Empfehlungen Hilfsmittel Ausblick Anmeldung STZ Osteoporose Empfehlungen Hilfsmittel Ausblick Anmeldung STZ

Absolutes Frakturrisiko mit Frax

Limitationen Frax Vorbehandelte Patienten Wirbelfrakturen Verlauf

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Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial Tsai J.N. et al. Lancet published online May 15, 2013

DATA-Studie: Denosumab und Teriparatid in Mono- oder Kombinationstherapie bei postmenopausaler Osteoporose Methodik: Design Offene, randomisierte, kontrollierte Studie 12 Monate Behandlung Patienten 94 postmenopausale Frauen mit hohem Frakturrisiko (mittleres Alter: 66 Jahre) Behandlung Entweder die Kombination Teriparatid 20ug täglich plus Denosumab 60mg alle 6 Monate oder jeweils mit einer der beiden Einzelnsubstanz allein im Verhältnis 1:1:1 Ausschluss-kriterien Vortherapie mit oralen BPs in den letzten 6 Monaten Vortherapie mit i.v. BPs oder Strontiumranelat Endpunkte Prozentuale Änderung der DXA-BMD an der Gesamthüfte, Schenkelhals, LWS und 1/3 Radius nach 12 Monaten Tsai et al. Lancet 2013

Effekt auf Knochendichte nach 12 Monate Kombinierte Behandlung mit Denosumab und Teriparatid: die DATA-Studie > Änderungen der Knochenmineraldichte Ergebnisse: Effekt auf Knochendichte nach 12 Monate * Tsai et al. Lancet 2013

BMD-Entwicklung nach 12 Monaten an der Lendenwirbelsäule Kombinierte Behandlung mit Denosumab und Teriparatid: die DATA-Studie > Änderungen der Knochenmineraldichte Ergebnisse: BMD-Entwicklung nach 12 Monaten an der Lendenwirbelsäule Kombination Teriparatid Denosumab Monate LWS BMD-Änderung (%) 12 6 2 4 8 10 p-Wert Dmab vs TPTD n.s. Kombi vs TPTD 0,0005 Kombi vs Dmab < 0,0001 Tsai et al. Lancet 2013

BMD-Entwicklung nach 12 Monaten an der Hüfte Kombinierte Behandlung mit Denosumab und Teriparatid: die DATA-Studie > Änderungen der Knochenmineraldichte Ergebnisse: BMD-Entwicklung nach 12 Monaten an der Hüfte Kombination Denosumab Teriparatid BMD-Änderung (%) Monate Schenkelhals 12 6 1 2 3 4 5 Kombination Denosumab Teriparatid BMD-Änderung (%) Monate Gesamthüfte 6 5 4 3 1 2 12 p-Wert Dmab vs TPTD n.s. Kombi vs TPTD < 0,001 Kombi vs Dmab 0,013 p-Wert Dmab vs TPTD 0,003 Kombi vs TPTD < 0,0001 Kombi vs Dmab 0,0001 Tsai et al. Lancet 2013

DATA-Studie: Denosumab und Teriparatid in Mono- oder Kombinationstherapie bei postmenopausaler Osteoporose Fazit: Die Kombinationstherapie mit Teriparatid plus Denosumab erhöhte die Knochendichte stärker als die jeweiligen Monotherapien an allen gemessenen Stellen Autoren suggerieren, dass diese Kombinationstherapie zu einem additiven Effekt auf beide kortikalen und trabekulären Knochen führte Diese Kombination könnte die Osteoporose-Behandlung bei Patientinnen mit hohem Frakturrisiko verbessern Tsai et al. Lancet 2013

Study Design The Pivotal Phase 3 Study – Extension International, multicenter, open-label, single-arm study Pivotal Phase 3 Fracture Trial Extension Study Year 1 2 3 4 5 6 7 8 9 10 R A N D O M I Z T Denosumab 60 mg SC Q6M (N = 3,902) Denosumab 60 mg SC Q6M (N = 2,343) Continued Denosumab Treatment Calcium and Vitamin D Placebo SC Q6M (N = 3,906) Denosumab 60 mg SC Q6M (N = 2,207) Cross-over Denosumab Treatment A total of 4,550 subjects who completed the pivotal phase 3 fracture trial (N = 7,808) enrolled into a 7-year, multinational, multicenter, open-label, single-arm extension study to evaluate the long-term safety and efficacy of denosumab1 All subjects in the extension study, regardless of treatment assignment in the pivotal phase 3 fracture study, received denosumab 60 mg Q6M SC, as well as daily calcium and vitamin D supplementation1 Primary endpoint of the extension study is assessment of safety and tolerability of up to 10 years of denosumab administration1 Secondary endpoints of the extension study include: changes in bone turnover and bone mineral density, and incidence of new vertebral and nonvertebral fractures1 The 7-year study extension remains ongoing, with a planned total exposure to denosumab of up to 10 years1 Brown JP, Bone HG, Chapurlat R, et al. Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the FREEDOM extension. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Year 1 2 3 4 5 6 7 Key Inclusion Criteria: Completed the Pivotal Phase 3 Fracture Trial (completed their 3-year visit, did not discontinue investigational product, and did not miss more than 1 dose). Not receiving any other osteoporosis medications. SC = subcutaneous; Q6M = once every six months Adapted from Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL.

Lumbar Spine BMD Total Hip BMD Change in Lumbar Spine and Total Hip BMD Through 6 Years with Denosumab Treatment The Pivotal Phase 3 Study – Extension Placebo Continued Denosumab Cross-over Denosumab Lumbar Spine BMD * –2 2 4 6 8 10 12 14 16 18 † 15.2% Percent Change From Baseline 1 3 5 Study Year 10.1% 9.4% Pivotal Phase 3 Fracture Trial Extension Study Total Hip BMD * –2 2 4 6 8 10 Study Year 1 3 5 7.5% † 5.7% 4.8% Pivotal Phase 3 Fracture Trial Extension Study In the open-label extension of the pivotal phase 3 fracture trial, BMD continued to significantly increase in years 4, 5, and 6 at the lumbar spine and total hip as compared to baseline of the Pivotal Phase 3 Fracture Trial1 Data represent only the subset of subjects from the pivotal phase 3 fracture trial who enrolled in the extension study1 Data from years 1 and 2 in the lumbar spine graph represent extension trial subjects from the BMD substudy of the pivotal phase 3 fracture trial2 Brown JP, Bone HG, Chapurlat R, et al. Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the FREEDOM extension. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med. 2009;361:756-765. 2005 1485 119‡ 122‡ 120‡ 2028 1923 Cross-over n 1962 1456 118‡ 2023 1998 2007 1896 2112 1588 139‡ 141‡ 142‡ 2148 2040 Continued n 2086 1565 140‡ 2149 2125 2134 2016 Data represents LS means and 95% CI. n = number of subjects with values at baseline and the time point of interest. *P < 0.05 vs Pivotal Phase 3 Study baseline; †P < 0.0001 vs Pivotal Phase 3 Study baseline and Extension baseline. ‡Represents subjects from the Pivotal Phase 3 Study DXA substudy. Orange numbers on the graphs represent the percent change in BMD while on denosumab treatment. BMD = bone mineral density; CI = confidence interval; LS = least-squares; DXA = dual-emission X-ray absorptiometry Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Cummings SR, et al. N Engl J Med. 2009;361:756-765.

Pivotal Phase 3 Fracture Trial Extension Study Yearly Incidence of New Vertebral Fractures Through 6 Years The Pivotal Phase 3 Study – Extension Placebo Continued Denosumab Cross-over Denosumab Pivotal Phase 3 Fracture Trial Extension Study Yearly Incidence of New Vertebral Fracture (%) In the extension study, the incidence of new vertebral fracture in the continued denosumab treatment group was 1.4% for years 4 and 5 (annualized rate), and 1.1% for year 6. Cross-over denosumab results were 0.9% for years 4 and 5 (annualized rate), and 1.5% for year 6.1 Radiographic x-rays of the spine were performed at year 5 only during the extension study; given this, new vertebral fracture incidence is presented as an annualized rate for year 4 and 5 since one cannot determine which year the vertebral fracture occurred.2 Fracture incidence was not evaluated as an efficacy endpoint in the extension study.2 Note: N = number of subjects in the primary efficacy analysis set who were still on study at the beginning of each period2 Brown JP, Bone HG, Chapurlat R, et al. Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the FREEDOM extension. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Data on file, Amgen. 18 98 35 107 24 82 n 32 58 23 34 1,610 3,186 3,247 3,400 3,453 3,691 N 3,702 2,101 1,509 1,980 Years of Denosumab Exposure Fracture incidence was not evaluated as an efficacy endpoint in the extension study n = number of patients with ≥1 fracture. N = number of randomized patients who remained on study at the beginning of each period and had available spine x-rays during the period of interest. *Annualized rate: (2-year rate)/2. Lateral radiographs (lumbar and thoracic) were not obtained at year 4 (year 1 of the Extension). Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Data on file, Amgen.

Pivotal Phase 3 Fracture Trial Extension Study Yearly Incidence of Nonvertebral Fractures Through 6 Years The Pivotal Phase 3 Study – Extension Placebo Continued Denosumab Cross-over Denosumab Pivotal Phase 3 Fracture Trial Extension Study Yearly Incidence of Nonvertebral Fracture (%) The incidence of nonvertebral fracture with denosumab in the continued denosumab treatment group was 1.4% for year 4, 1.2% for year 5, and 1.3% for year 6. Cross-over denosumab results were 2.4% for year 4, 1.8% for year 5, and 1.7% for year 6.1 Fracture incidence was not evaluated as an efficacy endpoint in the extension study2 Brown JP, Bone HG, Chapurlat R, et al. Six years of denosumab treatment in postmenopausal women with osteoporosis: results from the first three years of the FREEDOM extension. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Data on file, Amgen. 26 83 73 103 75 116 n 98 32 36 52 24 29 2,243 3,454 3,487 3,688 3,682 3,906 N 3,902 2,343 2,105 2,207 2,066 1,964 Years of Denosumab Exposure Fracture incidence was not evaluated as an efficacy endpoint in the extension study n = number of patients with ≥ 1 fracture. N = of randomized patients who remained on study at the beginning of each period. Percentages for nonvertebral fractures are Kaplan-Meier estimates. Adapted from: Brown JP, et al. Presented at: American College of Rheumatology Annual Scientific Meeting; November 8, 2011; Chicago, IL. Data on file, Amgen.

Neue Studien Ernährung und Exercise: Do-Health, Frau Prof H.Bischoff Geriatrie, ZAM, Senioren >70 Medikamente: Anti-Sclerostin, Resultate in 2-3 Jahren, Therapie: Therapiepause, Monitoring