Prescribing information can be - PowerPoint Presentation

1. Prescribing information can be found on the last Slide

2. 2PROF. BENTE LANGDAHLSPECIALIT IN ENDOCRINOLOGYAARHUS UNIVERSITY HOSPITAL

3. DISCLOSURESResearch grants: Novo Nordisk, AmgenAdvisory board and speakers bureau: Eli Lilly, Amgen, UCB and Teva3

4. OsteoporosisThe Silent Epidemic141. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017.200millionOsteoporosisis estimatedto affectwomen worldwide

5. OsteoporosisThe Silent Epidemic151 in 3 womenaged ≥50 years will experiencean osteoporotic fracture1. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017.

6. OsteoporosisThe Silent Epidemic161. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017.27%The lifetime risk of osteoporoticfracture in men aged ≥50 years is higher than the risk of prostate cancer

7. FracturesThe voice of the Osteoporosis Epidemic17Only one-third of vertebral fractures cometo clinical attention, andunderdiagnosis is a worldwide problem1. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017.

8. 80%FracturesThe voice of the Osteoporosis Epidemic18of patients at high risk for additional osteoporotic fractures are never identified or treated1Up to1. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017.

9. Patient case975 year old womenDXA 2013: T-score: -3.4 and -1.7Calcium and vitamin DDecember 2016: Admitted with severe back pain Frx of Th12 Hospitalized for 3 days and treated with physiotherapy and painkillersDXA: T-scores: -3.8 and -2.2Started Risedronate 35 mg weekly + calcium and vitamin DAugust 2017: New episode of back painReferred to AUH, frx of Th12 and L2DXA: T-scores -3.7 and -2.6The patient asked me:Will I get my life back?New fractureBMD loss

10. What whould you do?Reassure the patient – have her continue the current treatmentChange the treatment to zolendronic acid or denosumabChange to a bone forming treatment - teriparatide10New fractureBMD loss

11. THE FRACTURE CASCADE1111. Siris ES, et al. Osteoporos Int. 2007;18(6):761-770. 2. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017.5-foldincreaseFirst vertebral fractureSecond vertebral fractureThird vertebral fractureFourth or more vertebral fracture3-foldincreaseOVERALL RISKINCREASE286%8-foldincrease

12. Vertebral Fracture Risk in the first year following initial fracture112RR = 2.6 (1.4, 4.9)RR = 5.1 (3.1, 8.4)RR = 7.3 (4.4, 12.3)1. Lindsay R, et al. JAMA. 2001;285(3):320-323.RR = relative risk.

13. New Vertebral Fracture Risk by baseline fracture severity113Most severe prior vertebral fracture = greatest risk of new vertebral fracture(s)MORE = Multiple Outcomes of Raloxifene Evaluation trial1. Delmas PD, et al. Bone. 2003;33(4):522-532.*p<0.05 vs. women with severe fracture

14. CLASSIFICATION AND GRADING OF VERTEBRAL FRACTURES1Moderate deformities: Grade 2 (reduction in 25-40% vertebral body height)1. Genant HK, et al. J Bone Miner Res. 1993;8(9):1137-1148. Wedge deformityBiconcave deformityCrush deformityArrows indicate moderate wedge and biconcave deformities in the lumbar spine radiograph14

15. Addressing common Treatment Goals15 Prevent the next fractureImprove bonemineral density(BMD)Consider changing treatment to a therapy with a different mode of actionProvide support to start and stay on therapy for optimal outcomes

16. Pharmacologic Treatment Options1,2All patients should receive adjunctive calcium 1000 mg/day + vitamin D 800-1200 IU/day.16Antiresorptive TherapyBone-Forming TherapyHormone replacement therapyFORSTEO [rhPTH(1-34)=teriparatide]Selective estrogen receptor modulators (SERMs)RaloxifeneBazedoxifeneBisphosphonatesEtidronateAlendronateRisedronateIbandronateZoledronic acidDenosumabrhPTH = recombinant human parathyroid hormone.1. Kawai M, et al. Nat Rev Drug Discov. 2011;10(2):141-156. 2. Body JJ, et al. Osteoporos Int. 2010;21(10):1657-1680.

17. Forteo Alendronate Comparator Trial FACT117BMD = bone mineral density; SC = subcutaneous.1. McClung MR, et al. Arch Intern Med. 2005;165(16):1762-1768. RANDOMISEAmbulatory postmenopausal women with L-spine or femoral neck BMD T-score between -2.5 and -4.0 N=203Alendronate 10 mg orally daily + placebo SC dailyx18 monthsFORSTEOSC daily + oral placebo daily x18 monthsEndpoints:L-spine BMDHip BMDBiochemical markers of bone turnoverSafety n=102 n=101All patients received calcium 1000 mg + vitamin D 400-800 IUorally once daily

18. FACT = FORTEO Alendronate Comparator Trial; NTx = urinary N-telopeptide corrected for creatinine; P1NP = procollagen type 1 N-terminal propeptide; SE = standard error.1. McClung MR, et al. Arch Intern Med. 2005;165(16):1762-1768.FACTFORSTEO INCREASED MARKERS OF BONE REMODELLING118†*p<0.05; †p<0.001. †††*††*†††††††P1NPNTx

19. Skeletal Histomorphometry in Subjects on Teriparatide or Zoledronate Therapy TRIALshotz119Optional 12-Month Extension (n=21)12-Month Primary Study (n=58)FORSTEO SC daily (n=28)BaselineAdminister ZOLBegin FORSTEO InjectionsBone BiopsyFORSTEO SC daily (n=10)ZOL 5 mg/year IV infusion (n=11)Bone BiopsyAdminister ZOLZOL 5 mg/year IV infusion (n=30)Open-labelMonth1 month6 monthsRandomised, double-blindScreening122460IV = intravenous; SC = subcutaneous; ZOL, zoledronic acid.1. Dempster DW, et al. J Bone Miner Res. 2016;31(7):1429-39.Paired biopsy set: FORSTEO (n=10); ZOL (n=9)Endpoints:Histomorphometric indicesBone turnover markers

20. Tetracycline Labelling Shows NewCancellous Bone Formation with FORSTEO1 206 months24 monthsFORSTEOZoledronic acid1. Dempster DW, et al. J Bone Miner Res. 2016;31(7):1429-39.

21. Cancellous Bone Formation in a FORSTEO-Treated Subject at 24 Months11. Dempster DW, et al. J Bone Miner Res. 2016;31(7):1429-39.24 months6 months21

22. FORSTEO builds new cortical bone over 24 months across all 3 bone envelopes16 months24 months22FORSTEOZoledronic acid1. Dempster DW, et al. J Bone Miner Res. 2016;31(7):1429-39.

23. Cortical Pores Being Filled with New Bone in a FORSTEO-Treated Subject at 24 Months11. Dempster DW, et al. J Bone Miner Res. 2016;31(7):1429-39.23

24. FORSTEO: Mechanism Of Action1,21. Jiang Y, et al. J Bone Miner Res. 2003;18(11):1932-1941. 2. Ma YL, et al. J Bone Miner Res. 2006;21(6):855-864.Rapid and Sustained Stimulation of Osteoblasts24

25. FACTFORSTEO SIGNIFICANTLY IncreaseD BMD125*p<0.01; †p<0.001 alendronate vs. FORSTEO.*†††*BMD = bone mineral density; DXA = dual-energy X-ray absorptiometry; FACT = FORTEO Alendronate Comparator Trial; LS = least squares; QCT = quantitative computerised tomography; SE = standard error.1. McClung MR, et al. Arch Intern Med. 2005;165(16):1762-1768.*p<0.05; †p<0.01 alendronate vs. FORSTEO.FORSTEOAlendronate 10 mg/day(n=96)(n=91)(n=26)(n=23)

26. 3 Potential changes underlying BMD IncreaseBMD = bone mineral density.1. Seeman E, et al. N Engl J Med. 2006;354:2250-2261.increasingtrabecular numberincreasingtrabecular thicknessIncreasing“true (material)”densityIncreasing“Apparent”BMD3 Potential changes underlying BMD Increase126

27. therapeutic choices27BMD = bone mineral density; rDNA = recombinant DNA.1. FORTEO Prescribing Information. 2. Arlot M, et al. J Bone Miner Res. 2005;20(7):1244-1253.3. Jiang Y, et al. J Bone Miner Res. 2003;18(11):1932-1941. 4. Fleisch H. Endocr Rev. 1998;19(1):80-100. 5. Russell RG, et al. Osteoporos Int. 1999;9:S66-S80. 6. Riggs BL, Parfitt AM. J Bone Miner Res. 2005;20:177-184.Antiresorptive agents (bisphosphonates, denosumab, raloxifene)Bone-FormingagentFORSTEO (teriparatide [rDNA origin] injection)Fill in the remodelling space; mineralisation of existing bone4-6Bone resorption4,5Osteoclast activity4,5Osteoblast activity4,5Turnover4,5No effectInformation regarding mechanisms of action does not provide evidence of comparative fracture protection.New bone formation; skeletal mass1Turnover2Bonevolume3Osteoblast activity1New bone formation1Osteoclast activity1FunctionPrimaryeffectSecondaryeffectBone turnoverBMD effectBone volumeAction

28. FORSTEOan effective treatment for the management of severe osteoporosis28

29. 29RANDOMISE2-week run-in withplacebo SC dailyAll patients received calcium 1000 mg + vitamin D 400-1200 IUorally once dailyAmbulatory postmenopausal women with >1 moderate or ≥2 mild atraumatic vertebral fracturesN=1637Teriparatide 40 μgSC dailyPlacebo SC dailyFORSTEO SC dailyTreatment x24 months Endpoints:Vertebral fracturesNon-vertebral fracturesBMDSafetyBMD = bone mineral density; SC = subcutaneous.1. Neer RM, et al. N Engl J Med. 2001;344(19):1434-1441. n=541 n=552 n=554Fracture prevention Trial1

30. FPTFORSTEO SIGNIFICANTLY REDUCED THE RISK OF Fracture (QM Analysis)130ARR = absolute risk reduction; FPT = Fracture Prevention Trial; QM = quantitative morphometry; RRR = relative risk reduction.1. Prevrhal S, et al. Curr Med Res Opin. 2009;25(4):921-928.ARR = 9.6%RRR = 84%p≤0.001 vs. placebo

31. FPTFORSTEO SIGNIFICANTLY REDUCED THE RISK OF Non-vertebral Fragility Fractures131ARR = absolute risk reduction; FPT = Fracture Prevention Trial; RRR = relative risk reduction.1. Neer RM, et al. N Engl J Med. 2001;344(19):1434-1441.ARR = 2.9%RRR = 53%p=0.02 vs. placebo

32. Treatment with FORSTEO resulted in increased cortical thickness, trabecular bone volume and connectivity, as well as the conversion of rods to plates BMD increases because of increased bone volume32BaselineFollow-up at 21 monthsmicroCT images of iliac crest, postmenopausal patient in treatment groupBMD = bone mineral density; microCT = micro computerised tomography.1. Jiang Y, et al. J Bone Miner Res. 2003;18(11):1932-1941.FORSTEO builds bone1

33. FPTFORSTEO SIGNIFICANTLY Increased BMD133BMD = bone mineral density; FPT = Fracture Protection Trial; SE = standard error.1. Marcus R, et al. J Bone Miner Res. 2003;18(1):18-23.p<0.001 vs. placebo at each time point

34. Fracture Prevention trial extension (GHBJ)BMD increases ARE sustained even after no post-FORSTEO treatment134BMD = bone mineral density;1. Lindsay R, et al. Arch Intern Med. 2004;164(18):2024-2030.BMD change after FORSTEO treatment followed by bisphosphonate use for ≥12 monthsBMD change during and after FORSTEO treatmentBMD after FORSTEO treatment followed by no treatment with any osteoporosis drugAdapted from Lindsay R, et al. 2004.

35. 1. Neer RM, et al. N Engl J Med. 2001;344(19):1434-1441.FORSTEO safety profile1 *p<0.05 vs. placebo; †p<0.02; ‡Calcium concentration that exceeded 10.6 mg/dL (2.6 mmol/L).35Adverse EventPlacebo (n=544); n (%)FORSTEO (n=541); n (%)Dizziness33 (6)50 (9)*Nausea41 (8)51 (8)Headache45 (8)44 (8)Leg cramps6 (1)17 (3)† Mild hypercalcaemia‡ (2)(11)Withdrawn for adverse events32 (6)35 (6)

36. 36SC = subcutaneous.1. Langhdahl BL, et al. Calcif Tissue Int. 2009;85(6):484-493. 2. Fahrleitner-Pammer A, et al. Osteoporos Int. 2011;22(10):2709-2719.Postmenopausal women with a diagnosis of osteoporosis and about to begin FORSTEO treatmentPrimary endpoints:Vertebral fracturesNon-vertebral fracturesSecondary endpoints:Back painQuality of lifeCompliance with FORSTEOSafety (spontaneously reported adverse events)FORSTEO SC DAILY X18 MONTHS, THEN 18 MONTHS OF FOLLOW-UP N=1648(completed 18 months)N=1576 (completed 36 months)European forsteo observational study EFOS1,2

37. EFOSPersistent Effects of FORSTEO AFTER DISCONTINUATION137CI = confidence interval; EFOS = European FORSTEO Observational Study; OR = odds ratio.1. Fahrleitner-Pammer A, et al. Osteoporos Int. 2011;22(10):2709-2719.Treatment periodFollow-up periodn (%) = number of women who had≥1 fracturesOR: 0.71 (95% CI: 0.50, 1.00; p=0.052)

38. FORSTEOprevention of fracture in comparison with RIsedronate38

39. FORSTEO vs. RISEDRONATE IN SEVERE OSTEOPOROSIS VERO The largest controlled trial with FORSTEO and the first 24-month, randomised, active-controlled trial that assessed fracture risk reduction as the primary endpoint in postmenopausal women with osteoporosis39d = day; QW = once a week; SC = subcutaneous; VERO = VERtebral Fracture Treatment Comparisons in Osteoporotic Women trial.Kendler D, et al. Lancet. 2018;391:230-40.ScreeningphaseActive-treatment phaseAll patientsFORSTEO (SC) + oral risedronate QW-equivalent placebo Oral risedronate 35 mg QW + FORSTEO-equivalent placebo (SC)Calcium plus vitamin D2-4 weeks3 months3 months6 months6 months6 monthsVisit 1Visit 2Visit 3(3 months)Visit 4(6 months)Visit 5(12 months)Visit 6(18 months)Visit 7(24 months)Randomisation(1:1)

40. VERO: Key baseline characteristics 40SD = standard deviation; VERO = VERtebral Fracture Treatment Comparisons in Osteoporotic Women trial.Kendler D, et al. Lancet. 2018;391:230-40.CharacteristicsFORSTEO (N=680)Risedronate (N=680)Age (years), mean (SD)72.6 (8.77)71.6 (8.58)Bone mineral density, mean (SD)*Lumbar spine-2.27 (1.24)-2.29 (1.22)Femoral neck-2.27 (0.76)-2.24 (0.74)Patients with ≥1 vertebral fractures, n (%)679 (100) 679 (100)Patients with ≥1 non-vertebral fractures after 40 years of age, n (%)298 (44) 284 (42) Mean (SD) number of prevalent vertebral fractures2.7 (2.1) 2.7 (2.1)Grade of the most severe vertebral fracture, n (%)†SQ3606 (89)612 (90.0)*Number of SDs below the respective mean bone mineral density in young adults.

41. VERO: previous osteoporosis therapy 41ERT = estrogen replacement therapy; HRT = hormone replacement therapy; IQR = interquartile range; SD = standard deviation; VERO = VERtebral Fracture Treatment Comparisons in Osteoporotic Women trial.Kendler D, et al. Lancet. 2018;391:230-40. Number (%) of patientsTreatment duration (years), median (IQR)Previous osteoporosis therapyFORSTEO(N=680)Risedronate(N=680)FORSTEO(N=680)Risedronate(N=680)Patients with ≥1 previous osteoporosis drugs496 (73)485 (71)3.2 (1.0-6.8)3.3 (1.0-6.3)Antiresorptives418 (61) 410 (60)3.8 (1.2-7.0)3.7 (1.2-6.3) Bisphosphonates402 (59)386 (57)3.6 (1.1-7.0)3.6 (1.3-6.1)Calcium or vitamin D only64 (9%)69 (10%)0.3 (0.1-3.1)0.3 (0.1-2.2)Selective estrogen receptor modulators21 (3%)26 (4%)4.2 (1.2-6.2)2.5 (1.0-7.4)HRT or ERT9 (1%)3 (<1%)3.2 (2.8-4.0)14.9 (7.0-22.7)Other osteoporosis therapy*78 (12%)80 (12%)1.0 (0.5-2.1)0.7 (0.1-2.3)*Other therapies included: strontium ranelate (n=76), denosumab (n=49), calcitonin (n=34), 1α‑hydroxy-vitamin D (n=9), fluoride (n=4), and 1,25-di-hydroxy-vitamin D (n=1).

42. FORSTEO SIGNIFICANTLY REDUCEDNEW VERTEBRAL FRACTURES AT 12 AND 24 MONTHS primary endpoinT42ARR = absolute risk reduction; RRR = relative risk reduction.Kendler D, et al. Lancet. 2018;391:230-40.-48% RRR, p=0.019-56% RRR, p<0.0001-56% RRRARR = -6.6% RisedronateFORSTEO

43. FORsTEO SIGNIFICANTLY REDUCEDNEW MULTIPLE vertebral fractures SECONDARY NON-GATED endpoint43RRR = relative risk reduction.Kendler D, et al. Lancet. 2018;391:230-40.-84% RRR, p=0.007RisedronateFORSTEO

44. FORsTEO SIGNIFICANTLY REDUCEDCLINICAL vertebral FRACTURESEXPLORATORY endpoint44CI = confidence interval. Kendler D, et al. Lancet. 2018;391:230-4043210 Cumulative Incidence of clinicalvertebral fractures (%)Kaplan-Meier EstimateTime, MonthsRisedronateFORSTEO680631600579493680627606579501No. at riskFORSTEORisedronateHazard ratio: 0.29(95% CI: 0.14, 0.58)p=0.002

45. FORSTEO SIGNIFICANTLY REDUCEDCLINICAL FRACTURES 2nd sECONDARY GATED endpoint 45CI = confidence interval..Kendler D, et al. Lancet. 2018;391:230-40.*Clinical vertebral and non-vertebral fragility fractures: clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, or metatarsus.Hazard ratio: 0.48 (95% CI: 0.32, 0.74)p=0.00090Cumulative Incidence of clin frx* (%)Kaplan-Meier EstimatesTime, Months6801234567891011623589561508RisedronateFORSTEO680616584553502FORSTEORisedronateNo. at risk

46. The incidence of non-vertebral fragility fractures did not differ significantly between the Forsteo and risedronate treatment groups1 3rd sECONDARY GATED endpoint 46Cumulative Incidence of Non-Vertebral Fragility Fractures*: Kaplan-Meier EstimatesCI = confidence interval.1. Kendler D, et al. Lancet. 2018;391:230-40*Fractures of the clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, or metatarsus (excluding pathologic fractures and fractures of skull, face, fingers, metacarpals, and toes).Hazard ratio: 0.66(95% CI: 0.39, 1.10)p=0.100Cumulative Incidence (%)Time, Months6801234567625592565513680622595570518FORSTEORisedronateNo. at riskRisedronateFORSTEOModified from Kendler D, et al. Lancet, 2018.

47. The incidence of major non-vertebral fragility fractures was not statistically significantly different between Forsteo and risedronate treated patients1 4th sECONDARY GATED endpoint 47Cumulative Incidence of Non-Vertebral Major Fragility Fractures*: Kaplan-Meier EstimatesModified from Kendler D, et al. Lancet, 2018.CI = confidence interval.1. Kendler D, et al. Lancet. 2018;391:230-40.*Fracture of hip, radius, humerus, ribs, pelvis, tibia, or femur.Hazard ratio: 0.58(95% CI: 0.32, 1.05)p=0.060Cumulative Incidence (%)Time, Months680123456626596571520680624598576525FORSTEORisedronateNo. at riskRisedronateFORSTEO

48. FORSTEO REDUCED NON-VERTEBRAL FRAGILITY FRACTURES 3rd sECONDARY GATED endpoint 48CI = confidence interval.Kendler D, et al. Lancet. 2018;391:230-40.*Fractures of the clavicle, scapula, ribs, sternum, sacrum, coccyx, humerus, radius, ulna, carpus, pelvis, hip, femur, patella, tibia, fibula, ankle, calcaneus, tarsus, or metatarsus (excluding pathologic fractures and fractures of skull, face, fingers, metacarpals, and toes).Hazard ratio: 0.66(95% CI: 0.39, 1.10)p=0.100Cumulative Incidence ofnon-vert fragility fractures*(%)Kaplan-Meier EstimatesTime, Months6801234567625592565513680622595570518FORSTEORisedronateNo. at riskRisedronateFORSTEO

49. FORSTEO REDUCEDMAJOR NON-VERTEBRAL FRAGILITY FRACTURES 4th sECONDARY GATED endpoint 49Modified from Kendler DL, et al. Lancet, 2017.CI = confidence interval.Kendler D, et al. Lancet. 2018;391:230-40*Fracture of hip, radius, humerus, ribs, pelvis, tibia, or femur.Hazard ratio: 0.58(95% CI: 0.32, 1.05)p=0.060Cumulative Incidence of non-vertmajor fragility fractures* (%)Kaplan-Meier EstimatesTime, Months680123456626596571520680624598576525FORSTEORisedronateNo. at riskRisedronateFORSTEO

50. 50Fracture endpointFORSTEORisedronateRR or HR (95% CI)p-valuePrimary endpoint    New vertebral fracture 28 (5%)64 (12%)RR: 0.44 (0.290, 0.677)<0.0001Secondary gated endpoints    New or worsened vertebral fracture 31 (6%)69 (13%)RR: 0.46 (0.305, 0.682)<0.0001Pooled clinical fracture*30 (5%)61 (10%)HR: 0.48 (0.316, 0.739)0.0009Non-vertebral fragility fracture 25 (4%)38 (6%)HR: 0.66 (0.390, 1.101)0.10Major non-vertebral fragility fracture 18 (3%)31 (5%)HR: 0.58 (0.318, 1.052)0.06Secondary non-gated endpoints    New moderate (SQ2) or severe (SQ3) vertebral fracture 26 (5%)63 (12%)RR: 0.42 (0.270, 0.646)<0.001New multiple vertebral fractures 2 (<1%)12 (2%)RR: 0.16 (0.036, 0.744)0.007Pooled fragility and traumatic non-vertebral fracture40 (7%)57 (9%)HR: 0.70 (0.461, 1.050)0.08CI = confidence interval; HR = hazard ratio; SQ = qualitative visual semiquantitative grading; RR = relative risk; VERO = VERtebral Fracture Treatment Comparisons in Osteoporotic Women trial.Kendler D, et al. Lancet. 2018;391:230-40.*Pooled clinical vertebral and non-vertebral fragility fractures.prespecified major non-vertebral fracture locationsVERO: Fracture Efficacy Outcomes During 24 Months

51. VEROSAFETY Profile consistent with prescribing information51*All deaths were considered unrelated to study drug.VERO = VERtebral Fracture Treatment Comparisons in Osteoporotic Women trial.Kendler D, et al. Lancet. 2018;391:230-40.Adverse events summaryPatients, %Fisher’sp-valueFORSTEO (N=680)Risedronate (N=680)≥1 adverse events72.873.50.76Serious adverse events20.116.90.13Related to study drug12.89.70.07Related to study procedure0.60.61.000Leading to treatment discontinuation9.97.10.06Leading to death*2.21.00.13Selected adverse eventsPain in hands or feet5.42.60.013Dizziness4.41.80.007Hypercalcaemia2.20.1<0.001Pain1.50.30.038

52. VEROConclusions In postmenopausal women with established osteoporosis who are at high risk for fracture, FORSTEO significantly reduced vertebral and clinical fractures compared with risedronate FORSTEO is better at preventing fractures in patients with severe osteoporosis and confirms previous data in clinical trials of FORSTEO vs. bisphosphonates with fracture as a secondary endpoint Clinicians should consider FORSTEO for optimal management for patients with osteoporosis who have prevalent vertebral fracturesVERO = VERtebral Fracture Treatment Comparisons in Osteoporotic Women trial.Kendler D, et al. Lancet. 2018;391:230-40.52

53. Patient case5375 year old womenDXA 2013: T-score: -3.4 and -1.7Calcium and vitamin DDecember 2016: Admitted with severe back pain Frx of Th12 Hospitalized for 3 days and treated with physiotherapy and painkillersDXA: T-scores: -3.8 and -2.2Started Risedronate 35 mg weekly + calcium and vitamin DAugust 2017: New episode of back painReferred to AUH, frx of Th12 and L2DXA: T-scores -3.7 and -2.6The patient asked me:Will I get my life back?ForsteoNew fractureBMD loss

54. What whould you do?Reassure the patient – have her continue the current treatmentChange the treatment to zolendronic acid or denosumabChange to a bone forming treatment - teriparatide54New fractureBMD loss

55. What whould you do?Reassure the patient – have her continue the current treatmentChange the treatment to zolendronic acid or denosumabChange to a bone forming treatment - teriparatide55FORSTEO

56. BMD = bone mineral density.1. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017. 2. Siris ES, et al. Osteoporos Int. 2007;18(6):761-770. 3. FORTEO Prescribing Information. 4. Jiang Y, et al. J Bone Miner Res. 2003;18(11):1932-1941. 5. Marcus R, et al. J Bone Miner Res. 2003;18(1):18-23. 6. Kendler D, et al. Lancet. 2018;391:230-40.summary56Patients with osteoporosis have decreased bone strength, which leads to increased fracture risk1A first osteoporotic fracture leads to considerable risk of subsequent fractures and the fracture cascade1,2Clinicians should consider FORSTEO for optimal management for patients with osteoporosis who have prevalent vertebral fractures

57. BMD = bone mineral density.1. International Osteoporosis Foundation (IOF). Facts and statistics. https://www.iofbonehealth.org/facts-statistics. Accessed September 22, 2017. 2. Siris ES, et al. Osteoporos Int. 2007;18(6):761-770. 3. FORTEO Prescribing Information. 4. Jiang Y, et al. J Bone Miner Res. 2003;18(11):1932-1941. 5. Marcus R, et al. J Bone Miner Res. 2003;18(1):18-23. 6. Kendler D, et al. Lancet. 2018;391:230-40.summary57The potential benefits of FORSTEO therapy include:Fracture risk reduction3Improved BMD4Effects observed early in the course of therapy5More effective vertebral fracture prevention in patients with severe osteoporosis than risedronate6Stimulates osteoblasts and builds new bone3

58. QUESTIONS?58

59. 59FORSTEO® (teriparatide) PRESCRIBING INFORMATION