Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients


  • The data included in this paper were presented in part at the 5th International Workshop on Adverse Drug Reactions and Lipodystrophy in HIV, 8–11 July 2003, Paris, France.

Elena Seminari, Infectious Diseases Department, San Raffaele Scientific Institute, Via Stamira d'Ancona 20, 20122 Milano, Italy. Tel:+39 02 26437934; fax:+39 02 26437903; e-mail: elena.seminari@hsr.it



To characterize osteoprotegerin (OPG) levels, bone remodelling and bone mineral density (BMD) in heavily pretreated HIV-infected patients on antiretroviral therapy, and to evaluate the clinical factors associated with bone density decline.


Heavily pretreated (>5 years) HIV-positive patients were enrolled in this cross-sectional, observational study, which was based on a total body bone densitometry examination and a comprehensive evaluation of bone and mineral parameters.


Sixty-eight patients (55 male and 13 female) with a median age of 41 years (range 25–60 years) were included in the study. Their antiretroviral treatment lasted for 82 months. On the basis of the World Health Organization criteria, nine patients (13.2%) were osteoporotic [T-score<−2.5 standard deviation (SD)] and 19 patients (27.9%) were osteopenic (T-score between−1 and−2.5). The principal outcomes associated with the presence of a low BMD were high OPG and lysylpyridinoline/creatinine ratio (Dpd) values. Most of the patients (39 of 48; 81.25%) showed vitamin D insufficiency [Vitamin D (25(OH)D)<18 ng/mL] with secondary hyperparathyroidism (13 of 50 patients: 26%), which proved to be correlated to osteocalcin (BGP) levels [parathyroid hormone (PTH) vs. BGP: r=0.34; P<0.01]. There was an inverse correlation between T-scores and serum osteocalcin and alkaline phosphatase (AP) levels, on one hand, and Dpd, on the other. High AP and Dpd values were associated with relative risks of 4.1 [95% confidence interval (CI)=1.01–17.6] and 7.2 (95% CI=1.67–31.03), respectively, of a pathological T-score. Multivariate analysis revealed that the factors associated with the presence of osteopenia or osteoporosis were older age and lower body mass index.


About 40% of our heavily pretreated subjects with advanced HIV infection had a low BMD, and 56% (24 of 44 patients) showed a high bone turnover rate with marked osteoclast activation. High OPG levels may protect against bone resorption.