低創傷骨質疏鬆骨折與死亡率風險有關


  February 3, 2009 — 根據發表於2月3日美國醫學會期刊中的一篇前溯世代研究結果,60歲以上男女的低創傷骨質疏鬆骨折與死亡率風險增加有關。
  
  澳洲雪梨聖文森醫院、Garvan醫學研究中心的Dana Bliuc等人寫道,骨質疏鬆骨折的長期死亡率追蹤資料較少,也少有追蹤後續的骨折;就髖骨骨折來說,第一年的死亡率最高,而10年之後都還可能升高,但這還有爭議;在一篇案例控制研究中,臨床脊椎骨折後的死亡率,婦女在10年後仍然增加,男性則是在3年後仍增加。
  
  研究目標是檢視骨質疏鬆骨折後,男性和女性的長期死亡率風險,以評估此風險與後續骨折的關聯。
  
  研究世代包括了居住於澳洲杜博社區的60歲以上男性和女性,在1989年4月至2007年5月間發生過一次骨折,也是「Dubbo Osteoporosis Epidemiology Study」的研究對象,初級終點是與整體杜博地區人口相較之髖骨、脊椎、嚴重與輕微骨折之年紀與性別的特定標準化死亡率(SMRs)。
  
  952名女性發生低創傷骨折,之後有461人死亡;男性有343例骨折,之後有197人死亡;不論男女,年齡校正之SMRs在髖骨骨折之後 (SMRs, 2.43 [95%信心區間[CI], 2.02 - 2.93] 與3.51 [95% CI, 2.65 - 4.66])、脊椎骨折(SMRs, 1.82 [95% CI, 1.52 - 2.17] 與2.12 [95% CI, 1.66 - 2.72])、嚴重骨折(SMRs, 1.65 [95% CI, 1.31 - 2.08]與1.70 [95% CI, 1.23 - 2.36])、輕微骨折(SMRs, 1.42 [95% CI, 1.19 - 1.70]與1.33 [95% CI, 0.99 - 1.80])均增加。
  
  在各種年齡層,除了輕微骨折之外,死亡率均增加,75歲以上者的輕微骨折才會增加死亡率。各種骨折後5年的死亡率風險增加,髖骨骨折可到10年;根據骨折類型,可預期骨折後5年之絕對死亡率風險會增加,女性為每100人年增加1.2-13.2、男性為每100人年增加2.7-22.3。
  
  後續骨折的死亡率危險率也增加(女性1.91 [95% CI, 1.54 - 2.37]、男性2.99 [95% CI, 2.11 - 4.24]);不過,後續骨折之後的死亡率風險下降,但是在5年之後仍高於一般族群(女性SMR, 1.41 [95% CI, 1.01 - 1.97] 、男性SMR, 1.78 [95% CI, 0.96 - 3.31])。
  
  脆弱性骨折之後,男性和女性死亡率之預測因子,包括年紀、股四頭肌無力與後續骨折,但與共病症無關;女性的其他預測因子包括低骨密度、抽菸與搖晃;至於男性,體能活動力低也是預測因子。
  
  研究作者寫道,在年長男性和女性樣本中,各種低創傷骨折與5到10後的死亡率風險增加有關;後續骨折與之後5年的死亡率風險增加有關。
  
  研究限制包括並非設計來檢視死亡率的潛在原因;研究對象幾乎全都是白人;骨折研究對象的死亡率是與年齡相仿之一般族群的死亡率進行比較,而一般族群中可能也有骨折者。
  
  研究作者結論表示,這些資料認為,骨折是通報死亡率風險增加的訊息:對婦女來說,不論它是否與增加骨折和死亡率風險有關;而對男性來說,和骨折事件本身有關,這些都需要進一步探討。整體來說,此研究指出各種類型骨折的死亡率增加,特別是各種年齡的年長男女發生後續骨折之後。
  
  國家健康與醫學研究委員會、 MBF Living Well 基金會、Ernst Heine基金會;Amgen, Merck Sharp & Dohme、sanofi-aventis、Servier與Novartis等藥廠提供的聯合資金支持部份研究。兩名研究作者宣告與Amgen、deCode、Eli Lilly、GE Lunar、Merck Sharp & Dohme、Novartis、Organon、Pfizer、Roche-GSK、sanofi-aventis和/或Servier等藥廠有各種財務關係;其他研究作者宣稱沒有相關資金上的往來。

Low-Trauma Osteoporotic Fracture Linked to Mortality Risk

By Laurie Barclay, MD
Medscape Medical News

February 3, 2009 — Low-trauma osteoporotic fracture in women and men 60 years or older is linked to increased mortality risk, according to the results of a prospective cohort study reported in the February 3 issue of the Journal of the American Medical Association.

"There are few data on long-term mortality following osteoporotic fracture and fewer following subsequent fracture," write Dana Bliuc, MMed, from Garvan Institute of Medical Research, St. Vincent's Hospital in Sydney, Australia, and colleagues. "For hip fracture, mortality is highest in the first year, and although controversial, may remain elevated for more than 10 years. Mortality following clinical vertebral fractures has been reported to be increased for up to 10 years in women and 3 years in men in a case-control study."

The goal of this study was to examine long-term mortality risk in women and men following all osteoporotic fractures and to evaluate the association of subsequent fracture with that risk.

The study cohort consisted of community-dwelling women and men in Dubbo, Australia, aged 60?years and older, who sustained a fracture between April 1989 and May 2007 and who were enrolled in the Dubbo Osteoporosis Epidemiology Study. The primary endpoints were age- and sex-specific standardized mortality ratios (SMRs) for hip, vertebral, major, and minor fractures vs the overall Dubbo population.

Low-trauma fractures occurred in 952 women, followed by 461 deaths; for men, 343 fractures were followed by 197 deaths. For both women and men, age-adjusted SMRs were increased after hip fractures (SMRs, 2.43 [95% confidence interval [CI], 2.02 - 2.93] and 3.51 [95% CI, 2.65 - 4.66]), vertebral fractures (SMRs, 1.82 [95% CI, 1.52 - 2.17] and 2.12 [95% CI, 1.66 - 2.72]), major fractures (SMRs, 1.65 [95% CI, 1.31 - 2.08] and 1.70 [95% CI, 1.23 - 2.36]), and minor fractures (SMRs, 1.42 [95% CI, 1.19 - 1.70] and 1.33 [95% CI, 0.99 - 1.80]), respectively.

For all ages, mortality rate was increased for all fractures except for minor fractures, for which mortality rate was only increased for those older than 75 years. Mortality risk was increased for all fractures for 5 years and for hip fractures up to 10 years. Depending on fracture type, increases in absolute mortality rates for 5 years after fracture that were above expected, ranging from 1.3 to 13.2 per 100 person-years in women and 2.7 to 22.3 per 100 person-years in men.

Mortality hazard ratio was increased for subsequent fracture (1.91 [95% CI, 1.54 - 2.37] in women and 2.99 [95% CI, 2.11 - 4.24] in men). Although mortality risk after a subsequent fracture then decreased, it still remained higher vs the general population beyond 5 years (SMR, 1.41 [95% CI, 1.01 - 1.97] for women and SMR, 1.78 [95% CI, 0.96 - 3.31] for men).

After any fragility fracture, predictors of mortality for both men and women included age, quadriceps weakness, and subsequent fracture but not comorbidities. Additional predictors for women were low bone mineral density, having smoked, and sway; for men, less physical activity was also a predictor.

"In a sample of older women and men, all low-trauma fractures were associated with increased mortality risk for 5 to 10 years," the study authors write. "Subsequent fracture was associated with increased mortality risk for an additional 5 years."

Limitations of this study were that it was not specifically designed to examine the underlying causes of mortality; the population was almost entirely white; and mortality rates of the fracture participants were compared vs the mortality rates of an age-matched general population, which therefore included some individuals with fracture.

"These data suggest fracture is a signal event that heralds an increased mortality risk: whether it is related to an underlying increased risk for both fracture and mortality, which may be the case for women, or whether it is related to some aspect of the fracture event itself, as appears to be the case for men, needs further exploration," the study authors conclude. "Overall, this study highlights the premature mortality associated with all types of fractures, particularly that which occurs after subsequent fracture across the whole age spectrum of older men and women."

The National Health and Medical Research Council, the MBF Living Well Foundation, the Ernst Heine Foundation; and untied grants from Amgen, Merck Sharp & Dohme, sanofi-aventis, Servier, and Novartis supported this study in part. Two of the study authors have disclosed various financial relationships with Amgen, deCode, Eli Lilly, GE Lunar, Merck Sharp & Dohme, Novartis, Organon, Pfizer, Roche-GSK, sanofi-aventis, and/or Servier. The remaining study authors have disclosed no relevant financial relationships.

JAMA. 2009;301:513-521.

    
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