2. Postmenopause Issues for primary care physicians and gynecologists: –Hormonal changes –Cardiovascular disease –Osteoporosis –Post menopausal bleeding (PMB) –Abnormal PAP’s –Sexual Function –Depression –Cancer screening and prevention –Lifestyle and habits

3. Causes of Mortality Men and Women Cardiovascular Disease 2199.9/100,000 Heart disease 1772.2/100,000 Heart disease 1772.2/100,000 Cerebrovascular diseases 427.7/100,000 Cerebrovascular diseases 427.7/100,000 Malignant Neoplasms (all) 1316.6/100,000 Influenza and pneumonia 166.4/100,000

4. Postmenopause Cardiovascular Disease –Leading cause of death in men and women –Due to lack of protective effect of estrogen –Preventive measures Exercise Diet Quit smoking Moderate alcohol intake Low dose aspirin ??

5. Postmenopause Hot flushs –Very disturbing –Every few min to hours. Mostly first year –Less in obese women –treatment HRT Tibolone SSRIs may reduce by 60% Gabapentine (neurontoin) Clonidine (captopril)

7. Clinical Definitions Osteopenia- reduction in bone mass below the theoretical fracture threshold. Osteoporosis- reduction in the bone mass to a level where there is increased risk of fracture in the absence of trauma. Or a fracture has already occurred.

9. “I’ve lost six inches in height and none of my clothes fit me anymore. Plus, it’s hard to get clothes that look nice when my back is so hunched over.” Typical comments from people with osteoporosis

10. Overview Overview Bone with Osteoporosis Normal Bone Osteoporosis causes weak bones. In this common disease, bones lose minerals like calcium. They become fragile and break easily.

11. A woman’s hip fracture risk equals her combined risk of breast, uterine and ovarian cancer.

12. The most common breaks in weak bones are in the wrist, spine and hip.

13. Osteoporotic bone Osteoporotic fracture

14. Classification: Primary –Type 1- post menopausal –Type 2- senile Secondary –Medications –Steroid induced –Medical conditions Spinal cord injury

15. Type 1 (postmenopausal) Women > Men (6:1 ratio) Related to estrogen Affects trabecular bone Associated with vertebral fractures Unrelated to calcium intake High bone turnover Vertebral compression fractures

16. Type 2 (Senile Osteoporosis) Elderly Age >75yrs Women:Men 2:1 Calcium deficiency is major factor Affects trabecular and cortical bone Vertebral compression, hip, and distal radius fxs. Slow bone turnover

17. Common Locations of Osteoporotic Fractures in General Population Thoracic (vertebral) compression fractures Hip fractures Wrist/extremity fractures.

18. Medical Conditions Associated With Secondary Osteoporosis Endocrine and metabolic *Hypogonadism *Hyperadrenocorticism *Thyrotoxicosis *Anorexia nervosa *Hyperprolactinemia *Porphyria *Hypophosphatasia *Type 1 diabetes *Pregnancy *Hyperparathyroidism *Acromegaly Disorders of collagen metabolism *Osteogenesis imperfecta *Homocystinuria *Ehlers-Danlos syndrome *Marfan syndrome

19. Medical Conditions Associated With Secondary Osteoporosis Nutritional Malabsorption syndromes, malnutrition Chronic liver disease Gastric operations Vitamin D deficiency Alcoholism Other Rheumatoid arthritis Myeloma Certain cancers Immobilization Renal tubular acidosis Hypercalciuria Chronic obstructive pulmonary disease Organ transplantation Cholestatic liver disease Mastocytosis Thalassemia

20. Some Medications that can cause Secondary Osteoporosis Vitamin D Toxicity Phenytoin Glucocorticoids Phenobarbital Excessive thyroid hormone replacement Heparin Gonadotropin-releasing hormone antagonists

21. How does this obvious bone loss happen? Bone is a living, growing, tissue Healthy bones are not quiescent. They are constantly destruction, but imbalance between the formation being remodeled. This is not simply a problem of bony and destruction of bone. Two types of bone –Cortical –Trabecular

22. Cortical (Compact) Bone 80% of the skeletal mass Provides a protective outer shell around every bone in the body Slower turnover Provides strength and resists bending or torsion

23. Trabecular (Cancellous) Bone 20% of the skeletal mass, but 80% of the bone surface. less dense, more elastic, and higher turnover rate than cortical bone. appears spongy found in the epipheseal and metaphysal regions of long bones and throughout the interior of short bones. constitutes most of the bone tissue of the axial skeleton (skull, ribs and spine). interior scaffolding maintains bone shape despite compressive forces.

24. Types of Cells in Bone Tissue

25. Bone Remodeling OsteoBlasts Build Bone. OsteoClasts Create Cavities in bone.

26. Bone mass declines with age. Remodeling occurs at discrete foci called bone remodeling units (BRUs). Number of active BRUs increase with age, resulting in increased bone turn over. Osteoblasts are not able to completely fill cavities created by osteoclasts and less mineralized bone is formed. Endosteal bone loss is partially compensated by periosteal bone formation. This leads to trabecular thinning.

27. Bone Remodeling Unit Osteoclast Osteoblast New bone Lining cells

28. Scanning electron micrograph of slice of osteoporotic cancellous bone from the fourth lumbar vertebra of an elderly woman. www.grad.uc l.ac.uk

32. Bones are living organs Calcium is deposited and withdrawn from bones daily. Bones build to about age 30. We need to build up a healthy bone account while young and continue to make deposits with age.

33. After mid-30’s, you begin to slowly lose bone mass. Women lose bone mass faster after menopause, but it happens to men too. Bones can weaken early in life without a healthy diet and the right kinds of physical activity.

34. The good news: Osteoporosis is preventable for most people! Start building healthy bones while young. Healthy diet and lifestyle are important for BOTH men and women.

35. The National Osteoporosis Foundation (NOF) recommends FIVE simple steps to bone health and osteoporosis prevention … Simple Prevention Steps

36. Step 1 Get your daily recommended amounts of calcium and vitamin D.

37. Calcium requirements vary by age If this is your age Then you need this much calcium each day (mg) 0 to 6 months210 7 to 12 months270 1 to 3 years500 4 to 8 years800 9 to 18 years1,300 19 to 50 years1,000 Over 50 years1,200 Growth spurt

38. You need more vitamin D as you age Age Daily vitamin D needs in International Units (IU) 600 IU 200 IU 400 IU 0 100 200 300 400 500 600 up to 5051-70over 70

39. What about Vitamin D? Main dietary sources of vitamin D are: Fortified milk (400 IU per quart) Some fortified cereals Cold saltwater fish (Example: salmon, halibut, herring, tuna, oysters and shrimp) Some calcium and vitamin/mineral supplements

40. Vitamin D from sunlight exposure Vitamin D is manufactured in the skin following direct exposure to sun. Amount varies with time of day, season, latitude and skin pigmentation. 10–15 minutes exposure of hands, arms and face 2–3 times/week may be sufficient (depending on skin sensitivity). Clothing, sunscreen, window glass and pollution reduce amount produced.

41. Step 2 Engage in regular weight-bearing exercise. Even simple activities such as walking, stair climbing and dancing can strengthen bones.

42. Step 3 Avoid smoking and excessive alcohol & soft drinks 12 oz.5 oz. 1.5 oz. MyPyramid.gov recommends no more than 1 drink per day for women and 2 for men.

43. Step 4 Talk to your doctor about bone health.

44. Step 5 Have a bone density test and take medication when appropriate. Source of photo: USDA ARS Photo Unit Photo by Peggy Greb Testing is a simple, painless procedure.

45. Diagnostic Outline What is bone density testing? Why is it done? Who should be tested? When should it be repeated? How is it interpreted?

46. Why Should We Care About Bone Density? Osteoporosis is common - >50% of Saudi women have osteoporosis or low bone mineral density (BMD) Osteoporosis is serious - Osteoporotic fractures cause increased morbidity and mortality Osteoporosis is easy to diagnose - Bone density testing can detect osteoporosis before the first fracture occurs Good treatments are available- Fracture risk can be reduced by about 50%

47. Bone Densitometry Non-invasive test for measurement of BMD Major technologies –Dual-energy X-ray Absorptiometry (DXA) –Quantitative Ultrasound (QUS) –Quantitative Computerized Tomography (QCT) Many manufacturers Numerous devices Different skeletal sites

48. 48 Indications For Bone Density Testing All women age 65 and older ( 50 in Saudi) All men age 70 and older Adults with a fragility fracture Adults with a disease or condition associated with low bone density Adults taking medication associated with low bone density Anyone being treated for low bone density to monitor treatment effect Anyone not receiving therapy, in whom evidence of bone loss would lead to treatment Women discontinuing treatment should be considered for bone density testing according to the indications listed above.

49. DXA “Gold-standard” for BMD measurement Measures “central” or “axial” skeletal sites: spine and hip May measure other sites: total body and forearm Extensive epidemiologic data Correlation with bone strength in-vitro Validated in many clinical trials

50. DXA Technology X-ray Source (produces 2 photon energies with different attenuation profiles) Photons Collimator (pinhole for pencil beam, slit for fan beam) Patient Detector (detects 2 tissue types - bone and soft tissue) Very low radiation to patient. Very little scatter radiation to technologist

51. DXA Imaging of the Spine For Detection of Vertebral Fractures Hologic: IVA or RVA Normal Fracture GE: DVA or LVA Normal Fracture

52. Bone Density Testing Is Done For Three Reasons To diagnose osteoporosis To predict fracture risk To monitor therapy

53. What DXA Really Measures: Bone Mineral Content (BMC) In Grams and Area In cm 2 “Areal” BMD is calculated in g/cm 2 “T-score” compares the patient’s BMD with the young-normal mean BMD and expresses the difference as a standard deviation (SD) score

54. Which Skeletal Sites Should Be Measured? Every Patient Spine –L1-L4 Hip –Total Proximal Femur –Femoral Neck –Trochanter Some Patients Forearm (33% Radius) –If hip or spine cannot be measured –Hyperparathyroidism –Very obese Use lowest T-score of these sites

55. T-score Example: T-score = 0.7 g/cm 2 - 1.0 g/cm 2 0.1 g/cm 2 = - 3.0 Patient’s BMD – Young-Adult Mean BMD 1 SD of Young-Adult Mean BMD

56. WHO Study Group. 1994.56 Diagnostic Classification ClassificationT-score Normal-1 or greater OsteopeniaBetween -1 and -2.5 Osteoporosis-2.5 or less Severe Osteoporosis -2.5 or less and fragility fracture

57. Diagnosis Caveats T-score -2.5 or less does not always mean osteoporosis –Example: osteomalacia Clinical diagnosis of osteoporosis may be made with T-score greater than -2.5 –Example: atraumatic vertebral fracture with T-score equals -1.9 Low T-score does not identify the cause –Medical evaluation should be considered –Example: celiac disease with malabsorption

58. Why -2.5? Professor John Kanis says: “Such a cutoff value identifies approximately 30% of postmenopausal women as having osteoporosis using measurements made at the spine, hip or forearm. This is approximately equivalent to the lifetime risk of fracture at these sites.”

59. Fracture Risk Doubles With Every SD Decrease in BMD Bone Density (T-score) Relative Risk for Fracture

60. Bone Density & Age vs. Fracture Risk Ten Year Fracture Probability (%) Age 80 70 60 50 Probability of first fracture of hip, distal forearm, proximal humerus, and symptomatic vertebral fracture in women of Malmö, Sweden.

61. Why Do Serial BMD Testing? To monitor response to therapy by finding an increase or stability of bone density To evaluate for non-response by finding loss of bone density - suggesting the need for reevaluation of treatment and evaluation for secondary causes of osteoporosis To follow patients not being treated who are at risk of bone loss, in order to determine if treatment is needed

62. When Should Repeat BMD Testing Be Done? When expected change in BMD equals or exceeds the “Least Significant Change” (LSC) Intervals between BMD testing should be determined according to each patient’s clinical status –Consider one year after initiation or change of therapy –Longer intervals once therapeutic effect is established –Shorter intervals when rapid bone loss is expected

63. Always Compare BMD Never Compare T-scores

64. The Osteoporosis Challenge To educate all patients on measures to maintain good bone health To identify patients at high risk for osteoporosis To use bone densitometry to detect low bone density BEFORE a fracture occurs To use pharmacologic therapy appropriately

65. Postmenopause Osteoporosis Treatment –HRT/ERT –Bisphosphonates (Alendronate, Risedronate, Zoledronic acid) –SERM’s (Raloxifene, Tamoxifen) –Calcitonin –Parathyroid hormone and fluoride –Plus weight-bearing exercise, 1200 mg Calcium, and 800 u Vitamin D

66. *Hormone therapy (HRT). Estrogen + progesterone HRT Estrogen HRT The treatment of menopause symptoms (eg, vasomotor and urogenital ) remains the primary indication for EPT and ET #Benefits #Risks

67. *Significant risk for coronary heart disease (CHD) and venous thromboembolism observed during first year of therapy. CHD risk not significantly elevated in the following years breast cancer risk directly related to duration of therapy. Increased after 10 years of therapy the WHI study, fewer than 10 additional cases each of heart attack, stroke and breast cancer occurred each year among 10,000 women taking combination hormone therapy compared with 10,000 women taking placebo

68. WHI 2002 -- HRT vs Placebo: Outcomes, ave follow up 5.2 yrs (Hazard Ratio) –Invasive Breast Cancer = 38 vs 30/10,000 person yrs (1.26) –CHD = 37 vs 30/10,000 (1.29) –Stroke = 29 vs 21/10,000 (1.41) –Venous Thromboembolic disease = 34 vs 16/10,000 (2.11) –Colorectal cancer = 10 vs 16/10,000 (0.63) –Hip fracture = 10 vs 15/10,000 (0.66) –Vertebral fracture = 9 vs 15/10,000 (0.66) –No change in endometrial and lung CA

69. Bisphosphonates Proven to Prevent Bone Loss. Cyclic etidronate is shown to prevent BMD loss in acute SCI when given 800mg qd for 2 wks. Pearson et al, APMR, 1997. Pamidronate (iv) 30mg iv x 3 days given with vitamin D and calicum inhibits bone resorption and reverses inhibition of PTH. Chen and Stein, JSCM, 2001. 30mg pamidronate monthly for 6 months with calcium inhibits bone hyperresorption and significantly reduces bone loss. Nance et al, APMR, 1999. Aledronate (fusamax) 10 mg/d or 70 mg/wk and tiludronate have also been found to be effective. Several different bisphosphonates have been shown to be effective. No one drug is clearly better than the others. The long term effects and risks of treatment with bisphosphonates is unknown.

70. Mechanism of Action Bisphosphonates 1.Inhibit osteoclast mediated bone resorption 2.Inhibit osteoclast 1.Activity 2.Recruitment 3.Adhesion 3.Osteoclast apoptosis

71. N2 (nitrogen) Ca (calcium)

72. Eastell, R. N Engl J Med 1998;338:736-746 Effect of Therapy on Lumbar-Spine Bone Mineral Density in Postmenopausal Women with Osteoporosis

73. Postmenopause Sexual Function –At least 50% of postmenopausal women are sexually active –Ask them –H&P, ?Medications –Advise: OTC lubricants (Astroglide, KY, Replens), Vaginal estrogen (Vagifem, Premarin, Estrace), Topical testosterone

74. Postmenopause Depression –10-20% of people will have at least one episode of depression in their lifetime –Affects twice as many women as men –Risk of recurrence 50% with one episode 75% with two episodes 85% with >2 episodes

75. Postmenopause Depression –Medications: SSRI’s (Prozac, Zoloft, Celexa, Lexapro etc) Wellbutrin XR –Other treatments: Psychotherapy Physical activity Sleep Get involved

76. Postmenopause Cancer Screening and Prevention –Mammograms annually –Colonoscopy q 5 years –Annual hemoccult testing –Quit smoking –Regular physicals

77. Postmenopause Lifestyle and Habits –Physical Activity –Calcium 1200 mg/d –Vitamin D 800 units/d –Quit smoking –Low dietary fat intake, high fiber intake –Moderate Alcohol consumption –Sleep