Reproductive

936 views
901 views

Published on

0 Comments
1 Like
Statistics
Notes
  • Be the first to comment

No Downloads
Views
Total views
936
On SlideShare
0
From Embeds
0
Number of Embeds
2
Actions
Shares
0
Downloads
59
Comments
0
Likes
1
Embeds 0
No embeds

No notes for slide

Reproductive

  1. 1. RISK STARTIFICATION AND DENTAL MANAGEMENT OF PATIENTS WITH DYSREGULATION OF THE REPRODUCTIVE SYSTEM Géza T. Terézhalmy, D.D.S., M.A. Endowed Professor in Clinical Dentistry The UTHSCSA Dental School San Antonio, Texas [email_address]
  2. 2. Reproductive tract dysregulation <ul><li>Reproductive hormones </li></ul><ul><ul><li>Progestins, androgens, and estrogens </li></ul></ul><ul><ul><ul><li>Denote a number of related hormones in each category </li></ul></ul></ul><ul><ul><ul><ul><li>All are steroid hormones derived from cholesterol </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Progesterone is the common precursor of both androgens and estrogens </li></ul></ul></ul></ul></ul>
  3. 3. Reproductive tract dysregulation <ul><li>Gonadal reproductive hormones </li></ul><ul><ul><li>Progestins </li></ul></ul><ul><ul><ul><li>Progesterone </li></ul></ul></ul><ul><ul><ul><ul><li>Antiproliferative effect on the endometrium </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Promote endometrial secretions </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Essential to maintain pregnancy </li></ul></ul></ul></ul><ul><ul><li>Androgens </li></ul></ul><ul><ul><ul><li>Required to convert to male phenotype </li></ul></ul></ul><ul><ul><ul><ul><li>Dihydrotestosterone </li></ul></ul></ul></ul><ul><ul><li>Estrogens </li></ul></ul><ul><ul><ul><li>Feminizing properties </li></ul></ul></ul><ul><ul><ul><ul><li>17  -estradiol </li></ul></ul></ul></ul>
  4. 4. Reproductive tract dysregulation <ul><li>Hypothalamic-pituitary-gonadal axis </li></ul><ul><ul><li>GnRH </li></ul></ul><ul><ul><ul><li>Pulsating secretion </li></ul></ul></ul><ul><ul><ul><ul><li>LH and FSH </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Testes </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Ovaries </li></ul></ul></ul></ul></ul>
  5. 5. Reproductive tract dysregulation <ul><li>Testes </li></ul><ul><ul><li>LH </li></ul></ul><ul><ul><ul><li>Leydig cells </li></ul></ul></ul><ul><ul><ul><ul><li> testosterone synthesis </li></ul></ul></ul></ul><ul><ul><li>FSH </li></ul></ul><ul><ul><ul><li>Sertoli cells </li></ul></ul></ul><ul><ul><ul><ul><li> synthesis of androgen binding protein </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Aromatize testosterone to estrogen </li></ul></ul></ul></ul>
  6. 6. Reproductive tract dysregulation <ul><li>Ovaries </li></ul><ul><ul><li>LH </li></ul></ul><ul><ul><ul><li>Thecal cells </li></ul></ul></ul><ul><ul><ul><ul><li> androstenedionesynthesis </li></ul></ul></ul></ul><ul><ul><li>FSH </li></ul></ul><ul><ul><ul><li>Granulosa cells </li></ul></ul></ul><ul><ul><ul><ul><li> synthesis of testosterone </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Aromatize testosterone to estrogen </li></ul></ul></ul></ul>
  7. 7. Reproductive tract dysregulation <ul><li>Hypothalamic-pituitary-gonadal axis </li></ul><ul><ul><li>Feedback mechanisms </li></ul></ul><ul><ul><ul><li>Negative </li></ul></ul></ul><ul><ul><ul><li>Positive </li></ul></ul></ul>
  8. 8. Reproductive tract dysregulation <ul><li>Reproductive hormones in the adrenal cortex </li></ul><ul><ul><li>Zona glomerulosa </li></ul></ul><ul><ul><ul><li>Angiotensin II </li></ul></ul></ul><ul><ul><ul><ul><li>Aldosterone </li></ul></ul></ul></ul><ul><ul><li>Zona fasciculate </li></ul></ul><ul><ul><ul><li>ACTH </li></ul></ul></ul><ul><ul><ul><ul><li>Cortisol </li></ul></ul></ul></ul><ul><ul><li>Zona reticularis </li></ul></ul><ul><ul><ul><ul><li>Progesterone </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Testosterone </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Estrogen </li></ul></ul></ul></ul></ul>
  9. 9. Reproductive tract dysregulation <ul><li>Dysregulation of the reproductive system </li></ul><ul><ul><li>Three general mechanisms </li></ul></ul><ul><ul><ul><li>Disruption of the hypothalamic-pituitary axis </li></ul></ul></ul><ul><ul><ul><li>Inappropriate growth of estrogen-dependent or testosterone-dependent tissues </li></ul></ul></ul><ul><ul><ul><li>Decreased estrogen and/or androgen secretion </li></ul></ul></ul>
  10. 10. Reproductive tract dysregulation <ul><li>estrogen synthesis </li></ul>Pituitary prolactinoma <ul><li>Androgen synthesis </li></ul>Polycystic ovarian syndrome Hormone Disorder Disruption of the hypothalamic-pituitary-gonadal axis
  11. 11. Reproductive tract dysregulation Testosterone-dependent Prostatic hyperplasia Prostate cancer Estrogen-dependent Endometriosis Endometrial hyperplasia Breast cancer Hormone Disorder Inappropriate growth of hormone-dependent tissues
  12. 12. Reproductive tract dysregulation <ul><li>Estrogen </li></ul>Menopause  Estrogen and/or  Testosterone Hypogonadism Hormone Disorder Decreased estrogen and/or androgen secretion
  13. 13. Reproductive tract dysregulation <ul><li>Reproductive pharmacology </li></ul><ul><ul><li>The menstrual cycle </li></ul></ul><ul><ul><ul><li>Practical example of how reproductive hormones are integrated into a complex physiological system </li></ul></ul></ul>
  14. 14. Reproductive tract dysregulation <ul><li>Pharmacodynamics </li></ul><ul><ul><li>Reproductive hormones diffuse into circulation </li></ul></ul><ul><ul><ul><li>Bind to sex hormone-binding proteins </li></ul></ul></ul><ul><ul><ul><ul><li>Unbound fractions diffuse into target cells </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Interact with cytosolic receptors </li></ul></ul></ul></ul></ul>
  15. 15. Reproductive tract dysregulation <ul><li>Pharmacodynamics </li></ul><ul><ul><li>Estrogen receptors (ER  and ER  ) </li></ul></ul><ul><ul><ul><li>Dimerization of two estrogen-estrogen receptor complexes </li></ul></ul></ul><ul><ul><ul><ul><li>The dimer is transported into nucleus </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Binds to the estrogen receptor elements of DNA </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Co-activators or co-repressors enhance or inhibit the transcription of estrogen-dependent genes </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>The specific transcription factors seem to be tissue-dependent </li></ul></ul></ul></ul></ul>
  16. 16. Reproductive tract dysregulation <ul><li>Pharmacodynamics </li></ul><ul><ul><li>Androgen receptors </li></ul></ul><ul><ul><ul><li>In target tissues 5  -reductase converts testosterone into dihydrotestosterone </li></ul></ul></ul><ul><ul><ul><ul><li>Binds to cytosolic receptors, which are transported into nucleus </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Binds to the androgenic receptor elements of DNA </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Co-activators or co-repressors enhance or inhibit the transcription of androgen-dependent genes </li></ul></ul></ul></ul></ul>
  17. 17. Reproductive tract dysregulation <ul><li>Pharmaco-kinetics </li></ul><ul><ul><li>Absorption </li></ul></ul><ul><ul><ul><li>Route of administration </li></ul></ul></ul><ul><ul><li>Distribution </li></ul></ul><ul><ul><ul><li>Passive diffusion into target cells </li></ul></ul></ul><ul><ul><li>Metabolism </li></ul></ul><ul><ul><li>Excretion </li></ul></ul>
  18. 18. Reproductive tract dysregulation <ul><li>Pharmacotherapeutics </li></ul><ul><ul><li>Drugs are available to target most of the steps in gonadal physiology and pathophysiology </li></ul></ul><ul><ul><ul><li>Inhibitors of hormone synthesis </li></ul></ul></ul><ul><ul><ul><li>Hormones and hormone analogues for contraception </li></ul></ul></ul><ul><ul><ul><li>Hormones and hormone analogues for replacement </li></ul></ul></ul><ul><ul><ul><li>Hormone receptor antagonist </li></ul></ul></ul>
  19. 19. Reproductive tract dysregulation Promote ovulation Gonadorelin GnRH agonists Short-acting agents Breast and prostate cancer Goserelin Histrelin Leuprolide Nafarelin GnRH agonists Continuous administration Indications Drugs Mechanisms of action Inhibitors of hormone synthesis
  20. 20. Reproductive tract dysregulation Metastatic breast cancer Aminoglutethimidine Anastrozole Lerozole Exemestane Formestane Aromatase inhibitors Benign prostate hypertrophy Finasteride 5  -reductase inhibitors Indications Drugs Mechanisms of action Inhibitors of hormone synthesis
  21. 21. Reproductive tract dysregulation Induce ovulation Clomiphen Osteoporosis Raloxifen Breast cancer Tamoxifen Toremifen Selective hormone receptor modulators Indications Drugs Mechanisms of action Hormone receptor antagonists
  22. 22. Reproductive tract dysregulation - ? ? ? Clomiphen ? + - - Raloxifen ? + + - Toremifen ? + + - Tamoxifen + or - + + + Estrogen HPG axis Bone Endom-etrium Breast Drug Tissue-specific agonist (+)/antagonist activity of estrogen and SERMs
  23. 23. Reproductive tract dysregulation Medical abortion Mifepristone Progesterone receptor antagonist Polycystic ovarian syndrome Spironolactone Prostate cancer Flutamine Cyproterone Androgen receptor antagonists Indications Drugs Mechanisms of action Hormone receptor antagonists
  24. 24. Reproductive tract dysregulation Contraception Norgestrel Norethidrone Progestin-only contraceptives Contraception Estrogen/progestin (high-dose) Morning-after contraceptives Contraception Estrogen/progestin Combination oral contraceptives Indication Drugs Mechanisms of action Hormones for contraception
  25. 25. Reproductive tract dysregulation <ul><li>Combination oral contraceptives </li></ul><ul><ul><li>Estrogen inhibits mid-cycle surge of LH and FSH release </li></ul></ul><ul><ul><ul><li>Suppresses follicular development </li></ul></ul></ul><ul><ul><ul><ul><li>Inhibit ovulation </li></ul></ul></ul></ul><ul><ul><li>Progestin </li></ul></ul><ul><ul><ul><li>Limit the extent of endometrial growth </li></ul></ul></ul><ul><ul><li>Estrogen/progestin </li></ul></ul><ul><ul><ul><li>Alter tubal peristalsis and change cervical mucosal secretion </li></ul></ul></ul><ul><ul><ul><ul><li>Inhibit proper transport of both egg and sperm </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Inhibit fertilization </li></ul></ul></ul></ul></ul>
  26. 26. Reproductive tract dysregulation <ul><li>Combination oral contraceptives </li></ul><ul><ul><li>Adverse effects </li></ul></ul><ul><ul><ul><li>Long-term use </li></ul></ul></ul><ul><ul><ul><ul><li> Deep vein thrombosis </li></ul></ul></ul></ul><ul><ul><ul><ul><li> Pulmonary embolism </li></ul></ul></ul></ul><ul><li>Combination oral contraceptives have more beneficial than harmful effects </li></ul>
  27. 27. Reproductive tract dysregulation Amenorrhea Abnormal uterine bleeding Medroxy-progesterone Progestins Menopause Conjugated estrogen Estrogens Indications Drugs Mechanisms of action Hormones for replacement
  28. 28. Reproductive tract dysregulation Hypogonadism in men Testosterone Androgens Menopause Conjugated estrogen + Medroxy-progesterone Estrogen + Progestin Indications Drugs Mechanisms of action Hormones for replacement
  29. 29. Reproductive tract dysregulation <ul><li>Hormones for replacement </li></ul><ul><ul><li>Highly effective to reduce postmenopausal symptoms </li></ul></ul><ul><ul><ul><li>Hot flashes </li></ul></ul></ul><ul><ul><ul><li>Vaginal dryness and atrophy </li></ul></ul></ul><ul><ul><ul><li>Osteoporosis </li></ul></ul></ul><ul><li>The routine use of both unopposed estrogen and combined estrogen/progestin therapy have more harmful than beneficial effects </li></ul>
  30. 30. Reproductive tract dysregulation   Cholecystitis   Venous thrombosis  ≈ CHD  ≈ Colorectal Ca   Osteoporosis Combination Estrogen Incidence of Risks/benefits of hormone therapy
  31. 31. Reproductive tract dysregulation Unknown ≈ Quality of life   Breast Ca ≈  Endometrial Ca   Stroke    Cognition Combination Estrogen Incidence of Risks/benefits of hormone therapy
  32. 32. Reproductive tract dysregulation <ul><li>Androgens </li></ul><ul><ul><li>Various testosterone formulations </li></ul></ul><ul><ul><ul><li>Supraphysiological doses to enhance athletic performance </li></ul></ul></ul><ul><ul><ul><ul><li>Suppression of hypothalamic-pituitary-gonadal axis </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Reduced testicular function </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Decreased sperm production </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Impaired fertility </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Gynecomastia (androgen converted to estrogen) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Erythrocytosis </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Dyslipidemia </li></ul></ul></ul></ul></ul>
  33. 33. Reproductive tract dysregulation <ul><li>PRINCIPLES OF DENTAL MANAGEMENT </li></ul>
  34. 34. Reproductive tract dysregulation <ul><li>Goals </li></ul><ul><li>Develop and implement timely preventive and therapeutic strategies compatible with the patients’ physical and emotional ability to undergo and respond to dental care </li></ul>
  35. 35. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Disruption of the hypothalamic-pituitary-gonadal axis </li></ul></ul><ul><ul><ul><li>Polycystic ovarian syndrome </li></ul></ul></ul><ul><ul><ul><ul><li>Androgen receptor antagonist </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Infertility </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Selective estrogen receptor modulator </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>GnRH agonist (short-acting agent) </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Prolactinoma </li></ul></ul></ul><ul><ul><ul><ul><li>Infertility </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Selective estrogen receptor modulator </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>GnRH agonist (short-acting agent) </li></ul></ul></ul></ul></ul>
  36. 36. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Inappropriate growth of hormone dependent tissue </li></ul></ul><ul><ul><ul><li>Endometriosis </li></ul></ul></ul><ul><ul><ul><ul><li>Progestin </li></ul></ul></ul></ul><ul><ul><ul><li>Endometrial hyperplasia </li></ul></ul></ul><ul><ul><ul><ul><li>Progestin </li></ul></ul></ul></ul><ul><ul><ul><li>Breast cancer </li></ul></ul></ul><ul><ul><ul><ul><li>GnRH agonist (continuous administration) </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Aromatase inhibitor </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Selective estrogen receptor modulator </li></ul></ul></ul></ul>
  37. 37. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Inappropriate growth of hormone dependent tissue </li></ul></ul><ul><ul><ul><li>Prostatic hyperplasia </li></ul></ul></ul><ul><ul><ul><ul><li>5  -reductase inhibitor </li></ul></ul></ul></ul><ul><ul><ul><li>Prostate cancer </li></ul></ul></ul><ul><ul><ul><ul><li>Androgen-receptor antagonist </li></ul></ul></ul></ul>
  38. 38. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Decreased estrogen or androgen secretion </li></ul></ul><ul><ul><ul><li>Hypogonadism (before adolescence) </li></ul></ul></ul><ul><ul><ul><ul><li>Androgen </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Estrogen </li></ul></ul></ul></ul><ul><ul><ul><li>Adult hypogonadism (male) </li></ul></ul></ul><ul><ul><ul><ul><li>Androgen </li></ul></ul></ul></ul><ul><ul><ul><li>Menopause </li></ul></ul></ul><ul><ul><ul><ul><li>Conjugated estrogen </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Conjugated estrogen/progestin combination </li></ul></ul></ul></ul>
  39. 39. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Menopause </li></ul></ul><ul><ul><ul><li>Osteoporosis </li></ul></ul></ul><ul><ul><ul><ul><li>Selective estrogen receptor modulator </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Bisphosphonate </li></ul></ul></ul></ul><ul><ul><li>Contraception </li></ul></ul><ul><ul><ul><li>Combination oral contraceptive </li></ul></ul></ul><ul><ul><ul><li>Progestin-only contraceptive </li></ul></ul></ul><ul><ul><li>Self-administration of androgens </li></ul></ul><ul><ul><ul><li>Dyslipidemia </li></ul></ul></ul>
  40. 40. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Functional capacity </li></ul></ul><ul><ul><ul><li>An individuals ability to perform a spectrum of common daily tasks </li></ul></ul></ul><ul><ul><ul><ul><li>Expressed in terms of metabolic equivalents (METs) </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Ability of the CV system to meet metabolic demand for oxygen </li></ul></ul></ul></ul></ul>
  41. 41. Reproductive tract dysregulation <ul><li>Medical history </li></ul><ul><ul><li>Poor functional capacity </li></ul></ul><ul><ul><ul><li>Increased cardiovascular risk </li></ul></ul></ul><ul><ul><ul><ul><li>Less than 4 METs </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Dress, eat, or use the toilet </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Walk around the house indoors </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Do light work around the house (dusting, washing dishes) </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Walk a block on level ground at 3.2 km/h </li></ul></ul></ul></ul></ul>
  42. 42. Reproductive tract dysregulation <ul><li>Vital signs </li></ul><ul><ul><li>Blood pressure </li></ul></ul><ul><ul><ul><li>Useful marker for CAD </li></ul></ul></ul><ul><ul><ul><li><180/110 mm Hg </li></ul></ul></ul><ul><ul><ul><ul><li>Not an independent risk factor for cardiovascular risk in association with non-cardiac procedures </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>>180/110 mm Hg constitutes a medical emergency </li></ul></ul></ul></ul></ul>
  43. 43. Reproductive tract dysregulation <ul><li>Vital signs </li></ul><ul><ul><li>Pulse pressure, rate, and rhythm </li></ul></ul><ul><ul><ul><li>Pulse pressure correlates closely with systolic BP </li></ul></ul></ul><ul><ul><ul><ul><li>Reliable cofactor to either rule out or confirm significant CVD </li></ul></ul></ul></ul><ul><ul><ul><li>Pulse rate <50 or >120 beats/min constitutes a medical emergency </li></ul></ul></ul><ul><ul><ul><li>PVCs </li></ul></ul></ul><ul><ul><ul><ul><li>Significant finding </li></ul></ul></ul></ul>
  44. 44. Reproductive tract dysregulation <ul><li>Treatment considerations </li></ul><ul><ul><li>Patients taking oral contraceptives </li></ul></ul><ul><ul><ul><li>Gingivitis </li></ul></ul></ul><ul><ul><ul><ul><li>Pyogenic granulomas </li></ul></ul></ul></ul><ul><ul><ul><li>Alveolar osteitis </li></ul></ul></ul><ul><ul><ul><li>Mandibular radiopacities </li></ul></ul></ul><ul><ul><ul><li>Melasma (melanoma) </li></ul></ul></ul><ul><ul><ul><li>Venous thrombosis (cerebral venous sinuses) </li></ul></ul></ul><ul><ul><ul><ul><li>Unilateral facial paralysis </li></ul></ul></ul></ul><ul><ul><ul><li>Drug-drug interactions </li></ul></ul></ul><ul><ul><ul><ul><li>Antibacterial agents </li></ul></ul></ul></ul>
  45. 45. Reproductive tract dysregulation <ul><li>Contraceptives and antibacterial agents </li></ul><ul><ul><li>There are no pharmacokinetic data to support the contention that antibacterial agents reduce the efficacy of contraceptives </li></ul></ul><ul><ul><li>* J Am Acad Dermato 2002;46:917-923 </li></ul></ul><ul><ul><li>Scientific evidence regarding the alleged interaction between antibacterial agents and contraceptives does not satisfy the “ Daubert standard” of causality </li></ul></ul><ul><li>*J Law Med Ethics 1996;24:273-274 </li></ul>
  46. 46. Reproductive tract dysregulation <ul><li>Treatment considerations </li></ul><ul><ul><li>Postmenopausal patients </li></ul></ul><ul><ul><ul><li>Reduced salivary flow </li></ul></ul></ul><ul><ul><ul><ul><li>Increased caries </li></ul></ul></ul></ul><ul><ul><ul><li>Oral dysesthesia </li></ul></ul></ul><ul><ul><ul><li>Taste alterations </li></ul></ul></ul><ul><ul><ul><li>Periodontal disease </li></ul></ul></ul><ul><ul><ul><li>Osteoporosis </li></ul></ul></ul><ul><ul><ul><ul><li>Rolaxifene </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Thromboembolism </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Bisphosphonate therapy </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Osteonecrosis </li></ul></ul></ul></ul></ul>
  47. 47. Risk stratification of patients on bisphosphonates <ul><li>Bisphosphonates </li></ul><ul><li>Fosamax (alendronate) </li></ul><ul><li>Actonel (risendronate) </li></ul><ul><li>Boniva (ibandronate) </li></ul><ul><ul><li>Mechanisms of action </li></ul></ul><ul><ul><ul><li>Inhibit osteoclastic and reduce osteoblastic activity </li></ul></ul></ul><ul><ul><li>Indications </li></ul></ul><ul><ul><ul><li>Prevention and treatment of osteoporosis </li></ul></ul></ul>
  48. 48. Risk stratification of patients on bisphosphonates <ul><li>The oral disease burden of patients with DBM </li></ul><ul><ul><li>An increasing body of literature suggests that bisphosphonate use, especially intravenous preparations, may be associated with osteonecrosis of the jaws </li></ul></ul>
  49. 49. Risk stratification of patients on bisphosphonates <ul><li>Bisphosphonate-associated osteonecrosis (BON) </li></ul><ul><ul><li>Case definition must meet all of the following </li></ul></ul><ul><ul><ul><li>Current or previous treatment with BPs </li></ul></ul></ul><ul><ul><ul><li>Exposed, necrotic bone in the maxillofacial region that has persisted for more than 8 weeks </li></ul></ul></ul><ul><ul><ul><li>No history of radiation therapy to the jaws </li></ul></ul></ul><ul><li>(J Oral Maxillofac Surg 2007;65:369-376.) </li></ul>
  50. 50. Risk stratification of patients on bisphosphonates <ul><li>Bisphosphonate-related osteonecrosis of the jaw (BRONJ) </li></ul><ul><ul><li>Systematic review of the literature from 1966 through 31 January 2006 - 368 cases </li></ul></ul><ul><ul><ul><li>Female to male ration - 3:2 </li></ul></ul></ul><ul><ul><ul><li>Mandible - 65%; maxilla - 26%; both jaws - 9% </li></ul></ul></ul><ul><ul><ul><li>Multifocal or bilateral involvement </li></ul></ul></ul><ul><ul><ul><ul><li>Maxilla - 31%; Mandible 23% </li></ul></ul></ul></ul><ul><ul><ul><li>Most lesions were posterior to the lingual mandible near the mylohyoid ridge </li></ul></ul></ul><ul><ul><ul><li>60% of the cases occurred after a tooth extraction or other dentoalveolar surgery </li></ul></ul></ul><ul><ul><ul><li>94% of the patients were treated with IV bisphosphonates </li></ul></ul></ul><ul><li>(Ann Intern Med 2006;144:753-761.) </li></ul>
  51. 51. Risk stratification of patients on bisphosphonates <ul><li>IV bisphosphonate-related osteonecrosis of the jaw (BRONJ) </li></ul><ul><ul><li>Population-based analysis based on data from the Surveillance, Epidemiology, and End Results (SEER) program linked to Medicare claims - 16,072 cancer patients and 28,698 controls </li></ul></ul><ul><ul><ul><li>Absolute risk of inflammatory conditions or surgery of the jaw at 6 years </li></ul></ul></ul><ul><ul><ul><ul><li>5.48 events per 100 patients using IV BPs </li></ul></ul></ul></ul><ul><ul><ul><ul><li>0.30 events per 100 patients not using B </li></ul></ul></ul></ul><ul><li>(J Natl Cancer Inst 2007;991016-1024.) </li></ul>
  52. 52. Risk stratification of patients on bisphosphonates <ul><li>Oral bisphosphonate-related osteonecrosis of the jaw (BRONJ) </li></ul><ul><ul><li>Data from the fracture intervention trial (FIT) long-term extension (FLEX) - 1099 women with osteoporosis </li></ul></ul><ul><ul><ul><li>After being on alendronate for 5 years, 5 mg or 10 mg </li></ul></ul></ul><ul><ul><ul><ul><li>5 year extension: alendronate, 5mg (n=329; alendronate 10 mg (n=333); placebo (n=537 for 5 years) </li></ul></ul></ul></ul><ul><ul><ul><li>No cases of BRONJ </li></ul></ul></ul><ul><ul><ul><ul><li>Even the long-term use of oral BPs caries little risk of BRONJ </li></ul></ul></ul></ul><ul><li>(JAMA 2006;296:2927-2938.) </li></ul>
  53. 53. Risk stratification of patients on bisphosphonates <ul><li>Strategies for the dental management of patients on bisphosphonates </li></ul>
  54. 54. Risk stratification of patients on bisphosphonates <ul><li>Risk stratification </li></ul><ul><ul><li>At risk category A </li></ul></ul><ul><ul><ul><li>Patients who have been treated with oral BPs </li></ul></ul></ul><ul><ul><ul><ul><li>Incidence of BON </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>0 to 0.34 percent </li></ul></ul></ul></ul></ul><ul><ul><ul><li>No apparent exposed/necrotic bone </li></ul></ul></ul><ul><ul><li>At risk category B </li></ul></ul><ul><ul><ul><li>Patients who have been treated with IV BPs </li></ul></ul></ul><ul><ul><ul><ul><li>Incidence of BON </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>≈ 20 percent </li></ul></ul></ul></ul></ul><ul><ul><ul><li>No apparent exposed/necrotic bone </li></ul></ul></ul><ul><li>(J Oral Maxillofac Surg 2007;65:369-376.) </li></ul>
  55. 55. Risk stratification of patients on bisphosphonates <ul><li>Dental management </li></ul><ul><ul><li>At risk category A </li></ul></ul><ul><ul><ul><li>Patients who have been treated with oral BPs </li></ul></ul></ul><ul><ul><ul><ul><li>General </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Routine dental treatment generally should not be modified </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Periodontal disease </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Preventive therapy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Appropriate forms of non-surgical therapy </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Judicious surgical treatment </li></ul></ul></ul></ul></ul>
  56. 56. Risk stratification of patients on bisphosphonates <ul><ul><ul><ul><li>Implant placement </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Paucity of data </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Patient may be at increased risk of BON </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Oral and maxillofacial surgery </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Conservative surgical techniques with primary closure </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Endodontics </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Routine endodontic technique </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><li>Restorative dentistry and prosthodontics </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Routine restorative procedures generally should not be modified </li></ul></ul></ul></ul></ul>
  57. 57. Risk stratification of patients on bisphosphonates <ul><ul><li>Stage 1 BRONJ </li></ul></ul><ul><ul><ul><li>Exposed/necrotic bone in patients who are asymptomatic </li></ul></ul></ul><ul><ul><ul><ul><li>No evidence of infection </li></ul></ul></ul></ul><ul><ul><ul><li>Treatment strategies </li></ul></ul></ul><ul><ul><ul><ul><li>Antimicrobial mouth rinse </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Removal of mobile segments of bony sequestrum </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Clinical follow-up on a quarterly basis </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Patient education </li></ul></ul></ul></ul><ul><li>(J Oral Maxillofac Surg 2007;65:369-376.) </li></ul>
  58. 58. Risk stratification of patients on bisphosphonates <ul><ul><li>Stage 2 BRONJ </li></ul></ul><ul><ul><ul><li>Exposed/necrotic bone associated with infection </li></ul></ul></ul><ul><ul><ul><ul><li>Pain and erythema in the region of the exposed bone with or without purulent drainage </li></ul></ul></ul></ul><ul><ul><ul><li>Treatment strategies </li></ul></ul></ul><ul><ul><ul><ul><li>Symptomatic treatment with a broad-spectrum oral antibacterial agent </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Antimicrobial mouth rinse </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Pain control </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Superficial debridement to relieve soft tissue irritation </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Patient education </li></ul></ul></ul></ul><ul><li>(J Oral Maxillofac Surg 2007;65:369-376.) </li></ul>
  59. 59. Risk stratification of patients on bisphosphonates <ul><ul><li>Stage 3 BRONJ </li></ul></ul><ul><ul><ul><li>Exposed/necrotic bone in patients </li></ul></ul></ul><ul><ul><ul><ul><li>Pain, infection, and one or more of the following </li></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Pathologic fracture </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Extraoral sinus tract </li></ul></ul></ul></ul></ul><ul><ul><ul><ul><ul><li>Osteolysis extending to the inferior border </li></ul></ul></ul></ul></ul><ul><ul><ul><li>Treatment strategies </li></ul></ul></ul><ul><ul><ul><ul><li>As in Stage 2 BRONJ </li></ul></ul></ul></ul><ul><ul><ul><ul><li>Surgical debridement/resection for longer term palliation of infection and pain </li></ul></ul></ul></ul><ul><li>(J Oral Maxillofac Surg 2007;65:369-376.) </li></ul>
  60. 60. Reproductive tract dysregulation <ul><li>Treatment strategies </li></ul><ul><ul><li>Should take into consideration the patient’s overall health as reflected by the patient’s medical history and vital signs </li></ul></ul><ul><li>Preventive strategies </li></ul><ul><ul><li>Oral hygiene </li></ul></ul><ul><ul><ul><li>Conventional vs. electromechanical toothbrushes </li></ul></ul></ul><ul><ul><li>Antibacterial mouthwashes </li></ul></ul><ul><ul><li>Topical fluorides </li></ul></ul><ul><ul><li>Sialagogues </li></ul></ul><ul><ul><ul><li>Pilocarpine (Salagen) </li></ul></ul></ul><ul><ul><ul><li>Cevimeline (Evoxac) </li></ul></ul></ul>
  61. 61. Reproductive tract dysregulation <ul><li>Potential medical emergencies </li></ul><ul><ul><li>Anticipate medical emergencies based on the patient’s medical history and vital signs </li></ul></ul>
  62. 62. Reproductive tract dysregulation

×