Presentation on theme: "Critical Challenges in Osteoporosis and Women’s Health"— Presentation transcript:
1 Critical Challenges in Osteoporosis and Women’s Health Screen & InterveneCritical Challenges in Osteoporosis and Women’s HealthCritical Challenges in Osteoporosis Prevention and Treatment Completing the Journey From Trial- and Expert-Based Information to Clinical Application in The Primary Care Setting
2 Critical Challenges in Osteoporosis Prevention and Treatment What Have We Learned Thus Far—A SummaryOsteoporosis-An Undertreated ConditionComplications of Osteoporotic FracturesIndications for ScreeningInterpretation of BMD MeasurementsAggregate Analysis of Risk Factors
3 Critical Challenges in Osteoporosis Prevention and Treatment What Have We Learned Thus Far—A SummaryTreatment Indications and TriggersPharmacological Therapy for Fracture PreventionRelationship between BMD changes and Vertebral/Nonvertebral FracturesVertebral and Nonvertebral Fracture PreventionWe 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-Adherence How Large is The Problem? Studies of patient behavior show that LESS THAN 50% of the people who leave a doctor's office with a prescription adhere and comply with drug therapy
6 Persistence with Lipid-Lowering Therapy Simons, et al MJA 1996; 164:208.
7 The Effects of Non-Adherence 1) Poor patient outcomes due tosub-optimal therapeutic response2) Increased cost burden to societyOsterberg L,Blaschke T, N Engl J Med 2005;353:487-97
8 Poor Patient OutcomesIncreased Morbidity due to disease “exacerbations”More treatment “Failures” with potential for addition or switching of medications due to perceived inefficacyMore frequent Physician VisitsIncreased HospitalizationsExcess MortalityOsterberg 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 yearBillion 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)POOR ADHERENCELack of positive reinforcement?Disruption to daily routine?(need for frequent dosing)Concern about side effects?
11 Health LiteracyThe 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-careWorse self-management skillsLower use of screeningLower medication compliance ratesHigher rates of hospitalization and morbidityLiteracy 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 diagnosisBelieve other diseases are more importantBelieve side effects outweigh benefitsConcerned about their ability to carry out recommended actionAARP Survey, 1985National Prescription Buyers’ Survey, USA 1985
14 Lack of CommunicationStudy of 300 medical encounters: doctors spent average 1.3 minutes giving information1Study of 264 visits to family physicians.- during patient initial statement of the problem, physician interrupted after average of 23 seconds.250% of patients leave office visit not understanding what the doctor said3Clement, Diab Care 1995;18:1204. Waitzkin. JAMA 1984;252:24411Kravitz et al. Arch Intern Med 1993;153:Roter and Hall. Ann Rev Public Health 1989;10:163. Marvel JAMA 1999;281:283. 3
15 Physicians Contribute to Patients’ Poor Adherence By: Prescribing complex regimensFailing to explain the benefits and side effects of a medication adequatelyNot giving consideration to the patient’s lifestyle or the cost of the medicationsOsterberg 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 3025201510520% to 25% of Patients Abandon Therapy Within 7 Months26%19%19%Patients Abandoning Treatment (%)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 Mean follow-up was 7 months.Tosteson ANA, et al. Am J Med. 2003;115:
18 Adherence With Oral Bisphosphonates Is Suboptimal, Regardless of Dosing Percentage of Patients on Therapy(defined as having at least 1 day of medication supply in the month)P<0.001 vs daily therapy102030405060708090100Oct 2002NovDecJanFebMarAprMayJunJulAugSepOct 2003Patients on Therapy (%)Daily Bisphosphonates (n=33,767)Weekly Bisphosphonates (n=177,552)54.6%36.9%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 Long-term adherence rates with any medication are poor (~50%) Surgeon General’s Report Cites Need to Improve Adherence With Osteoporosis TherapiesLong-term adherence rates with any medication are poor (~50%)Follow-up strategies that improve adherence to should be applied to osteoporosisSimplifying the treatment regimenCounselingAddressing patient concerns about side effectsMaintaining an encouraging provider-patient relationshipUS 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 Adherence to Osteoporosis Therapy Poorer clinical outcomesLess effective suppression in the rate of bone turnover1Lower gains or greater losses in bone mineral density1,2Greater risk of fractures3Higher medical costs41. 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;15:4. McCombs JS, et al. Maturitas. 2004;48:
21 Non-Adherence to Osteoporosis Medication Affects BMD Lumbar BMDYood R, et al Osteoporosis int 14:
22 Non-Adherence to Osteoporosis Medication Increases Fracture Risk 11,249 women suffering from osteoporosis with a mean age of 68.4 years and average follow-up of 2 yearsFracture Rate %16% decreaseCaro JJ et al. Osteoporosis Int 14, 2003, Suppl 7
23 Better Long-term Compliance Reduces the Risk of Fracture Compliance With Bisphosphonates and Fracture Risk Over 2 Years in Women ≥45 Years With Postmenopausal Osteoporosis (n=6825)% Patients With Fracture(n=3400)(n=3425)*†9.4%12.6%* P<† 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 ( ).Siris E, et al. Presented at: Sixth International Symposium on Osteoporosis. April 6-10, 2005; Washington, DC.
25 Improving Adherence by Reinforcing Treatment Efficacy Patient monitoring may be helpful in demonstrating effects of treatment1-3BMDBiochemical markers of bone turnoverFrequent visits or calls from staffClowes et al. JCEM. 2004;89: ).Deal CL. Curr Rheumatol Rep. 2001;3:3. Chapurlat RD, Cummings SR. Osteoporos Int. 2002;13:
26 Improving Adherence Through Modifying Dosing Interval: Focus on Bisphosphonates Survey data suggests that patients prefer more widely-spaced dosing intervalsRetrospective data suggest improved adherence with once-weekly versus daily bisphosphonatesTo date, there are no prospective data demonstrating that extended dosing regimens improve patient adherence and clinical outcomes
27 Women Preferred Weekly over Daily Alendronate288 postmenopausal women with osteoporosis4 weeks of alendronate Weekly followed by 4 weeks alendronate Daily4 weeks of alendronate Daily followed by 4 weeks alendronate WeeklyAt the final visit, patients completed a preference study questionnaire: Which Treatment Routine…Patients (%)From medical department approved MCO Slide set.38 United States Centers, randomized, open label, preference study that evaluated Fosamax 10mg once-daily versus Fosamax 70mg once-weekly.Women with postmenopausal osteoporosis were enrolled to receive 9 weeks of treatment in crossover fashion.Each woman received 4 weeks with each study regimen separated by a 1 week washout period Page 1873 Simon JA, et al. Clin Ther. 2002;24:Do You Prefer?Is More Convenient?Would Be Easier to Comply With For a Long Period of Time?Simon JA et al Clin Ther 2002;24:
28 Women Preferred Monthly over Weekly Patients Say They Prefer a Once-a-month Over a Once-a-week Dosing ScheduleDosing Schedule Preference(n = 367)*Once a week33%67%Once a monthFrom medical department approved MCO Slide set.Standard deviations weekly (4.8%) monthly (4.8%)Patients who preferred monthly more likely to beyounger p = 0.05;employed full time p =0.017;initiated therapy <3 yrs ago p = 0.009Page 33 Simon JA et al. The Female Patient 2005;30:31-6.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 dosingSimon JA et al Female Patient 2005;30:31-6
29 BALTO- Study DesignA randomized, prospective, 6 month Phase IIIB, open-label, multi-center, crossover studyPrimary Endpoint – Proportion (%) of patients preferring once-monthly dosing of ibandronate over once-weekly dosing of alendronateSecondary Endpoint – Proportion (%) of patients perceiving the once-monthly dosing of ibandronate to be more convenient versus once-weekly dosing of alendronateSlide summarized from slide s in BALTO Protocol Review Daiva MThis was a six month prospective, randomized open-label, multi-center (48 centers), 2-period and 2-sequence crossover study. After a screening period of up to 30 days, eligible patients were randomized into either Sequence A or B (Figure 1).Patients randomized to Sequence A received oral ibandronate once-monthly 150 mg for three calendar months(Period 1), followed by oral alendronate once-weekly 70 mg for 12 weeks (Period 2).Patients assigned to Sequence B received alendronate once-weekly for 12 weeks (Period 1) followed by ibandronate once-monthly for three calendar months (Period 2).The crossover (Visit 3) took place once the patient had completed three calendar months of treatment with ibandronate (Sequence A) or 12 weeks treatment with alendronate (Sequence B). There was no wash-out period between the two treatment regimens.The study duration was approximately six months (3 months and 12 weeks). A follow-up period of 15 days after the completion of treatment was included to assure collection of additional information on safety.Emkey R et al Curr Med Res Opin Dec;21(12):
30 Patient Preference: Ibandronate Monthly vs Alendronate Weekly (Patients Expressing Preference)Patients (%)n = 197n = 79Source: Boniva® (ibandronic acid) Clinical Study Report BALTO I (Protocol MA Research Report ). PagesIbandronate CI 65.7, 76.6The primary analysis of the primary endpoint was analyzed using Gart’s test which excluded patients who did not express an opinion for one treatment over the other (see Section ). Two hundred seventy six patients were included in this analysis and 22 patients were excluded because they did not express a preference for either treatment regimen.Of those patients who expressed a preference for one treatment over the other (92.6% of the patients declared a preference), significantly more patients preferred the 150 mg once-monthly oral ibandronate tablet (71.4%, n= 197, 95% CI 65.7, 76.6) than the 70 mg once-weekly oral alendronate tablet (28.6%, n = 79) (P<0.0001).The order of intake of the two medications did not have an impact on patient preference for once-monthly ibandronate over once-weekly alendronate (Gart-order-effect P=0.1855).Preferred Treatment* p < vs alendronateExcludes those patients who did not express a preference for one treatment / m ITT populationTwenty-two patients did not express preferenceEmkey R et al Curr Med Res Opin Dec;21(12):
31 Patient Preference: Ibandronate Monthly vs Alendronate Weekly (Those Expressing Convenience)Patients (%)n = 197n = 67Significantly more women found it more convenient to take once-monthly ibandronate than once-weekly alendronate (74.6% versus 25.4%, P<0.0001). Two hundred sixty-four patients were included in the primary analysis of convenience. Thirty-two patients (10.8%) were excluded from this analysis as they considered the two treatments to be equally convenient (Table 16). The order of the intake of the two medications did not have an impact on this opinion (Gart-Order-Effect P=0.1570).More Convenient Therapy* p < vs alendronateExcludes those patients who did not express a preference for treatmentThirty-two patients found both treatments equally convenientEmkey R et al Curr Med Res Opin Dec;21(12):
32 Principles of Evidence-Based Medicine Acquire the EvidenceCritically Appraise the EvidenceApply the Evidence to the Individual Patient
33 Evidence-Based Medicine: Integrate Findings With Clinical Expertise and Patient Needs Clinical expertise IS important!Why?Experience with patients:improves efficiency of diagnosis and treatmentImproves ability to determine applicability of research data to your patientsAllows consideration of patient preferencesEBM is the process of systematically finding the most recent applicable research,appraising its validity, andusing it as the basis for clinical decisions.Clinical Expertiseimproves efficiency of Dx and Rxconsiders patient preferencesOverestimates usefulness of therapy-ResearchEvidencePatient PreferencesRxAdapted 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 utilizationNeed to improve communication and education of patients utilizing all available resourcesAmong 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 Approach Case 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 or height lossShe is of average height and weight (5’2”, 137 pounds)She has an intact uterusThere is no family history of OPShe had never undergone BMD testing However, you ordered a DXA which showed a T-score of -1.8 in lumbar spine and -1.5 in femoral neck
38 Case 1Diagnosed as osteopeniaWhat would you do?Would you treat with an antiresorptive therapy?
39 Case 1With 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%/yNo utility for bone markers in this age groupNo treatments have been proven to reduce fx risk in women in their 50s with osteopenia, although several treatments may reduce bone lossBisphosphonates 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 outcomeRaloxifene is an optionMay lower risk of breast caMay aggravate hot flashesCalcium and vitamin D
41 Case 1: What Mrs. LR Chose To Do… Chose to decline any pharmacologic interventionAgreed to calcium supplementation 500mg bid, a MVI, and an exercise programBegan to experiment with soy preparationsNo 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 bonesWhen she heard the WHI results she discontinued HTShe 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 MVIShe is lactose intolerantShe has lost 2 inches in heightApproximately 10 years ago she broke her forearm when she slipped on the sidewalkNo FH of OP
45 Case 2: History Mrs. RGAt age 65 she had a DXA which showed spine T-score of -2.0 and total hip T-score of -2.2She has OP based on relatively low BMD and history of fractureHer absolute risk of fracture in 5 years will be high, assuming that HRT effects on bone will diminish with time
46 Need to exclude secondary OP Case 2Need to exclude secondary OPSerum calciumTSH25 OH D24 hour urinary calcium
47 Case 2: Medical Recommendations Mrs. RG Calcium supplementation 1200 mg800 IU vitamin D (her MVI has 400 IU)ExerciseMedication options:Bisphosphonates weekly or monthlySERMSFollow-up BMD in two years
48 Case 2: What Mrs. RG DidIbandronate 150 mg once monthly1000 mg calcium supplementation400 IU vitamin D plus her MVI
50 Case 3: Mrs. RW70 year old woman with low BMD and multiple vertebral fractures who has been on a weekly bisphosphonate, ca, vitamin D for two yearsHer lumbar spine T-score in Jan 2001 was -3.0A repeat DXA today shows a lumbar spine T-score of -3.5, and a FN T-score of -3.0She has significant midback pain and has new OP fx of the thoracic spine with significant deformityVertebroplasty was recommended by her PCP
52 Case 3: The Magnitude of the Loss is Troublesome Consider the following:Is she a non-responder?Is she taking her bisphosphonate?Is the bisphosphonate being absorbed?Are there secondary causes of osteoporosis contributing to her bone loss and fractures?What therapeutic interventions both pharmacologic and nonpharmacologic should we consider?
53 Case 3: What Mrs. RW Did Treated aggressively with opioids Refused vertebral body augmentationInitially switched to another oral bisphosphonate but untx was high at 5525 OHD level 35Calcium supplementation to 1500 mg/dailySwitched to ForteoBack pain diminished6% increase in lumbar spine BMD at 6 months
55 Case 4: Mrs. PRAn 80-year-old frail, community dwelling woman who lives aloneShe has no hx of fx but falls often during the yearShe takes 1000 mg calcium daily and a MVIShe does not go out in the sunShe has difficulty walkingShe has a long hx of GERDShe has HBP treated with beta blockersBMD T-score of -2.8 at hip and -2.0 in spine
56 Case 4: Medical Recommendations Mrs. PR Falls assessmentCheck vitamin DShe had 25 OHD level of 8 ng/ml50,000 U of oral vitamin D weekly for 3 monthsTake calcium in divided dosesExercise programHip protectorsHer risk of NVF is high 10%/yearStarted on a bisphosphonate
57 Case 4: What Mrs. PR Did50,000 U ergocalciferol weekly for 3 monthsChose weekly bisphosphonatePT programShe refused hip protectors
58 Clinical Risk Factors Femoral neck T-score + Age Previous low trauma fractureCurrent cigarette smokingRheumatoid arthritisHigh alcohol intake (> 2 units/day)Parental history of hip fracturePrior or current glucocorticoid useAdapted from Kanis JA et al. Osteoporos Int. 2005;16:
59 Intervention Threshold A fracture probability above which it is cost-effective to treat with pharmacological agentsBased on statistical modeling using many medical, social, and economic assumptions
61 Patient Case #5 70 year old post menopausal female Wrist fracture at age 62T-score lumbar spine = -0.8T-score femoral neck and total hip = -1.5Should she receive pharmacological therapy?What would you choose and why?Would you choose a different therapy if her T-score was –3.5?
63 Patient Case #6 52 year old post menopausal female Mother had hip fracture at age 69T-score lumbar spine = -1.5, femoral neck -1.6Should she receive pharmacological therapy?Would bone markers help your decision?
64 Patient Case #6 What therapy would you choose? Hormone therapySERMBisphosphonate- which one?She refuses pharmacological therapy: she would like to try calcium and vitamin D aloneHow and how often would you monitor her?
66 Patient Case #7 67 year old post menopausal female with osteoporosis On risedronate 35 mg QW for 2 yearsRepeat DXA reveals 5% loss at the spine and 4.5% loss at the total hipWhat should you do?
67 Patient Case #7Her DXAs were performed at the same facility: her bone loss is statistically significant according to their precisionShe insists that she has taken her bisphosphonate every week and has followed proper administration instructionsWhat labs would you order?
68 Patient Case #7Her serum calcium, phosphorus, alkaline phosphatase, albumin and creatinine are normal24 hour urine calcium = 175 mg25-OH vitamin D = 35 ng/mlTissue transglutaminase- negativeWould you change her treatment?What would you change her to?
70 Patient Case #8A 66 year old female has a heel ultrasound performed at a health fairHer T-score at the heel = -2.5Does she have osteoporosis?What other tests, if any, should be performed?
71 Patient Case #8A DXA reveals a T-score at the spine of –2.7 and at he femoral neck of –1.9Lab workup is negative except for a 25-OH D level of 18 ng/mlWhat therapy would you choose?Hormone therapySERMTeriparatideBisphosphonate- which one?
73 Patient Case #9 67 year old postmenopausal female History: Heart disease, high cholesterol, hypertension and osteoporosisShe takes alendronate 70 mg QW for OPComplains about taking multiple pillsOften forgets to take her medicationsRequests help in simplifying her medication schedulesWhat are some other options?
74 Patient Case #9 You offer her ibandronate 150 mg once-a-month How can you help her remember to take her pill every month?What other methods could you use to re-inforce effectiveness of therapy and persistence?Mention MyBoniva program of letters, phone calls, faxes and s to patients that sign up for programCould perform markers after 6 months, repeat visits or calls from staff reinforcing persistence
75 Clinical Risk Factors Femoral neck T-score + Age Previous low trauma fractureCurrent cigarette smokingRheumatoid arthritisHigh alcohol intake (> 2 units/day)Parental history of hip fracturePrior or current glucocorticoid useAdapted from Kanis JA et al. Osteoporos Int. 2005;16:
76 Intervention Threshold A fracture probability above which it is cost-effective to treat with pharmacological agentsBased on statistical modeling using many medical, social, and economic assumptions