Association between hepatitis B virus infection and risk of osteoporosis: a systematic review and meta-analysis: A protocol for systematic review.

BACKGROUND: The potential association between hepatitis B virus (HBV) infection and development of osteoporosis has drawn significant attention from clinicians and researchers in recent years due to the increasing prevalence of HBV infection. This study aims to perform a systematic review and meta-analysis of the literature to show whether HBV infection is associated with an increased risk of osteoporosis. METHODS: Case-control, cohort, and cross-sectional studies that report the incidence of osteoporosis, osteoporotic fracture, osteopenia, and bone mineral density level in populations with HBV infection will be selected. Four databases from their inception to October 2019 will be searched. All data were assessed and extracted by 2 authors independently. The Newcastle-Ottawa scale and (Agency for Healthcare Research and Quality) Agency for Healthcare Research and Quality checklist will be used to assess the quality of the selected studies. Stata 15.1 (Stata Corp, College Station, TX) will be used to conduct meta-analysis. RESULT: The results of this systemic review and meta-analysis will be submitted to a recognized journal for publication. CONCLUSION: This systemic review and meta-analysis will determine whether HBV infection is associated with an increased risk of osteoporosis. We hope this review can provide a reliable evidence. REGISTRATION: PROSPERO (registration number CRD42020140522).

Trabecular bone scores in young HIV-infected men: a matched case-control study.

BACKGROUND: Screening for osteoporosis with dual-energy X-ray absorptiometry (DXA) is recommended for male HIV-infected patients only above the age of 50. Recently, trabecular bone score (TBS) has been introduced as a novel tool to assess bone microarchitecture using DXA of the lumbar spine. Few studies have reported TBS values in HIV-infected individuals younger than 50 years of age. This study compared TBS values in young males infected with HIV and matched controls, and investigated the associations between TBS and demographic parameters, clinical parameters, and bone mineral density (BMD) scores. METHODS: A cross-sectional study of BMD and TBS in HIV-infected men (n = 80) aged between 18 and 50 years and age- and sex-matched controls (n = 80) was conducted. RESULTS: The proportion of patients with low BMD (Z-score ≤ - 2) was significantly greater among HIV-infected patients than among matched controls (21.3% [17/80] vs. 8.8% [7/80], p = 0.027). Mean TBS values were significantly lower in HIV-infected patients than in controls (1.41 ± 0.07 vs. 1.45 ± 0.07, p = 0.008). In both groups, TBS values were positively correlated with BMD at the lumbar spine, femoral neck, and total hip (p < 0.001); however, TBS was not correlated with body mass index. In the HIV group, TBS was negatively correlated with the duration of tenofovir disoproxil fumarate(TDF) exposure (p = 0.04). CONCLUSION: Young men infected with HIV had abnormal bone trabecular microarchitecture, as assessed by both TBS and BMD. TBS values were correlated with both BMD and the duration of TDF exposure.

Association between Herpes Zoster and Osteoporosis: A Nested Case-Control Study Using a National Sample Cohort.

OBJECTIVES: Chronic inflammatory disease might affect osteoporosis; however, few studies have reported the association between herpes zoster and osteoporosis. The goal of this study was to estimate the association between herpes zoster and osteoporosis in Korean residents. METHODS: The Korean National Health Insurance Service-National Sample Cohort, which includes individuals aged ≥ 50 years, was assessed from 2002 to 2013. In total, 68,492 osteoporosis participants were matched with 68,492 control participants at a ratio of 1:1 by age, sex, income, and region of residence. We assayed the prior histories of herpes zoster in the osteoporosis and control groups. The diagnoses of herpes zoster and osteoporosis were based on ICD-10 codes and claim codes. Crude and adjusted models of odds ratios (ORs) were explored using conditional logistic regression analyses, and the 95% confidence intervals (CIs) were computed. The participants were stratified according to age, sex, income, and region of residence. Subgroup analyses were performed to investigate the role of age and sex. RESULTS: The rate of herpes zoster in the osteoporosis group (5.1% [3,487/68,492]) was higher than that in the control group (4.0% [2,738/68,492]). The adjusted OR of herpes zoster in the osteoporosis group was 1.17 (95% CI = 1.11-1.24). In the subgroup analyses, the adjusted OR was 1.34 (95% CI = 1.01-1.78) among males aged < 65 years, 1.20 (95% CI = 1.12-1.29) among females aged < 65 years, and 1.19 (95% CI = 1.04-1.36) among males aged ≥ 65 years. CONCLUSION: The ORs of herpes zoster were increased among the osteoporosis patients. This correlation was reliable in all subgroups by age and sex except group of women ≥ 65 years old.

Evaluation of screening practices for low bone mass and prevalence of osteoporosis and fractures in people living with human immunodeficiency virus attending a sexual health clinic.

BACKGROUND: Adults with human immunodeficiency virus (HIV) infection commonly experience fractures and have a high prevalence of osteoporosis. The reasons for low bone mineral density (BMD) in HIV patients are multifactorial and there are now guidelines for screening. AIMS: The aims of this study were to determine the screening practices for osteoporosis at this sexual health clinic, the prevalence of osteoporosis and to examine the risk factors for bone disease. METHODS: We performed a retrospective cohort study of all HIV patients attending the Sunshine Coast Health Service District Sexual Health Clinic. Through chart review we collected the following details: patient demographics, co-morbid conditions, HIV status and anti-retroviral therapy, BMD screening, fractures, screening for secondary causes of bone disease and treatment interventions for osteoporosis. RESULTS: A total of 243 patients with HIV attended the sexual health clinic. Of these, 149 met screening criteria for BMD assessment and 93 (61%) of those eligible underwent BMD examination. In those who had a BMD performed, 13 (19%) had sustained a previous fracture, 28 (30%) had osteoporosis and 42 (45%) had osteopenia. In the osteoporosis group, 21 (78%) were treated with vitamin D and calcium, 7 (26%) had a change in ART, 19 (68%) were treated with anti-resorptive therapy and 9 received testosterone replacement. CONCLUSIONS: In this cohort, there was a high prevalence of low bone mass and BMD screening rates of 60%. Our results highlight the importance of this condition and the need to improve screening and availability of BMD assessment.

CD4 T cell count is inversely associated with lumbar spine bone mass in HIV-infected men under the age of 50 years.

HIV-infected men under the age of 50 years had a lower bone mass compared to that of HIV-uninfected men. Lower CD4 T cell counts, independent of whether antiretroviral therapy (ART) was used, were associated with lower BMD. HIV-infected patients with low CD4 T cell counts may need follow-up and intervention regarding bone health, including younger patients. INTRODUCTION: HIV-infected patients have a low bone mineral density (BMD) owing to multifactorial interaction between common osteoporosis risk factors and HIV-related factors, including chronic inflammation and ART. Although HIV infection and ART might affect bone metabolism, little data is available for patients aged under 50 years. We aimed to investigate the association of HIV infection-induced low CD4 T cell counts and ART with BMD in men aged under 50 years. METHODS: We performed an age- and body mass index-matched case-control study. BMD values of HIV-infected and HIV-uninfected men (< 50 years) were compared, and HIV-infected men were stratified by CD4 T cell counts and ART use. RESULTS: After adjusting confounders, HIV-infected men with CD4 T cell counts ≥ 500 cells/µL (n = 28) and < 500 cells/µL (n = 139) had lower BMD at the femoral neck (FN, p < 0.001) and total hip (TH, p < 0.001) than HIV-uninfected men (n = 167). HIV-infected men with CD4 T cell counts < 500/µL had lower BMD at the lumbar spine (LS, p = 0.034) than those with counts of ≥ 500 cells/µL, but not at FN and TH. The CD4 T cell count (γ = 0.169, p = 0.031) was positively correlated with BMD at LS. There was no significant difference in the BMD (p = 0.499-> 0.999) between the ART-naïve (n = 75) and ART-user group (n = 92). CONCLUSIONS: Despite their relatively younger age, HIV-infected men had a lower BMD than HIV-uninfected men. Lower CD4 T cell counts, irrespective of ART, might result in lower bone mass.

The association between hepatitis and osteoporosis: a nested case-control study using a national sample cohort.

The prevalence of hepatitis B was higher in osteoporosis patients than the control group, especially in females. However, the prevalence of hepatitis C was not different. The matching for various factors improved to have same conditions between osteoporosis patients and the control group. PURPOSE: Although chronic liver disease, including hepatitis B and hepatitis C, has been associated with osteoporosis in previous studies, the evidence was insufficient, and some findings were inconsistent. The aim of this study was to evaluate the relationship between hepatitis B or hepatitis C and osteoporosis. METHODS: We used the Korean National Health Insurance Service-National Sample Cohort with ≥ 50-year-old participants from 2002 to 2013. Age was determined at osteoporosis diagnosis. We extracted 68,492 osteoporosis patients (ICD-10 codes E7001-E7004, HC341-HC345) with a 68,492-member control group at a ratio of 1:1 by age, sex, income, region of residence, hypertension, diabetes, and dyslipidemia. We analyzed previous histories of hepatitis B (ICD-10 codes B18.0-B18.1) and hepatitis C (ICD-10 code B18.2) in the osteoporosis patients and control groups. The logistic regression with the crude and adjusted model was analyzed. Additionally, subgroup analyses divided by age and sex were performed. RESULTS: The adjusted odds ratios for hepatitis B and hepatitis C were 1.19 (95% confidence interval (CI) = 1.11-1.28, P < 0.001) and 1.04 (95% CI = 0.90-1.19, P > 0.05), respectively, in osteoporosis patients. Subgroup analyses showed that the risk of hepatitis B was higher in osteoporosis patients in female groups but not in male groups. CONCLUSION: Hepatitis B virus infection might be a risk factor for osteoporosis.

Use of quantitative ultrasound as bone mineral density evaluation in an Italian female population living with HIV: A real-life experience.

This is a multicenter cross-sectional study where we aimed to detect the rate of osteopenia/osteoporosis in an HIV female population (WLWHIV) by means of "heel quantitative ultrasound" (QUS) measurement. We enrolled 273 patients, mean age 48.1 years, 36% menopausal, 96% on combination antiretroviral therapy (cART). Calcaneal measure of bone mass index by QUS revealed osteopenia and osteoporosis in 76 (27.8%) and 16 (5.9%) WLWHIV. Our data underline the correlation between low QUS parameters and traditional risk factors for osteoporosis rather than with cART exposure, thus suggesting the crucial importance of detection and correction of traditional risk factors for osteoporosis in WLWHIV.

Reduced bone mineral density in human immunodeficiency virus-infected individuals: a meta-analysis of its prevalence and risk factors.

A meta-analysis was conducted to evaluate the prevalence of osteopenia/osteoporosis in human immunodeficiency virus (HIV)-infected individuals. The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was significantly higher than respective controls. Evidence regarding bone loss within first year of HIV infection or ART initiation was preliminary. PURPOSE: The aim of the study is to systematically review published literature on the prevalence of osteopenia/osteoporosis and its associated risk factors in HIV-infected individuals. METHODS: A literature search was conducted from 1989 to 2015 in six databases. Full text, English articles on HIV-infected individuals ≥ 18 years, which used dual X-ray absorptiometry to measure BMD, were included. Studies were excluded if the prevalence of osteopenia/osteoporosis was without a comparison group, and the BMD/T-score were not reported. RESULTS: Twenty-one cross sectional and eight longitudinal studies were included. The prevalence of osteopenia/osteoporosis was significantly higher in both HIV-infected [odds ratio (OR) = 2.4 (95%Cl: 2.0, 2.8) at lumbar spine, 2.6 (95%Cl: 2.2, 3.0) at hip] and ART-treated individuals [OR = 2.8 (95%Cl: 2.0, 3.8) at lumbar spine, 3.4 (95%Cl: 2.5, 4.7) at hip] when compared to controls. PI-treated individuals had an OR of 1.3 (95%Cl: 1.0, 1.7) of developing osteopenia/osteoporosis compared to controls. A higher proportion of tenofovir-treated individuals (52.6%) had lower BMD compared to controls (42.7%), but did not reach statistical significance (p = 0.248). No significant difference was found in the percent change of BMD at the lumbar spine, femoral neck, or total hip from baseline to follow-up between HIV-infected, PI-treated, tenofovir-treated, and controls. Older age, history of bone fracture, low BMI, low body weight, being Hispanic or Caucasian, low testosterone level, smoking, low CD4 cell count, lipodystrophy, low fat mass, and low lean body mass were associated with low BMD. CONCLUSIONS: The prevalence of osteopenia/osteoporosis in HIV-infected and antiretroviral therapy (ART)-treated individuals was two times more compared to controls. However, evidence concerning bone loss within the first year of HIV infection and ART initiation was preliminary.

The Differential Effects of Human Immunodeficiency Virus and Hepatitis C Virus on Bone Microarchitecture and Fracture Risk.

Background: Human immunodeficiency virus (HIV)/hepatitis C virus (HCV)-coinfected individuals have a significantly greater osteoporotic fracture risk than HIV-monoinfected persons, despite the fact that HIV/HCV coinfection has not been associated with lower bone mineral density (BMD) than HIV or HCV alone. To evaluate if changes in bone microarchitecture, measured by trabecular bone score (TBS), could explain these differences, we performed a prospective, cross-sectional cohort study of virologically suppressed HIV-infected subjects, untreated HCV-infected subjects, HIV/HCV-coinfected subjects, and uninfected controls. Methods: We enrolled 532 male subjects: 57 HIV/HCV coinfected, 174 HIV infected, 123 HCV infected, and 178 controls. We conducted analysis of covariance comparing BMD and TBS between groups, controlling for age, race, body mass index, and smoking. We used linear regression to evaluate predictors of BMD and TBS and evaluated the effects of severity of HCV infection and tenofovir disoproxil fumarate use. Results: Despite both infections being associated with decreased BMD, only HCV, but not HIV, was associated with lower TBS score. Also, HIV/HCV-coinfected subjects had lower TBS scores than HIV-monoinfected, HCV-monoinfected, and uninfected subjects. Neither the use of TDF or HCV viremia nor the severity of HCV liver disease was associated with lower TBS. Conclusions: HCV infection is associated with microarchitectural changes at the lumbar spine as assessed by the low TBS score, suggesting that microstructural abnormalities underlie some of the higher fracture risk in HCV infection. TBS might improve fracture risk prediction in HCV infection.

TDF and quantitative ultrasound bone quality in African patients on second line ART, ANRS 12169 2LADY sub-study.

BACKGROUND: Bone demineralization, which leads to osteoporosis and increased fracture risk, is a common metabolic disorder in HIV-infected individuals. In this study, we aimed to assess the change in bone quality using quantitative ultrasound (QUS) over 96 weeks of follow-up after initiation of second-line treatment, and to identify factors associated with change in bone quality. METHODS AND FINDINGS: In a randomized trial (ANRS 12169), TDF and PI-naïve participants failing standard first-line treatment, from Burkina Faso, Cameroon, and Senegal were randomized to receive either TDF/FTC/LPVr, ABC/ddI/LPVr or TDF/FTC/DRVr. Their bone quality was assessed using calcaneal QUS at baseline and every 24 weeks until week 96. Stiffness index (SI) was used to measure bone quality. Out of 228 participants, 168 (74%) were women. At baseline, median age was 37 years (IQR: 33-46 years) and median T-CD4 count was 199 cells/µl (IQR: 113-319 cells/µl). The median duration of first-line antiretroviral treatment (ART) was 52 months (IQR: 36-72 months) and the median baseline SI was 101 (IQR: 87-116). In multivariable analysis, factors associated with baseline SI were sex (ß = -10.8 [-18.1,-3.5] for women), age (ß = -8.7 [-12.4,-5.1] per 10 years), body mass index (BMI) (ß = +0.8 [0.1,1.5] per unit of BMI), and study site (ß = +12.8 [6.5,19.1] for Cameroon). After 96 weeks of second-line therapy, a reduction of 7.1% in mean SI was observed, as compared with baseline. Factors associated with SI during the follow-up were similar to those found at baseline. Exposure to TDF was not associated with a greater loss of bone quality over time. CONCLUSION: Bone quality decreased after second-line ART initiation in African patients independently of TDF exposure. Factors associated with bone quality include age, sex, baseline BMI, study site, and duration of follow-up.

Osteoporosis and osteopenia are not associated with T-cell activation in older cART-treated HIV-infected patients.

BACKGROUND: A higher risk of developing osteopenia/ osteoporosis has been seen in HIV-infected patients. We compared HIV-infected patients, all treated with combination antiretroviral therapy (cART), with a low bone mineral density (BMD) (T-score < -1) to those with a normal BMD (T-score > -1), examining the relation with T-cell activation and bone turnover markers (c-terminal telopeptide (CTX) and procollagen type 1 amino-terminal propeptide (P1NP)). METHODS: In this single visit pilot study, bone turnover markers, T-cell activation (CD38 + HLA - DR +) and senescence (CD57+) of T cells were measured in patients who had previously undergone dual energy X-ray absorptiometry scanning. RESULTS: All study participants (n = 16) were male, on cART, with a median age of 61 years (IQR 56-66). Nine patients had osteopenia/osteoporosis. When comparing the patients with osteopenia/osteoporosis with those with a normal BMD, no differences in activation and senescence were found. A relation was seen between higher bone formation (P1NP) and patients who were on cART for longer. The median length of cART use was 5.5 years (IQR 4.5-7.8), with all patients on nucleoside reverse transcriptase inhibitors, 88% on tenofovir, 63% on non-nucleoside reverse transcriptase inhibitors (NNRTIs) and 38% on protease inhibitors. Osteopenia/osteoporosis was seen in 100% of the patients on protease inhibitors versus 30% of those on NNRTIs. CONCLUSION: This study did not find an association between activated T cells and BMD, thus did not explain the higher prevalence of osteopenia/osteoporosis in HIV-infected patients. Interestingly, this small pilot showed that cART might influence BMD, with a possible negative effect for protease inhibitors and a possible protective effect for NNRTIs. These results warrant further investigation.

Frailty in HIV infected people: a new risk factor for bone mineral density loss.

OBJECTIVE: The study aims to assess the association between bone mineral density (BMD) and frailty in a cohort of HIV-infected patients. DESIGN: A cross-sectional study in an HIV outpatient unit where nearly 1000 patients are monitored. METHODS: Study participants undergoing bone densitometry were proposed an evaluation of frailty using criteria of the Cardiovascular Health Study (CHS) and the Study of Osteoporotic Fractures (SOF). Frailty markers were weight-loss, self-reported exhaustion, physical activity, grip strength, chair stands, and slow gait. Patients' characteristics were collected from an electronic medical record. Associations of frailty with BMD and osteoporosis were tested using multivariate linear and logit regression models, respectively. RESULTS: In total, 175 HIV-infected patients, 121 (69.14%) men, were analyzed. Prevalence of frailty markers, osteopenia, and osteoporosis were comparable among sexes. Despite a younger age, spinal and femoral neck BMD were lower in women (P < 0.05). Linear regression model adjusting by age, duration of HIV follow-up, BMI, smoking status, osteoarthritis, osteoporosis treatment, and the age at menopause showed a negative association of spinal and femoral BMD with frailty according to SOF criteria in women (P < 0.05). In men, SOF-defined frailty was associated with osteoporosis (odds ratio 28.79; 95% confidence interval 2.15-386.4) in a model adjusting for age, duration of HIV follow-up, CD4 nadir, CD4 T-cell count, tobacco consumption, exposure to tenofovir (TDF) and protease inhibitors. No significant associations were found between BMD and CHS-defined frailty. CONCLUSION: Our study shows that frailty according to SOF criteria is associated with low spinal BMD values in female and osteoporosis in male HIV-infected patients.

Decreased serum bone specific alkaline phosphatase and increased urinary N-terminal telopeptide of type I collagen as prognostic markers for bone mineral density loss in HIV patients on cART.

OBJECTIVES: Bone mineral density (BMD) loss is a major chronic complication in HIV patients. We performed a prospective study to determine the time course of BMD changes and to find prognostic factors of BMD loss in HIV patients on combination antiretroviral therapy (cART). PATIENTS AND METHODS: Subjects were 54 male Japanese HIV patients who had been on cART ≥1 year with no therapeutic agents for osteoporosis. Patients were observed for ≥1 year (median 3.1 years) and underwent annual BMD analyses using dual energy X-ray absorptiometry. Changes in BMD at lumbar spine and femoral neck were calculated for each person-year of all the patients. Clinical factors were also collected simultaneously with BMD examinations to determine prognostic factors for BMD loss. RESULTS: In total, 173 person-years in 54 patients were observed. One third (19, 35.2%) and slightly over half (30, 55.6%) patients showed BMD decreases at lumbar spine and femoral neck, respectively. However, the median BMD changes at lumbar spine and femoral neck were 0.0% and -0.52% per year, respectively. Monovariant and mixed model analyses determined that decreased serum bone specific alkaline phosphatase (BAP, p = 0.0047) and increased urinary N-terminal telopeptide (uNTx, p = 0.0011) were prognostic factors for BMD loss at lumbar spine and femoral neck, respectively. CONCLUSIONS: BMD at both lumbar spine and femoral neck changed little on average in HIV patients on cART. Decreased serum BAP or increased uNTx may be helpful to predict progressive BMD loss in the following year and to select patients for BMD follow-up or initiation of anti-osteoporosis treatment.

Brief Report: HIV Infection Is Associated With Worse Bone Material Properties, Independently of Bone Mineral Density.

Low bone mineral density (BMD) in HIV-infected individuals has been documented in an increasing number of studies. However, it is not clear whether it is the infection itself or the treatment that causes bone impairment. Microindentation measures bone material strength (Bone Material Strength index) directly. We recruited 85 patients, 50 infected with HIV and 35 controls. Median Bone Material Strength index was 84.5 (interquartile range 83-87) in HIV-infected patients and 90 (88.5-93) in controls (P < 0.001). No significant differences in BMD between cases and controls at any of the sites examined (total hip, femoral neck, and lumbar spine). HIV infection is associated with bone damage, independently of BMD.

Brief Report: Macrophage Activation in HIV-Infected Adolescent Males Contributes to Differential Bone Loss by Sex: Adolescent Trials Network Study 021.

Accumulating evidence suggests that rates of low bone mass are greater in HIV-infected males than females. Of 11 biomarkers assessed by sex and HIV-status, HIV-infected males had increased levels of soluble CD14 which inversely correlated with bone mineral content and bone mineral density measures, suggesting macrophage activation as a possible mechanism of differential bone loss.

High Prevalence of Low Bone Mineral Density and Substantial Bone Loss over 4 Years Among HIV-Infected Persons in the Era of Modern Antiretroviral Therapy.

HIV-infected persons are living longer on combination antiretroviral therapy (cART) but experiencing more comorbidities including low bone mineral density (BMD). Using data from the Study to Understand the Natural History of HIV and AIDS in the Era of Effective Therapy (SUN Study), we determined the prevalence of low BMD (T-score below one standard deviation of the reference mean) and compared it with matched controls from the National Health and Nutrition Examination Survey (NHANES). We also assessed 4-year longitudinal BMD changes among participants virologically suppressed on cART. Of 653 participants included in this analysis (77% male, 29% black, median age 41 years, median CD4(+) cell count 464 cells/mm(3), 89% with HIV RNA <400 copies/ml), 51% and 10% had baseline osteopenia and osteoporosis, respectively. Low BMD at the femoral neck was significantly more prevalent than for the NHANES controls (47% versus 29%, p<0.001). Lower body mass index, nonwhite race, longer tenofovir exposure, older age, being unemployed or retired, and lower apolipoprotein E were independently associated with baseline osteoporosis. Among 170 participants virologically suppressed on cART and with longitudinal BMD data, 31% experienced substantial bone loss (≥5% BMD decline from baseline) over 4 years. Female sex, current smoking, and longer stavudine use were more common among participants who had substantial bone loss, although these variables failed to reach statistical significance. Low BMD was highly prevalent among HIV-infected persons. One-third of participants experienced substantial bone loss despite cART, suggesting the need for monitoring and potential clinical interventions.

Serum total estradiol, but not testosterone is associated with reduced bone mineral density (BMD) in HIV-infected men: a cross-sectional, observational study.

SUMMARY: By investigating the relationship between serum testosterone, estradiol, and bone mineral density (BMD) in a large cohort of HIV-infected men, estradiol was associated with BMD, relative estrogen deficiency being involved in bone loss in men with hypogonadism, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. INTRODUCTION: The purpose of this study is to evaluate the relationship between serum testosterone, estradiol, and BMD in a large cohort of HIV-infected men. METHODS: We investigated biochemical, hormonal parameters, and BMD in 1204 HIV-infected men (age 45.64 ± 7.33 years) participating in a cross-sectional, observational study. Among other parameters, the main outcome measures were serum total testosterone and estradiol, gonadotropins, 25-hydroxyvitamin D [25(OH)D], parathormone (PTH), calcium, phosphorous, femoral, and lumbar BMD. RESULTS: In men with HIV, the prevalence of osteoporosis and osteopenia is 15.1 and 63.2% with 25(OH)D insufficiency being very common (60.1%). After age adjustment, BMD is positively associated with estradiol, but not testosterone, at linear (p < 0.001) and stepwise (p < 0.05) multiple regression. Lumbar BMD significantly increases across the estradiol quartiles but not among testosterone quartiles. Femoral and lumbar BMD are significantly higher in men with estradiol ≥ 27 pg/mL than in those with estradiol <27 pg/mL. Apart from estradiol, only age, calcium, and BMI predict BMD at stepwise linear multiple regression, but the strength of this association is weak. CONCLUSIONS: Estradiol, but not testosterone, is associated with BMD in HIV-infected men and exerts a protective role on bone especially when it is above 27 pg/mL. Relative estrogen deficiency is a potential mechanism involved in bone loss in hypogonadal HIV-infected men, in addition to all HIV-related factors. Increased aromatization in adipose tissue does not counteract HIV-related bone loss. Finally, reduced BMD in young-to-middle-aged HIV-infected men might be considered a peculiar hallmark of HIV infection due to its relevant prevalence, representing one of the several pieces composing the complicated puzzle of premature aging related to HIV infection.

Association Between Chronic Hepatitis B Virus Infection and Risk of Osteoporosis: A Nationwide Population-Based Study.

The effect of hepatitis B virus (HBV) infection on bone mineral density in patients without advanced liver disease remains unclear. Hence, we assessed the association between HBV infection and the risk of osteoporosis. From 2000 to 2011, patients older than 20 years with HBV infection were identified from the Longitudinal Health Insurance Database 2000. Of the 180,730 sampled patients, 36,146 and 144,584 patients were categorized into HBV infection and comparison cohorts, respectively. Compared with the comparison cohort, the HBV infection patients had a higher risk of osteoporosis (adjusted hazard ratio [aHR]: 1.14, 95% confidence interval [CI]: 1.03-1.25) after adjusting for age, sex, frequency of medical visits, and comorbidities of diabetes, hypertension, hyperlipidemia, heart failure, cirrhosis, chronic kidney disease, thyroid diseases, medication of steroid, PPI, warfarin, aspirin, and estrogen replacement therapy. The patients with HBV infection exhibited a 1.13-fold (95% CI = 1.03-1.25) higher risk of developing osteoporosis, but the risk of osteoporotic fracture was comparable between patients with HBV infection and the comparison cohort (aHR = 1.20, 95% CI = 0.77-1.86). The incidence of osteoporosis increased with the increment of age (age  ≤ 49: aHR = 1; age 50-64: aHR = 5.67, 95% CI = 5.09-6.32; age  ≧ 65: aHR = 13.3, 95% CI = 11.8-14.9) and coexisting cirrhosis (aHR = 1.62, 95% CI = 1.24-2.12). However, the osteoporosis risk contributed by HBV infection decreased with age and the age-specific risk analyses showed that patients with HBV infection exhibited the highest risk of osteoporosis than patients without HBV infection for the patients aged ≤49 (aHR = 1.42, 95% CI = 1.19-1.70). Furthermore, the osteoporosis risk contributed by HBV infection has decreased with the presence of comorbidity (aHR = 1.27, 95% CI = 1.09-1.48 vs aHR = 1.04, 95% CI = 0.91-1.15). HBV increases the risk of osteoporosis, but HBV infection may be less influential than other risk factors. Moreover, HBV has no detrimental effect on osteoporotic fracture in this study.

Is there enough evidence to use bisphosphonates in HIV-infected patients? A systematic review and meta-analysis.

An increased prevalence of osteopenia and osteoporosis has been observed in HIV-infected cohorts. We investigated the effect of bisphosphonates on bone mineral density in adults with HIV infection. Outcomes of interest were bone mineral density changes measured by dual-energy X-ray absorptiometry at the lumbar spine, femoral neck, and total hip, and adverse events. Data were pooled using the fixed-effects model. We identified eight randomized controlled trials meeting our inclusion criteria, involving 328 participants. Five trials compared alendronate with placebo or no intervention; in three trials the intervention arm received zoledronate. A significant increase in bone mineral density at the lumbar spine was observed in the bisphosphonate group at 48 weeks (MD: 2.84%; 95% CI: 2.11-3.57) and 96 weeks (MD: 6.76%; 95% CI: 4.98-8.54); analogously, bisphosphonates were associated with an increase in total hip bone mineral density at 48 weeks (MD: 2.12%; 95% CI: 1.43-2.81) and 96 weeks (MD: 3.2%; 95% CI: 1.52-4.88). Bisphosphonates were generally well tolerated; no drug-related withdrawals were reported in the five randomized controlled trials assessing alendronate, whereas two patients out of 104 receiving zoledronate experienced acute-phase reactions. In conclusion, administration of oral and intravenous bisphosphonates was associated with increased bone mineral density at the lumbar spine and total hip over two years in HIV-positive patients. However, none of the included trials were long enough to detect the impact of bisphosphonates on a clinically important outcome such as fracture risk. Larger studies with extended follow-up are warranted.