提早停用類固醇可以減少移植後的骨折風險


  【24drs.com】根據發表於美國骨骼與骨質研究協會(ASBMR)2011年會的研究,接受腎臟移植的病患在移植後及早停用以皮質類固醇為基礎的免疫抑制療法(CSBI)可以顯著降低骨折發生率。
  
  紐約市哥倫比亞大學醫學院的Thomas L. Nickolas醫師表示,皮質類固醇對於造骨細胞是有害物質,而這類藥品在腎臟移植後往往需要給予高劑量,極可能會引起骨質流失。
  
  他解釋,腎臟移植病患一般會先給予相當高劑量的靜脈注射皮質類固醇,調降到高劑量口服、小劑量口服,歷時6個月,但是,在移植後的前6個月內,大部份會發生骨質流失。
  
  研究顯示,移植後的前6個月內,腰椎和髖骨骨質流失範圍從2%到高達10%。
  
  Nickolas醫師表示,骨質流失與高劑量皮質類固醇有關。
  
  為了確認及早停用皮質類固醇是否可以預防骨質流失而降低骨折風險,Nickolas醫師等人評估了US Renal Data System內92,699名病患的資料,這些病患在2000年1月1日至2006年12月31日之間接受腎臟移植。
  
  皮質類固醇的使用是根據聯合器官分享網路在腎臟移植時完成的免疫抑制表格,依據疾病與相關健康問題國際統計分類碼第9版判斷移植後是否有需要住院的骨折事件。
  
  平均5年的追蹤期間內發現,腎臟移植後的骨折發生率,接受CSBI的病患為3.3%,及早停用皮質類固醇的病患為1.8%(P < .001)。
  
  CSBI組的骨折率相當於每年每1,000名病患有8.2例,提早停用組為每年每1,000名病患有6.3例,提早停用皮質類固醇使病患的骨折風險降低28%(風險比為0.72;P < .001)。
  
  提早停用皮質類固醇降低骨折風險的效果在移植後29個月變得顯著。
  
  骨折風險增加的因素包括年長、移植前就有骨折、女性、身體質量指數低、移植前有糖尿病、曾經移植過、移植前有洗腎。
  
  除了提早停用皮質類固醇,亞裔或非裔者的骨折風險也較低。
  
  這些研究有許多值得一提的限制因素,包括僅納入需要住院的骨折案例,Nickolas醫師推論結果時並未將門診病患納入考量,這可能會低估了骨折風險。
  
  他表示,發表的結果指出,需要住院之髖骨骨折的嚴重骨折風險較低,但是我們不知道那些不需要骨折的案例,我們也不確定門診病患的情況;再者,我們無法評估有多少病患在移植後有使用類固醇。
  
  紐約市西奈山大學醫學院內科與老人醫學科教授Sol Epstein醫師表示,對於移植病患,骨折的潛在風險相當多。
  
  Epstein醫師指出,這是相當複雜的疾病,所以重點在知道病患使用的其他免疫抑制劑(如calcineurin抑制劑)、維他命D的情況、副甲狀腺素值、糖尿病情況與其他可能影響骨質流失的議題。
  
  他表示,不管這些因素,需要換腎且進行腎臟移植已經讓病患處於較高的骨折風險。即便你讓一個病患提早停用這類藥物,他們的骨折發生率依舊高於年齡相仿的對照組。
  
  因為他們是骨折高風險族群,因此,在移植後的情況下,要盡可能給病患最低劑量的糖皮質類固醇,然後儘可能儘快停用,或者,你想要用比較不會像糖皮質類固醇或calcineurin抑制劑那樣影響骨骼的新藥。
  
  資料來源:http://www.24drs.com/professional/list/content.asp?x_idno=6618&x_classno=0&x_chkdelpoint=Y
  

Early Steroid Withdrawal Reduces Posttransplant Fracture Risk

By Nancy A. Melville
Medscape Medical News

September 27, 2011 (San Diego, California) — Patients who receive kidney transplants who are withdrawn from corticosteroid-based immunosuppression (CSBI) as early as possible after transplantation have significantly lower fracture rates compared with patients who continue receiving corticosteroids, according to research presented here at the American Society for Bone and Mineral Research (ASBMR) 2011 Annual Meeting.

Corticosteroids are known to be toxic to osteoblasts, and the drugs are typically given in exceptionally high doses after kidney transplants, potentially causing substantial bone loss, said coauthor Thomas L. Nickolas, MD, from Columbia University Medical School in New York City.

"Kidney transplant patients typically initially get very high intravenous doses of corticosteroids that are tapered down to a high oral dose, then to a small oral dose, by 6 months, but it is in that first 6 months after transplantation when the majority of bone loss occurs," he explained.

Studies show that the bone loss at the lumbar spine and the hip during that initial 6 months posttransplantation can range from 2% to as much as 10%, he said.

"The degree of bone loss correlates with the high dose of corticosteroids," Dr. Nickolas stated.

In an effort to determine whether the bone loss prevention that results from earlier corticosteroid withdrawal translates to a reduced fracture risk, Dr. Nickolas and his team evaluated data on 92,699 patients in the US Renal Data System who received kidney transplants between January 1, 2000, and December 31, 2006.

Corticosteroid use was evaluated according to United Network for Organ Sharing immunosuppression forms completed at the time of the kidney transfer, and first fracture events requiring hospitalization were identified from discharge International Statistical Classification of Diseases and Related Health Problems, Ninth Revision, codes after the transplant.

During an average of about a 5-year follow-up, the results indicated the incidence of fracture after kidney transplant was 3.3% among patients receiving CSBI compared with 1.8% among patients with early corticosteroid withdrawal (P < .001).

Fracture rates equaled 8.2 per 1000 patients per year for the CSBI group compared with 6.3 per 1000 patients per year for the early withdrawal group, with a 28% reduction in fracture risk among the patients with early corticosteroid withdrawal (hazard ratio, 0.72; P < .001).

The reduced fracture risk in the early corticosteroid withdrawal group became significant 29 months posttransplant.

Factors that increased fracture risk in both groups included older age, pretransplant fractures, female sex, low body mass index, pretransplant diabetes, a prior transplant, and pretransplant kidney dialysis.

In addition to early corticosteroid withdrawal, being Asian or black also represented a lower fracture risk.

The study had several notable limitations, including the fact that only fractures that required hospitalization were included, and Dr. Nickolas speculated that the results may in fact underestimate the reduced risk for fracture by not taking into account fractures in the outpatient setting.

"What this represents is that there is a lower risk of having a serious fracture like a hip fracture that requires hospitalization, but we don't know what it means for fractures that don't require hospitalization," he said. "We're not sure what it means with regard to the outpatient community."

He added, "Furthermore, we were unable to evaluate how many patients were put back on steroids posttransplant."

Sol Epstein, MD, a professor of medicine and geriatrics at Mt. Sinai University School of Medicine in New York City, agreed that with a transplant population, the array of other potential risk factors for fracture is broad.

"It's a very complex disease, so it's important to know what other immunosuppresants the patients were on, such as calcineurin inhibitors, their vitamin D status, parathyroid levels, diabetes status, and other issues that all can affect bone loss," said Dr. Epstein.

Regardless of those factors, simply needing and having a kidney transplant puts the patients at a higher fracture risk, he added. "Even if you take a patient who was withdrawn from the drugs early, their incidence of fracture is still higher than age-matched normal controls," he explained.

"As a population they are at a greater risk for fracture. So the bottom line is, in a posttransplant situation, you want to give them the lowest dose of glucocorticosteroids as possible and take them off as soon as possible, or you may want to utilize new drugs which do not appear to affect the bones in the way that glucocorticosteroids or calcineurin inhibitors do."

The study was supported by the Doris Duke Charitable Foundation. Dr. Thomas and Dr. Epstein have disclosed no relevant financial relationships.

American Society for Bone and Mineral Research (ASBMR) 2011 Annual Meeting: Abstract 1092. Presented September 18, 2011.

    
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