1. WHO OWNS THE BONES? “Patchwork Quilt” of Women’s Health Who screens? Who treats? Who teaches/ to whom? Whose job it it? RheumatologyEndocrinology Primary Care GynecologyGerontologyOrthopedicsOrganizationsNOFNAMSISCD

2. Overview Prevention and Treatment of Osteoporosis DemographicsScreeningPrevention/Lifestyle Risk Factors PharmaceuticalsNutriceuticals

3. Definition Osteoporosis is a skeletal disorder characterized by compromised bone strength predisposing to an increased fracture risk. BONE DENSITY=BONE DENSITY (70%) + BONE STRENGTH (30%) BONE DENSITY: grams of mineral per area BONE QUALITY: architecture, turnover, damage accumulation, and mineralization NIH Consensus Development Conference on Osteoporosis, 2000

4. Demographics 10 Million People have Osteoporosis 34 Million People have Osteopenia 1:2 Women will have an osteoporotic fracture in their lifetime 1.5 Million Fractures Annually –20% die within one year $18B Annually www.nof.org

5. Screening DEXA is most cost-effective screen today –All women at least 65 yo – Perimenopausal, if risk factors –Any adult > 50 yo with a fracture –Adults with a condition or on a medication associated with bone loss –Patients considering or currently on a medication for osteoporosis –Postmenopausal women considering discontinuation of HRT NOF Clinicians Guide to Prevention and Treatment of Osteoporosis

6. Unrecognized Vertebral Fractures in Hospitalized Patients

7. Undertreatment of Hip Fracture in Hospitalized Patients

8. Densitometry How often? –Not more than every 2 years Which bones? –Spine, Hip, Femoral Neck When to treat? –Osteoporosis –Osteopenia with another risk factor Lifestyle –Exercise, Calcium, Vitamin D, Smoking, Alcohol Risk Factors –Age, activity, diet, meds (steroids>3 months), stability, previous fracture, BMI 3 months), stability, previous fracture, BMI<21,hip fx in a parent, current smoking

9. Bone Densitometry Values T Score: Standard Deviation comparison of a patient’s bone density to a normal 25 yo. We now have comparison tables by sex and ethnic group. Normal –T score >-1.0 Osteoporosis –T score < -2.5 “Osteopenia” –T score -1.0 to -2.5

10. National Osteoporosis Risk Assessment (NORA) Bone DensityRR95% CI Normal BMD1 Osteopenia1.81.49-2.18 Osteoporosis4.033.59-4.53

11. FRAX SCORE WHO Fracture Risk Assessment Tool Uses calculations based on patient data to determine a 10-year risk of hip and major osteoporosis-related fracture http://www.shef.ac.uk/FRAX/index.htm

12. NAMS Recommendations Use lowest T-score to define diagnosis Prevention and nutritional measures first Drug Treatment: Any Vertebral Fracture All T-scores < -2.5 Anyone on steroids >3 months T-scores of -2 to -2.5 if one risk factor BMI<21 Fragility Fracture History Hip Fracture History in a Parent

13. Medical Workup 25-OH Vitamin D Levels FSHTSH Parathyroid Hormone Creatinine Clearance Alkaline Phosphatase Liver Enzymes Celiac Antibodies Protein Electrophoresis 24-hr. Urine –Calcium, Creatine, Sodium, Free Cortisol

14. Risk Factors used in FRAX Geographic Region RaceSexHeight/Weight Previous Fragility Fracture Family History of Osteoporosis Current Smoking Steroid Use (5 mg/da for over 3 months) Rheumatoid Arthritis Secondary Osteoporosis Alcohol (3 or more units daily) BMD (T score at femoral neck)

15. So Whom Do We Treat? Patients with previous hip or vertebral fracture T score of -2.5 or less at femoral neck, total hip, or spine T score of -1.0 to -2.5 (Osteopenia) AND: –Other prior fracture –Secondary cause associated with high fracture risk –FRAX risk of 3% or more at hip –FRAX risk of 20% or more for major osteoporosis related fracture at any site

16. Trends in Treatment Recommendations 2003 Patients with previous hip or vertebral fracture T-score of -2 at hip T-score of -1.5 to -2 at hip PLUS additional risk factor. 2008 Patients with previous hip or vertebral fracture T-score of -2.5 at femoral neck, total hip, or spine T-score of -1 to -2.5 at femoral neck, total hip, or spine AND: –Other fracture –Other risk factors –FRAX of 3% or more at hip –FRAX of 20% for other site

17. Treatment Options Nutrition and Supplements Exercise Fall Prevention Alcohol and Nicotine Avoidance Pharmaceuticals –Bisphosphanates –SERMs –PTH –HRT –Calcitonin

18. Bisphosphanates Generic AlendronateRisendronateIbandronate Zoledronic Acid PamidronateEtidronateTiludronate Brand Name FosamaxActonelBonivaReclastArediaDidronelSkelid

19. Bisphosphanates PreventionTreatmentComments Alendronate (Fosamax) 5 mg/da 35 mg/wk 10 mg/da 70 mg/wk Must take on empty stomach, early am, with 8 oz. water, no food for 30 min. Risendronate (Actonel) 5 mg/da 35 mg/wk 75 mg 2 days/wk 150 mg/mo 5 mg/da 35 mg/wk 75 mg 2 days/wk 150 mg/mo Same directions as for Alendronate Ibandronate (Boniva) 2.5 mg/da 150 mg/mo 3mg/3mo IVP Check creatinine before injection. Same directions as for Alendronate, but no food for 1hr. Zoledronic Acid (Reclast) 5 mg. annually IVPAcute phase reaction – muscle aches Some concern for atrial fibrillation

20. Bisphosphanates All are indicated for prevention and/or treatment of postmenopausal osteoporosis Bind permanently to bone to decrease osteoclastic activity and increase bone mass Concerns about bone quality (“frozen” bone) Implications for fertility – contraindicated in women planning pregnancy

21. Bisphosphanates Similar efficacy Adverse effects: Esophageal erosion, hypocalcemia, bone pain Contraindications: esophageal dysmotility, significant renal dysfunction, hypocalcemia Osteonecrosis of Jaw (ONJ): <1 case/100,000 years of exposure. Usually with high IV doses for cancer Rx. Khann. J.Rheumatol. 2009;Mar;36(3):478-90.

22. Estrogen Agonist/Antagonist (Formerly called SERMS) Raloxifene (Evista) Bind to ER, activating some/ blocking others Bind to ER, activating some/ blocking others Decrease vertebral fractures, but no significant effect on hip fractures Decrease vertebral fractures, but no significant effect on hip fractures One 60 mg tab daily One 60 mg tab daily Adverse Effects: hot flashes, VTE, leg cramps Adverse Effects: hot flashes, VTE, leg cramps Ettinger et al. JAMA 1999;282:637-645.

23. Pharmacologic Treatment Options Anabolics –Teriparatide (Forteo) Antiresorptives –Calcitonin –Estrogens –SERMS (Raloxifene/Evista) –Bisphosphanates AlendronateRisendronateIbandronate Zoledronic Acid

24. Recombinant Parathyroid Hormone (r-PTH:Teriparatide (Forteo) Stimulates new bone formation New fractures are significantly decreased –Vertebral decreased by 65% –Non vertebral decreased by 55% Concern about malignancies in mice Dosage –20 mcg SQ daily for 2 years Cost - $20. per day Neer, RM, et al. NEJM 2001;344:1434- 41

25. Calcitonin (Miacalcin, Fortical) Naturally occuring hormone which antagonizes the effects of PTH Reduces osteoclastic bone resorption 200 IU intranasal spray achieves 33% reduction in vertebral fractures in postmenopausal women with prior vertebral fractures (PROOF study) Chestnut et al. Am J. Med. 2000;109:267-276.

26. Compliance FACT After being prescribed a pharmaceutical for osteoporosis or osteopenia, less than 50% of patients have continued therapy at 6 mo Cost issues Side effect issues “Silent Disease” issues How can we affect this statistic???

27. Lifestyle Issues ExerciseCalcium Vitamin D Medications

28. Poor Consumption of Vitamin D NHANES III DATA National Health and Nutrition Evaluation Survey J.Amer Diet Assn. 2004:104:980-983

29. Bone Health Calcium: 35 RCTs document that calcium prevents or reduces bone loss in adults Dose –Premenopausal (or on HRT): 1000 mg daily –Postmenopausal: 1500 mg daily Vitamin D: Oral Vitamin D between 700-800 IU/d significantly reduces the risk of fractures 400 IU/d is not sufficient for prevention

30. Working Smarter, not Harder Shared Medical Appointments (SMA) Basics –Number served –Confidentiality statement –Charges (99214) 25-40’. 50% Counseling Dexa SMA –Data reviewed and distributed –Diagnoses established –Lifestyle measures –Therapies discussed

31. FINISH Thank you

32. Prescription Nutritionals 3 Primary Concerns for Women’s Health: Bone Health Cardiovascular Health Mental Well-Being Primary Nutrients with Supporting Evidence: Calcium Vitamin D Omega-3 Fatty Acids Folic Acid Vitamin B 6

33. Cardiovascular Health Omega-3 Fatty Acids: Eskimo observational studies Nurses Health Study Physician’s Health Study –RR 0.77 decreased mortality –850 mg can be expected to save 20 lives per 1000 patients with CHD over 3.5 yrs. Folic Acid Lowers homocysteine Improves endothelial function B Vitamins Nurses Health Study –RR 0.55 of MI in groups with highest levels of Folate and B 6 SHEEP Study –RR 0.66 of MI in women taking B vitamin supplements Calcium Significantly increases HDL:LDL Ratio Suggests 30% reduction in CV events

34. Mental Well-Being Omega-3 Fatty Acids Reverses inflammation from Omega-6 and dysmenorrhea Significant reduction in menstrual symptoms in adolescents Calcium 48% fewer PMS symptoms than placebo group Osteoporosis risk much greater in women with history of PMS Folic Acid Low folate has been linked to depression Depressed patients have increased homocysteine levels

35. Prescribing Nutriceuticals Write out above recommendations and send the patient to a pharmacy, healthfood store, Nutritionist, or Sams Club, Or.... Prescribe Nutriceuticals ENCORAMETAGENICS

36. Ideal Dosing of Nutritional Supplements for Women Calcium 1200 mg for women >51 (IOM) Doses >500 mg should be divided Better utilized if larger dose is at HS Vitamin D 400 IU (IOM) wrong New evidence suggests 700-800 IU Needed to absorb calcium and prevent hyperparathyroidism Omega-3 Fatty Acids 500/d in those at risk for CHD 1000 mg/d if documented CHD (AHA) Folic Acid 400 mcg/d (IOM) 0.8-5 mg being studied for CV benefit Larger dose in AM (prime time for MI)