實證醫學文獻查證競賽

臨床藥學部

參賽組別:第七組

陳成桃、葉爵榮、金秦瑩

98.04.25

98年第一次EBM活動競賽規則• 每組發表時間以10分鐘為限，由評審團進行評分

‧使用單槍投射器進行發表，並能於20公尺處看清楚為原則

‧8分鐘時響鈴兩短聲，10分鐘時以響鈴一長聲做為提醒，超過10分鐘者應立即停止發表

簡報大綱建議

1. 形成PICO的內容2. 呈現搜尋資料的策略、使用資料庫及搜尋結果3. 文獻評讀

4. 以去學術化術語的方式(plain language)回答病人的問題

5. 比較透過EBM的介入方式與傳統介入方式之醫療照護品質之差異

情境一

一位54歲外觀無恙之停經後婦女最近在一次遊園活動中接受了足踝部位之骨質疏鬆檢查，結果骨密度指數為 -2.6 SD ，負責檢查的人員告知婦人有骨質疏鬆症並向婦人推銷骨質疏鬆症藥物。

這位女士返家後上網找到一些有關骨質疏鬆症之資料並來到本院門診，她並無其他共病存在，首先提及不太瞭解骨質疏鬆症是如何診斷的，是否足踝部位之骨密度檢查就能確定她有骨質疏鬆症，是否應做一比較精確的檢查來確定診斷?

情境一

若不治療會有何種後果，會不會影響生命安全? 如果要治療用何種方式或何種藥物較為恰當? 這些藥物是否會有副作用? 她聽說有 “副甲狀腺素 (PTH)” ，“雙磷酸鹽 (bisphosphonates)” ， “補骨挺疏(strontium ranelate)” 等藥物效果很好，不知如何選擇。你答應她壹週後向她說明。

What are the patient’s concern?1 是否足踝部位之骨密度檢查就能確定她有骨質疏鬆症?

2 是否應做一比較精確的檢查來確定診斷?

3 若不治療會有何種後果， 會不會影響生命安全?

4 這些藥物是否會有副作用?

5 她聽說有“副甲狀腺素(PTH)”， “雙磷酸 (bisphosphonates)” ，“補骨挺疏(strontium ranelate)” 等藥物效果很好，如果要治療用何種方式或何種藥物較為恰當?

Five Steps of EBM

1 Ask a Clinical Question?

2 Tracking down the best Evidence3 Critically Appraise Evidence4 Apply to your patient

5 Evalution

一位54歲接受了足踝部位之骨質疏鬆檢查，結果骨密度指數為 -2.6 SD ，是否應做一比較精確的檢查來確定診斷? 是否需治療? 治療使用何種藥物較為恰當? 藥物是否會有副作用?

Step 1. Ask a Clinical Question?

PICO型式:治療性 關鍵字

P A 54-year-old postmenopausal woman R/O Osteoporosis Osteoporosis,postmenopausal

I Pharmacological therapy Therapy(Bisphosphonates, PTH, Strontium Ranelate, SERMs, Calcitonin, Estrogen, Calcium,Vitamin D)

C Non Pharmacological therapy Exercise, Placebo

O Treatment effect Fracture, Treatment effect,Effectiveness, Cost-effectiveness

Step 2. Tracking down the best Evidence

Search Databases

Studies

SynthesesPrimary database

Secondary database

Synopses

Summaries

Systems

The Taiwanese Osteoporosis Association骨質疏鬆症之診斷原則

骨質密度(bone mineral density, BMD)之測定，以中軸型

的雙能量X光吸收儀(dual-energy X-ray absorptiometry，

DEXA)為準。

定量超音波儀器或其它部位之雙光子或單光子吸光檢查

(周邊骨質密度測定儀)，在目前只宜當做初步篩檢的工具

；若發現異常，則應以上述DEXA施行髖骨或腰椎檢查來確認。

Harrison

National Guideline Clearinghouse

Osteoporosis and

Postmenopausal

To employ lifestyle practices

Management of Osteoporosis in postmenopausal women

Indications for treatment:(1) T scores below -2.5 in the absence of risk factors(2) T scores -1.0 to -2.5 if other risk factors present(3) Prior vertebral or hip fracture

Treatment recommendations are based on both efficacydata and clinical parameters.

Bisphosphonates are the first-line drugs for treatingpostmenopausal woman with osteoporosis

Osteoporosis and

postmenopausal

Overview of the management of osteoporosis in postmenopausal

Drug Choose GradeBisphosphonates First-line therapy Grade 2BRaloxifene Who cannot tolerate

bisphosphonates Grade 2B

PTH therapy At least one fragility fracture who are unable to tolerate any of the available bisphosphonates

Grade 2B

Strontium Ranelate An effective and well-tolerated therapy for women with established osteoporosis

Search Databases

• Cochrane Library

• Pub Med

Osteoporosis and postmenopausal and therapy and fracturewomen AND osteoporosis AND treatments AND

effectiveness

(Ann Interm Med, 2008)

(Level:1a)

搜尋結果

Step 3. Critical appraisal Evidence

Is the systematicreview valid

Are the result Important?

Can the resultshelp me?

1 Is this a systematic review of high-qualitystudies which are relevant to your question?

**Comparative Effectiveness of Treatments to prevent fractures in men and women with lowBone Density or Osteoporosis.

**Randomized, double-blind, placebocontrolled, with concealed allocation.

**Level:1a

Yes

2 Does the methods section adequately describe:(a) finding and including all relevant trials?(b) assessing their individual validity?

** The author’searched Medline, ACP , Cochrane,for relevant randomized controlled trials publishedbetween 1966-2006.

** Two independent reviews abstracted all informationand data using standardized data abstraction forms, with a third reviewer verifying.

Yes3 Are the studies consistent, both clinically and

statistically?

**The groups of patients, interventions andoutcome measures were similar enough tomerit combining their results.

Yes

Are the Valid results of this systematic review important?**Measure of efficacy: RR**Measure the benefits and harm of

the therapy: NNT**Precise are these results: 95% CI

Yes

Favors treatment Favors Control

Relative Risk (95% CI)Drug NNT

Bisphosphonates Alendronate 16Etidronate 12Ibandronate 40Pamidronate 20Risedronate 14Zoledronic acid 48

Estrogen Estrogen 14PTH PTH 11SERMs Raloxifene 15

Can you apply this valid, important evidence from a systematic review in caring for your patient?

1. Is your patient so different from those in the studythat its results cannot apply?

No

2. Treatment feasible in your patient in your setting? Yes

3. Do you and your patient have a clear assessment of their values and preferences?

Yes

4. Are they met by this regimen and its consequences? Yes

Drug Dose Primary Prevention

Secondary Prevention

Alendronate 10 mg/day

Clinically important reduction in vertebral fractures

Clinically important and statistically significant reduction in vertebral, nonvertebral, hip, and wrist fractures.

Etidronate 400 mg/day

No clinically or statistically important benefit

Clinically important and statistically significant reduction in vertebral fractures.

Risedronate 5 mg/day

No statisticallysignificant reductions in vertebral and nonvertebral fracture.

Clinically important and statistically significant reduction in vertebral, nonvertebral, and hip fractures

Cochrane Database Syst Rev 2008 Jan 23;(1):CD001155, CD004523, and CD003376

Health economicsIn women with low BMD without previous fractures, treatment with alendronate or risedronate appeared to be cost effective across countries (UK, US, Denmark).

(From:The cost effectiveness of bisphosphonates for The prevention andtreatment of osteoporosis: a structured review of the literature. Pharma-

coeconomics. 2007;25(11):913-33. review)

「骨質疏鬆症」治療藥物健保給付範圍

Drug 健保給付範圍Bisphosphonate Alendronate(如Fosamax®)

(1)停經後婦女或男性因骨質疏鬆症引起之脊椎壓迫性骨折或髖骨骨折病患。

(2)血清肌酸酐(serum creatinine)小於或等於1.6mg/dl的患者。

Raloxifene hydrochloride(如Evista®60mg Tablets)

1.停經後婦女因骨質疏鬆症引起之脊椎壓迫性骨折或髖骨骨折病患

2.每日最大劑量60mg。

Teriparatide(如Forteo®注射劑)

1.適用於因嚴重骨質疏鬆症而造成二個(含)以上脊椎或一個髖骨骨折之患者。

2.使用期限不得逾18個月。

drug adverse reactions

Bisphosphonates Esophageal and gastric irritation

Raloxifene (a SERM) increase in vasomotor symptoms

Parathyroid hormone (PTH)

muscle cramps and infrequent hypercalcemia, nausea, and dizziness

Estrogen plus progestin therapy (EPT).

increased risk of breast cancer, stroke, coronary heart disease, thromboembolic events, and dementia

Calcitonin Nausea, local inflammation, and flushing of the face or hands

Calcium gastrointestinal (GI) adverse effects (i.e., gaseousness, constipation).

Vitamin D Doses higher than 2,000 IU/day may introduce risks such as hyper-calciuria and hypercalcemia

Strontium Ranelate gastrointestinal disturbances, headache, diarrhea

Management of osteoporosis in postmenopausal women: 2006 position statement of The North American Menopause Society. Menopause 2006 May-Jun;13(3):340-67.

TSGH Osteoporosis Drug 分類 學名 商品名 價錢 外觀

Bisphosphonates

ALENDRONATE SODIUM, CHOLECALCIFEROL

FOSAMAX PLUS TAB 70MG

健保價:2621 tab per weekMonth:1048元

Estrogens Raloxifene Evista 60 mg 健保價:43.21 tab per dayMonth:1210元

others StrontiumRanelate

PROTOS 2 GM 自費:75.601 patch per dayMonth:2116元

Parathyroid Calcitonin Miacalcic 200IU Nasal Spray

健保價:1946Per 2 weekMonth:3892元

Parathyroid Teriparatide FORTEO INJ 250 MCG/ML 3 ML

健保價:15766per monthMonth:15766元

1. 足踝部位的骨密度檢查，只能當作初步篩檢工具，建議您找骨科醫師做進一步檢查。

2. 停經後婦女，骨質易流失，建議您平常飲食需攝取足夠鈣質與維生素D、適度運動也有助於減少骨質流失。

3. 若經醫生評估後，需藥物治療，目前是以雙磷酸鹽類為主，此類藥物除了少數腸胃道不適，在安全性及療效上都是可以放心的。