Pathological fractures in AIDS patients with osteopenia and osteoporosis induced by antiretroviral therapy

Osteopenia and osteoporosis have recently been included among the metabolic complications of antiretroviral therapy in HIV-infected patients. The pathogenesis and particularly the role of each individual medication are currently poorly understood. The prevalence and natural history of these conditions have been evaluated only in cross-sectional studies [1], so that their clinical evolution is still unclear. Avascular osteonecrosis has also been described among AIDS patients receiving or not receiving antiretroviral therapy, suggesting that this is a real phenomenon and not a spurious association [2–6]. However, pathological bone fractures have never been reported in patients with bone alterations induced by antiretroviral therapy. We report on two AIDS patients, one with osteopenia and the other with osteoporosis, who suffered fractures after trivial trauma. Both had moderate central and peripheral lipodystrophy, without any significant alterations in lipid metabolism. A dual energy X-ray absorptiometry (DEXA) scanner was used to determine the bone mineral density of the whole body, lumbar spine (L1–L5) and proximal femur. Case 1 A 49-year-old man had a history of known HIV infection and chronic hepatitis C since 1989. He was affected with extrapulmonary tuberculosis in 1990 and with Pneumocystis carinii pneumonia in 1994. Zidovudine monotherapy was started in 1990 and highly active antiretroviral therapy (stavudine, lamivudine and indinavir) was initiated in April 1997. Indinavir was discontinued one year later because of hepatic toxicity, whereas stavudine and lamivudine have been continued to the present. In March 2000, when his CD4 cell count was 1657/mm3 and viral load branched DNA was 2347 copies/ml, the patient had influenza and after a minor sneezing attack he felt a sudden thoracic pain. Chest X-ray showed a fracture of the seventh right rib and DEXA examination documented osteopenia (Table 1) One month later the rib fracture was partly consolidated, and pain subsided. Subsequent DEXA evaluation was unmodified.Table 1: Characteristics of the patients. Case 2 A 51-year-old man had a history of AIDS dementia documented in 1996. HAART was started in February 1997, and has been continued ever since with stavudine, lamivudine and indinavir. In February 2000, when his CD4 cell count was 522/mm3 and viral load bDNA was less than 50 copies/ml, the patient suffered a trivial trauma while walking, as a result of a gait disorder associated with the AIDS dementia complex. An X-ray showed a fracture of the body of L1, and DEXA examination documented osteoporosis (Table 1). An anterior vertebral collapse developed 4 months later. These two case reports suggest that osteopenia and osteoporosis induced by antiretroviral therapy can cause pathological fractures after trivial traumas. Further investigations are needed to understand the history and evolution of accelerated bone mineral loss in HIV-infected patients receiving antiretroviral medications. One patient (case 2) was on HAART when the fracture occurred, whereas the other (case 1) was taking only two nucleoside reverse transcriptase inhibitors at the time of the event. Therefore, it seems that the administration of protease inhibitors is not a constant prerequisite for these complications. It should also be stressed that both our patients had a high CD4 cell count and a low viral load, although they presented with moderate to severe bone demineralization. The patients also had a mixed lipodystrophy syndrome, but neither had a severe lipid metabolism disorder that could primarily be responsible for the observed bone alterations. In conclusion, pathological fractures can represent novel complications of antiretroviral therapy in AIDS patients, despite sustained immunological and virological responses. Giovanni Guaraldi Paolo Ventura Massimo Albuzzaa Gabriella Orlando Andrea Bedini Grazia Amorico Roberto Esposito