Comparison of two different strategies of treatment with zoledronate in HIV-infected patients with low bone mineral density: single dose versus two doses in 2 years E Negredo, 1,2,3 * A Bonjoch, 1,2 * N Pérez-Álvarez, 1,2,4 A Ornelas, 1,2,5 J Puig, 1,2 C Herrero, 1,2 C Estany, 1,2 L del Río, 6 S di Gregorio, 6 P Echeverría 1,2 and B Clotet 1,2,3,7 1 Lluita contra la Sida Foundation, Germans Trias i Pujol University Hospital, Badalona, Spain, 2 Universitat Autònoma de Barcelona, Badalona, Spain, 3 Universitat de Vic-Universitat central de Catalunya, Spain, 4 Statistics and Operations Research Department, Universitat Politècnica de Catalunya, Barcelona, Spain, 5 Department of Econometrics, University of Barcelona, Barcelona, Spain, 6 CETIR Centre Mèdic, Barcelona, Spain and 7 Irsicaixa Foundation, Germans Trias i Pujol University Hospital, Badalona, Spain Objectives Given the need for easily managed treatment of osteoporosis in HIV-infected patients, we evaluated the efficacy and tolerability of two doses of zoledronate, by comparing three groups of patients: those with annual administration, those with biennial administration (one dose in 2 years) and a control group with no administration of zoledronate. Methods We randomized (2:1) 31 patients on antiretroviral therapy with low bone mineral density (BMD) to zoledronate (5 mg administered intravenously; 21 patients) plus diet counselling and to a control group (diet counselling; 10 patients). At week 48, patients treated with zoledronate were randomized again to receive a second dose (two-dose group; n = 12) or to continue with diet counselling only (single-dose group; n = 9). Changes in lumbar spine and hip BMD and bone turnover markers were compared. Results The median percentage change from baseline to week 96 in L1-L4 BMD was -1.74% [interquartile range (IQR) -2.56, 3.60%], 7.90% (IQR 4.20, 16.57%) and 5.22% (IQR 2.02, 7.28%) in the control, two-dose and single-dose groups, respectively (P < 0.01, control vs. two doses; P = 0.02, control vs. single dose; P = 0.18, two doses vs. single dose). Hip BMD changed by a median of 2.12% (IQR -0.12, 3.08%), 5.16% (IQR 3.06, 6.74%) and 4.47% (IQR 1, 5.58%), respectively (P = 0.04, control vs. two doses; P = 0.34, two doses vs. single dose). No differences between the two-dose and single-dose groups were detected in bone markers at week 96. Conclusions The benefits for BMD of a single dose of zoledronate in 2 years may be comparable to those obtained with two doses of the drug after 96 weeks, although this study is insufficiently powered to exclude a real difference. Future studies should explore whether biennial administration of zoledronate is a useful alternative in the treatment of osteoporosis in HIV-infected patients. Keywords: annual administration, biennial administration, bisphosphonate, bone mineral density, dual-energy X-ray absorptiometry scan, HIV, osteoporosis, zoledronate. Accepted 14 January 2015 Correspondence: Dr Eugenia Negredo, Lluita contra la SIDA Foundation, Hospital Universitari Germans Trias i Pujol, 08916 Badalona, Catalonia, Spain. Tel: ++34 93 465 88 87; fax: ++34 93 465 76 02; E-mail: enegredo@flsida.org *These authors contributed equally to the study. DOI: 10.1111/hiv.12260 © 2015 British HIV Association HIV Medicine (2015), 16, 441–448 ORIGINAL RESEARCH 441