Osteoporosis in HIV-infected patients

Bone disorders have emerged in the last 5 yr as additional long-term complications of human immunodeficiency virus (HIV) infection and its treatment. In particular, multiple studies suggest that HIV-infected patients receiving potent antiretroviral therapy have an increased prevalence of both osteopenia and osteoporosis. Studies prior to the era of potent antiretroviral therapy suggest that HIV infection has a modest effect on bone turnover. Treatment of HIV increases bone turnover with a greater effect on bone resorption. The mechanisms for increased bone demineralization in HIV-infected patients are unclear, although there is some evidence that specific drugs may inhibit bone formation in vitro. Small studies suggest that, in general, bone loss is not progressive over a short period of follow-up, and that the bisphosphonates may be useful in management; however, larger studies are needed to confirm these findings and assess the long-term implications of bone loss in HIV-infected persons.     

Bone Changes and Fracture Risk in Individuals Infected With HIV

The life expectancy of individuals infected with HIV has improved greatly since the institution of combination antiretroviral therapy. However, many metabolic derangements have been discovered with long-term combination antiretroviral treatment, including lipodystrophy; insulin resistance; and, more recently, abnormal bone metabolism. It is well-documented that bone mineral density (BMD) in HIV-positive patients is lower compared with the expected BMD in non–HIV-positive patients. The underlying cause of lower BMD is unknown but is thought to be a multifactorial process. Conflicting evidence exists regarding the effect of antiretroviral exposure and duration of treatment, antiretroviral type, and cumulative HIV viral exposure on bone health. Here we review the bone changes that occur with HIV infection and treatment.     

Bone loss in the HIV-infected patient: evidence, clinical implications, and treatment strategies

Osteoporosis is common in human immunodeficiency virus (HIV)-infected persons. The etiology of osteoporosis in HIV-infected patients is likely multifactorial, involving traditional risk factors such as low body weight, hypogonadism, and smoking, as well as direct effects of chronic HIV infection and antiretroviral therapy. Emerging evidence suggests that the increasing prevalence of osteoporosis in HIV-infected persons translates into a higher risk of fracture, likely leading to excess morbidity and mortality as the HIV-infected population ages. This review addresses the epidemiology of osteoporosis, discusses the causes of low bone mineral density in HIV-infected persons, including the impact of specific antiretroviral therapies, and offers recommendations on screening and treating vitamin D deficiency and osteoporosis.     

The Aging Skeleton: Differences Between HIV-Infected Patients and the Uninfected Aging Population

In the past 10?years, a great attention has been given to bone metabolism impairment in patients with human immunodeficiency virus (HIV) as a specific organ damage associated with long-term toxicities of antiretroviral therapy. More recently, this issue has been better contextualized in the setting of the overlapping epidemic between HIV and aging. The objective of this review is to describe the aging skeleton as a paradigm of the biological aging process affecting patients with HIV infection. An increased prevalence of osteoporosis and osteopenia has been reported in both men and women infected with HIV, but the mechanism and consequences of these changes are not fully understood. Cohort studies have reported controversial data regarding the increase in fracture rates affecting HIV-infected patients compared with controls. Major determinants of bone mineral density changes over time include antiretroviral therapy exposure, body mass index, and lifestyle. Low CD4 cell count has been associated with fracture risk, suggesting that chronic immune activation and persistent inflammation may play an important role in bone demineralization and fracture development. Whether these findings will apply particularly to older HIV-infected people, who experience a higher chronic inflammation burden and are at highest risk of fragility fractures, is unknown. Definitively, the care of patients with HIV is becoming more complex as patients grow older and confront unique challenges.     

Osteopenia, Osteoporosis, and Fractures in HIV-Infected Patients: Extent of the Problem

In HIV-infected persons, osteoporosis is common and has a multifactorial etiology including traditional risk factors, such as smoking and low body weight, as well as direct effects of HIV infection and antiretroviral therapy. Multiple studies indicate that HIV-infected persons are at increased risk of low bone mass as compared to the general population. Emerging data suggest that the increased prevalence of reduced bone mass in HIV infection predisposes patients to an increased risk of fracture. This review discusses the epidemiology of low bone mass and fracture in HIV-infected persons, addresses the multiple causes of reduced bone mineral density in HIV infection, and offers recommendations on screening HIV-infected persons for bone loss.     

Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy

OBJECTIVE: To describe the alterations in the bone metabolism of HIV-seropositive patients and evaluate the effects of antiretroviral therapies. DESIGN: Cross-sectional analytical study. METHOD AND MATERIALS: A total of 142 subjects (113 male, 29 female), aged 20-45 years were divided into four groups: group A, 33 HIV-seropositive antiretroviral-naive patients; group B1, 36 HIV-seropositive patients on antiviral therapy for over 1 year, without protease inhibitors (PI); group B2, 42 HIV-seropositive patients on combined therapy containing PI for over 1 year; and group C, 15 healthy, HIV-seronegative subjects. Bone mineral density (BMD) were determined by dual energy X-ray absorptiometry in total body, lumbar spine and proximal femur; and evaluation of serum osteocalcin, d-pyridinoline, parathyroid hormone (THP), calcium and phosphate, and urine calcium. RESULTS: BMD was significantly lower in HIV-seropositive patients in comparison with healthy controls, in all sites studied. However, no statistical differences were observed among all groups of HIV-infected patients, independently of the antiretroviral therapy. There was a significantly higher occurrence of osteopenia and osteoporosis in HIV-infected patients in comparison with controls (P < 0.0001), with no differences among treatment-naive patients and either of the treatment groups. Bone formation and resorption markers were similar among all studied groups. There was a significant correlation in all bone sites between time of infection and BMD (P < 0.02). CONCLUSIONS: BMD was significantly lower in HIV-seropositive patients in comparison with controls in lumbar spine, proximal femur and total body, without significant differences among treatment-naive patients and either of the treatment groups. Only time with HIV infection and not specific therapy was associated with BMD decreases.     

Prevalence and risk factors of osteopenia/osteoporosis in Turkish HIV/AIDS patients

BackgroundRecent studies showed a high frequency of low bone mineral density (BMD) in HIV-infected patients and no reports have been issued in Turkey. Our aim was to evaluate BMD and risk factors for osteopenia/osteoporosis in HIV-infected patients that attended an outpatient clinic in Istanbul, Turkey.MethodIn order to determine the prevalence of BMD, 126 HIV-infected patients had been studied with dual energy X-ray absorptiometry (DEXA). The association between BMD and age, gender, body mass index (BMI), habits, 25(OH)vitamin D, HIV RNA, CD4 lymphocyte nadir, using and duration of highly active antiretroviral treatment (HAART) were investigated by using multivariate analysis.ResultsMedian age was 40.1 years (range, 20–70); 84% were male; 35.7% patients had AIDS, 63.5% were treated with HAART. Osteopenia and osteoporosis were diagnosed in 53.9% and 23.8%, respectively. Mean plasma HIV RNA was 5.2 (SD 1.0) log₁₀ copies/mL and CD4 lymphocyte nadir was 313.8 (SD 226.2)/mm³. Factors associated with bone loss were high viral load (p = 0.034), using (p = 0.033) and duration of HAART (p = 0.008). No correlation had been seen between sex and osteopenia/osteoporosis (p = 0.794). However, males showed higher rates of osteoporosis than females (p = 0.042).ConclusionsOur results show a very high prevalence of bone mass reduction in Turkish HIV-infected patients. This study supports the importance of both HIV and antiretroviral therapy in low BMD.     

Fragility fractures in HIV-infected patients: need for better understanding of diagnosis and management

HIV infection, AIDS, and antiretroviral therapy (ART) have been associated with bone fragility fractures, although the prevalence and incidence are not well studied by researchers. In HIV and ART, osteopenia and osteoporosis are multifactorial, and health promotion or medical health maintenance should anticipate and prevent morbidity of bone fragility fractures.     

The Crosstalk Between Bone and Fat in HIV-Infected Patients, with a Focus on Lipodystrophy

Low bone mineral density and osteoporosis are prevalent in cohorts of HIV-positive patients, with increased fracture rates also described. HIV is a disease characterised by abnormalities in body fat metabolism, particularly HIV-associated lipodystrophy, a common long-term side effect of antiretroviral therapy for HIV infection. Given the close metabolic relationships between bone and fat, the presence of these two conditions raises questions as to potential pathogenic links between the two. This review discusses both conditions and identifies potential factors that may link abnormalities in fat distribution with decreased bone mineral density.     

Prevalence and risk factors associated with decreased bone mineral density in patients with haemophilia

Summary.  Osteoporosis in adult males is an under-recognized problem. Patients with haemophilia have several predisposing factors for developing decreased bone mineral density (BMD) including prolonged periods of immobility, reduced weight bearing and co-morbidities associated with bone loss. To establish prevalence and risk factors associated with decreased BMD in patients with haemophilia. Adults with moderate or severe haemophilia A or B underwent dual-energy X-ray absorptiometry (DXA). BMD was correlated to laboratory values, joint mobility measurements and physical activity questionnaires. Thirty patients completed evaluations. The median age was 41.5 years (range 18–61). Median lowest T-score by DXA was −1.7 (range: −5.8 to +0.6), with the femoral neck being the site of the lowest T-scores. Based on World Health Organization criteria, 70% of patients had decreased BMD. Twenty-seven per cent of the participants ( n  = 8) had osteoporosis and 43% ( n  = 13) had osteopenia. Variables associated with increased bone loss included lower serum 25-hydroxyvitamin D levels ( P  = 0.03), lower body mass index ( P  = 0.047), lower activity scores ( P  = 0.02), decreased joint range of motion ( P  = 0.046), HIV ( P  = 0.03), HCV ( P  = 0.02), history of inhibitor ( P  = 0.01) and age ( P  = 0.03). Adults with haemophilia are at increased risk for developing osteoporosis. A history of HCV and HIV infections, decreased joint range-of-motion, decreased activity levels, history of an inhibitor and low body weight predict bone loss and suggest a population to target for screening. A high prevalence of vitamin D insufficiency was observed. Future studies should investigate interventions, including vitamin D supplementation, to prevent bone loss and fractures for this at-risk population.     

The burden of liver disease in human immunodeficiency virus-infected patients

Introduction of effective combined antiretroviral therapy has made human immunodeficiency virus (HIV) infection a chronic illness. Substantial reductions in the number of acquired immunodeficiency syndrome- (AIDS-) related deaths have been accompanied by an increase in liver-related morbidity and mortality. Liver diseases rank in the first three most-common causes of death in HIV-infected persons. Mortality is mainly due to cirrhosis and hepatocellular carcinoma induced by hepatitis C virus and hepatitis B virus coinfection. However, antiretroviral drugs toxicity also plays a role. Nonalcoholic fatty liver disease is a common cause of liver injury as well. Nevertheless, alcohol consumption probably plays a pivotal role. Noncirrhotic portal hypertension, an uncommon condition observed in less than 1% of patients, is increasingly described. Finally, acute hepatitis A virus (HAV) and acute and even chronic hepatitis E virus infection have also been reported as causes of liver damage in HIV. Anti-HAV vaccination is thus recommended in persons at risk living with HIV.     

高效抗逆转录病毒治疗对人类免疫缺陷病毒感染患者骨密度的影响

目的 评价高效抗逆转录病毒治疗(HAART)对HIV感染患者骨密度(BMD)的影响及其相关因素.方法 收集2007-2008年间50例接受HAART的HIV/MDS患者(治疗组)、12例未用HAART的HIV/AIDS患者(未治疗组)、20例健康对照者(对照组)的临床资料,采用双能X线BMD吸收仪(DEXA)测定BMD以及T值,分别对其数据进行统计分析.结果 治疗组中19例(38.0%)患者发生骨量减少,1例(2.0%)患者发生骨质疏松.对照组中5例(25.0%)发生骨量减少,无骨质疏松者.未治疗组中6例(50.0%)患者发生骨量减少,2例(16.7%)患者发生骨质疏松.未治疗组骨量减少/骨质疏松发生率较对照组显著增高(P=0.02).HIV/AIDS组(包括未治疗组和治疗组)的股骨、股骨颈、大粗隆的BMD[(0.97±0.14)、(0.91±0.13)、(0.76 4-0.12)g/cm2]明显低于对照组[(1.04±0.12)、(0.98±0.14)、(0.84±0.11)g/cm2,P<0.05];而未治疗组和治疗组的BMD差异无统计学意义.治疗组中,骨量减少/骨质疏松与体重<60 kg(r=0.074,P=0.004)、使用HAART前血浆病毒载量(r=5.103,P=0.021)呈正相关.结论 未接受HAART的HIV/AIDS患者较健康人骨量减少/骨质疏松发生率高.HIV/MDS患者BMD较健康人低,接受HAART和未接受HAART治疗的HIV/AIDS患者BMD相当.接受HAART患者中,体重<60 kg、治疗前HIV RNA是发生骨量减少/骨质疏松的危险因素.     

Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review

INTRODUCTION: Prevalence estimates of osteopenia and osteoporosis (reduced bone mineral density; BMD) in HIV-infected patients and the role of antiretroviral therapy (ART) varies in the literature. METHODS: We conducted a meta-analytical review of cross-sectional studies published in English to determine the pooled odds ratios (OR) of reduced BMD and osteoporosis in the following groups: HIV-positive versus HIV-negative; ART-treated versus ART-naive; protease inhibitor (PI)-treated versus PI-untreated. We searched the MEDLINE, PubMed, and EMBASE databases for eligible references between January 1966 and November 2005. Random effects models were used to generate pooled OR estimates and confidence intervals. RESULTS: Of 37 articles identified, 20 met the inclusion criteria. Of the 884 HIV-infected patients, 67% had reduced BMD, of whom 15% had osteoporosis, yielding a pooled OR of 6.4 and 3.7, respectively, compared with HIV-uninfected controls (n = 654) using 11 studies with available data. Compared with ART-naive patients (n = 202, 10 studies), ART-treated individuals (n = 824) had a 2.5-fold increased odds of prevalent reduced BMD. The risk of prevalent osteoporosis (seven studies) was similarly elevated in ART-treated individuals. Compared with non-PI-treated HIV patients (n = 410, 14 studies), PI-treated patients (n = 791) had increased odds of reduced BMD and osteoporosis (12 studies). Few studies adjusted for important covariates such as HIV disease severity or treatment duration. CONCLUSION: The prevalence of osteoporosis in HIV-infected individuals is more than three times greater compared with HIV-uninfected controls. ART-exposed and PI-exposed individuals had a higher prevalence of reduced BMD and osteoporosis compared with their respective controls. The influence of other disease and treatment variables on these estimates could not be determined.     

HIV infection and bone disease

The success of antiretroviral therapy in treating HIV infection has greatly prolonged life expectancy in affected individuals, transforming the disease into a chronic condition. A number of HIV‐associated non‐AIDS comorbidities have emerged in the ageing HIV‐infected population, including osteoporosis and increased risk of fracture. The pathogenesis of fracture is multifactorial with contributions from both traditional and HIV‐specific risk factors. Significant bone loss occurs on initiation of antiretroviral therapy but stabilizes on long‐term therapy. Fracture risk assessment should be performed in HIV‐infected individuals and bone mineral density measured when indicated. Lifestyle measures to optimize bone health should be advised and, in individuals at high risk of fracture, treatment with bisphosphonates considered.     

Atherosclerosis in HIV-positive patients

Worldwide, human immunodeficiency virus (HIV) infection is one of the main health subjects. Even, the human immunodeficiency virus primarily effects the immune system, HIV infection also has an impact on other organs. Cardiovascular manifestations in HIV-infected patients could occur by the HI-virus itself or by opportunistic infections. Reports of myocardial infarction in young HIV-infected patients, who received protease inhibitors, have raised concerns about premature arteriosclerosis and coronary artery disease in this population. In the pre-protease inhibitor era, autopsy reports were the first to describe an association between coronary artery disease and HIV infection. Long-term antiretroviral therapy, including protease inhibitors, significantly reduced mortality, morbidity and revolutionized the care of HIV-infected patients. However, class-specific metabolic side effects, such as elevated total cholesterol and triglyceride levels and insulin resistance, have been described. These metabolic alterations of antiretroviral therapy impair the cardiovascular risk profile of HIV-infected patients. Even epidemiological studies found no significant effect of antiretroviral treatment type on coronary heart disease or myocardial infarction, an increase of arteriosclerosis in HIV-infected patients is suspected. Recent results of autopsy studies and analyses of endothelial function in patients with HIV infection described an effect of HIV and antiretroviral therapy on premature arteriosclerosis. The present article gives an overview about arteriosclerosis and coronary events in HIV-infected patients and the impact of antiretroviral therapy.     

Antiretroviral-naïve HIV-infected patients had lower bone formation markers than HIV-uninfected adults

ABSTRACT

There are limited studies regarding bone health among people living with HIV (PLHIV) in Asia. We compared bone mineral density (BMD), serum 25-hydroxyvitamin D (25(OH)D) status and bone turnover markers (serum procollagen type1 N-terminal propeptide (P1NP), osteocalcin (OC) and C-terminal cross-linking telopeptide of type1 collagen) among 302 antiretroviral therapy (ART) naive PLHIV compared to 269 HIV-uninfected controls from Thailand. People aged ≥30 years, with and without HIV infection (free of diabetes, hypertension, and active opportunistic infection) were enrolled. BMD at the lumbar spine, total hip, and femoral neck were measured using Hologic DXA at baseline and at 5 years. We analyzed BMD, serum 25(OH)D levels, and bone turnover markers at the patients’ baseline visit. PLHIV were 1.5 years younger and had lower BMI. PLHIV had higher mean serum 25(OH)D level and similar BMD to the controls. Interestingly, PLHIV had significantly lower bone formation (serum P1NP and OC), particularly those with low CD4 count. Only a few participants had low bone mass. ARV naïve middle-aged PLHIV did not have lower BMD or lower vitamin D levels compared to the controls. However, PLHIV had lower bone formation markers, particularly those with low CD4 count. This finding supports the benefit of early ART.     

Molecular Bases of Osteoporosis in HIV: The Role of the Virus and Antiretroviral Therapy

In addition to immune system, HIV infection can determine the onset of functional dysfunctions of several organs and tissues such as central nervous system, cardiovascular system, kidney, and bone. It is noteworthy that HIV-infected individuals show an increased risk of bone mass loss with subsequent osteopenia and osteoporosis development. Interestingly, antiretroviral therapy is not able to tackle the bone derangement but, on the contrary, it can induce a progressive bone mass loss, especially when specific antiretroviral drugs are used. In this report, we summarized the HIV and antiretroviral-related mechanisms involved in the osteopenia and osteoporosis induction.     

Osteoporosis e infección por el virus de la inmunodeficiencia humana

Life expectancy and quality of life among human immunodeficiency virus (HIV-1)-infected patients has dramatically improved with the advent of highly active antiretroviral therapy (HAART). However, with the transformation of HIV infection into a chronic disease, a series of long-term consequences, including osteoporosis, has emerged.Bone mass is lower in patients with HIV-1 infection than in healthy individuals and the prevalence of osteopenia and osteoporosis is higher. The incidence and prevalence of fragility fractures does not appear to be on the increase; however, as the HIV-infected population ages, an increase in fragility fractures can be expected. The causes that favor the occurrence of bone-related disorders are multiple and are related to HIV infection and its treatment.     

Bone mineral density is not reduced in HIV-infected Caucasian men treated with highly active antiretroviral therapy

OBJECTIVE: Recent studies have reported low bone mineral density (BMD) in patients infected with human immunodeficiency virus (HIV). Frequently these findings have been attributed to treatment with highly active antiretroviral therapy (HAART). We sought to determine whether BMD in HIV-infected men treated with HAART for at least 3 months is different from that in healthy controls, and, if so, what HIV-related factors might explain this finding. DESIGN: Cross-sectional analysis. PATIENTS: Fifty-nine HIV-infected Caucasian men treated with HAART, and 118 healthy community-dwelling controls. Each HIV-infected man was age-matched (within 5 years) to two controls. MEASUREMENTS: All participants had measurements of BMD and bone-related laboratory parameters. RESULTS: The mean duration of known HIV infection was 8.5 years, and of treatment with HAART was 52 months. There was no significant difference in mean BMD between groups at the lumbar spine (HIV group: 1.23 g/cm2, controls: 1.25 g/cm2; P = 0.53) or total body (HIV group: 1.18 g/cm2, controls: 1.20 g/cm2; P = 0.09). At the total hip the HIV-infected group had significantly lower BMD than the control group (HIV group: 1.03 g/cm2, controls: 1.09 g/cm2; P = 0.01). The HIV-infected group were, on average, 6.3 kg lighter than the controls. After adjusting for this weight difference, HIV infection was not an independent predictor of BMD at any site (lumbar spine P = 0.79; total hip P = 0.18; total body P = 0.76). CONCLUSIONS: HIV-infected men treated with HAART are lighter than healthy controls. This weight difference is responsible for a small decrement in hip BMD. Overall, BMD is not significantly reduced in HIV-infected Caucasian men treated with HAART.