2nd International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV 13-15 September 2000, Toronto, Canada

SERUM AND URINE MARKERS OF BONE MINERAL METABOLISM IN HIV-INFECTED PATIENTS TAKING PROTEASE INHIBITOR-CONTAINING POTENT ANTIRETROVIRAL THERAPY

Antiviral Therapy 2000; 5(Suppl. 5):18 (abstract no. O29)

P Tebas, KE Yarasheski, M Whyte, S Claxton, D DeMarco and WG Powderly
Washington University School of Medicine, St Louis, Mo., USA

BACKGROUND: We recently described an increased incidence of bone demineralization in patients taking protease inhibitor (PI)-containing potent antiretroviral therapy (ART). Whether the pathogenesis involves impaired bone formation or resorption processes is unknown.

OBJECTIVES: To evaluate several indirect markers of bone formation and resorption and compare them to lumbar spine and femoral head bone mineral density in HIV-infected individuals receiving PI-based ART.

DESIGN: Serum and urine markers of bone metabolism, spine and hip bone mineral density (DEXA) were determined in 73 HIV-positive patients receiving PI-ART. Bone markers included: serum: creatinine, PTH panel, bone-specific alkaline phosphatase, osteocalcin, 25-0H-vitamin D3, and 1,25-(OH)₂-vitamin D3; urine: creatinine, free cortisol, calcium, pyridinoline, deoxypyridinoline (urine N-teleopeptide or NTX-polypeptide).

RESULTS: Fifty percent of the patients excreted >200 mg of urinary calcium/day. On average, patients had increased serum bone alkaline phosphatase (188±152 IU/L), increased serum osteocalcin (20±26 )µg/l), urine pyridinoline (41±22 nmol/mmol creat) and urine deoxypyridinoline (10±6 nmol/mmol creat). Serum bone alkaline phosphatase and urine n-teleopeptides were inversely correlated with t- and Z-scores for the lumbar spine.

CONCLUSIONS: These data suggest an increased rate of bone turnover in patients with DEXA evidence of bone demineralization while receiving PI-based ART. Whether this reflects a direct effect on bone metabolism or an indirect effect mediated through vitamin D metabolism or renal handling of calcium requires further study.

Supported by DK49393, DK54163, DK56341, AI01612, and The Campbell Foundation

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