin the gingival
sulcus
↓ CD4 T and
B
lymphocytes
during
pregnancy,
thus
CD4/CD8
ratio also
decreases,
leading to an
immunodef-
icient state.
↓ levels of
Plasminogen
activator
inhibitor type
2 (PAI-2), an
important
inhibitor of
tissue
proteolysis
Peripheral
blood
lymphocytes
showed a
decreased
response to
bacterial
antigens
↓ IL-6
production
by human
gingival
fibroblasts
(upto
50%)

78. Pregnancy Gingivitis
 Gingival enlargement occur in 2 forms:
1. marginal and generalized
2. single or multiple tumor like masses

79. 1. Marginal enlargement
 Generalized enlargement, more prominent
interproximally than on facial/lingual surface.
 Enlarged gingiva is bright red or magenta,
soft, friable and has a smooth shiny surface
 Spontaneous bleeding or on slightest
provocation

80. 2. Tumor like enlargement
- discrete, mushroom shaped, flattened spherical mass that
protrudes from gingival margin / interproximal space
- Tends to expand laterally, and pressure from tongue and
cheek perpetuate its flattened appearance
- Dusky red or magenta, with smooth, glistening surface that
often exhibits numerous deep red, pinpoint markings.

81. - Superficial lesion, that do not invade underlying bone.
- Usually painless, unless complicated by plaque
accumulation.
Site –
anterior papilla of maxillary teeth (most common)
Gingiva is involved in 70% of cases, followed by tongue,
lips and buccal mucosa.

82.  Histopathology
 Angiogranuloma
 Both marginal and tumor like enlargements consisting
of central mass of CT with numerous diffusely
arranged, newly formed engorged capillaries
 Chronic inflammatory infiltrate
 Thickened stratified squamous epithelium, with
prominent rete pegs, intercellular bridges, and
leukocytic infiltration.

83. TREATMENT
 Pregnant women need to be educated on the consequences of pregnancy
on gingival tissues and thoroughly motivated in plaque control measures,
with professional treatment as required.
 They are likely to be more comfortable to receive dental treatment during
the second trimester than in the first or third trimester of pregnancy,
although emergency treatment is permissible at any stage during
pregnancy

84.  Scaling and root planing
 Treatment of tumor like gingival
enlargements consist of surgical excision
The enlargement recurs unless all irritants
are removed.

85.  Penicillin and cephalosporin are relatively safer but
patient obstetrician consultation is warranted.
 Paracetamol is the safest anti inflammatory drug

86. When to Treat
 Gingival lesions in pregnancy should be treated
as soon as they are detected, although not
necessarily by surgical means. 2nd trimester is
the safest period of surgical excision.
 SRP and adequate oral hygiene measures may
reduce the size of the enlargement. Gingival
enlargements do shrink after pregnancy, but
they usually do not disappear.

87.  Lesions should be removed surgically during pregnancy
only if they interfere with mastication or produce an
esthetic disfigurement that the patient wishes to remove.
 After pregnancy, the entire mouth should be reevaluated,
radiographs should be taken, and the necessary treatment
undertaken.
 Emphasis should be on 1) preventing gingival disease
before it occurs (by doing scaling in each trimester) and 2)
treating existing gingival disease before it worsens.

88. MENOPAUSE

89. Menopausal Gingivostomatitis
• There is overall ↓ in estrogen output with estrone as the predominant form
• ↓ salivary gland flow
• Oral discomfort, burning sensation(20-90%), xerostomia or bad taste
• Atrophic gingivitis develop in some cases, in which gingival tissues develop
abnormal paleness.

90. Menopausal Gingivostomatitis
• Some may develop menopausal gingivostomatits, in which gingival tissues are
shiny and dry, bleed readily, and appear pale to erythematous in color.
• Gingival lesions during this phase tend to be desquamative in nature
• Patients with periodontitis have more chances of osteoporosis.

91.  Osteoporosis is frequently seen in women during
menopause due to decreased production of
estrogen. It causes suppression of calcium
absorption, increase in calcium excretion and
osteocyte apoptosis.
 Periodontitis in such patients release TNF-α that
induce collagenase activity, resulting in more bone
loss

92. TREATMENT
 During menopause, women with both periodontitis
and osteoporosis should be treated for both.

93. ORAL
CONTRACEPTIVES

94. HORMONAL CONTRACEPTIVES
 Contraceptives utilize synthetic gestational hormones (estrogen and
progesterone), to reduce the likelihood of ovulation/implantation
 Less dramatic but similar effects to pregnancy are sometimes observed
in the gingiva of hormonal contraceptive users.
 The most common oral manifestation of elevated levels of ovarian
hormones is an increase in gingival inflammation with an
accompanying increase in gingival exudate.

95. Effect on tissue response
Gingivitis can be minimized by establishing low plaque levels at the beginning of oral contraceptive
therapy
Human gingiva has receptors for progesterone and estrogen providing evidence that
gingiva is a target tissue for both gestational hormones.
Both estrogen and progesterone increase gingival exudate, associated with
inflammatory edema

96. OSTEOPOROSIS

97. OSTEOPOROSIS
Osteoporosis means literally
_porous bone, a condition
where there is too little bone to
provide mechanical support.
Osteopenia- reduction in bone
mineral density below than
what is required for mechanical
support.

98. Relationship between Periodontal disease and
Osteoporosis
 Many studies have shown positive association
between osteoporosis and alveolar crest
resorption.
 Fractures are very common in these patients
 Calcium and Vitamin D supplements have shown
positive impact on osteoporosis and periodontal
disease.

99.  Osteoporosis is frequently seen in women during
menopause due to decreased production of
estrogen. It causes suppression of calcium
absorption, increase in calcium excretion and
osteocyte apoptosis.
 Periodontitis in such patients release TNF-α that
induce collagenase activity, resulting in more bone
loss

100.  Harmone relacement therapy (HRT) is estrogen therapy that decrease osteoclast
formation and increase lifespan of osteoblasts and osteocytes. Dentist should refer
to medical practitioner for this.
 Nasal and subcutaneous calcitonin are available for postmenopausal
osteoporosis. Calcitonin is inhibitor of osteoclastic activity.
 HRT, Parathyroid harmone (PTH), Teriparatide improve osteoporosis and
periodontal regeneration
TREATMENT

101. ORAL
HYPERPARATHYROIDISM

102. HYPERPARATHYROIDISM
Osteitis fibrosa cystica or Von Recklinghausen's bone disease
• Generalized demineralization of the skeleton.
• Increased osteoclasis with proliferation of the connective tissue in the
enlarged marrow spaces.
• Cause hypercalcemia, hypercalciuria and decreased bone density.

103. Oral changes-
• Malocclusion, spacing in teeth, tori, exostosis, teeth
sensitive to percussion and mastication, tooth mobility,
high risk of bone fractures.
• Cause preferential loss of cortical bone and preservation
of trabecular bone. Tori and exostosis seen are due to
expansion of trabecular bone at expense of cortical
bone with possible contribution from mechanical forces
present in oral cavity.

104. Oral changes-
• Radiographic evidence: widening of the periodontal space,
absence of the lamina dura, soft tissue calcification (pulp stones)
radiolucent cyst like spaces- brown tumors
• Brown tumors are radiolucent osteolytic lesions and are red
brown masses.
• Sometime radiolucency in periapical region misdiagnosed
as lesion due to endodontic origin. Medical history is very
important for correct diagnosis.