Decreased bone formative and enhanced resorptive markers in human immunodeficiency virus infection: Indication of normalization of the bone-remodeling process during highly active antiretroviral therapy

As cytokines and 1,25-dihydroxyvitamin D [1,25-(OH)(2)D] appear to have an important role in bone homeostasis, we examined the possibility that human immunodeficiency virus (HIV)-infected patients, characterized by enhanced l evels of proinflammatory cytokines and 1,25-(OH)(2)D deficiency, have distu rbed bone metabolism by analyzing serum markers of bone formation (osteocal cin) and bone resorption (C-telopeptide) in 73 HIV-infected patients. HIV-i nfected patients with advanced clinical and immunological disease and high viral load were characterized by increased C-telopeptide and particularly b y markedly depressed osteocalcin levels. HIV-infected patients had enhanced activation of the TNF system. Serum concentrations of p55 and p75-TNF rece ptors were negatively correlated with osteocalcin, and p75-TNF receptor was positively correlated with C-telopeptide. HIV-infected patients with advan ced disease also had decreased serum concentrations of 1,25-(OH)(2)D, but t his parameter was not correlated with osteocalcin or C-telopeptide. During 24 months with highly active antiretroviral therapy there was a marked rise in serum osteolcalcin levels together with a profound fall in viral load a nd TNF components and a marked rise in CD4(+) T cell counts. Also, there wa s a shift. from no correlation to a significant correlation between osteoca lcin and C-telopeptide levels during such therapy. The present study sugges ts disturbed bone formation and resorption during HIV infection. Our findin gs indicating synchronization of bone remodeling during highly active antir etroviral therapy may represent a previously unrecognized beneficial effect of such therapy and expand our knowledge of the interactions between cytok ines and bane in the bone-remodeling process.