ReviewHIV and bone disease
Introduction
Advances in anti-retroviral therapy have resulted in a dramatic decline in mortality for individuals infected with human immunodeficiency virus (HIV)1 and have ensured HIV-positive individuals are living longer [1]. A fall in the incidence of new HIV infections has been offset by the dramatic decline in the mortality associated with acquired immune deficiency syndrome (AIDS), so that the prevalence of HIV infection continues to increase globally, with an estimated 42 million people infected worldwide [2]. A Danish population-based cohort study has estimated the median survival for a young person diagnosed with HIV infection between 2000 and 2005 to be more than 35 years [3]. A multinational collaboration of HIV cohort studies in Europe and North America has estimated the average number of years remaining to be lived in a 20 year old infected with HIV to be at least two-thirds that of the general population and this figure will likely continue to rise with advances in therapy [4].
The decrease in mortality in HIV-infected persons initially was the result of improved prophylaxis and treatment of opportunistic infections but was considerably accelerated with the introduction of highly-active antiretroviral therapy (HAART) – the use of combinations of three or more anti-retroviral (ARV) agents – in the mid-1990s [1].
In the post-HAART era, opportunistic infections have been replaced by long-term complications of HIV infection itself and of HAART, resulting in cardiovascular, renal or hepatic toxicity [5], or in a range of metabolic complications [6]. Over the past decade, reduced bone mineral density (BMD) has emerged as one of these complications (as reviewed by Amorosa et al. [7]). There is an increasing concern that this could lead to a fragility fracture epidemic in an ageing cohort of individuals living with HIV infection, with related consequences for HIV-associated morbidity and mortality. The surveillance and treatment of these complications will increasingly be a focus of HIV care as the HIV-positive population ages.
In this review we discuss evidence linking metabolic bone disease to HIV infection and its treatment, with an emphasis on the extent of the problem, the risk factors, the pathogenic mechanisms, clinical assessment and management.
Section snippets
Prevalence
Heterogeneous cross-sectional cohort studies, performed over the past ten years, have described a significantly higher prevalence of bone disease in HIV-positive individuals when compared to age-, race- and sex-matched HIV-negative individuals (see Table 1) [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], [19], [20], [21], [22], [23], [24], [25], [26], [27]. The prevalence of reduced BMD in HIV-infected individuals – defined as a T-score <−1 when measured by Dual X-ray
HIV-independent risk factors
Validated risk factors for reduced BMD and fragility fracture are well established for the general population [35]. In addition to previous fragility fracture and low BMD at the femoral neck, these include: increasing age; low BMI; parental history of hip fracture; glucocorticoid exposure; rheumatoid arthritis; current smoking; alcohol consumption ⩾3 units per day; hypogonadism, including post-menopausal status in women; prolonged immobility; malabsorption and liver cirrhosis [35]. In addition,
Fracture risk assessment in HIV-positive individuals
As stated previously, the HIV-positive population has a high prevalence of risk factors for metabolic bone disease and increased fracture risk. To date, however, there have been no published studies on the use of osteoporosis risk or fracture risk assessment tools in HIV-positive individuals.
Recently, the WHO Collaborating Centre for Metabolic Bone Diseases in Sheffield has undertaken a comprehensive review and a number of meta-analyses of published risk factors within the general population.
Conclusions
The prevalence of reduced BMD and possibly also fracture incidence are increased in HIV-positive individuals compared with HIV-negative controls. There are many potential explanations for this – an increased prevalence of established osteoporosis risk factors in the HIV-positive population, a likely direct effect of HIV infection itself and a possible contributory role of ARV therapy – with potential mechanisms identified for both HIV infection and ARV therapies. At present there is no adequate
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