Fracture healing in HIV-positive populations

Abstract

Highly active anti-retroviral therapy has transformed HIV into a chronic disease with a long-term asymptomatic phase. As a result, emphasis is shifting to other effects of the virus, aside from immunosuppression and mortality. We have reviewed the current evidence for an association between HIV infection and poor fracture healing. The increased prevalence of osteoporosis and fragility fractures in HIV patients is well recognised. The suggestion that this may be purely as a result of highly active anti-retroviral therapy has been largely rejected. Apart from directly impeding cellular function in bone remodelling, HIV infection is known to cause derangement in the levels of those cytokines involved in fracture healing (particularly tumour necrosis factor-alpha) and appears to impair the blood supply of bone. Many other factors complicate this issue, including a reduced body mass index, suboptimal nutrition, the effects of anti-retroviral drugs and the avoidance of operative intervention because of high rates of wound infection. However, there are sound molecular and biochemical hypotheses for a direct relationship between HIV infection and impaired fracture healing, and the rewards for further knowledge in this area are extensive in terms of optimised fracture management, reduced patient morbidity and educated resource allocation. Further investigation in this area is overdue.

Fracture management in HIV positive individuals: a systematic review

“…Previous basic science research has suggested that HIV infection may associated with delayed and nonunion of fractures [23]. Researchers have hypothesized that altered cytokine environment arising from HIV infection may modify the inflammatory response which subsequently triggers the process of bone healing.…”

“…There is increasing evidence to suggest that HIV seropositivity alone affects bone turnover, and in particular, may inhibit bone formation, which could contribute to issues with union. Furthermore, reports of osteonecrosis in HIV-positive patients without other risk factors poses the question as to whether HIV may compromise the reliability of the blood supply required for fracture healing [23].…”

“…There has been an association shown between issues of non-union and the use of ART [23]. However, the multiple sources of heterogeneity such as duration of treatment, different drug regimens and differing degrees of immunosuppression make it difficult to truly assess the effect.…”

“…These have suggested that HIV and/or ART are associated with delayed fracture healing and may result in non-union [23,24]. The molecular and cellular mechanisms driving this remain unclear and the true effect of HIV and ART on bone healing is very poorly understood.…”

The roles of immune cells in bone healing; what we know, do not know and future perspectives

“…Conversely, as shown in immune-compromised animal model, bone marrow (BM) transplantation greatly enhanced the process of bone healing [17]. In addition to experimental findings, immunecompromised HIV patients can have delayed or non-union of fractures [18]. Thus, both animal and human studies confirmed the critical importance of innate and adaptive immune cells.…”