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。
  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。
  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)。
  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。

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September 27, 2011 (San Diego, California) — Patients who receive kidney transplants who are withdrawn from corticosteroid-based immunosuppression (CSBI) as early as possible after transplantation have significantly lower fracture rates compared with patients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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