β阻斷劑單獨或與Thiazide利尿劑合併使用能降低骨折風險


  Sept. 14, 2004 - 根據一項刊載於9月號JAMA期刊之大型回顧的人口導向研究結果顯示,β阻斷劑單獨或與Thiazide利尿劑合併使用能降低骨折風險。
  
  來自瑞士Basel 醫院Raymond G. Schlienger博士及其同事指出,動物實驗顯示,propanololβ阻斷劑促進骨頭形成,但是單獨或與Thiazide利尿劑合併使用能降低人類的骨折風險,也提及Thiazide利尿劑被認為能藉由減少尿中鈣濃度而保護骨頭的免於流失。
  
  使用英國一般診療研究資料庫(GPRD),研究人員辨識出在1993至1999年間,年齡30至79歲,30,601名意外骨折病患資紀錄;120,819名沒有持續骨折及在年齡、性別、病例時間和處理組相配的列為控制組 。
  
  目前β阻斷劑單獨或與Thiazide利尿劑或類Thiazide利尿劑使用者,被定義為在骨折前的60天內已經接受處方,長期的使用者定義為至少已經接受了20個處方,每個處方代表1至3個月的治療。
  
  前腕部/下臂(42.0%)及腳部(15.1%)骨折是最常見的,分析骨折和藥物治療之相關性,藥物治療包含抽菸、體重指數 、門診次數、使用鈣通道阻滯藥、血管收縮素轉化酵素抑制劑、抗精神病藥物、抗抑鬱劑、statins降膽固醇藥、抗顛癇藥、治療焦慮症、類固醇藥及動情激素。
  
  結果顯示,相較於沒有使用β阻斷劑或Thiazide利尿劑者,β阻斷劑使用者骨折風險顯著降低,(比值比 [OR],0.77;95% 信賴區間 [CI],0.72 - 0.83),Thiazide利尿劑使用者(比值比 [OR],0.50;95% 信賴區間 [CI],0.74 - 0.86),合併使用者有相對最低之骨折風險(比值比 [OR],0.71;95% 信賴區間 [CI],0.64 - 0.79)。
  
  研究人員進一步指出,在調整門診次數(健康狀況的表示)、醫療護理及用藥次數,長期的β阻斷劑使用者對男性有較強的保護作用對抗骨折(OR,0.69),而女性(OR,0.92),男性、女性在用藥上的差異,不能解釋長期β阻斷劑使用者影響大小的差異,差異應在未來的研究被探討。
  
  研究人員表示,目前大型控制組分析顯示,β阻斷劑單獨或與Thiazide利尿劑合併使用,能顯著降低骨折風險的證據,也提出進行額外的觀察研究及控制實驗是必須的,以利上述發現的確認。
  
  很多老年高血壓病患有發展成骨質疏鬆的風險,能利用相對便宜的β阻斷劑和Thiazide利尿劑合併使用來改善。
  
  其中一名研究人員接受瑞士國家科學基金會的贊助。

Beta-Blockers Alone or in Comb

By Yael Waknine
Medscape Medical News

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Sept. 14, 2004 — Beta-blocker therapy is associated with a significantly reduced risk of fractures when prescribed alone or in combination with thiazide diuretics, according to the results of a large, retrospective, population-based study published in the Sept. 15 issue of JAMA.

"Animal studies suggest that the β-blocker propanolol increases bone formation, but data on whether use of β-blockers (with or without concomitant use of thiazide diuretics) is associated with reduced fracture risk in humans are limited," writes Raymond G. Schlienger, PhD, MPH, from the University Hospital Basel in Switzerland, and colleagues, noting that thiazide diuretics are thought to protect against bone loss by reducing urinary calcium excretion.

Using the U.K. General Practice Research Database (GPRD), investigators identified the records of 30,601 patients aged 30 to 79 years with an incident fracture diagnosis between 1993 and 1999. Control subjects (n = 120,819) had not sustained a fracture and matched the case patients with respect to age, sex, calendar time, and general practice attended.

Current users of beta-blockers, thiazides, or thiazide-like diuretics were defined as those having received a prescription within 60 days prior to the date of fracture. Long-term users were defined as those having received at least 20 prescriptions, each representing one to three months of therapy.

Fractures of the hand/lower arm (42.0%) and foot (15.1%) were most common. Data analysis correlating fracture incidence with drug therapy included adjustments for smoking, body mass index, number of practice visits, and use of calcium channel blockers, angiotensin-converting enzyme inhibitors, antipsychotics, antidepressants, statins, antiepileptics, benzodiazepines, corticosteroids, and estrogens.

Results showed that current beta-blocker users had a significantly reduced risk of fracture (odds ratio [OR], 0.77; 95% confidence interval [CI], 0.72 - 0.83), as did current users of thiazides (OR, 0.80; 95% CI, 0.74 - 0.86) compared with nonusers of beta-blockers or thiazides. Current users of both beta-blockers and thiazides had the lowest relative risk of fracture (OR, 0.71; 95% CI, 0.64 - 0.79) compared with nonusers.

Long-term use of beta-blockers had a stronger protective effect against fractures in men (OR, 0.69) than in women (OR, 0.92) after adjustments for number of practice visits (indicative of health status), medical attention, and number of drugs used. "[T]he differences in drug use between men and women may not explain the differences in effect size with longer-term β-blocker use," the authors comment. "This difference should be explored in future studies.

"[T]he present large case-control analysis provides evidence that use of β-blockers — alone or in combination with thiazide diuretics — is associated with a significantly decreased fracture risk," the authors write, noting that additional observational studies and controlled trials are needed to confirm these findings.

"Many elderly patients with hypertension who are at risk of developing osteoporosis may potentially benefit from combined therapy with [relatively inexpensive] β-blockers and thiazides," the authors conclude.

One of the authors is the recipient of a grant from the Swiss National Science Foundation.

JAMA. 2004;292:1326-1332

Reviewed by Gary D. Vogin, MD

    
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