對特定病患 合併兩種骨質疏鬆症藥物會比一種好
作者：Alice Goodman
出處：WebMD醫學新聞
October 27, 2009（費城）－根據一項發表於美國風濕免疫學會（ACR）2009年的隨機分派研究結果，結合Zoledronic acid與Teriparatide，兩種作用機轉不同，用來治療骨質疏鬆症的藥物，對於同時有風濕性關節炎與骨質疏鬆症的特定高風險病患來說，可能是個有價值的策略。
伯明罕阿拉巴馬大學醫學院Jane Knight Lowe教授Kenneth Saag醫師解釋，過去使用alendronate（一種用來預防骨骼溶解，類似zoledronic acid，但效價較低）以及teriparatode的研究發現，對於骨質密度（BMD）並沒有好處，推測是因為抑制新骨形成。
目前這項研究使用每年注射一次的zoledronic acid，這個藥物並沒有顯示具有抑制teriparatide促進新骨形成的作用。
Saag醫師表示，結合zoledronic acid與teriparatide對於高風險病患來說是一個選擇，包括那些髖骨BMD很低、過去有骨折、風濕性關節炎以及其他我們希望達到更快速反應的嚴重狀況。
在這項為期一年、雙盲、多中心研究中，收納了412位65歲以上停經後罹患骨質疏鬆症女性（BMD T分數低於最高骨質2.5個標準差），或是BMD較高但過去曾發生過骨折。這些病患被隨機分派在第一天時接受一次zoledronic acid 5 mg靜脈注射，加上每日皮下注射teriparatide 20mg，或是同樣劑量單獨使用這些藥物。
在第52週時，合併治療組的脊椎BMD與teriparatide組相仿（分別是7.51%與7.05%）；在zoledronic acid組，脊椎BMD為4.37%（合併組與teriparatide組相較於zoledonic acid組，P值<0.001）。
在52週時，相較於僅使用teriparatide，合併治療組與zoledronic acid顯著增加髖骨BMD（P<0.005）。
Saag醫師指出，在這項為期一年，不同時間點監測的結果看來，相較於單獨使用，合併治療提升BMD的速度顯然較快。
在這項研究中，骨折被紀錄為不良反應，且是罕見的，治療之間並沒有太大差異，但是有傾向合併治療組的趨勢。死亡、嚴重不良反應、或是停藥比例在三組之間並沒有顯著差異。
【結果並非出人意料】
俄亥俄州克里夫蘭診所基金會骨質疏鬆與代謝骨骼疾病中心主任Chad Deal醫師表示這些數據是令人感到興趣的；Deal醫師是這項研究數據發表會的共同引言人。
他指出，骨折發生率應該是此類臨床研究的一個重要終點，但是這項研究的樣本數目太小，所以無法顯示骨折率的顯著差異。他表示，我們留下BMD，這是一個骨折的不完美替代終點。
這項研究確實沒有顯示治療組之間發生了什麼事情。QTC（定量電腦斷層）掃描將可以提供這項研究使用的DXA（雙能X射線吸收計）更準確的資訊。Deal醫師表示，我們從過去的研究知道DXA並不如QTC準確。
安大略漢米爾敦曼徹斯特大學的Jonathan Adachi醫師表示，我並沒有對這些激勵我們的結果感到驚訝。風濕性關節炎病患常見骨質疏鬆的問題，肇因於未經控制的發炎反應、以及活化蝕骨細胞造成局部侵蝕的媒介物。
Adachi醫師表示，最理想的研究應該是這項研究使用的合併治療相互比較，或是依序治療，先使用teripararide兩年，緊接著使用zoledronic acid，來確認這些治療是更有效的。
Saag醫師表示與Eli Lilly Co、Merck、Novartis、Amgen、Roche、Procter & Gamble、Aventis、TAP與GlaxoSmithKline有資金上的關係。Deal醫師表示與Novartis藥廠有資金上的往來。Adachi醫師表示接受Novartis、Eli Lilly、Amgen、AstraZeneca、GSK-Merck、Nyocmed、Pfizer、Procter & Gamble、Sanofi-Aventis與Servier的顧問費。
Two Osteoporosis Drugs May Be Better Than 1 in Selected Patients
By Alice Goodman
Medscape Medical News
October 27, 2009 (Philadelphia, Philadelphia) — The combination of zoledronic acid and teriparatide, 2 drugs with different mechanisms of action to treat osteoporosis, might be a valuable strategy in selected high-risk patients with rheumatoid arthritis and osteoporosis, according to a randomized study presented here at American College of Rheumatology (ACR) 2009.
Previous studies of alendronate (a bisphosphonate that prevents bone resorption similar to, but less potent than, zoledronic acid) and teriparatide found no beneficial effect on bone mineral density (BMD), presumably because of suppression of new bone formation, explained Kenneth Saag, MD, Jane Knight Lowe Professor of Medicine at the University of Alabama, Birmingham.
The current study used 1 annual injection of zoledronic acid, which did not appear to inhibit the bone-forming effects of teriparatide.
"The combination of zoledronic acid and teriparatide is one to consider in selected high-risk patients, including those with low hip BMD, previous fractures, rheumatoid arthritis, and other serious conditions where we want to achieve a more rapid response," Dr. Saag said.
The 1-year, partial double-blinded, multicenter study enrolled 412 postmenopausal women older than 65 years with osteoporosis (BMD T-score of 2.5 standard deviations below peak bone mass) or better BMD but 1 previous bone fracture. Patients were randomized to receive 1 intravenous injection of zoledronic acid 5 mg on day 1 plus daily subcutaneous teriparatide 20 mg, or either agent alone at the same doses.
At week 52, spine BMD increase was similar for the combination group and the teriparatide group (7.51% and 7.05%, respectively); for the zoledronic acid group, spine BMD was 4.37% (P < .001 for the combination and the teriparatide group vs the zoledronic acid group).
Both combination therapy and zoledronic acid increased total hip BMD at 52 weeks, compared with teriparatide alone (P < .005).
Dr. Saag said that the combination appeared to increase BMD faster than either drug alone, as reflected by BMD measurements at different intervals over the course of the 1-year trial.
In this study, fractures were recorded as an adverse event and were rare, with no significant difference between treatment groups but with a trend favoring combination therapy over either drug alone. No significant differences in deaths, serious adverse events, or study discontinuations were reported for the 3 groups.
Results Not Unexpected
Chad Deal, MD, head of the Center for Osteoporosis and Metabolic Bone Disease at the Cleveland Clinic Foundation, in Ohio, called these data "interesting." Dr. Deal was comoderator of the session in which the results were presented.
He said that fracture rates would be an important end point in a clinical trial like this one, but noted that this study was too small to show a significant difference in fracture rates. "We are left with BMD, which is an imperfect surrogate for fracture," he said.
"This study really doesn't show what is happening to the respective treatment groups. A QTC [quantitative computed tomography] scan would have provided more accurate information on bone density than DXA [dual energy X-ray absorptiometry], which was used in this study. We know from previous trials that DXA is not nearly as accurate as a QTC," Dr. Deal said.
"I'm not surprised by these encouraging results. Osteoporosis is common in [rheumatoid arthritis], driven by uncontrolled inflammation and mediators that activate osteoclasts leading to local erosions," said Jonathan Adachi, MD, from McMaster University in Hamilton, Ontario.
Dr. Adachi said the ideal trial would be a head-to-head comparison of the concomitant therapy used in this trial and sequential therapy — teriparatide for 2 years followed by zoledronic acid — to determine which treatment is more effective.
Dr. Saag reports financial ties with Eli Lilly Co, Merck, Novartis, Amgen, Roche, Procter & Gamble, Aventis, TAP, and GlaxoSmithKline. Dr. Deal reports financial ties with Novartis Pharmaceutical Corporation. Dr. Adachi reports receiving consultant fees from Novartis, Eli Lilly, Amgen, AstraZeneca, GSK-Merck, Nyocmed, Pfizer, Procter & Gamble, Sanofi-Aventis, and Servier.
American College of Rheumatology (ACR) 2009: Abstract 112-A. Presented October 18, 2009.
