Reduced bone mineral density in HIV-infected patients: prevalence and associated factors
Cazanave, Charlesa; Dupon, Michela; Lavignolle-Aurillac, Valéried; Barthe, Nicoleb; Lawson-Ayayi, Sylvied,g; Mehsen, Nadiac; Mercié, Patrickd,e; Morlat, Philliped,f; Thiébaut, Rodolphed; Dabis, Françoisd,g; for the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine
From the aFédération de Maladies Infectieuses et Tropicales, France
bService de Médecine Nucléaire, France
cService de Rhumatologie, Hôpital Pellegrin, France
dINSERM U593, ISPED, Université Victor Segalen, France
eService de Médecine Interne et Maladies Tropicales, France
fService de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, France
gCentre d'Information et de Soins de l'Immunodéficience Humaine, Bordeaux, France.
Received 12 March, 2007
Revised 31 August, 2007
Accepted 5 November, 2007
Correspondence to Dr C. Cazanave, Fédération de Maladies Infectieuses et Tropicales, Hôpital Pellegrin, Place A, Raba-Léon, 33076 Bordeaux cedex, France. E-mail: firstname.lastname@example.org
Background: There is a high prevalence of bone demineralization among HIV-infected patients but mechanisms of alteration of bone turnover are still unclear and it is thought to be multifactorial.
Methods: A cross-sectional survey of 492 HIV-infected patients within the Aquitaine cohort estimated the prevalence of osteoporosis/osteopenia and investigated associated factors. Bone mineral density of total body, lumbar spine and femoral neck was measured by dual-energy X-ray absorptiometry. Multivariable analyses of the association with HIV disease status, treatment and anthropometric parameters were stratified according to gender.
Results: Median age was 43 years (interquartile range, 38–50); 73% were male; 19.7% patients had reached AIDS, 93.1% were treated with HAART; and 28.5% had lipodystrophy. Based on World Health Organization criteria, osteopenia was diagnosed in 54.6% of men [95% confidence interval (CI), 49.4–59.7) and 51.1% of women (95% CI, 42.6–59.6) and osteoporosis in 33.7% of men (95% CI, 28.8–38.6) and 8.3% of women (95% CI, 3.6–13.9). Using a polytomous logistic regression, older age, homosexual transmission group, low body mass index and low HIV plasma viral load were associated with the diagnosis of bone abnormalities in men, whereas older age and low CD4 lymphocyte count nadir were independently associated with osteoporosis/osteopenia in women. The use of HAART was not related to osteoporosis after adjustment (P = 0.58).
Conclusions: This cohort-based survey showed a high prevalence of osteopenia and osteoporosis of multifactorial origin. Mechanisms and consequences of these bone disorders need to be investigated.
Use of HAART has drastically improved the prognosis of patients infected with HIV . Long-term HAART is associated with several metabolic and morphological complications, including lipodystrophy, insulin resistance, diabetes and dyslipidaemia . Accelerated bone mass loss, osteopenia and osteoporosis, have recently been described in HIV-infected subjects, particularly in middle-aged men, with variable prevalence estimates [3,4] mostly a consequence of limited sample sizes and possible selection of patients. A recent meta-analytic review has shown a prevalence of osteoporosis of 15% in HIV-infected individuals, 3.7 times greater than in HIV-uninfected controls . Underlying mechanisms leading to these complications are still unclear but it is thought to be a multifactorial process [3–13]. There have been few studies of factors considered to be possibly associated with bone metabolism in HIV-infected patients, including the long-term use of HAART, and results have been inconclusive [3,12]. Among the potential causes of osteoporosis, a direct effect of HIV upon osteogenic cells, the persistent activation of proinflammatory cytokines and alterations in the metabolism of vitamin D have been most often quoted, but all remain a matter of speculation [14–18].
The present study sought an accurate estimate of the prevalence of reduced bone mineral density (BMD) in a large cohort of French HIV-1 infected patients that had unrestricted enrolment, contained individuals with varying risk characteristics and of both sexes. The study also investigated systematically potential factors associated with such disorders.
A cross-sectional survey was carried out within the ANRS CO3 Aquitaine cohort. The Aquitaine cohort is an open and dynamic prospective hospital-based cohort of HIV-1-infected patients under routine clinical management in southwestern France . It was initiated in 1987 in the Bordeaux University Hospital and four other public hospitals in this region by the Groupe d'Epidémiologie Clinique du Sida en Aquitaine (GECSA). Inclusion criteria for the cohort were adults attending in- or outpatient services of the participating hospitals, HIV-1 infection confirmed by Western blot, regardless of clinical stage, either at least one follow-up after the first clinic visit or with a known date of death, and having given informed consent.
Patients were included consecutively in the present study between November 2004 and May 2005. Patients were eligible if they were still alive and followed on 1 November 2004 and without chronic kidney failure (creatinine clearance < 70 ml/min), liver failure (prothrombin rate < 70%) or prolonged immobilization (> 30 days). Written informed consent was obtained from all participants for this specific study.
Patient characteristics registered included gender; age; HIV transmission group; date of HIV diagnosis and AIDS stage according to US Centers for Disease Control and Prevention (CDC) classification; hepatitis B and C virus serological status; alcohol and tobacco consumption; medication intake; and type and duration of specific antiretroviral classes used, including nucleoside and nucleotide reverse transcriptase inhibitors (NRTI), nonnucleoside reverse transcriptase inhibitors (NNRTI) and protease inhibitors (PI). All these variables were extracted from the cohort data base and checked with medical records. A specific questionnaire was filled during the first clinic visit during the study period to document body mass index (BMI), calcium consumption and physical activity (physical activity, professional or leisure, > 30 min/day was considered sufficient).
Bone mineral density assessment
Total mean BMD and total mean T-score of total body, lumbar spine and femoral neck were measured by dual-energy X-ray absorptiometry (DEXA; Hologic, Bedford, Connecticut, USA) by a single radiologist. The study equipment was registered in a French centralized quality control programme validated by the Groupe de Recherche et d'Information sur les Ostéoporoses. This quality control included a daily phantom scan, allowing follow up of the stability of BMD over time, and the use of Shewhart rules and Cusum tests to monitor changes in scanner performances. The manufacturer checked the scanner regularly to verify precision and ensure examination reproducibility with a calibration error < 0.5%. The coefficient of variation of phantom BMD was evaluated at 0.42% for the study period. The T-score is the SD interpreted by comparison with the maximum value reached by young adults (30 years) of the same sex. Measurement was made on the total body to explore bone mass, fatty mass and lean mass, and on two specific anatomic sites: the femoral neck, which allows a quantitative evaluation of cortical bone tissue, and the lumbar spine L2–L4, which allows a quantitative evaluation of trabecular bone tissue.
The database used to assess T-scores for women was the French database (ISOS, OFELY and GENSET studies), validated by the Groupe de Recherche et d'Information sur les Ostéoporoses. For men, reference curves for the total body and the femoral neck were lacking in France, and the American databases (TK curves) were used for the femoral neck, the lumbar spine and the total body .
The World Health Organization (WHO) classification was used for diagnosis purposes . Osteopenia was defined as a T-score between −1 and −2.5 SD, and osteoporosis was defined as a T-score less than −2.5 SD.
HIV plasma RNA was measured by real-time PCR using the COBAS AmpliPrep/Cobas TaqMan HIV-1 Test (Roche Molecular Systems, Branchburg, New Jersey, USA), and CD4 cell counts were measured using flow cytometry.
Prevalence of bone abnormalities at the time of the study was estimated for each diagnostic category, dividing the number of patients fulfilling the above diagnostic criteria by the total number of patients screened. Data were stratified according to gender because the reference curves differed by gender (see above). A multivariable analysis using polytomous logistic regression evaluated factors associated with the presence of osteopenia or osteoporosis. Variables with P < 0.25 in univariable analyses were included in the full models. The final models were selected by using a stepwise descending procedure. Fits of final models were checked by Hosmer and Lemeshow χ2 test. Analyses were processed with the use of SAS software (SAS Institute, Cary, North Carolina, USA).
Characteristics of the study sample
The study comprised 492 patients, who did not differ statistically from the 3182 patients followed actively in the Aquitaine Cohort in 2004–2005 according to sociodemographics and HIV characteristics (gender, median age, HIV transmission group, years since HIV diagnosis, AIDS stage, hepatitis B and C virus serological status, alcohol and tobacco consumption, CD4 cell count, plasma HIV RNA; data not shown). There were 359 men (73.0%); 31 of the 133 women were menopausal (23.3%). Median age was 43 years [interquartile range (IQR), 39–51] for men and 41 years (IQR, 38–46) for women (P = 0.01).
The median follow-up since the date of HIV infection diagnosis was 10.9 years (IQR, 5.9–15.3) for men and 11.9 years (IQR, 6.3–15.2) for women (P = 0.38). Transmission risk among men was predominantly homosexual (men who have sex with men; 57.1%) followed by heterosexual transmission (19.5%), whereas 69.9% of women were classified as heterosexual transmission followed by 18.1% by intravenous drug use. All patients combined, 97 (19.7%) had developed AIDS. Median plasma viral load was < 1.7 log copies/ml (IQR, < 1.7–3.0) (i.e., < 50 copies/ml); plasma viral load was < 500 copies/ml in 354 patients (72.0%). The median CD4 cell count was 459 cells/μl (IQR, 315–643); 45 patients had < 200 cells/μl. The median nadir CD4 cell count was 200 cells/μl (IQR, 100–300). The median plasma calcium concentration was 2.34 mmol/l (IQR, 2.27–2.41) and the median plasma phosphate was 1.06 mmol/l (IQR, 0.94–1.18). No patient had major kidney failure (creatinine clearance was > 70 ml/min for all patients). Chronic active hepatitis C (HCV RNA positive) occurred in 103 patients (21.6%); 36 (7.6%) had chronic hepatitis B (HBV surface antigen positive); and 10 (2.1%) had both. Daily alcohol consumption > 10 g was reported by 117 patients (23.8%), 13 (2.7%) of whom had an excessive consumption (> 30 g per day). Ever smoking tobacco (> 1 cigarette per day) was reported by 343 patients (69.7%) [265 men (73.9%) and 78 women (58.6%); P = 0.005)] of whom 181 (37.0%) smoked more than 15 pack-years. Of 423 patients with data available on calcium consumption, only 39 patients (7.9%) consumed more than 1 g calcium per day in their diet. Eighty-two patients (16.7%) did not report any physical activity (< 30 min/day); these patients were more likely to be unemployed and at the most advanced stages of HIV disease. At the time of the survey, 93.1% of the patients were taking antiretroviral drugs; 80.0% were treated with NRTI-based HAART: 37.0% with tenofovir, 28.7% with NNRTI and 52.0% with PI. The median cumulated duration on treatment was 71.8 months (IQR, 30.0–103.0) for NRTI, 7.4 months (IQR, 0.0–30.1) for NNRTI and 20.0 months (IQR, 0.0–52.0) for PI. Fifty patients (10.2%) presented at least one pathological fracture (i.e., for a low-energy traumatism), acquired before or after the diagnosis of HIV infection.
Data on BMI were available for 482 patients, 353 men and 129 women. BMI was < 19 kg/m2 in 57 of these patients (11.8%) and < 20.6 kg/m2 in 118 patients (24.5%) [comprising 68 of the 353 men (19.3%) and 50 of the 129 women (38.8%); P < 0.0001]. Clinically defined lipodystrophy was diagnosed in 140 patients (28.5%), 54 (11.0%) had lipoatrophy, 32 (6.5%) had lipoaccumulation and 54 (11.0%) had a mixed syndrome.
Statistically significant differences between men and women occurred for age (men were older), BMI (women had lower BMI) and tobacco consumption (men smoked more than women). There were no statistical differences on the other parameters described above.
Main patient characteristics are summarized in Tables 1 and 2 for men and women, respectively.
Based on WHO criteria, osteopenia was diagnosed in 264 patients (53.7%), 54.6% among men [95% confidence interval (CI), 49.4–59.7) and 51.1% among women (95% CI, 42.6–59.6). Osteopenia was diagnosed in 50.0% (95% CI, 40.0–60.0) and 54.8% (95% CI, 37.5–72.5) of premenopausal and menopausal women, respectively. Osteoporosis was diagnosed in 132 patients (26.8%), 33.7% among men (95% CI, 28.8–38.6) and 8.3% among women (95% CI, 3.6–13.0). Osteoporosis was diagnosed in 3.9% (95% CI, 0.2–7.8) and 22.6% (95% CI, 7.9–37.3) of premenopausal and menopausal women, respectively. Table 3 shows the distribution of median BMD according to gender, site and patients' diagnostic category. Osteoporosis predominated at the femoral neck for men (median BMD, 0.66 g/cm2) and for women (median BMD, 0.59 g/cm2).
Correlates of low bone density
Among men, the following factors significantly associated with the diagnosis of bone mass loss in the univariable model were included in the multivariable analysis: age, follow-up time since HIV diagnosis, transmission group, AIDS clinical stage, HIV plasma viral load < 500 copies/ml, log-based plasma viral load, tobacco consumption, physical activity, cumulative exposure to antiretroviral drug class, BMI < 20.6 kg/m2 and lipodystrophy. Independent factors associated with the diagnosis of osteoporosis were older age, homosexual HIV transmission, low BMI and HIV plasma viral load < 500 copies/ml (Table 4). Only older age and lower BMI were marginally associated with osteopenia (Table 4). In women, all bone disorders were pooled without distinction between osteopenia and osteoporosis because of the lower number of observations in each subgroup. Factors analysed in the multivariable model were menopausal status, age, follow-up time since HIV diagnosis, transmission group, AIDS clinical stage, HIV plasma viral load < 500 copies/ml, log-based plasma viral load zenith, CD4 lymphocyte count nadir, alcohol consumption, calcium intake > 1 g/day, physical activity, cumulative exposure to antiretroviral drug class and lipodystrophy. Older age [odds ratio (OR), 1.69; 95% CI, 1.10–2.60; P = 0.02] and low CD4 cell count nadir (OR, 1.43; 95% CI, 1.10–1.85; P = 0.008) were identified as factors associated with reduced BMD. To explore further whether the association between low HIV plasma RNA and osteoporosis in men was related to antiretroviral exposure, the effect of cumulative exposure to HAART was analysed without adjustment for HIV plasma RNA. Three different multivariable models were developed but in none was the treatment variable effect significant: cumulative exposure to any antiretroviral drug (OR, 1.01; 95% CI, 1.00–1.02; P = 0.07), cumulative exposure to HAART (OR, 1.02; 95% CI, 0.95–1.10; P = 0.58), and naive versus drug experienced status (OR, 0.28; 95% CI, 0.06–1.31; P = 0.11). Furthermore, this analysis was carried out for each drug class, again without being significant: cumulated NRTI (OR, 1.01; 95% CI, 1.00–1.02; P = 0.06), cumulated NNRTI (OR, 1.01; 95% CI, 1.00–1.03, P = 0.43) and cumulated PI (OR, 1.01; 95% CI, 1.00–1.03; P = 0.09).
This cross-sectional survey within the Aquitaine cohort of HIV-infected patients was conducted to estimate the prevalence of BMD disorders and to investigate associated factors. Among the 492 patients, representative of the Aquitaine cohort, who were recruited, the percentage of bone abnormalities was 80.5%, with 53.7% osteopenia and 26.8% osteoporosis. Osteoporosis prevalence was high in spite of the young age of the population and reflected well the early demineralization problem faced by HIV-infected patients. This frequency is higher than that reported in other studies, which had prevalence rates ranging from 0% to 22% [11,13,18,22–31], with narrow boundaries.
Another interesting finding of this osteodensitometry-based survey is the site of bone demineralization. For men, there is preferentially cortical anatomic osteoporosis, whereas for women, there are trabecular abnormalities. Apart from HIV disease, male osteoporosis in normal populations has a cortical predominance, especially in secondary osteoporosis, whereas for women, the postmenopausal osteoporosis is classically trabecular, first involving the spine. The few studies that have described BMD abnormalities according to the anatomic site have been inconclusive [4,17,24].
The main strength of our study is the relatively large number of patients included and the number of pathological fractures (10.2%). No publication provides such an estimate and we could only identified some individual case reports . The potential impact of BMD reduction on fracture risk remains unclear for HIV-infected patients. This may be because the majority are young, have few visual or balance problems and are not prone to falls. As the HIV-infected population gets older, clinicians may see an increase in the fracture rate.
The main limitation in the interpretation of our report is the absence of French references for the T-score for men. This could explain the surprising high male prevalence of BMD disorders detected in our group. There is a French reference of BMD values for women, but an American database had to be used for males in the three anatomic sites. Consequently, we may have overestimated the frequency of male osteoporotic events, because Americans have a diet that is richer in vitamin D than the French and so have a higher bone mineralization peak. By using an American reference, we are perhaps overinterpreting the BMD results from the whole body and the femoral neck. For males, we have compared the T-scores obtained for the spine here based on data in American databases with the T-scores that we would have obtained using French databases, in order to see if the use of a non-French reference database was important, and found no statistical significance between the two sets of T-scores (data not shown). The gender stratification, imposed by the difference in reference frame between men and women, led to a loss in statistical power of the study as it generated two weaker samples statistically. This element partly explains the low number of associated factors highlighted in multivariate analysis.
Among the factors found to be associated with BMD, some were expected, such as older age or lower BMI, but others are described for the first time, such as homosexual HIV transmission group, low HIV plasma RNA and low CD4 cell count nadir. The link with homosexual transmission group could indicate that this is a proxy for the abuse of substances that might be toxic for bone metabolism or coinfection, such as human herpes virus 8 and Kaposi disease. Our finding of higher risk of BMD disorder with low plasma viral load does not agree with some previously published reports [15,18], which hypothesized a potential role of the virus itself. In our study, low plasma viral load was the consequence of successful reduction of viral replication with antiretroviral drug exposure. This indicates, indirectly, a bone harmful effect of treatment itself; however, the investigations of the effect of the antiretroviral treatment, unadjusted for the plasma viral load, did not show a significant difference. Therefore, an effect on bone of antiretroviral drugs does not explain why a plasma viral load < 500 copies/ml arose as a risk factor for the osteoporotic men.
The potential effect of CD4 cell count nadir has been studied previously among HIV-positive women and was not recognized as a factor associated with weakening osteopathies . Such a linkage in our study is an original finding. CD4 cell count nadir is directly linked to the severity and length of immunosuppression. This suppression will lead to immunological disorders and an increase in proinflammatory cytokines, inducing modifications of bone tissue metabolism at the beginning of an early demineralization. Another possible explanation of the effect of the CD4 cell nadir observed is that patients with a low CD4 cell nadir are those who have been treated for a longer period with antiretroviral drugs. This would also indirectly support a negative role for antiretroviral drugs on bone metabolism.
The cumulated exposure to PI drugs was significantly associated with bone abnormalities in univariate analysis, as seen by Nolan et al.  and Moore et al. , but this factor was not significant in the multivariate model. Finally, neither lipodystrophy nor reduced physical activity was associated with early demineralization.
In consideration of the high frequency of diagnosed osteoporosis, it would be useful to propose osteodensitometry for HIV-infected patients in a targeted way: that is for patients with both the traditional risk factors of osteoporosis and the specific risk factors of HIV infection highlighted in this study. Moreover, our analysis indicates a cortical prevalence of bone demineralization, especially for men; consequently, particularly vigilant is suggested for this risk, in particular for femoral neck fractures.
Ongoing studies will provide better knowledge of the physiopathological mechanisms at the initiation of early demineralization among HIV-infected patients, thus allowing better diagnostic, preventive and therapeutic evaluation to support care for this chronic infection in the coming years.
Composition of the Groupe d'Epidémiologie Clinique du SIDA en Aquitaine. C. Cazanave, M. Dupon, V. Lavignolle-Aurillac, N. Barthe, S. Lawson-Ayayi, H. Dutronc, N. Mehsen, T. Schaeverbeke, P. Mercie. P. Morlat, J.L. Pellegrin, R. Thiébaut and F. Dabis (TISSOS Study Group); F. Dabis (Coordinator); G. Chêne, F. Dabis, S. Lawson-Ayayi, C. Lewden, R. Thiébaut (epidemiology and methodology); M. Bonarek, F. Bonnal, F. Bonnet, N. Bernard, O. Caubet, L. Caunègre, J. Ceccaldi, C. De La Taille, S. de Witte, M. Dupon, H. Dutronc, S. Farbos, T. Galpérine, K. Lacombe, D. Lacoste, S. Lafarie, P. Loste, D. Malvy, P. Mercié, P. Morlat, D. Neau, A. Ochoa, J.L. Pellegrin, J.M. Ragnaud, S. Tchamgoué, J.F. Viallard (infectious diseases and internal medicine); P. Blanco, J.F. Moreau (immunology); H. Fleury, M.E. Lafon, B. Masquelier, I. Pellegrin (virology); D. Breilh (pharmacology); G. Miremont-Salamé (pharmacovigilance); E. Balestre, M.J. Blaizeau, M. Decoin, S. Delveaux, S. Geffard, C. Hannapier, S. Labarrère, V. Lavignolle-Aurillac, B. Uwamaliya-Nziyumvira (data collection and data management); G. Palmer, D. Touchard (data processing).
Note: Preliminary results have been presented in part at the Third International AIDS Society Conference on HIV Pathogenesis and Treatment. Rio de Janeiro, July 2005 [abstract TuPe2.2B19] and at the Thirteenth Conference on Retroviruses and Opportunistic Infections. Denver, February 2006 [abstract 229].
This study was supported by a grant from Ensemble contre le SIDA/SIDACTION (15th call for proposals). The Aquitaine cohort is supported by a multiyear grant of the French Agency for Research on AIDS and viral Hepatitis (ANRS).
1. Palella FJ Jr, Delaney KM, Moorman AC, Loveless MO, Fuhrer J, Satten GA, et al
. Declining morbidity and mortality among patients with advanced human immunodeficiency virus infection. HIV Outpatient Study Investigators. N Engl J Med 1998; 338:853–860.
2. Carr A, Samaras K, Burton S, Law M, Freund J, Chrisolm DJ, et al
. A syndrome of peripheral lipodystrophy, hyperlipidemia and insuline resistance in patients receiving HIV protease inhibitors. AIDS 1998; 12:F51–F58.
3. Tebas P, Poxderly WG, Claxton S, Marin D, Tantisiriwat W, Teitebaulm SL, et al
. Accelerated bone mineral loss in HIV-infected patients receiving potent antiretroviral therapy. AIDS 2000; 14:F63–F67.
4. Knobel H, Guelar A, Valecillo G, Nogues X, Diez A. Osteopenia in HIV-infected patients: is it the disease or is it the treatment? AIDS 2001; 15:807–808.
5. Brown TT, Qaqish RB. Antiretroviral therapy and the prevalence of osteopenia and osteoporosis: a meta-analytic review. AIDS 2006; 20:2165–2174.
6. Mondy K, Tebas P. Emerging bone problems in patients infected with human immunodeficiency virus. Clin Infect Dis 2003; 36(Suppl 2):S101–S105.
7. Mondy K, Yarasheski K, Powderly WG, Whyte M, Claxton S, DeMarco D, et al
. Longitudinal evolution of bone mineral density and bone markers in human immunodeficiency virus-infected individuals. Clin Infect Dis 2003; 36:482–490.
8. McDermott AY, Terrin N, Wanke C, Skinner S, Tchetgen E, Shevitz AH. CD4+ cell count, viral load, and highly active antiretroviral therapy use are independent predictors of body composition alterations in HIV-infected adults: a longitudinal study. Clin Infect Dis 2005; 41:1662–1670.
9. Bongiovanni M, Fausto A, Cicconi P, Aliprandi A, Cornalba G, Bini T, et al
. Nonnucleoside-reverse-transcriptase-inhibitor-based HAART and osteoporosis in HIV-infected subjects. J Antimicrob Chemother 2006; 58:485–486.
10. Amorosa V, Tebas P. Bone disease end HIV infection. Clin Infect Dis 2006; 42:108–114.
11. Arnsten JH, Freeman R, Howard AA, Floris-Moore M, Santoro N, Schoenbaum EE. HIV infection and bone mineral density in middle-aged women. Clin Infect Dis 2006; 42:1014–1020.
12. Bolland MJ, Grey AB, Horne AM, Briggs SE, Thomas MG, Ellis-Pegler RB, et al
. Bone mineral density is not reduced in HIV-infected Caucasian men treated with highly active antiretroviral therapy. Clin Endocrinol 2006; 65:191–197.
13. Overton ET, Mondy K, Bush T, Conley L, Kojic E, Henry K, et al. Factors associated with low bone mineral density in a large cohort of HIV-infected US adults: baseline results from the SUN Study. 14th Conference on Retroviruses and Opportunistic Infections
. Los Angeles, February 2007 [abstract 836].
14. Kühne CA, Heufelder AM, Hofbauer LC. Bone and mineral metabolism in human immunodeficiency virus infection. J Bone Miner Res 2001; 16:2–9.
15. Fessel WJ, Hurley LB. Is HIV sequestered in bone? Possible implications of virological and immunological findings in some HIV-infected patients with bone disease. AIDS 2003; 17:255–257.
16. Cozzolino M, Vidal M, Arcidiacono MV, Tebas P, Yarashesky KE, Dusso AS. HIV-protease inhibitors impair vitamin D bioactivation to 1,25-dihydroxyvitamin D. AIDS 2003; 17:513–520.
17. Amiel C, Ostertag A, Slama L, Baudoin C, N'Guyen T, Lajeunie E, et al
. BMD is reduced in HIV-infected men irrespective of treatment. J Bone Miner Res 2004; 19:402–409.
18. Fausto A, Bongiovanni M, Cicconi P, Menicagli L, Ligabo EV, Melzi S, et al
. Potential predictive factors of osteoporosis in HIV-positive subjects. Bone 2006; 38:893–897.
19. Thiebaut R, Morlat P, Jacqmin-Gadda H, Neau D, Mercie P, Dabis F, et al
. Clinical progression of HIV-1 infection according to the viral response during the first year of antiretroviral treatment. Groupe d'Epidémiologie du SIDA en Aquitaine (GECSA). AIDS 2000; 14:971–978.
20. Kelly T. Bone mineral density reference databases for American men and women. J Bone Miner Res 1990; 5(Suppl 2):S249.
21. Kanis JA. Assessment of fracture risk and its application to screening for postmenopausal osteoporosis: synopsis of a WHO report. WHO Study Group. Osteoporos Int 1994; 4:368–381.
22. Nolan D, Upton R, McKinnon E, John M, James I, Adler B, et al
. Stable or increasing bone mineral density in HIV-infected patients treated with nelfinavir or indinavir. AIDS 2001; 15:1275–1280.
23. Moore AL, Vashisht A, Sabin CA, Mocroft A, Madge S, Phillips AN, et al
. Reduced bone mineral density in HIV-positive individuals. AIDS 2001; 15:1731–1733.
24. Carr A, Miller J, Eisman JA, Cooper DA. Osteopenia in HIV-infected men: association with asymptomatic lactic acidemia and lower weight preantiretroviral therapy. AIDS 2001; 15:703–709.
25. Bruera D, Luna N, David DO, Bergoglio LM, Zamudio J. Decreased bone mineral density in HIV-infected patients is independent of antiretroviral therapy. AIDS 2003; 17:1917–1923.
26. Dolan SE, Huang JS, Killilea KM, Sullivan MP, Aliabadi N, Grinspoon S. Reduced bone density in HIV-infected women. AIDS 2004; 18:475–483.
27. Brown TT, Ruppe MD, Kassner R, Kumar P, Kehoe T, Dobs AS, et al
. Reduced bone mineral density in human immunodeficiency virus-infected patients and its association with increased central adiposity and postload hyperglycemia. J Clin Endocrinol Metab 2004; 89:1200–1206.
28. Seminari E, Castagna A, Soldarini A, Galli L, Fusetti G, Dorigatti F, et al
. Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients. HIV Med 2005; 6:145–150.
29. Konishi M, Takahashi K, Yoshimoto E, Uno K, Kasahara K, Mikasa K. Association between osteopenia/osteoporosis and the serum RANKL in HIV-infected patients. AIDS 2005; 19:1240–1241.
30. Bongiovanni M, Fausto A, Cicconi P, Menicagli L, Melzi S, Ligabo VE, et al
. Osteoporosis in HIV-infected subjects: a combined effect of highly active antiretroviral therapy and HIV itself? J Acquir Immune Defic Syndr 2005; 40:503–504.
31. Garcia Aparicio AM, Munoz Fernandez S, Gonzalez J, Arribas JR, Pena JM, Vazquez JJ, et al
. Abnormalities in the bone mineral metabolism in HIV-infected patients. Clin Rheumatol 2006; 25:537–539.
32. Guaraldi G, Ventura P, Albuzza M, Orlando G, Bedini A, Amorico G, et al
. Pathological fractures in AIDS patients with osteopenia and osteoporosis induced by antiretroviral therapy. AIDS 2001; 15:137–138.
33. Yin M, Dobkin J, Brudney K, Becker C, Zadel JL, Manandhar M, et al
. Bone mass and mineral metabolism in HIV+ postmenopausal women. Osteoporos Int 2005; 16:1345–1352.
This article has been cited 30 time(s).
Journal of Korean Medical SciencePrevalence and Risk Factors of Low Bone Mineral Density in Korean HIV-Infected Patients: Impact of Abacavir and ZidovudineJournal of Korean Medical Science
Presse MedicaleVitamin D supplementation: A iatrogenic hypercalcemia concerning an HIV-infected patient with disseminated tuberculosisPresse Medicale
Osteoporosis InternationalLong-term HIV infection and antiretroviral therapy are associated with bone microstructure alterations in premenopausal womenOsteoporosis International
PharmacotherapyBone Health and Human Immunodeficiency Virus InfectionPharmacotherapy
Clinical NutritionVitamin D status in young HIV infected women of various ethnic origins.: Incidence of vitamin D deficiency and possible impact on bone densityClinical Nutrition
Bmc Infectious DiseasesEarly loss of bone mineral density is correlated with a gain of fat mass in patients starting a protease inhibitor containing regimen: the prospective Lipotrip studyBmc Infectious Diseases
Plos OneAbnormal Liver Stiffness Assessed Using Transient Elastography (Fibroscan (R)) in HIV-Infected Patients without HBV/HCV Coinfection Receiving Combined Antiretroviral TreatmentPlos One
Pediatric NephrologyUpdate on tenofovir toxicity in the kidneyPediatric Nephrology
Bone alterations during HIV infection
New Microbiologica, 31(2):
Journal of Infectious DiseasesLow Bone Mineral Density, Renal Dysfunction, and Fracture Risk in HIV Infection: A Cross-Sectional StudyJournal of Infectious Diseases
AIDS Patient Care and StdsHighly Prevalent Vitamin D Deficiency and Insufficiency in an Urban Cohort of HIV-Infected Men Under CareAIDS Patient Care and Stds
TherapieAdverse Reactions of Atazanavir, Fosamprenavir and Tipranavir in "Real Life"Therapie
BoneAntiretroviral therapy and bone mineral measurements in HIV-infected youthsBone
British Medical BulletinBone health in HIV infectionBritish Medical Bulletin
Metabolic Syndrome and Related DisordersHuman Immunodeficiency Virus and Highly Active Antiretroviral Therapy-Associated Metabolic Disorders and Risk Factors for Cardiovascular DiseaseMetabolic Syndrome and Related Disorders
Thrombosis and HaemostasisBone mineral density in haemophilia patientsThrombosis and Haemostasis
Journal of Clinical Endocrinology & MetabolismFracture prevalence among human immunodeficiency virus (HIV)-infected versus non-HIV-infected patients in a large US healthcare systemJournal of Clinical Endocrinology & Metabolism
InfectionWomen Facing HIV. Key Question on Women with HIV Infection: Italian Consensus WorkshopInfection
Clinical RheumatologyOsteonecrosis of the femoral head in patients with type 1 human immunodeficiency virus infection: clinical analysis and reviewClinical Rheumatology
Arquivos Brasileiros De Endocrinologia E Metabologia
Bone mineral density in HIV-infected women taking antiretroviral therapy: a systematic review
Arquivos Brasileiros De Endocrinologia E Metabologia, 54(2):
Journal of Clinical DensitometryLongitudinal Study of Body Composition of 101 HIV Men With Lipodystrophy: Dual-Energy X-Ray Criteria for Lipodystrophy EvolutionJournal of Clinical Densitometry
European Review for Medical and Pharmacological Sciences
Vitamin D deficiency in HIV infection: an underestimated and undertreated epidemic
European Review for Medical and Pharmacological Sciences, 17(9):
JAIDS Journal of Acquired Immune Deficiency SyndromesLoss of Bone Mineral Density After Antiretroviral Therapy Initiation, Independent of Antiretroviral RegimenJAIDS Journal of Acquired Immune Deficiency Syndromes
Current Opinion in Infectious DiseasesRecent developments in HIV and the kidneyCurrent Opinion in Infectious Diseases
AIDSMetabolic bone disease in HIV infectionAIDS
bone mineral density; HIV; osteopenia; osteoporosis
© 2008 Lippincott Williams & Wilkins, Inc.
Highlight selected keywords in the article text.