Screen & Intervene Critical Challenges in Osteoporosis and Women’s Health

1. Critical Challenges in OsteoporosisPrevention and TreatmentCompleting the Journey From Trial- andExpert-Based Information to Clinical Applicationin The Primary Care Setting Screen & Intervene Critical Challenges in Osteoporosis and Women’s Health

2. Critical Challenges in OsteoporosisPrevention and Treatment What Have We Learned Thus Far—A Summary • Osteoporosis-An Undertreated Condition • Complications of Osteoporotic Fractures • Indications for Screening • Interpretation of BMD Measurements • Aggregate Analysis of Risk Factors

3. Critical Challenges in OsteoporosisPrevention and Treatment What Have We Learned Thus Far—A Summary • Treatment Indications and Triggers • Pharmacological Therapy for Fracture Prevention • Relationship between BMD changes and Vertebral/Nonvertebral Fractures • Vertebral and Nonvertebral Fracture Prevention • We will now discuss Adherence/Compliance, and Their Relationship to Outcomes

4. Definitions • Initiation- Getting the prescription filled. About 10% of prescriptions are never filled.     • Adherence- Taking the medicine. Often defined as taking more than  80% of pills over a specified period of time.     • Compliance- Taking the pills correctly. Important issue with bisphosphonates.     • Persistence- Still taking the pills. Often measured at the one year time point.

5. Non-AdherenceHow Large is The Problem? Studies of patient behavior show that LESS THAN 50%of the people who leave a doctor's office with a prescriptionadhere and comply with drug therapy

6. Persistence with Lipid-Lowering Therapy n = 610 Simons, et al MJA 1996; 164:208.

7. The Effects of Non-Adherence 1) Poor patient outcomes due to sub-optimal therapeutic response 2) Increased cost burden to society Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

8. Poor Patient Outcomes • Increased Morbidity due to disease “exacerbations” • More treatment “Failures” with potential for addition or switching of medications due to perceived inefficacy • More frequent Physician Visits • Increased Hospitalizations • Excess Mortality Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

9. Costs To Society • 10% excess in all hospital admissions • 125,000 to 200,000 deaths per year • 50-100 Billion dollars excess cost per year in the U.S. Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

10. What Are the Possible Causes of Poor Adherence? “Target disease" eclipsed by other chronic conditions? Complex dosing guidelines? Poor patient education (Health Illiteracy) POORADHERENCE Lack of positive reinforcement? Disruption to daily routine? (need for frequent dosing) Concern about side effects?

11. Health Literacy The degree to which individuals have the capacity to obtain, process, and understand basic information and make appropriate decisions about their health* 90 million people in the United States, nearly half of all adults, have difficulty understanding and using health information** *(Selden et al. 2000; Healthy People 2010, HHS 2000; Ratzan & Parker 2000) **(Institute of Medicine report- 2004)

12. Literacy Level Predicts Health Outcomes • Less knowledge of disease and self-care • Worse self-management skills • Lower use of screening • Lower medication compliance rates • Higher rates of hospitalization and morbidity • Literacy level is more important than racial or ethnic group, age, employment, income or education in predicting poor outcome

13. Patient Beliefs Affect Compliance • Don’t believe diagnosis or the seriousness of the diagnosis • Believe other diseases are more important • Believe side effects outweigh benefits • Concerned about their ability to carry out recommended action AARP Survey, 1985 National Prescription Buyers’ Survey, USA 1985

14. Lack of Communication • Study of 300 medical encounters: doctors spent average 1.3 minutes giving information1 • Study of 264 visits to family physicians.-during patient initial statement of the problem, physician interrupted after average of 23 seconds.2 • 50% of patients leave office visit not understanding what the doctor said3 Clement, Diab Care 1995;18:1204. Waitzkin. JAMA 1984;252:24411 Kravitz et al. Arch Intern Med 1993;153:1869. 2 Roter and Hall. Ann Rev Public Health 1989;10:163. Marvel JAMA 1999;281:283. 3

15. Physicians Contribute toPatients’ Poor Adherence By: • Prescribing complex regimens • Failing to explain the benefits and side effects of a medication adequately • Not giving consideration to the patient’s lifestyle or the cost of the medications Osterberg L,Blaschke T, N Engl J Med 2005;353:487-97

16. Nonadherence to Osteoporosis Medications: How Common Is It?

17. Adherence With Osteoporosis Medications Is Sub-optimal 30 25 20 15 10 5 0 20% to 25% of Patients Abandon Therapy Within 7 Months 26% 19% 19% Patients AbandoningTreatment (%) Hormone Replacement Therapy (n=334) Bisphosphonate (n=366) Selective Estrogen Receptor Modulator (n=256) Telephone survey of 956 randomly selected women with postmenopausal osteopenia or osteoporosis who initiated therapy in 2000-2001. Mean follow-up was 7 months. Tosteson ANA, et al. Am J Med. 2003;115:209-216.

18. Adherence With Oral Bisphosphonates Is Suboptimal, Regardless of Dosing 100 90 80 70 60 Patients on Therapy (%) 54.6% 50 40 36.9% 30 P<0.001 vs daily therapy Weekly Bisphosphonates (n=177,552) 20 Daily Bisphosphonates (n=33,767) 10 Oct2002 Nov Dec Jan Feb Mar Apr May Jun Jul Aug Sep Oct2003 Percentage of Patients on Therapy (defined as having at least 1 day of medication supply in the month) A HIPAA-compliant, longitudinal patient database of prescriptions dispensed from ~25% of US retail pharmacies was used to assess discontinuation of bisphosphonates over a 12-month period in women aged ≥50 years.* * Primary usage in osteoporosis; however, data may include use in other indications. Ettinger M, et al. Arthritis Rheum. 2004;50(suppl):S513-S514. Abstract 1325.

19. Surgeon General’s Report Cites Need toImprove Adherence With Osteoporosis Therapies • Long-term adherence rates with any medication are poor (~50%) • Follow-up strategies that improve adherence to should be applied to osteoporosis • Simplifying the treatment regimen • Counseling • Addressing patient concerns about side effects • Maintaining an encouraging provider-patient relationship US Department of Health and Human Services. Bone Health and Osteoporosis: A Report of the Surgeon General. Rockville, MD: US Department of Health and Human Services, Office of the Surgeon General; 2004.

20. Potential Consequences of Poor Adherenceto Osteoporosis Therapy • Poorer clinical outcomes • Less effective suppression in the rate of bone turnover1 • Lower gains or greater losses in bone mineral density1,2 • Greater risk of fractures3 • Higher medical costs4 1. Eastell R, et al. Calcif Tissue Int. 2003;72:408. Abstract P-297. 2. Finigan J, et al. Osteoporos Int. 2001;12:S48-S49. Abstract P110. 3. Caro JJ, et al. Osteoporos Int. 2004;15:1003-1008. 4. McCombs JS, et al. Maturitas. 2004;48:271-287.

21. Non-Adherence to OsteoporosisMedication Affects BMD Lumbar BMD Yood R, et al Osteoporosis int 14:2003. 965-68

22. 11,249 women suffering from osteoporosis with a mean age of 68.4 years and average follow-up of 2 years Non-Adherence to OsteoporosisMedication Increases Fracture Risk Fracture Rate % 16% decrease Caro JJ et al. Osteoporosis Int 14, 2003, Suppl 7

23. Better Long-term Compliance Reducesthe Risk of Fracture 12.6% % Patients With Fracture * 9.4% † (n=3400) (n=3425) Compliance With Bisphosphonates and Fracture Risk Over 2 Years in Women ≥45 Years With Postmenopausal Osteoporosis (n=6825) * P<0.0001. †Compliant is defined as taking medication ≥80% of the time over a 24-month period. Retrospective cohort study that used longitudinal medical and pharmacy claims data from Medstat MarketScan® Research Databases to assess adherence and fracture risk over 24 months (1999-2003). Siris E, et al. Presented at: Sixth International Symposium on Osteoporosis. April 6-10, 2005; Washington, DC.

24. How Can Adherence Be Improved?

25. Improving Adherence byReinforcing Treatment Efficacy • Patient monitoring may be helpful in demonstrating effects of treatment1-3 • BMD • Biochemical markers of bone turnover • Frequent visits or calls from staff • Clowes et al. JCEM. 2004;89:1117-1123). • Deal CL. Curr Rheumatol Rep. 2001;3:233-239. 3. Chapurlat RD, Cummings SR. Osteoporos Int. 2002;13:738-744.

26. Improving Adherence Through Modifying Dosing Interval: Focus on Bisphosphonates • Survey data suggests that patients prefer more widely-spaced dosing intervals • Retrospective data suggest improved adherence with once-weekly versus daily bisphosphonates • To date, there are no prospective data demonstrating that extended dosing regimens improve patient adherence and clinical outcomes

27. Women Preferred Weekly over Daily Alendronate • 288 postmenopausal women with osteoporosis • 4 weeks of alendronate Weekly followed by 4 weeks alendronate Daily • 4 weeks of alendronate Daily followed by 4 weeks alendronate Weekly • At the final visit, patients completed a preference study questionnaire: Which Treatment Routine… Patients (%) Do You Prefer? Is More Convenient? Would Be Easier toComply With For aLong Period of Time? Simon JA et al Clin Ther 2002;24:1871-1886

28. Women Preferred Monthly over Weekly Patients Say They Prefer a Once-a-month Over a Once-a-week Dosing Schedule Dosing Schedule Preference (n = 367)* Once a week 33% 67% Once a month p <0.001 * Among women expressing a preference, 67% prefer once-a-month dosing, a statistically significantly higher proportion than the 33% who prefer once-a-week dosing Simon JA et al Female Patient 2005;30:31-6

29. BALTO- Study Design • A randomized, prospective, 6 month Phase IIIB, open-label, multi-center, crossover study • Primary Endpoint – Proportion (%) of patients preferring once-monthly dosing of ibandronate over once-weekly dosing of alendronate • Secondary Endpoint – Proportion (%) of patients perceiving the once-monthly dosing of ibandronate to be more convenient versus once-weekly dosing of alendronate Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903

30. Patient Preference: Ibandronate Monthlyvs Alendronate Weekly (Patients Expressing Preference) Patients (%) n = 197 n = 79 Preferred Treatment * p < 0.0001 vs alendronate Excludes those patients who did not express a preference for one treatment / m ITT population Twenty-two patients did not express preference Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903

31. Patient Preference: Ibandronate Monthlyvs Alendronate Weekly (Those Expressing Convenience) Patients (%) n = 197 n = 67 More Convenient Therapy * p < 0.0001 vs alendronate Excludes those patients who did not express a preference for treatment Thirty-two patients found both treatments equally convenient Emkey R et al Curr Med Res Opin. 2005 Dec;21(12):1895-903

32. Principles of Evidence-Based Medicine • Acquire the Evidence • Critically Appraise the Evidence • Apply the Evidence to the Individual Patient

33. Evidence-Based Medicine: Integrate Findings With Clinical Expertise and Patient Needs Clinical Expertise Research Evidence Patient Preferences Rx Adapted from: Sackett DL et al. Evidence-Based Medicine: How to Practice and Teach EBM. 2nd ed. Churchill Livingstone; 2000

34. Summary • Adherence to daily and weekly bisphosphonates is suboptimal • Poor adherence may compromise clinical outcomes and may increase healthcare utilization • Need to improve communication and education of patients utilizing all available resources • Among other factors, dosing frequency may be an important determinant of adherence with bisphosphonates

35. “Drugs don’t work in people that don’t take them” C. Everett Koop, M.D.

36. Applying Evidence to Practice—Prevention and Treatment of Patients Suspected or Confirmed Osteoporosis:An Interactive Case Study ApproachCase Study # 1: Low BMD in An Early Postmenopausal Woman

37. Case 1 • LR is a 52 year old newly menopausal white woman • She has hot flashes but no fractures orheight loss • She is of average height and weight (5’2”,137 pounds) • She has an intact uterus • There is no family history of OP • She had never undergone BMD testingHowever, you ordered a DXA which showed aT-score of -1.8 in lumbar spine and -1.5 in femoral neck

38. Case 1 • Diagnosed as osteopenia • What would you do? • Would you treat with an antiresorptive therapy?

39. Case 1 • With no history of fx or FH, her absolute risk for an osteoporotic spine, hip or wrist fx over the next 5 years is very low at <0.12%/y • No utility for bone markers in this age group • No treatments have been proven to reduce fx risk in women in their 50s with osteopenia, although several treatments may reduce bone loss • Bisphosphonates or PTH although effective would probably be unjustified based on her low absolute risk and the high NNT of 2000

40. Case 1 • Consider preventive approaches • At her age with a uterus she is more likely to have an AE from HRT (VTE, MI, breast CA) than a beneficial outcome • Raloxifene is an option • May lower risk of breast ca • May aggravate hot flashes • Calcium and vitamin D

41. Case 1: What Mrs. LR Chose To Do… • Chose to decline any pharmacologic intervention • Agreed to calcium supplementation 500mg bid, a MVI, and an exercise program • Began to experiment with soy preparations • No evidence that these agents reduce fx risk or prevent bone loss

42. Case 2. A postmenopausal woman who recently discontinued HRT but has low BMD

43. Case 2 • RG is a 68-year-old woman who has been on HT since menopause • She initially took HT for hot flashes but continued when she was told of benefits for her heart and bones • When she heard the WHI results she discontinued HT • She has scheduled a visit with you to discuss whether she needs additional therapy to treat or prevent OP

44. Case 2: History Mrs. RG • Meds: no calcium or vitamin D supplements • She takes a MVI • She is lactose intolerant • She has lost 2 inches in height • Approximately 10 years ago she broke her forearm when she slipped on the sidewalk • No FH of OP

45. Case 2: History Mrs. RG • At age 65 she had a DXA which showed spine T-score of -2.0 and total hip T-score of -2.2 • She has OP based on relatively low BMD and history of fracture • Her absolute risk of fracture in 5 years will be high, assuming that HRT effects on bone will diminish with time

46. Case 2 • Need to exclude secondary OP • Serum calcium • TSH • 25 OH D • 24 hour urinary calcium

47. Case 2:Medical Recommendations Mrs. RG • Calcium supplementation 1200 mg • 800 IU vitamin D (her MVI has 400 IU) • Exercise • Medication options: • Bisphosphonates weekly or monthly • SERMS • Follow-up BMD in two years

48. Case 2: What Mrs. RG Did • Ibandronate 150 mg once monthly • 1000 mg calcium supplementation • 400 IU vitamin D plus her MVI

49. Case 3.Severe postmenopausal osteoporosis

50. Case 3: Mrs. RW • 70 year old woman with low BMD and multiple vertebral fractures who has been on a weekly bisphosphonate, ca, vitamin D for two years • Her lumbar spine T-score in Jan 2001 was -3.0 • A repeat DXA today shows a lumbar spineT-score of -3.5, and a FN T-score of -3.0 • She has significant midback pain and has new OP fx of the thoracic spine with significant deformity • Vertebroplasty was recommended byher PCP