HIV病患的低骨密度、脆性骨折風險增加
作者：Barbara Boughton
出處：WebMD醫學新聞
February 23, 2010 (加州舊金山) — 研究者在第17屆逆轉錄病毒及伺機性感染年會(CROI)中宣稱，三篇新研究強調HIV病患的低骨密度(BMD)與脆性骨折風險增加。
研究者向與會聽眾表示，研究顯示低BMD風險之增加與一般使用的HIV治療有關，此外，骨折風險則與低CD4值與HIV陽性有關。
在一篇晚期的臨床試驗發表中，俄亥俄州克里夫蘭凱斯西儲大學的Grace McComsey醫師等人，研究了4種不同的HIV處方對於年齡中位數為38歲的269名HIV病患的四肢脂肪與BMD的效果。
ACTG A5202的子試驗「AIDS Clinical Trials Group (ACGT) A5224s」試驗是abacavir/lamivudine或tenofovir/emtricitabine併用efavirenz或atazanavir/ritonavir，用於之前無治療之HIV陽性病患的前瞻、隨機部分雙盲第3期試驗。
這些病患被追蹤96週，結果指出，全部這4組的BMD都顯著降低；在治療的第一年時有最顯著的改變。
結果顯示，相較於使用abacavir/lamivudine者，使用tenofovir/emtricitabine治療者的腰椎BMD與整體BMD有顯著降低。相較於使用efavirenz者，使用atazanavir/ritonavir者的腰椎BMD有顯著降低，但是臗骨BMD則無。
McComsey醫師向Medscape HIV/AIDS表示，對於醫師們而言，這是很重要的訊息，特別是對於那些停經期間與停經後的HIV婦女來說，將有助於醫師調整藥物處方。
發表於CROI的第二篇研究中，研究者發現，相對年輕(年紀範圍25-54歲)之HIV病患的脆性骨折風險比一般人增加。
研究者分析「HIV Outpatient Study」這項開放型前瞻性研究中的5826名HIV病患的資料，始於1993年，病患來自美國8個城市的10處診所。將2002-2008年間的骨折比率和同一時期的全國出院調查記錄比較，該調查的資料包括緊急照護、急診照護與住院病患。
研究者發現，HIV病患的骨折比率是一般人的4.3倍，脆性骨折也更常見，HIV病患的骨折比率隨著時間增加。
HIV病患中，CD4數量少於200 cell/mm3 (風險比[HR]，1.60)、同時有糖尿病(HR，1.62)、感染C型肝炎(HR，1.61)以及物質濫用(HR，1.52)等與骨折風險增加無關。
該研究的第一作者、喬治亞州亞特蘭大疾病控制預防中心流行病學家Christine Dao小姐表示，未來的研究須評估HIV與病毒血症這兩者以及抗逆轉錄病毒治療對於骨折風險的影響，還有HIV成人病患的骨密度和骨折風險的關連。
發表於CROI的第三篇研究中，研究對象是男性退伍軍人，也發現HIV患者的脆性骨折風險增加，不過，根據第一研究者、West Haven的退伍軍人管理局、康乃狄克健康照護體系的Julie Womac博士，增加的風險程度屬中等。
該研究中，研究者分析「Veterans Aging Cohort Study」這項前瞻觀察型世代研究的資料，研究對象是1997-2009年間、條件相仿的HIV感染男性與無感染的退伍軍人。
在8年的追蹤期間，研究者發現，HIV感染之男性的脆性骨折盛行率比沒有感染的男性增加，發生骨折時的平均年紀為55歲。
當研究者評估感染組與未感染組的髖骨和脊椎骨折發生率時，他們發現，HIV感染之男性的脆性骨折風險(HR)增加1.53倍，但是，當研究者校正已知的脆性骨折風險因素之後，增加的風險變成1.38倍。
Womack博士向Medscape HIV/AIDS表示，雖然HIV對於脆性骨折的風險影響屬中等，但仍顯著且與其它變項無關。
她表示，50歲以上退伍軍人的HIV感染特別可能造成風險增加(HR，1.37；95%信心區間為1.06- 1.78)。
Womack博士表示，HIV狀態之外的風險因素更可能與骨折風險增加有關，這些因素包括惡病質、腦血管疾病、種族、酒精使用異常以及年長。
HIV患者中，與脆性骨折風險增加有關的唯一額外因素是CD4數量降低，研究者的結果並未指出風險之增加與所用的治療HIV藥物有關。
Womack博士與她的研究員結論表示，雙能量X光吸收儀(DXA)掃描無法用於只有HIV這個風險因素的病患，不過，對於有多種脆性骨折臨床風險因素如中風史或惡病的HIV病患而言，DXA掃描是重要的。
McComsey醫師表示，其他研究顯示，HIV患者的脆性骨折相當常見，雖然在退伍軍人研究顯示骨折風險增加屬於中等，但是的確是增加的，而就這些男性的年紀而言，實際上，其骨折風險不應該增加。
McComsey醫師、Womack博士與Dao小姐皆宣告沒有相關財務關係。
第17屆逆轉錄病毒及伺機性感染年會(CROI)：晚期摘要106LB、摘要128與摘要129。發表於2010年2月18日。
Low Bone Mineral Density, Fragility Fracture Risk Increased in HIV Patients
By Barbara Boughton
Medscape Medical News
February 23, 2010 (San Francisco, California) — Three new studies have highlighted the increased risk for low bone mineral density (BMD) and fragility fractures in those with HIV, researchers announced here at the 17th Conference on Retroviruses and Opportunistic Infections (CROI).
It appears that the increased risk for low BMD is associated with commonly used therapies for HIV. In addition, the risk for fractures might be linked to low CD4 counts and HIV-positive status, investigators told meeting attendees.
In a late-breaking clinical trial presentation, Grace McComsey, MD, from Case Western Reserve University in Cleveland, Ohio, and colleagues studied the effects of 4 different HIV regimens on limb fat and BMD in 269 subjects with HIV. The median age of the study cohort was 38 years.
The AIDS Clinical Trials Group (ACGT) A5224s trial, a substudy of ACTG A5202, is a prospective randomized partially blinded phase?3 trial of abacavir/lamivudine or tenofovir/emtricitabine, combined with either efavirenz or atazanavir/ritonavir, for treatment-naive HIV-positive patients.
Patients were followed for 96 weeks. Results indicated that in all 4 groups, BMD decreased significantly; the most significant changes were seen in the first year of treatment.
Results indicated that those treated with tenofovir/emtricitabine had a significantly larger decline in lumbar spine and overall BMD than those treated with abacavir/lamivudine. Patients who received atazanavir/ritonavir had more significant losses in lumbar spine but not in hip BMD than those who received efavirenz.
"This is important information for clinicians, especially those who treat peri- or postmenopausal women with HIV because it can help them tailor medication regimens," Dr. McComsey told Medscape HIV/AIDS.
In a second study presented at CROI, researchers found an increased risk for fragility fractures in relatively young HIV patients (age range, 25 to 54 years), compared with the general population.
The researchers analyzed data from 5826 HIV patients from the HIV Outpatient Study, an open prospective study that began in 1993 and includes patients from 10 clinics in 8 American cities. Fracture rates between 2002 and 2008 were compared with those recorded during the same time period in the National Hospital Discharge Survey, which includes data from urgent care, emergency care, and inpatient settings.
The researchers found that fracture rates were 4.3 times higher in HIV patients than in the general population, and fragility fractures were also more common. Rates of fracture in HIV patients increased over time.
Among HIV patients, a CD4 count of less than 200?cell/mm3 (hazard ratio [HR], 1.60), comorbid diabetes (HR, 1.62), hepatitis?C infection (HR, 1.61), and substance abuse (HR, 1.52) were independently associated with increased fracture risk.
"Future studies need to assess the contribution of both HIV and viremia, as well as antiretroviral therapy, to fracture risk, and the association of bone mineral density to fracture risk among HIV-infected adults," said Christine Dao, MPH, an epidemiologist at the Centers for Disease Control and Prevention in Atlanta, Georgia, and lead author of the study.
A third study presented at CROI of male veterans also found an increased risk for fragility fractures in those with HIV, although the increased risk was "modest," according to lead researcher Julie Womack, PhD, from the Veterans Administration Connecticut Healthcare System in West Haven.
In that study, the researchers analyzed data from the Veterans Aging Cohort Study, a prospective observational cohort, in which HIV-infected men were matched with uninfected veterans from 1997 to 2009.
During the 8-year follow-up, the researchers found an increased prevalence of fragility hip fractures in HIV-infected men, compared with uninfected men. The mean age at fracture was 55 years.
When the researchers evaluated the incidence of hip and vertebral fractures in both the infected and uninfected groups, they found that the increased risk (HR) for fragility fractures among HIV-infected men was 1.53. But when the researchers adjusted for established risk factors for fragility fractures, the increased risk dropped to 1.38.
"While the effect of HIV on fragility fracture risk is modest, it's significant and independent of other variables," Dr. Womack told Medscape HIV/AIDS.
HIV infection in veterans older than 50 years was particularly likely to contribute to increased risk (HR, 1.37; 95% confidence interval, 1.06?- 1.78), she said.
Risk factors other than HIV status were more likely to be linked to increased fracture risk, Dr. Womack said. These factors include cachexia, cerebrovascular disease, race, alcohol use disorder, and older age.
Among those with HIV, the only additional factor associated with increased fragility fracture risk was decreased CD4 count. The researchers' results did not indicate that medications used to treat HIV were associated with increased risk.
Dr. Womack and her fellow researchers concluded that dual-energy x-ray absorptiometry (DXA) scans might not be indicated for patients whose only risk factor is HIV. However, DXA scans might be important for HIV-infected individuals who have multiple clinical risk factors for fragility fractures, such as a history of stroke or cachexia, she said.
"Other studies have shown that fragility fractures are more common in people with HIV," said Dr. McComsey. "Even though the reported increase in fracture risk in the veterans' study was modest, it is increased. And this is a population of men who are at an age when they shouldn't be at increased risk for fractures," she added.
Dr. McComsey, Dr. Womack, and Ms. Dao have disclosed no relevant financial relationships.
17th Conference on Retroviruses and Opportunistic Infections (CROI): Late-breaker abstract?106LB, abstract?128, and abstract?129. Presented February?18, 2010.
