Osteonecrosis in HIV positive patients is associated with increased levels of CRP and D-dimer

Simon Collins, HIV i-Base

A retrospective case control study of 43 HIV positive patients with MRI-confirmed osteonecrosis of the femoral head (n=26 symptomatic, n=17 asymptomatic) had significantly elevated levels of the biomarkers C-reactive protein (CRP) and D-dimer compared to a control group of 50 HIV positive patients with negative MRI results.

This was a US study by Caryn Morse and colleagues from the National Institute of Health Clinical Centre and results were published as a concise communication in the 20 February 2013 edition of AIDS. [1]

All participants were already enrolled in other NIH studies, including a natural history study of osteonecrosis,

CRP is an inflammation marker commonly associated with cardiovascular disease and D-dimer is a coagulation degradation product and both have been associated with increased risk of mortality and serious complications in HIV positive cohorts, independently of CD4 and viral load.

Samples were used from osteonecroisis diagnosis (+/- 2 months) and from at least 6 months prior to and post diagnosis for the active group, with the control using samples from the time of negative MRI and 6 months later. Values below the detection limit of the assay were assigned a value of 0.21 mg/mL for D-dimer and of 0.16 mg/L for CRP.

Although baseline characteristics (at time of MRI) was similar for both groups, significant differences included longer median (range) duration of HIV infection (11.7 (1.6–19.5) vs 8.8 (0.4–16.4) years, p=0.003) and lower median (Range) CD4count (465 (12–1117) vs 686 (71–1705) cells/mm3, p=0.008) for the active vs control group respectively. Most participants were male (~90%) and on ART (~90%) with only 50% in each group having viral load <50 copies/mL. A high percentage of both groups had prior use of IL-2 (40% vs 60%, respectively).

Median levels of both D-dimer (0.32 vs 0.22 mg/mL; p=0.016) and CRP (2.52 vs 1.23 mg/L; p=0.003) were significantly higher in the active vs control group and remained significant after adjustment for viral load and anticardiolipin antibody status.

However, in linear regression analysis, the patterns of elevations were different for each biomarker after adjusting for viral load. D-dimer increased from the prediagnosis to diagnosis time point only in the osteonecrosis group (from 0.2 ug/L to 0.4 ug/L vs 0.2 ug/mL in controls). CRP levels remained stable (slope = zero) in each group over time. No difference was seen in D-dimer or CRP levels between the asymptomatic and symptomatic patients in the osteonecrosis group.

In the discussion, the authors noted that elevations in D-dimer are associated with the development of osteonecrosis, but that CRP elevation predate the development of osteonecrosis, suggesting that at-risk patients have persistently higher levels of chronic inflammation; and that both markers could potentially help identify patients at higher risk of osteonecrosis.


Morse CG et al. Elevations in D-dimer and C-reactive protein are associated with the development of osteonecrosis of the hip in HIV-infected adults. AIDS 27(4):591–595. 20 February 2013. doi: 10.1097/QAD.0b013e32835c206a.

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