Increased Risk of Fragility Fractures among HIV Infected Compared to Uninfected Male Veterans

University of Cape Town, South Africa
PLoS ONE (Impact Factor: 3.23). 02/2011; 6(2):e17217. DOI: 10.1371/journal.pone.0017217
Source: PubMed


HIV infection has been associated with an increased risk of fragility fracture. We explored whether or not this increased risk persisted in HIV infected and uninfected men when controlling for traditional fragility fracture risk factors.
Cox regression models were used to assess the association of HIV infection with the risk for incident hip, vertebral, or upper arm fracture in male Veterans enrolled in the Veterans Aging Cohort Study Virtual Cohort (VACS-VC). We calculated adjusted hazard ratios comparing HIV status and controlling for demographics and other established risk factors. The sample consisted of 119,318 men, 33% of whom were HIV infected (34% aged 50 years or older at baseline, and 55% black or Hispanic). Median body mass index (BMI) was lower in HIV infected compared with uninfected men (25 vs. 28 kg/m²; p<0.0001). Unadjusted risk for fracture was higher among HIV infected compared with uninfected men [HR: 1.32 (95% CI: 1.20, 1.47)]. After adjusting for demographics, comorbid disease, smoking and alcohol abuse, HIV infection remained associated with an increased fracture risk [HR: 1.24 (95% CI: 1.11, 1.39)]. However, adjusting for BMI attenuated this association [HR: 1.10 (95% CI: 0.97, 1.25)]. The only HIV-specific factor associated with fragility fracture was current protease inhibitor use [HR: 1.41 (95% CI: 1.16, 1.70)].
HIV infection is associated with fragility fracture risk. This risk is attenuated by BMI.

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Available from: Joseph Goulet, Oct 10, 2015
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    • "Low bone mass and high bone turnover have been reported in HIV-infected individuals, both as a consequence of HIV infection itself [1-4], as well as from treatment with highly active antiretroviral therapy (HAART) [5-7]. The rapid decline in bone mineral density (BMD) and rise in bone turnover markers (BTM) that has been observed in patients treated with HAART is especially pronounced during the first six months after initiation of HAART, and is followed by eventual stabilization of these parameters after one to two years [8-10]. "
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    ABSTRACT: Low bone mass and high bone turnover have been reported in HIV-infected individuals, both as a consequence of HIV infection itself, as well as from treatment with highly active antiretroviral therapy (HAART). The purpose of this study is to evaluate the impact of HAART on bone mineral density and bone turnover in HIV-1 infected Chinese patients. Forty HIV-1 infected patients were enrolled in this study; all patients were followed through 48 weeks, and 17 patients completed 96 weeks. Bone mineral density (BMD), procollagen type 1 N-terminal propeptide (P1NP), collagen type 1 cross-linked C-telopeptide (beta-CTX), parathyroid hormone (PTH), and 25-OH vitamin D levels were measured at baseline, 48 and 96 weeks. Baseline measurements were compared with an age-, gender-, and BMI-matched healthy control population. At baseline, raw BMD in the lumbar spine of HIV-1 infected patients was significantly lower than that of healthy controls (1.138 +/- 0.112 g/cm2 vs. 1.195 +/- 0.139 g/cm2, p = 0.047). During the first 48 weeks after initiating HAART, BMD of lumbar spine, femoral neck, and total hip decreased significantly in HIV-1 infected patients, with annual percent decline ranging from 1.78-3.28%. However, from week 48 to 96, BMD remained stable. Baseline levels of beta-CTX (0.31 +/- 0.16 ng/mL vs. 0.42 +/- 0.19 ng/mL, p = 0.008) and P1NP (32.96 +/- 14.00 ng/mL vs. 55.82 +/- 26.87 ng/mL, p = 0.05)were lower in HIV-infected patients compared with controls, respectively. Both beta-CTX and P1NP levels increased after onset of HAART until week 48, and remained elevated during the next 48 weeks. 25-OH vitamin D in HIV-infected patients was lower at baseline compared to healthy controls, but this difference was not statistically significant. PTH, however, was higher in HIV patients at baseline, and showed a significant increase throughout the study. Chinese adults with HIV-1 infection have low bone turnover prior to HAART as well as lower raw BMD of the lumbar spine compared with healthy controls, with further bone loss occurring following the initiation of HAART. The long-term clinical implications of these findings remain unclear at this time.
    BMC Musculoskeletal Disorders 07/2013; 14(1):224. DOI:10.1186/1471-2474-14-224 · 1.72 Impact Factor
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    • "However, despite these benefits, several co-morbidities, including osteoporosis [1], have emerged. In HIV-infected patients, osteoporosis is present with an overall prevalence of about 15%, and fragility fractures are becoming more frequent than in the general population [2,3]. Therefore, screening and prevention strategies should be implemented to diagnose bone alterations. "
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    ABSTRACT: Increased risk of fractures and osteoporosis have been associated with the use of antiretroviral drugs. There is a paucity of prospective evaluations of bone markers after the initiation of drugs currently recommended to treat HIV infection and results on the evolution of these markers are conflicting. Lastly, the effect of tenofovir on 1,25-(OH)₂ vitamin D is uncertain. We performed a prospective study on the evolution of bone markers, parathormone and 1,25-(OH)₂ vitamin D before and after standard antiretroviral regimens. This was a sub-study of a trial conducted in antiretroviral-naïve patients randomized to tenofovir + emtricitabine in combination with either atazanavir/ritonavir (ATV/r) or efavirenz (EFV). Follow-up lasted 48 weeks. The following bone markers were analyzed: C-terminal cross-laps (CTx), osteocalcin (OC), osteoprotegerin (OPG), and receptor activator of nuclear factor κB ligand (RANKL). Mixed-factorial analysis of variance with random-coefficient general linear model was used to compare their trends over time and linear multivariable regression was performed with a backward selection method to assess predictors of their variations from baseline to week 48. Trends of parathormone and 1,25-(OH)₂ vitamin D were also evaluated. Seventy-five patients were studied: 33 received EFV and 42 ATV/r. Significant increases were found for all markers except for RANKL. There was a significant direct association between CTx and OC increases. Multivariable analysis showed that higher glomerular filtration rate (estimated through cystatin C clearance) predicted greater OPG increase, while older age, higher HIV RNA at baseline and use of ATV/r predicted greater CTx increase. A significant increase of parathormone accompanied the evolution of the study markers. 1,25-(OH)₂ vitamin D remained stable, though a seasonality variation was demonstrated. These data demonstrate CTx increase (bone resorption marker) corresponding to OC increase (bone formation marker) early upon HAART initiation. Moreover, predictors of bone marker increases have been suggested, possibly indicating that a stricter monitoring of bone health and pro-active interventions are needed in older patients, those with higher HIV RNA, prescribed ATV/r rather than EFV, and with decreased renal function at baseline. Further studies are needed to clarify the mechanisms responsible for up-regulation of bone turnover markers, as well as to understand if and what markers are best correlated or predictive of pathological fractures.
    BMC Infectious Diseases 02/2012; 12(1):38. DOI:10.1186/1471-2334-12-38 · 2.61 Impact Factor
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    ABSTRACT: Current knowledge suggests that both HIV and antiretroviral drugs are likely to contribute to bone disorders in patients with HIV infection. This article includes a review and update on the part played by the virus and the drugs in the low bone mineral density of HIV-infected patients, and a discussion about their implications in clinical practice. HIV viral proteins may affect osteoblast and osteoclast function, and many clinical studies have shown that during antiretroviral therapy, especially at the beginning, there is an accelerated bone mineral loss associated with bone resorption markers, which may be of differing intensity depending on the HIV drugs used. Vitamin D insufficiency/deficiency is highly prevalent and in some investigations it has been associated with antiretroviral therapy, more often with regimens based on efavirenz. Recent data suggest that immune reconstitution may play a major role in early antiretroviral therapy-related bone loss. Given the complex interaction between HIV and drugs in causing low bone mineral density, optimization of antiretroviral therapy and preemptive strategies aimed to prevent bone loss during therapy may be of paramount importance.
    AIDS reviews 04/2011; 13(2):109-18. · 3.79 Impact Factor
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