兩個新的骨質疏鬆藥物增加BMD的效果比Alendronate好


  October 30, 2008(加州舊金山)-根據一項新研究指出,Teriparatide預防長期服用類固醇藥物病患,例如prednisone,骨質流失與增加骨質密度(BMD)的效果比Alendronate佳;在另一項研究中,denosumab增加停經後婦女的骨質質量。這兩篇研究都發表在美國風濕醫學會2008年會上。
  
  這項比較Teriparatide(Forteo)與Alendronate(Fosamx)使用於長期服用類固醇病患效果的隨機分派研究,是第一個將Teriparatide使用時間延長到36個月的研究。研究團隊隨機分派214位病患接受Teriparatide每天20 μg或Alendronate每天10 mg。
  
  雖然這兩組的骨質質量都有增加,但研究團隊發現,使用Teriparatide相較於使用Alendronate的病患,在腰椎(11%相較於5.3%)與股骨(6.3%相較於3.4%)BMD平均增加百分比達顯著差異,這兩個都是服用類固醇病患最常發生骨折的位置;他們也發現使用Teriparatide的病患,發生脊椎骨折的比例比使用Alendronate的低(1.7%相較於7.7%)。
  
  伯明罕阿拉巴馬大學醫學與流行病學教授,同時也是這項研究的主要作者Kenneth Saag醫師表示,Teriparatide刺激成骨細胞的活性,與抑制破骨細胞的細胞凋亡,因此使用在這個狀況下是合理的;這是個可以考慮使用於因類固醇引起之骨質疏鬆的治療策略。
  
  然而,這兩組的非脊椎骨折數目相差不多,這兩個藥物的耐受性都很好;在Teriparatide組僅有一位病患出現有症狀的高血鈣,但並沒有任何一位Alendronate組的病患發生這個不良反應。
  
  就像其他使用類固醇的病患,這項研究中的受試者發生骨折的風險顯著較高;所有病患服用5 mg的Prednisone至少3個月以上,大部分病患的骨質質量介於骨質低下範圍,且有些病患被診斷罹患骨質疏鬆症,超過40%病患過去發生過非脊椎性骨折。
  
  Saag醫師表示,這是個處於風險的族群,這些研究結果顯示,Teriparatide可以是這些病患的另一個選擇;他告訴聽眾,這些長期使用類固醇病患發生骨折的機率,據估計達50%。
  
  在第二個雙盲隨機分派研究中,研究團隊比較denosumab與alendronate對停經後女性骨質質量的影響;Denosumab是一個對抗RANKL的全人類化單株抗體,RANKL則是一個對成骨細胞存活與發育非常重要的配位子。
  
  研究團隊追蹤1,189位骨質密度過低的停經後女性,這些病患被隨機分派每6個月接受denosumab 60 mg,以及每週一次的口服安慰劑,或是每6個月接受安慰劑注射,與每週一次的alendronate 70 mg,受試者的平均腰椎T指數為-2.6。
  
  結果顯示,在12個月後,Denosumab組髖骨BMD(62%比上39%)與腰椎BMD(77%比上65%)增加超過3%的病患數目比Alendronate組高。Denosumab在5個骨質評估位置上,增加BMD的效果都比較好,這些位置包括髖骨、腰椎、股骨頸部、轉子以及尺骨遠端。
  
  Denosumab也會在1個月的治療內顯著降低骨質更替的血清指標,例如血中第一型碳端多胜與原膠原蛋白第一型氮端多胜,且這個效應可以持續長達12個月。兩組之間的不良反應發生率相差不多。
  
  主要作者、俄亥俄州克里夫蘭診所骨質疏鬆症與代謝性骨骼疾病中心的主任Chad Deal醫師在一項記者會上表示,這兩個藥物另一個顯著差異是它們的半衰期,Fosamax對於骨骼的殘留效應很長,特別是對使用超過5年以上的病患,但是Denosumab的效果比較快發生,也比較快結束。
  
  同樣的,研究團隊在美國骨骼與礦物質研究學會於9月召開的年會上報告,在一項收納7,868位骨質疏鬆婦女的臨床研究中,Denosumab也可以顯著地降低非脊椎與髖骨骨折發生率。
  
  荷蘭阿姆斯特丹自由大學的風濕學教授Willem Lems醫師指出,研究結果顯示,這些藥物對於類固醇引起的骨質疏鬆是有效的,這對骨質疏鬆的停經後婦女來說,是個非常嚴重的問題;未參與這兩個發表會的Lems醫師表示,這兩項研究的研究數據非常吸引人。
  
  Lems醫師表示,Denosumab具有增加骨質疏鬆病患順應性的潛力,我們現在聽到的研究顯示許多病患偏好每6個月注射一次藥物,而非每個星期口服一次。
  
  Teriparatide的研究是由禮來公司贊助。Saag醫師表示接受來自Amgen、Eli Lilly、Merck、Novartis、Roche Savient與Tap藥廠的顧問費。Denosumab研究則由Amgen藥廠贊助。Deal 醫師表示接受Amgen、Eli Lily、GlaxoSmithKline、Merck Human Health、Merck、Novartis、Proctor & Gamble與Roche Pharmaceuticals的顧問費。Lems醫師表示沒有相關資金上的往來。
  

Two New Osteoporosis Drugs Increase BMD More Than Alendronate

By Barbara Boughton
Medscape Medical News

October 30, 2008 (San Francisco, California) — Teriparatide prevents bone loss and increases bone mineral density (BMD) over the long term in patients taking glucocorticoids, such as prednisone, compared with alendronate, according to a new study. In a second study, denosumab increased bone mass in postmenopausal women. Both papers were presented here at the American College of Rheumatology 2008 Annual Scientific Meeting.

The double-blind randomized controlled trial that compared the effects of teriparatide (Forteo) and alendronate (Fosamax) in patients taking glucorticoids was the first to extend teriparatide use to 36 months. The researchers randomized 214 patients to either teriparatide 20?μg per day or alendronate 10?mg per day.

Although both groups experienced increases in bone mass, the researchers found that the mean percent increase in BMD was significantly greater in patients taking teriparatide than in those taking alendronate at the lumbar spine (11% vs 5.3%) and femoral neck (6.3% vs 3.4%), both frequent fracture sites for patients taking glucocorticoids. They also noted that fewer patients taking teriparatide than taking alendronate experienced vertebral fractures (1.7% vs 7.7%).

“Teriparatide stimulates osteoblastic activity and inhibits osteblast apoptosis, so there’s a rationale for its use in this condition. It’s a therapeutic strategy that could be considered for glucocorticoid-induced osteoporosis, particularly those at high risk for fracture,” said Kenneth Saag, MD, professor of medicine and epidemiology at the University of Alabama, in Birmingham, and lead investigator in the study.

However, the number of nonvertebral fractures was similar in both groups, although both drugs were well tolerated. One patient exhibited symptomatic hypercalcemia in the teriparatide group, but no patient in the alendronate group experienced this adverse event.

Like many patients taking glucorticoids, the population in the study was at significantly increased risk for fracture. All had been taking at least 5?mg of prednisone for at least 3 months. Most had bone mass within the osteopenic range, and some had been diagnosed with osteoporosis. More than 40% had experienced a previous nonvertebral fracture.

“This was an at-risk population,” Dr. Saag said. “The results show that teriparatide can be another alternative for these patients. Many such patients have an estimated rate of fractures approaching 50% with chronic glucocorticoid use,” he told the attendees.

In the second double-blind randomized controlled trial, the researchers compared the effects of denosumab and alendronate on bone mass in postmenopausal women. Denosumab is a fully humanized monoclonal antibody against RANKL, a ligand that is critical for osteoclast survival and development.

The researchers followed 1189 postmenopausal women with low bone mass who were randomly assigned to receive either a 60-mg injection of denosumab every 6 months and a weekly oral placebo, or an injection of placebo every 6 months and a weekly 70-mg dose of alendronate. The subjects had a mean lumbar spine T-score of –2.6.

Results showed that a greater number of patients in the denosumab group gained more than 3% of BMD than those in the alendronate group at the total hip (62% vs 39%) and at the lumbar spine (77% vs 65%) after 12 months. Denosumab also caused superior gains in BMD at all 5 skeletal sites evaluated: the total hip, lumbar spine, femoral neck, trochanter, and distal third of the radius.

Denosumab also suppressed serum markers of bone turnover, such as serum type?1 C-telopeptide and procollagen type?1 N-propeptide within 1 month of treatment, and this effect was sustained over 12 months. Adverse events were similar in both groups.

Another significant difference between the drugs is their half-lives. “Fosamax has a long residual effect on bone, particularly for patients who take it for 5 years or more. But denosumab has both a quicker onset and a quicker offset,” said lead investigator Chad Deal, MD, head of the Center for Osteoporosis and Metabolic Bone Disease at the Cleveland Clinic, in Ohio, at a press conference.

In a trial of 7868 women with osteoporosis, reported by the same researchers at the American Society for Bone and Mineral Research meeting in September, denosumab also significantly decreased the risk for nonvertebral and hip fractures.

“The results show that both these medications are effective for glucocorticoid-induced osteoporosis, a very serious problem, and for postmenopausal women with osteoporosis,” said Willem Lems, MD, professor of rheumatology at Free University Hospital in Amsterdam, the Netherlands. “Together, they are very attractive data,” said Dr. Lems, who attended both presentations.

Dr. Lems noted that denosumab has the potential to increase patient compliance in those with osteoporosis. “The research we’re hearing now shows us that many patients prefer to take an injection every 6 months than weekly oral medications,” he said.

The teriparatide study was funded by Eli Lilly. Dr. Saag has reported consulting fees from Amgen, Eli Lilly, Merck, Novartis, Roche Savient, and Tap Pharmaceuticals. The denosumab study was funded by Amgen. Dr. Deal has reported receiving consulting fees from Amgen, Eli Lily, GlaxoSmithKline, Merck Human Health, Merck, Novartis, Proctor & Gamble, and Roche Pharmaceuticals. Dr. Lems has disclosed no relevant financial relationships.

American College of Rheumatology (ACR) 2008 Annual Scientific Meeting: Abstracts 2101 and 2102. Presented October 29, 2008.

    
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