Definitions
Osteoporosis is characterised by low bone mineral density (BMD), and changes in bone architecture, leading to decreased bone strength and an increased fracture risk.1 The World Health Organisation (WHO) has defined osteoporosis on the basis of the T-score.2 Osteoporosis is defined as a T-score of -2.5 or below, osteopaenia as a T-score of between -1.0 and -2.5 and normal as -1.0 or above.
Prevalence
In the general Australian population of those in the 50-69 age group, 3% of men and 13% of women have osteoporosis. Higher levels are seen in those aged over 70 years.1 Rates of osteoporosis appear to be higher in those with HIV. A meta-analysis showed an overall prevalence of 15% and a 3.68-fold increased risk of osteoporosis compared to their HIV-uninfected counterparts.3 In addition, the risk of fracture in these individuals is increased. A US study found an increased risk of fracture in HIV-infected persons, starting after age 30 in men and age 40 in women. This risk continued to increase with age.4 Other studies have confirmed increased fracture rates in HIV-infected populations with rates 30-70% higher than among uninfected matched controls.6 In a meta-analysis, the pooled estimate incidence rate ratio (IRR) was 1.58 for all fractures and 1.35 for fragility fractures.7
Aetiology
The cause of accelerated osteoporosis in HIV appears to be multifactorial including factors such as inflammation, HIV medication, established risk factors for osteoporosis, and high rates of tobacco and alcohol use.7,6 HIV itself has effects on bone, causing loss of bone mass. HIV proteins increase osteoclastic activity and promote osteoblast apoptosis, leading to decreased bone formation.6,2 HIV gp 120 has been shown to increase the rate of apoptosis in primary osteoblasts and can induce a shift of mesenchymal cell differentiation from osteoblasts to adipocytes.53 HIV gp 120 modulates the function and development of osteoclasts by upregulating RANKL, thus increasing osteoclastic activity. Systemic inflammation associated with HIV infection is associated with increased levels of cytokines such as macrophage colony stimulating factor and tumour necrosis factor. These increase osteoclast activity and subsequent bone resorption.53 The HIV proteins Tat and Nef have been shown, in vitro, to promote mesenchymal stem cell senescence and alter osteoblastic differentiation.54B cell dysfunction associated with HIV has also been postulated to contribute to bone loss.38 Associated co-morbidities that are themselves associated with low bone mass are common in HIV-infected populations.47 In particular, hypogonadism is common in HIV, and is associated with osteoporosis.5
Regardless of what initial anti-retroviral therapy (ART) is used, initial therapy is associated with a 2-6% loss of BMD.6 In the START bone sub-study, early initiation of ART was associated with greater bone loss than delayed therapy. In the first year of this study, 2% loss of BMD was observed, similar to the bone loss that occurs with the administration of glucocorticoids.36
Certain antiretroviral drugs, such as the nucleoside reverse transcriptase inhibitor tenofovir disoproxil fumarate (TDF), have been more strongly associated with decreases in BMD. Protease inhibitors have been implicated to a lesser extent.8 The bone toxicity associated with TDF is thought to be associated with proximal tubule toxicity, resulting in phosphate wasting and increased bone turnover.6
Rates of osteoporosis and fracture have been found to be higher in HIV/HCV co-infected patients. A meta-analysis found a prevalence of osteoporosis of 22% in co-infected patients with an unadjusted OR of 1.63, compared to those with HIV mono-infection.37 The risk of fractures was 2-fold higher in the co-infected group. It is not clear why HCV infection increases the risk of low BMD.38