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Osteoporosis diagnosis and treatment

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How do we diagnose osteoporosis and making a treatment decission using BMD as a diagnostic tool. It also covers how do we assess clinical risk factors to make an intervention and to minimize fracture

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Osteoporosis diagnosis and treatment

  1. 1. Osteoporosis ManagementOsteoporosis ManagementEfficacy and safety of bisphosphonates
  2. 2. Today’s talk :Today’s talk : Burden of the disease.Burden of the disease. Screening and treatment guidelines.Screening and treatment guidelines. Bisphosphonates.Bisphosphonates. Once yearly bisphoshonateOnce yearly bisphoshonate Controversial topics : Association ofControversial topics : Association ofbisphosphonates withbisphosphonates with ONJONJ Atypical femoral fracturesAtypical femoral fractures Atrial fibrillation.Atrial fibrillation. Esophageal cancer.Esophageal cancer.
  3. 3. Classic presentation
  4. 4. Burden of DiseaseBurden of Disease2.52.5 million people in Indonesiamillion people in Indonesiahave Osteoporosishave Osteoporosis88 million people in Indonesiamillion people in Indonesiahave Osteopenia.have Osteopenia.
  5. 5. Burden of DiseaseBurden of Disease> 0,5 million> 0,5 millionfractures/year due to either.fractures/year due to either.75,00075,000 HIP fractures.HIP fractures.150,000150,000 vertebral fractures.vertebral fractures.35,00035,000 pelvic factures.pelvic factures.Bone health and osteoporosis: Department ofBone health and osteoporosis: Department of
  6. 6. Burden of Disease :Burden of Disease :Hip fracturesHip fractures ::50 %50 % Permanent impairedPermanent impairedmobility.mobility.25 %25 % Loose skills to liveLoose skills to liveindependently.independently.Increased all cause mortality : firstIncreased all cause mortality : first 33monthsmonths after hip fracture.after hip fracture.1.2010 position statement of the North American Menopause Society. Menopause 2010.1.2010 position statement of the North American Menopause Society. Menopause 2010.
  7. 7. Annual incidenceAnnual incidence
  8. 8. Etiology of Bone loss in OsteoporosisEtiology of Bone loss in OsteoporosisOSTEOCLAST - RESORPTIONOSTEOBLAST - FORMATIONPrimary cause is estrogen deficiency+
  9. 9. OsteoporosisOsteoporosis
  10. 10. Risk factorsRisk factors
  11. 11. Vertebral FracturesSemi-quantitative reading / visual scoringGenant et al., J Bone Miner Res 1993, 8:137Normal(Grade 0)Wedge fracture Biconcave fracture Crush fractureMild fracture(Grade 1, ~20-25%)Moderate fracture(Grade 2, ~25-40%)Severe fracture(Grade 3, ~40%)
  12. 12. Who to screenWho to screen Women > 65 years.Women > 65 years. Men > 70 years.Men > 70 years. Postmenopausal women /men >50 yearsPostmenopausal women /men >50 yearswith clinical risk factors.with clinical risk factors. H/o fracture at age > 50 years.H/o fracture at age > 50 years. Chronic steroid use.Chronic steroid use.
  13. 13. Direct measurement of BMD by DXA andas well as CT allows us to diagnose osteopenia
  14. 14. DXA
  15. 15. Fracture risk calculationFracture risk calculation
  16. 16. Who to treat ?Who to treat ?Prior h/o hip/vertebral #Prior h/o hip/vertebral #ororT Score < -2.5T Score < -2.5ororT Score -1 to -2.5 &10 yr risk (FRAX) :HIP # > 3 % ormajor osteoporotic # > 20 %T Score -1 to -2.5 &10 yr risk (FRAX) :HIP # > 3 % ormajor osteoporotic # > 20 %Postmenopausal women /men > 50 yrswith
  17. 17. Recommendation for women and men > 50 yoRecommendation for women and men > 50 yo•• Counsel on the risk of osteoporosis and related fractures.Counsel on the risk of osteoporosis and related fractures.•• Advise on a diet rich inAdvise on a diet rich in fruits and vegetablesfruits and vegetables and that includesand that includesadequate amounts of totaladequate amounts of total calcium intakecalcium intake (1,000 mg per day(1,000 mg per dayfor men 50-70; 1,200 mg per day for women 51 and olderfor men 50-70; 1,200 mg per day for women 51 and olderand men 71 and older).and men 71 and older).•• Advise onAdvise on vitamin Dvitamin D intake (800-1,000 IU per day), includingintake (800-1,000 IU per day), includingsupplements if necessary for individuals age 50 and older.supplements if necessary for individuals age 50 and older.•• Recommend regularRecommend regular weight-bearing and muscle-strengtheningweight-bearing and muscle-strengtheningexercise to improve agility, strength, posture and balance andexercise to improve agility, strength, posture and balance andreduce the risk of falls and fractures.reduce the risk of falls and fractures.
  18. 18.  ••AssessAssess risk factorsrisk factors for falls and offerfor falls and offerappropriate modifications :appropriate modifications : home safety assessment,home safety assessment, balance training exercises,balance training exercises, correction of vitamin D insufficiency,correction of vitamin D insufficiency, avoidance of certain medications andavoidance of certain medications and bifocals use when appropriatebifocals use when appropriate
  19. 19. Calcium and vitamin DCalcium and vitamin D
  20. 20. Anti-resorptiveAnabolic‘Dual action’
  21. 21. Bone marrow precursorsBone marrow precursorsOsteoblastsOsteoblastsOsteoclastOsteoclastLining cellsLining cellsStimulators ofStimulators ofBone FormationBone FormationFluorideFluoridePTH analogsPTH analogsSr Ranelate (?)Sr Ranelate (?)Inhibitors ofInhibitors ofBone ResorptionBone ResorptionEstrogen, SERMsEstrogen, SERMsBisphosphonatesBisphosphonatesCalcitoninCalcitoninInhibitors ofRANKLCathepsin KTherapeutic strategiesTherapeutic strategies
  22. 22. Treatments & EfficacyVertebral Fx Non-vertebral FxOther Fx Hip FxOralHRT Yes Yes YesEtidronate* YesAlendronate* Yes Yes YesRisedronate* Yes Yes YesIbandronate* Yes [Yes]Raloxifene* YesCalcitriol* YesStrontium Ranelate* Yes Yes [Yes]
  23. 23. Vertebral Fx Non-vertebral FxOther Fx Hip FxSubcutaneousTeriparatide* Yes Yes1-84 PTH* YesDenosumab* Yes Yes YesIntravenousPamidronateIbandronate*Zoledronate* Yes Yes YesIntranasal or SubcutaneousCalcitonin* Yes
  24. 24. Vertebral Fx Nonvertebral FxOther Fx Hip FxAlendronate* Yes Yes YesRisedronate* Yes Yes YesZoledronic acid* Yes Yes YesPTH* Yes Yes ???Strontium ranelate* Yes Yes ???Denosumab* Yes Yes YesAppropriate use of appropriate treatmentsAppropriate use of appropriate treatmentscan halve the incidence of fracturescan halve the incidence of fractures* plus calcium + vitaminD
  25. 25. Mainstay ofMainstay of treatmenttreatment ::BisphosphonatesBisphosphonatesApproval in US for osteoporosisApproval in US for osteoporosis Alendronate : 1995Alendronate : 1995 Risedronate : 2000Risedronate : 2000 Ibandronate : 2005Ibandronate : 2005 Zoledronate : 2007.Zoledronate : 2007.
  26. 26. ContraindicationsContraindications
  27. 27. Duration of treatmentDuration of treatment
  28. 28. Cost factorCost factor Alendronate: $4 -Alendronate: $4 -$40/month$40/month Risedronate : $60 -Risedronate : $60 -$120/month$120/month Ibandronate (oral):Ibandronate (oral):$90 - $130/month$90 - $130/month IV Ibandronate :IV Ibandronate :$1300/year$1300/year IV Zoledronate :IV Zoledronate :$1300/year$1300/year
  29. 29. Hot topicsHot topics
  30. 30. Osteonecrosis of jawOsteonecrosis of jaw
  31. 31. ONJONJOsteoporosis :Osteoporosis : Reporting rate 1/100,000 - 1/250.000.Reporting rate 1/100,000 - 1/250.000. True incidence may be higher.True incidence may be higher. Malignancy/skeletal metastasis :Malignancy/skeletal metastasis : Estd. Incidence: 1- 10 %Estd. Incidence: 1- 10 %
  32. 32. Risk factorsRisk factors
  33. 33. RecommendationsRecommendations
  34. 34. Atypical fracturesAtypical fractures
  35. 35. Atypical fracturesAtypical fractures ? Long term over suppression of bone? Long term over suppression of boneturnover.turnover. Incidence : 1 in 10,000.Incidence : 1 in 10,000. Associated median treatment duration : 7Associated median treatment duration : 7years.years. Causality : long term bp/ atypical #Causality : long term bp/ atypical #unproven.unproven. Further large scale studies needed.Further large scale studies needed.
  36. 36. RecommendationsRecommendations Educate physician/patient aboutEducate physician/patient aboutProdromal pain.Prodromal pain. Evaluate with urgent X-Ray.Evaluate with urgent X-Ray. If negative, may consider MRI.If negative, may consider MRI. Stop BP’s if atypical fracture confirmed.Stop BP’s if atypical fracture confirmed.
  37. 37. Atrial fibrillationAtrial fibrillation FDA recommends physiciansFDA recommends physicians to not alterto not altertheir prescribing patterntheir prescribing patterns while it continuess while it continuesto monitor post marketing reports of AF into monitor post marketing reports of AF insuch patients.such patients. In v/o above and absence of definitiveIn v/o above and absence of definitivedata : Benefits of treatment outweigh risks.data : Benefits of treatment outweigh risks.
  38. 38. Esophageal cancerEsophageal cancer 23 cases reported in last 223 cases reported in last 2decades. (Wysowski et al)decades. (Wysowski et al) 31 cases from31 cases fromEurope/Japan.Europe/Japan. Median time from use toMedian time from use todiagnosis : 1-2 yr.diagnosis : 1-2 yr. Time from exposureTime from exposureinconsistent w/ causalinconsistent w/ causalrelation.relation. Further studies neededFurther studies needed..
  39. 39. Renal safetyRenal safety Safe for creatinine clearance > 30 -35 mlSafe for creatinine clearance > 30 -35 ml/min./min. Lack of experience < 30 ml/min.Lack of experience < 30 ml/min. No data for use in ESRD.No data for use in ESRD. Exact bone disease unknown unless biopsy.Exact bone disease unknown unless biopsy. Expert opinion: half the dose could be usedExpert opinion: half the dose could be usedfor 3 years in ESRD once bone biopsyfor 3 years in ESRD once bone biopsyconfirms osteoporosis.confirms osteoporosis.
  40. 40. FractureBoneStrengthMaterialPropertiesRemodelingFallsShape &ArchitectureExercise &LifestyleHormonesNutritionBoneMassPosturalReflexesSoft TissuePaddingReproduced with permission from Heaney RP. Bone 33:457-465, 2003Factors Leading to Osteoporotic Fracture:Role of Bone Remodeling2004
  41. 41. HIP FRACTURE – Female Age 75 and overGive single oral dose 100,000 IU vitaminD @ as soon as feasible post hip fracture & start 1000mgCaCO3+800IU vitaminD asap, (if on this already – continue)Already on a BP(bisphosphonate)?NoYesGood prognosis & eGFR 30 or overDuration of treatment?Yes No1. Patient or resident carer understandconcepts of osteoporosis, fracture riskreduction & protocol for ingesting oral BPAND2. No contraindications to oral BPs[dysphagia / oesophageal stricture /achalasia /hypocalcaemia].YesOral ALN 70mg / wkNoPatient suitable for IV BP& eGFR 35 or overYes NoArrange IV zoledronic acid 5mginfusion (over at least 15min),4-6/52 after hip fractureConsider oral BP or, if at riskequivalent to that of fractureplus T-score -2.4 or less,consider strontium ranelate.Continue b.d. calcium + vitaminDContinue b.d.oral calcium + vitaminDMore than 2yr 2yr or lessOptimal compliance with / adherenceto BP & BP well toleratedYesNoContinue oral BPIF eGFR is 30 or moreOtherwise continueb.d. calcium + vitaminDGREATER GLASGOW & CLYDE PROTOCOL FOR FRACTURE SECONDARY PREVENTION AFTER HIP FRACTURE IN WOMEN AGE 75+
  42. 42. Zoledronic acid 5 mgIV once a year
  43. 43. Once Yearly Zoledronic AcidOnce Yearly Zoledronic AcidReduces FracturesReduces FracturesHORIZON Pivotal Fracture TrialMulti-national, multi-center, RCT7,736 women age 65-89 with T-score <-2.5 or fracture plus T-score < -1.5Calcium 1000-1500 mg/day vit D (400-1200 IU/day)Zoledronic acid IV infusion 5 mglack et al. NEJM 356:1809-1822, 2007
  44. 44. ZOLZOL reducesreduces hiphip fracturefracture*Relative risk reduction (95% confidence interval) vs placeboBlack et al. NEJM 356:1809-1822, 2007P = .00241230Placebo (n = 3861)ZOL 5 mg (n = 3875)CumulativeIncidence(%)Time to First Hip Fracture (months)0 3 6 9 12 15 18 21 24 27 30 33 3641%*(17%, 58%)
  45. 45. P < .0001CumulativeIncidence(%)Time to First Clinical Vertebral Fracture (months)0 3 6 9 12 15 18 21 24 27 30 33 3677%(63%, 86%)Placebo (n = 3861)ZOL 5 mg (n = 3875)1230ZOLZOL reducesreduces vertebralvertebralfxfx*Relative risk reduction (95% confidence interval) vs placeboBlack et al. NEJM 356:1809-1822, 2007
  46. 46. P = .0002Time to First Clinical Non-vertebral Fracture (months)246810120 3 6 9 12 15 18 21 24 27 30 33 3625%(13%, 36%)Placebo (n = 3861)ZOL 5 mg (n = 3875)0CumulativeIncidence(%)ZOLZOL reducesreduces non-vertebralnon-vertebralfxfx*Relative risk reduction (95% confidence interval) vs placeboBlack et al. NEJM 356:1809-1822, 2007
  47. 47. Zoledronic Acid will ImproveZoledronic Acid will Improve PatientPatientCompliance asCompliance as Once-Yearly IV Therapy isOnce-Yearly IV Therapy isPreferredPreferredData from Lindsay R, et al. Poster presented at ECCEO6; March 15-18, 2006; Vienna, Austria.16.418.9Both Are EqualOnce-Yearly IVOnce-Weekly PillMore convenientMore willing totake long termOverallpreferenceN = 12266.459.80 20 40 60 80 10068.066.415.618.020.515.619.713.9% of PatientsMoresatisfying
  48. 48. Take home pointsTake home points Osteoporosis :Osteoporosis : significant burden of diseasesignificant burden of disease.. Main stay treatment :Main stay treatment : bisphosphonatesbisphosphonates.. ? Duration of treatment : individualized.? Duration of treatment : individualized. Patient compliancePatient compliance Patient educationPatient education  once yearly IV BPonce yearly IV BP More research needed to confirm associationMore research needed to confirm associationwith ONJ, Sub trochanteric fracture.with ONJ, Sub trochanteric fracture. Benefits of treatmentBenefits of treatment outweigh risks inoutweigh risks inosteoporosis.
  49. 49. Thank youThank youKeep your bone healthyKeep your bone healthy

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