少數HIV陽性的停經後女性較容易發生骨折

作者：Nancy Fowler Larson  
出處：WebMD醫學新聞

　　January 7, 2010 — 根據一項線上發表於1月6日的臨床內分泌與代謝學期刊的研究結果，少數受HIV感染的停經後女性，因為骨質密度下降和骨質更迭指標較高，發生骨折的風險較高。
　　
　　紐約市哥倫比亞大學醫學中心的Michael Yin醫師與其同事們寫到，感染HIV病毒的男性與女性，經常有骨質密度（BMD）較低的問題，且骨折發生率也可能較高。假設停經後女性可能特別容易發生HIV感染或是抗反轉錄病毒（ART）藥物治療對骨骼的不良反應，我們進行了一項縱向研究，以評估骨質疏鬆症/骨質低下的盛行率、以及HIV陽性停經後西班牙裔與非裔美國居民低BMD以及骨質流失的決定因子和病因學，這些人種構成美國新感染女性的絕大多數。
　　
　　ART的廣泛使用已經顯著增加HIV陽性患者的生命週期。作者們預測在2015年，超過一半的美國HIV感染病患，年齡將會超過50歲，因而會有許多與老化有關的疾病，包括骨質疏鬆症。
　　
　　在2002年，研究者們發起了一項縱向研究，針對92位HIV陽性與95位HIV陰性停經後女性（無月經超過1年、且濾泡刺激荷爾蒙[FSH]> 30mIU/ml；FSH >20 mIU/ml且雌性激素 <30 pg/ml；或是年齡>55歲，不論FSH與雌性激素濃度）。研究作者評估參與者的BMD、骨折盛行率、促鈣與促性腺釋放荷爾蒙、骨更迭指標、發炎指標的血清濃度（腫瘤壞死因子阿法[TNFα]、介白素6）。使用雙能X射線吸收儀評估腰椎、股頸、髖骨、非慣用三分之一橈骨的骨質密度（BMD）、還有身體質量指數（BMI）。
　　
　　檢驗的數據收集到2007年，研究作者們發現，HIV陽性受試者的髖骨未經校正後的BMD（g/cm2）低了5.9%。兩組之間脊椎、股骨頸、或是橈骨並無顯著差異。在校正幾個重大BMD預測因子，包括年齡、人種/種族以及BMI後，HIV陽性女性在腰椎的BMD低了4.5%，且在橈骨與髖骨的BMD有低了3%~4%的趨勢。
　　
　　在HIV陽性女性方面，T分數低於-1.0的盛行率在三個部位較高，分別是脊椎（78%相較於64%；P<0.05）、髖骨（45%相較於29%；P<0.05）、股骨頸（64%相較於46%；P<0.05）。當校正BMI後，HIV陽性女性在同樣部位的Z指數仍然較低。HIV陽性受試者的血清TNF-α、N端肽、C端肽濃度較高，這項發現在接受ART女性最為明顯。容許年齡、種族、BMI與飲用酒精後，HIV陽性狀態獨立地且負向地與脊椎及髖骨BMD有關。
　　
　　作者們寫到，少數HIV陽性停經後女性BMD較低、低BMD盛行率高、以及骨更迭標記較高可能讓她們處於未來發生骨折的風險下。
　　
　　研究者們也發現HIV陽性女性的骨更迭指標與TNF-α較高，且推定多變項模式可能左右HIV對BMD的效應。
　　
　　作者們表示他們的研究有幾個限制：
　　* 控制組的健康狀況很好可能造成HIV陽性與HIV陰性女性BMD差異較大，因為比較健康的女性自然BMD較高。
　　* HIV陽性女性年紀顯著較輕（56±1歲相較於60±1歲；P<0.01），這可能造成HIV陽性組BMD較高的差異誤差。
　　* 樣本數目較小，因而無法針對特定ART療程進行分析。
　　* 這項研究並未透過電腦斷層掃描測量臟器脂肪組織。
　　
　　HIV陽性女性骨質流失的原因目前仍然未知，可能與促骨質溶解細胞激素濃度上升有關。透過持續追蹤試驗受試者，研究者們希望進一步了解HIV狀態、ART與骨骼健康的關係。
　　
　　作者們寫到，完成進行中的縱向研究應該可以讓我們評估高齡停經後後女性與ART有關的骨更迭增加是否會轉化成骨質流失、且增加骨折機率。
　　
　　國家衛生研究院贊助這項研究。研究作者們表示已無相關資金上的往來。


Bone Fractures More Likely in HIV-Positive Postmenopausal Minority Women

By Nancy Fowler Larson
Medscape Medical News

January 7, 2010 — HIV-infected postmenopausal minority women are at greater risk for bone fractures because of decreased bone density and higher bone turnover markers, according to a study published online January 6 in the Journal of Clinical Endocrinology Metabolism.

"Low bone mineral density (BMD) is commonly reported in young men and women with [HIV] infection, and fracture rates may be higher," write Michael Yin, MD, MS, from the Columbia University Medical Center, New York City, and colleagues. "Hypothesizing that postmenopausal women might be particularly vulnerable to any adverse effects of HIV infection or [antiretroviral therapy] (ART) on the skeleton, we initiated a longitudinal study to assess the prevalence of osteoporosis/osteopenia, determinants and etiology of low BMD and rates of bone loss in HIV+ postmenopausal Hispanic and African American women, who constitute the majority of new infections in women in the United States."

The now-widespread use of ART has substantially increased the lifespan of HIV-positive patients. The authors predicted that by 2015, more than half of HIV-positive persons in the United States will be older than 50 years, and therefore subject to diseases of aging, including osteoporosis.

In 2002, the researchers launched their longitudinal study of bone health in 92 HIV-positive and 95 HIV-negative postmenopausal (>1 year of amenorrhea and follicle-stimulating hormone [FSH] > 30 mIU/mL; FSH > 20 mIU/mL and estradiol < 30 pg/mL; or age > 55 years, regardless of FSH and estrogen) minority women. The study authors assessed the participants' BMD, fracture prevalence, calciotropic and gonadal hormones, bone turnover markers, and serum levels of inflammatory cytokines (tumor necrosis factor alpha [TNFα], interleukin 6). Dual x-ray absorptiometry was used to measure BMD of the lumbar spine, femoral neck, total hip, and nondominant one third radius, along with body mass index (BMI).

Examining results collected through 2007, the authors found that unadjusted BMD (g/cm2) was 5.9% lower in HIV-positive subjects at the total hip. There was no significant difference at the spine, femoral neck, or radius between the 2 groups. After adjusting for several major BMD predictors, including age, race/ethnicity, and BMI, BMD was 4.5% lower in HIV-positive women at the lumbar spine, and a trend emerged toward a 3% to 4% lower BMD at the radius and total hip.

In HIV-positive women, the prevalence of T scores lower than ?1.0 was higher in 3 sites: the spine (78% vs 64%; P < .05), total hip (45% vs 29; P < .05), and femoral neck (64% vs 46%; P < .05). When adjusted for BMI, Z scores were lower in HIV-positive women in the same locations. HIV-positive participants had much higher serum TNFα, N-telopeptide, and C-telopeptide levels — a finding most notable in women receiving ART. After allowing for age, ethnicity, BMI, and alcohol use, HIV-positive status was independently and negatively associated with spine and hip BMD.

"The lower BMD, higher prevalence of low BMD and higher levels of bone turnover markers detected in HIV+ postmenopausal minority women could place them at high risk for future fractures," the authors write.

The researchers also noted higher bone turnover markers and TNF-α in HIV-positive women receiving ART and posited that multivariate modeling may mediate HIV's effect on BMD.

The authors stated several limitations to their study:

The control group's excellent health may have contributed to the greater BMD differences between HIV-positive and HIV-negative women because healthier women naturally have a higher BMD.
The HIV-positive women were significantly younger (56 ± 1 vs 60 ± 1 years; P < .01), which may have resulted in a different bias of higher BMD in the HIV-positive group.
The small sample size prohibited detailed analysis of specific ART regimens.
The study did not incorporate measurement of visceral adipose tissue through computed tomography scans.
Reasons for bone loss in HIV-positive women remain unclear, although it may be related to increased levels of proresorptive cytokines. By continuing to follow up the study subjects, researchers hope to further comprehend the relationships among HIV status, ART, and bone health.

"Completion of the ongoing longitudinal study should permit assessment of whether increased bone turnover associated with ART translates into accelerated bone loss and increased fracture rates in aging postmenopausal women," the authors write.

The National Institutes of Health supported the study. The study authors have disclosed no relevant financial relationships.

J Clin Endocrinol Metab. Published online January 6, 2010.