認識骨質疏鬆症 PSR Name Venue-Date.

Presentation on theme: "認識骨質疏鬆症 PSR Name Venue-Date."— Presentation transcript:

1 認識骨質疏鬆症 PSR Name Venue-Date

2 何謂骨質疏鬆症？ 骨質疏鬆症定義 骨質疏鬆症後果
世界衛生組織(WHO)於1994公佈成年人骨質疏鬆症的定義：『一種 因骨量減少或骨密度降低而使骨骼微細結構發生破壞的病，惡化的結 果將導致骨骼脆弱，並使骨折危險明顯增高』 骨質疏鬆症後果 容易造成骨折，特別是前臂骨、股骨及脊椎骨。最明顯的症狀，就是 脊椎壓迫性骨折，它會引起背部酸痛，身高變矮，及駝背現象，常見 的「老倒勼」即是指這種現象。 正常的骨骼 罹患骨質疏鬆症的骨骼 衛生署骨質疏鬆症臨床治療指引、衛生署官方網站衛教宣導-認識骨質疏鬆

3 人體骨骼會不斷的新陳代謝 當分解速度>生成速度時，骨骼開始流失

4 平均每3位50歲以上女性，就有1位會發生骨質疏鬆引起的骨折
骨質疏鬆症常發生嗎? 平均每3位50歲以上女性，就有1位會發生骨質疏鬆引起的骨折 Osteoporosis is common, and is a growing and under-recognised threat Osteoporosis affects 75 million women in the US, EU and Japan.1 Osteoporotic fractures affect 1 in 3 women aged > 50 years old.1 In addition, the prevalences of osteoporosis and hip fracture are continuing to rise in an increasingly elderly population.1 The International Osteoporosis Foundation acknowledges the extent of the threat of osteoporosis worldwide.2 References International Osteoporosis Foundation. Facts and statistics about osteoporosis and its impact. Available at Last accessed May 2009. International Osteoporosis Foundation. Healthcare Professionals. Available at Last accessed May 2009. 1. International Osteoporosis Foundation. Facts and statistics about osteoporosis and its impact. Available at Last accessed May 2009

5 骨鬆引起的嚴重後果-骨折 骨質疏鬆症引起的骨折常發生的部位1 脊椎骨 髖骨 手腕骨
Osteoporotic fractures occur throughout the skeleton1 Hip, vertebral body and distal forearm fractures have long been regarded as ‘typical’ osteoporotic fractures.1 However, osteoporotic fractures in individuals with low bone mineral density can occur at any skeletal site.1 Reference 1. Cole ZA et al. Current Rheumatology Reports 2008;10:92–96. 1. Cole ZA et al. Current Rheumatology Reports 2008;10:92– World Health Organization. WHO Scientific Group on the Assessment of Osteoporosis at Primary Health Care Level: Summary Meeting Report. 5–7 May, 2004; Brussels, Belgium.

6 骨鬆骨折可嚴重影響生活！ 以髖部骨折為例…
40% 無法獨立行走 30% 永久殘障 20% 一年內死亡 80% Patients (%) 無法單獨進行至少一項的日常活動 患者數 (%) 與晚期乳癌相當！ [Source of notes below: Slide 7, 'Understanding today's EU burden of osteoporosis' Slide deck, Prof. Adolfo Diez Perez] The disease burden of osteoporosis can be seen from this slide, which shows outcomes for patients one year after hip fracture: 20% of patients die within one year 30% of patients suffer permanent disability 40% are unable to walk independently 80% are unable to carry out at least one independent activity of daily living.1 [Source of notes below: Slide 5, 'Understanding today's EU burden of osteoporosis' Slide deck, Prof. Adolfo Diez Perez] Other studies, which are not shown on this slide, have found that: Permanent functional disability remains in 50% of patients who experience a hip fracture.2 Pain and disability from a new clinical vertebral fracture can last for 3 or more years.3 1. Cooper C. Am J Med 1997;103(2A):12S–17S 2. Gullberg B et al. Osteoporos Int 1997;7:407–413. 3. Ross PD et al. J Clin Epidemiol 1994;47:231–239. 髖部骨折一年之後 Cooper C. Am J Med 1997;103(2A):12S–17S

7 為什麼會骨質疏鬆?

8 婦女在更年期(停經)過後骨量快速減少! 骨量 10 20 40 50 60 70 80 30 進入更年期停經期* 骨量邁向巔峰 年齡
骨骼成骨作用> 骨骼蝕骨作用 骨量巔峰 骨量減少 骨骼蝕骨作用> 骨骼造骨作用 ！Key Point Changes in the balance between resorption and formation drive the increases and decreases in bone mass that occur over a woman’s lifetime1. Supplemental Information Bone is a dynamic tissue that undergoes a process of bone loss (resorption) and build-up (formation), collectively called remodeling1. There is a period of rapid bone accrual during puberty; approximately 40% of peak bone mass accrues over 4 years2. Peak bone mass is attained by the age of 183. Bone mass remains stable until menopause, when a reduction in oestrogen levels, together with aging, can drive a phase of relatively rapid bone loss4. Following menopause, bone loss slows. From about the age of 70, however, a second phase of accelerated bone loss may occur5 that may be driven by factors including vitamin D deficiency and decreased muscle mass6. Boyle WJ, et al. Nature 2003;423: Weaver CM, et al. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. 2008: Sambrook P, et al. Baillieres Clin Rheumatol 1993;7: Recker R, et al. J Bone Miner Res 2000;15: Burger H, et al. Am J Epidemiol 1998;147: Kiel DP, et al. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. 2008: * Menopause occurs for approximately one year period during this timeframe Lanham-New SA. Proc Nutr Soc. 2008;67: ; Burger H, et al. Am J Epidemiol 1998;147: ; Recker R, et al. J Bone Miner Res 2000;15: ; Sambrook P, et al. Baillieres Clin Rheumatol 1993;7: ; Weaver CM, et al. Primer on the Metabolic Bone Diseases and Disorders of Mineral Metabolism. 7th ed. 2008:

9 更年期後的女性 保骨素(OPG)作用不足造成骨質流失！
= 更年期前的婦女 雌激素(賀爾蒙) 水平維持理想狀況 健康骨骼 保骨素 RANKL 蛋白質 = 保骨素 更年期後的婦女 雌激素(賀爾蒙) 水平降低 加速骨質流失 導致罹患骨質疏鬆 RANKL 蛋白質

10 骨質疏鬆症的診斷

11 骨質疏鬆症篩檢-理學檢查 1.現在身高以及年輕時身高 2.體重資料
如果現在身高低於年輕時身高超過3公分以上應當強烈懷疑可能有骨質疏鬆症。同時每半年定期追蹤身高的變化也可以知道是否有新的骨鬆性腰椎骨折的現象。然而許多人可能無法清楚記住年輕時的身高而使此項數據無法明確運用。 2.體重資料 體重與骨密度成反比關係，體重過輕是骨質疏鬆症的危險因子之一。尤其當身體質量指數[計算方式＝體重(公斤)/ 身高的平方(公尺)2]小於18.5 kg/m2時更要提高警覺。亞洲人骨質疏鬆症自我評量表 (Osteoporosis Self-assessment Tool for Asians, OSTA)是一套簡易的婦女自我評估方法(如圖一)。從最主要的體重與年齡變項發現，體重越輕或年紀愈大的人較常發生骨質疏鬆症。把體重與年齡分級化為簡易明瞭的表格如下，讓民眾可以迅速的自我評估可能的危險程度。 台灣成人骨質疏鬆症防治之共識及指引 2011

12 骨質疏鬆症篩檢-理學檢查 (2) 3.頭枕部與牆間距 (wall-occiput distance, WOD )
這是篩檢潛伏性胸椎壓迫性骨折的快速方法。請病患靠牆站立，兩眼自然平視，此時測量頭後枕部與牆壁的水平間距。正常人應當幾乎沒有距離或小於1公分，如果距離超過3公分要強烈懷疑，超過6公分時(或是一個拳頭距離)幾乎可以肯定為異常。(圖二Ａ) 4.肋骨下緣與骨盆間距 (rib-pelvis distance, RPD) 這是篩檢潛伏性腰椎壓迫性骨折的快速方法。請病患站立，兩手自然平舉，此時測量測面肋骨最下緣與骨盆上緣的垂直間距。正常人應當有2-3指寬或大於5公分，如果距離小於一指幅寬(2公分)幾乎可以肯定脊椎異常。(圖二Ｂ, 取自JAMA 2004;292: ) 圖二A 頭枕部與牆間距圖 WOD>3cm 圖二B 肋骨下緣與骨盆間距圖 RPD<2cm 台灣成人骨質疏鬆症防治之共識及指引 2011

13 骨質疏鬆症臨床診斷標準 主要依據骨密度測量值為臨床診斷標準 此標準採用T值的方式評估 僅使用雙能量X光吸光式測定儀之測定數值
(DXA,Dual Energy X-ray Absorptiometry) 通常檢查部位為髖部、股骨頸、腰椎 以年輕婦女之平均值及標準差為準 T值＞-1：正常 -1＞T值＞-2.5：骨量不足 -2.5 ＞ T值：骨質疏鬆症 正常 骨量不足 (骨流失) T-score - 1.0 - 2.5 骨質疏鬆症 資料來源：衛生署骨質疏鬆症臨床治療指引

14 定量超音波儀器篩檢(QUS) 快速，成本較低 可做為初步篩檢的工具 台灣成人骨質疏鬆症防治之共識及指引 2011
QUS device by GE

15 利用FRAX 問卷評估骨折風險 世界衛生組織的骨折風險評估問卷-FRAX 骨折風險影響因子
估算每個人未來10年的骨質疏鬆症相關骨折的風險（包含脊椎骨折、前臂骨 折、髖骨骨折或肩部骨折）以及髖骨骨折率，以提供預防和治療上的參考。防 止嚴重骨質疏鬆所造成之骨折及其併發症 骨折風險影響因子 年齡 體重(公斤) 身高(公分) 過去骨折歷史 父母髖骨骨折 是否服用類固醇 類風濕性關節炎 是否發生過續發性骨折 每日喝酒三單位(或以 上) 股骨頸密度 Key Point BMD and age are independent risk factors for fracture1-3. Supplemental Information Other risk factors for fracture are generally less predictive of fracture risk, and tend to vary in importance according to age. Nevertheless, recent meta-analyses have shown international consistency for low body mass index, a prior history of fracture, a family history of hip fracture, current smoking, high intake of alcohol and rheumatoid arthritis as risk factors for fracture that are partly independent of BMD3. Glucocorticoids are also recognised as an important cause of osteoporosis and fractures; the fracture risk conferred by the use of corticosteroids is not solely dependent upon bone loss, and BMD independent risks have been identified3. Kanis JA et al. Osteoporos Int 2001;12: Kanis JA, et al. Osteoporos Int 2001;12: Kanis JA, et al. Osteoporos Int 2005;16: 台灣成人骨質疏鬆症防治之共識及指引中華民國骨質疏鬆症學會 Dec 2011

16 FRAX 問卷填寫方式 網址: 請參考問卷下方有說明來填寫 填寫完按 “計算” ，即可得出骨折風險機率 經骨折風險評估表估算未來10年的骨質疏鬆症相關骨折的(包括髖骨、脊柱體、肱骨及橈骨)風險超過20%，或髖骨骨折風險超過3%，屬於高骨折風險，應考慮積極治療。 台灣成人骨質疏鬆症防治之共識及指引中華民國骨質疏鬆症學會 Dec 2011

17 哪些人應接受骨密度檢查? 台灣成人骨質疏鬆症防治之共識及指引 2011

18 保持骨骼健康的基本3步驟 陽光 運動 飲食

19 骨質疏鬆症的照護 非藥物治療 (生活方式的改變) 注意營養的補充 (鈣質和維生素D) 藥物治療
適當的運動 (增加骨密度，增強肌力，改善平衡功能，減少跌倒和骨折) 戒菸和戒酒 預防跌倒 注意營養的補充 (鈣質和維生素D) 藥物治療 Management of osteoporosis There are three approaches to managing osteoporosis: Non-pharmacological therapy Nutritional recommendations Pharmacological therapy Non-pharmacological therapy is the foundation for managing osteoporosis. Nutritional recommendations and pharmacological therapy are discussed on later slides. Weight-bearing exercise Weight-bearing and muscle-strengthening exercises improve agility, strength, posture, and balance, and thus may reduce the risk of falls. Regular physical activity also increases vertebral bone mineral density and strengthens muscles in postmenopausal women. Exercise, such as walking, jogging, stair climbing, or dancing, for 30 minutes on most days is recommended as part of a healthy lifestyle. Avoidance of tobacco or excessive alcohol use Smokers are generally thinner, undergo menopause earlier, have increased breakdown of oestrogen, and are more likely to experience fractures. Moderate alcohol consumption has no detrimental effect on the bone, but excessive alcohol consumption (≥3 drinks per day) can increase the risk of falling. Fall prevention Measures include vision and hearing correction, neurological evaluation, medication review, home safety improvement, and use of hip protectors.

20 維生素D 與鈣質是必要的營養素 自食物/營養品攝取 在早上10點前、下午2點後，每天曬15分鐘的陽光來獲得維生素D
每日鈣質與維生素建議攝取量 鈣質 維生素D 1300mg IU

21 食物中所含的鈣質

22 骨質疏鬆症的藥物治療 抗溶蝕藥物：抑制骨質溶蝕 同化藥物：刺激造骨作用 其他藥物 類保骨素藥物: 雙磷酸鹽類藥物
保骼麗 (PROLIA) 雙磷酸鹽類藥物 Fosamax®福善美 Bonviva®骨維壯 Aclasta®骨力強 Actonel® 選擇性雌激素受體調節劑(SERMs): Evista®鈣穩 抑鈣激素: Miacalcic®密鈣息 同化藥物：刺激造骨作用 其他藥物 鍶: Protos® 副甲狀腺素: Forteo®骨穩

23 骨鬆藥物在預防骨折的效果比較 預防脊椎骨折 預防非脊椎骨折 預防髖骨骨折 Calcitonin (Miacalcin,Fortical)
Yes 未呈現其效果 Raloxifene (Evista) Ibandronate (Bonviva) Alendronate (Fosamax) Risedronate (Actonel) Zolendronic acid (Aclasta) Denosumab (Prolia) Teriparatide (Forteo) 雙磷酸鹽 類保骨素針劑 (RANKL inhibitor) Adapted from Endocrine Practice Vol 16 (Suppl 3) NOV/DEC 2010 Table 20 Aclasta is called Reclast in USA Risedronate (Actonel) is not marketed in Taiwan

24 骨鬆患者多為中高年齡，用藥上應注意病患 腎功能狀況
根據NHANES III 中7120位女性的研究結果顯示， 高達 23.8% 的骨鬆患者其腎功能CCR <35，達到中重度腎功能不全的狀況 Osteoporos Int (2003) 14: 570–576

25 使用雙磷酸鹽類藥物，需注意病患腎功能情形
雙磷酸鹽: 經腎臟代謝或排除 不建議用於肌酸酐排除率小於30-35mL/min 的病患 美國FDA 曾針對zolendronic acid 提出腎功能影響的安全警訊acid

26 藥物治療應注意長期遵醫囑情形 骨質疏鬆症治療的服藥遵從性不佳 約有50%用藥三個月後即中斷治療

27 雙磷酸鹽實際用藥低於50%，幾乎等同於未治療的結果
*Siris ES, et al. Mayo Clin Proc. 2006;81:

28 服藥順從性不佳 恐增後續骨折風險 低 高 p < 0.0001 p = 0.0002 p = 0.12 骨折風險的增加 高 低
服藥順從性不佳 恐增後續骨折風險 低 骨折風險 (依服藥順從性高低排列) 高 p < p = p = 0.12 1 1.09 1.18 1.21 骨折風險的增加 Key Point Poor adherence is directly linked to an increased risk of fracture Supplemental Information Huybrechts, et al analyzed a managed care database which included over 38,000 women over the age of 45 who had been treated for osteoporosis with a bisphosphonate (alendronate and risedronate) or hormone replacement therapy. By measuring the medication possession ratio (MPR) each woman’s adherence to her prescribed osteoporosis regimen was determined and assigned to a gradient of adherence [excellent (>90% adherent), good (80-90% adherent), medium (50-<80% adherent), and poor (<50% adherent)]. Huybrechts, et al found that adherence to osteoporosis therapies is very low in the real world and that this low adherence is associated with a higher risk of fracture. When adherence dropped from over >90% MPR (excellent) to 80-90% MPR (good) there was a corresponding 9% higher risk of fracture. When adherence dropped from over 80-90% MPR (good) to 50-<80% MPR (medium) there was a corresponding 9% higher risk of fracture (18% higher fracture risk when compared to excellent adherence). When adherence dropped from over 50-<80% MPR (medium) to below 50% MPR (poor) there was a corresponding 3% higher risk of fracture (21% higher fracture risk when compared to excellent adherence). Huybrechts KF, et al. Bone. 2006;38: 高 服藥順從性 低 Data from 38,000 women in a managed care database Huybrechts KF, et al. Bone. 2006;38:

29 全新骨鬆治療藥物 保骼麗注射液 PROLIA(denosumab)

30 更年期後的女性 保骨素(OPG)作用不足造成骨質流失！
= 更年期前的婦女 雌激素(賀爾蒙) 水平維持理想狀況 健康骨骼 保骨素 RANKL 蛋白質 = 保骨素 更年期後的婦女 雌激素(賀爾蒙) 水平降低 加速骨質流失 導致罹患骨質疏鬆 RANKL 蛋白質

31 類保骨素骨鬆針- 保骼麗注射液(PROLIA) 全新藥物作用機轉，有效調控蝕骨細胞的形成、作用與存活
透過模仿保骨素(OPG)的作用方式 可以有效調控蝕骨細胞的形成、作用與存活 CFU-GM RANKL蛋白質 RANK 保骨素 RANKL 抑制劑 蝕骨細胞-預(融)合作用 抑制蝕骨細胞形成 雌激素生長 因子細胞激素 抑制蝕骨細胞 發揮作用與存活 首支仿效人體「保骨素」作用機轉、能專一抑制RANKL的單株抗體生物製劑，為目前唯一可用於治療骨鬆的生物製劑，可 造骨細胞 蝕骨作用被抑制 造骨作用 CFU-GM=colony forming unit granulocytemacrophage; M-CSF=macrophage colony stimulating factor. Boyle WJ, et al. Nature 2003;423:

32 保骼麗 Prolia 獨特作用機轉 榮獲時代雜誌(TIME)評選為10大醫療突破之一

33 保骼麗 Prolia 的臨床特點 100% 人類蛋白質藥物 半年1次皮下注射，使用便利 有效降低骨鬆常發生的脊椎、非脊椎與髖骨骨折風險
不經腎臟代謝排除，不需考慮病患腎功能調整用藥 不會有注射後急性反應，如:發燒、疼痛等類流感副作用，注射部位反應與安慰劑相當。

34 類保骨素骨鬆針 Prolia 快速的作用效果
Denosumab rapidly decreases active osteoclasts within hours of administration as measured by bone turnover markers, and increases BMD from as early as month 1 of treatment (P < 0.05)1 Serum CTX Lumbar Spine BMD - 5 - 4 - 3 - 2 - 1 - 0 Percentage Change from Baseline (%) Lumbar Spine BMD - 20 - 0 - -40 - -60 - -80 Change (%) From Baseline Mean  SE Seum CTX 不同於口服或IV infusion, 6個月皮下注射是非常方便的給藥方式 在double-dummy 的研究結果顯示 , 77% 的病患偏好6個月皮下注射的方式勝過每週口服用藥. 顯示Prolia 會是病患接受度較好的骨鬆治療方式, 增進長期治療依從性 (附註: double-dummy 是兩組都注射也吃口服藥, 一組是Prolia + 口服安慰劑, 對照組是吃alendronate + 注射安慰劑) A simple 6-monthly subcutaneous injection is preferred by patients as compared to weekly oral pills In two head-to-head, double-dummy studies, 77% of patients reported a preference for a subcutaneous injection every 6 months compared with a once weekly oral pill.1 Reference 1. Kendler DL. Osteoporos Int 2010;21:837–846. 2 4 6 8 10 12 Time (Month) McClung MR, et al. N Engl J Med. 2006;354: ; Vasikarin SD. Crit Rev Clin Lab Sci .2008;45:

35 類保骨素骨鬆針 Prolia治療方式 可以降低骨鬆常發生骨折的各部位骨折風險
根據FREEDOM 研究, 類保骨素骨鬆針可明顯降低可降低脊椎骨折風險68%, 髖骨骨折風險降低達40%, 非脊椎骨折也減少了20%。 安慰劑 類保骨素骨鬆針 Prolia 對於骨鬆骨折常發生的脊椎, 髖骨, 甚至非脊椎都有顯著的療效, FREEDOM 7800多位的大型試驗結果顯示, Prolia 可降低脊椎骨折風險68%, 髖骨骨折風險降低達40%, 非脊椎骨折也減少了20%. Prolia 可以全方位保護身體各部位骨骼, 降低骨鬆骨折的風險 FREEDOM: Prolia® reduced the risk of fracture throughout the skeleton Prolia® significantly reduced the risk of fracture throughout the skeleton vs. placebo.1 Prolia® reduced the relative risk of new vertebral fracture by 68% (95% CI 0.26–0.41; P < 0.001), hip fracture by 40% (95% CI 0.37–0.97; P = 0.04) and non-vertebral fracture by 20% (95% CI 0.67–0.95; P = 0.01).1 Reference Cummings SR et al. N Engl J Med 2009;361:756–765. *All non-vertebral fractures. However, fractures of the skull, face, mandible, metacarpals, fingers, or toes were excluded because they are not associated with decreased bone mineral density. Pathological fractures and those associated with severe trauma were also excluded. 1. Cummings SR et al. N Engl J Med 2009;361:756–765.

36 臨床研究證實 類保骨素骨鬆藥物Prolia 骨密度增加效果優於常用藥物alendronate 所有部位的結果都達統計上顯著差異
Prolia®: superior BMD increases vs. alendronate (DECIDE)1 在效用上. Head to head 臨床試驗結果證實, 使用Prolia 對病患骨密度的增進效果顯著優於alendronate, 在骨密常量測的各部位- 橈骨, total hip, 腰椎, 骨轉子, 與股骨頸都看到比alendronate 更好的效果 (時間考量, 不一定要講到每個部位增加的數據, 但要強調每個部位量測的結果都優於alendronate) DECIDE: Prolia® delivered superior increases in BMD vs. alendronate At 12 months, Prolia® treatment resulted in significantly greater increases in the percentage change from baseline in BMD (least squares mean) at all skeletal sites measured compared with alendronate. At the total hip (primary endpoint), statistically significant increases in BMD were observed for the Prolia® group compared with those treated with alendronate (3.5% vs. 2.6%; P < ).1 Prolia® also significantly increased BMD from baseline compared with that of alendronate at the lumbar spine (5.3% vs. 4.2%; P < ), distal 1/3 radius (1.1% vs. 0.6%; P = ), trochanter (4.5% vs. 3.4%; P < ) and femoral neck (2.4% vs. 1.8%; P = ).1 Reference 1. Brown JP et al. J Bone Miner Res. 2009;24:153–161. *Relative computation from absolute increase in BMD. 1. Brown JP et al. J Bone Miner Res. 2009;24:153–161.

37 原本使用口服雙磷酸鹽alendronate的病患 轉換到Prolia 也會有較佳的骨密增加效果
而另一個head to head 臨床試驗結果顯示, 對於目前正在使用alendronate的病患, 如果轉換使用Prolia , 可以觀察到各部位的骨密度效果都顯著優於繼續使用alendronate的病患 基於上面介紹的兩個試驗, 我們可以了解使用Prolia 在骨密度比alendronate更好的效果 STAND: Prolia® provided significantly greater BMD increases at all key skeletal sites in patients transitioning from alendronate vs. continuing on alendronate Treatment with Prolia® resulted in significantly greater gains in BMD than continued alendronate therapy at all key skeletal sites measured.1 At the total hip (primary endpoint), Prolia® significantly increased BMD vs. alendronate (difference between groups was 0.85%, 95% CI 0.44–1.25%; P < for superiority testing).1 Prolia® significantly increased lumbar spine BMD vs. alendronate (difference between groups was 1.18%, 95% CI 0.63–1.73% ; P < for superiority testing).1 Reference 1. Kendler DL et al. J Bone Miner Res 2010;25:72–81. P-values are vs. alendronate. 1. Kendler DL et al. J Bone Miner Res 2010;25:72–81.

38 類保骨素骨鬆針Prolia 治療方式 可持續增加脊椎骨密度13.7%
LS Mean (95% CI) *p < 0.05 compared with FREEDOM baseline; ^p < 0.05 compared with FREEDOM and EXTENSION baseline 安慰劑 類保骨素骨鬆針 * ^ 10 8 6 4 2 -2 0.5 1 3 5 16 14 12 Percent Change From Baseline 腰椎 全髖骨 Year 年 FREEDOM 試驗經過3年與安慰劑比較後, 所有病患經同意轉換至Prolia 使用持續follow-up.預期這群病人將follow 10年.在今年(2011)3月已有5年結果發表, 結果顯示, 使用Prolia 可持續增加骨密度, 5年期間骨密度年年改善, 並未有停滯或倒退的情形 原先使用安慰劑的病患開始用Prolia , 骨密度也有顯著的改善效果 骨折風險沒有對照組比較, 但發生比率仍維持前3年用藥的低發生率的效果 38 38

39 保骼麗 Prolia 耐受性良好，不良反應發生比率與安慰劑相當
Adverse events, n (%) Placebo (n = 3,876) Denosumab 60 mg Q6M (n = 3,886) P value All adverse events 3,607 (93.1) 3,605 (92.8) 0.91 Serious adverse events 972 (25.1) 1,004 (25.8) 0.61 Deaths 90 (2.3) 70 (1.8) 0.08 AEs leading to study discontinuation 81 (2.1) 93 (2.4) 0.39 AEs leading to discontinuing the study drug 202 (5.2) 192 (4.9) 0.55 PROLIA 常見(>2%)比未用藥(安慰劑)較多的不良反應為皮疹與脹氣 使用PROLIA 不會增加注射部位不良反應、也不會有注射後發燒、全身痠 痛等類流感症狀 不需考量病患的腎功能情況 AEs = adverse events Adapted from: Cummings SR, et al. N Engl J Med. 2009;361:

40 半年皮下注射治療骨鬆，簡易方便 研究證實是病患較偏好的治療方式
根據研究結果顯示，77% 的病患偏好6個月皮下注射的方式勝過口服用藥. 類保骨素藥物不影響腎功能, 腎功能不佳的患者也可以使用，無需調整用藥 每半年皮下注射 每周一次口服藥物 不同於口服或IV infusion, 6個月皮下注射是非常方便的給藥方式 在double-dummy 的研究結果顯示 , 77% 的病患偏好6個月皮下注射的方式勝過每週口服用藥. 顯示Prolia 會是病患接受度較好的骨鬆治療方式, 增進長期治療依從性 (附註: double-dummy 是兩組都注射也吃口服藥, 一組是Prolia + 口服安慰劑, 對照組是吃alendronate + 注射安慰劑) A simple 6-monthly subcutaneous injection is preferred by patients as compared to weekly oral pills In two head-to-head, double-dummy studies, 77% of patients reported a preference for a subcutaneous injection every 6 months compared with a once weekly oral pill.1 Reference 1. Kendler DL. Osteoporos Int 2010;21:837–846. Among patients reporting a preference: n = 1, % of the Prolia® group and 64% of the alendronate group stated they preferred the 6-monthly injection, giving an average of 64% patients who preferred the 6-monthly injection. 19% of patients in both groups preferred the once-weekly tablet, meaning that overall 83% of patients expressed a preference. Therefore, of patients who expressed a preference, 77% (64/83) preferred the 6-monthly injection. 1. Kendler DL. Osteoporos Int 2010;21:837–846.

41 保骼麗Prolia 健保給付標準 限用於停經後婦女 因骨質疏鬆症（需經DEXA 檢測BMD之T score ＜ -2.5）引起脊椎或髖部骨折
健康骨骼 骨質不足 T-score - 1.0 - 2.5 骨質疏鬆 限用於停經後婦女 因骨質疏鬆症（需經DEXA 檢測BMD之T score ＜ -2.5）引起脊椎或髖部骨折 或因骨質疏少症（經DEXA 檢測BMD之-2.5 ＜ T score ＜ -1.0）引起脊椎或髖部2處或2次(含)以上之骨折 治療時，一次限用一項藥物，不得併用其他骨質疏鬆症治療藥物。 年長或停經後的婦女易誘發骨質疏鬆症，現在只要由醫師研判患者T值小於-2.5，引起脊椎或髖部骨折；或因骨質疏少症，T值介於-1到-2.5之間，引起脊椎或髋部2處或以上之骨折，自今年3月份起開立類保骨素骨鬆針即可健保給付。

42 保骼麗Prolia 注射方式

43 謝謝大家的聆聽