title: Switching from tenofovir to abacavir in HIV-1-infected patients with low bone mineral density: changes in bone turnover markers and circulating sclerostin levels.
abstract: BACKGROUND
  Tenofovir is involved in accelerated bone mineral density (BMD) loss.
  
  
  METHODS
  We recently published a hip BMD improvement at week 48 [+2.1% (95% CI: -0.6, 4.7) (P = 0.043)] in HIV-infected patients with osteopenia/osteoporosis randomized to switch from tenofovir to abacavir (n = 26), although without reaching statistical significance compared with those who maintained tenofovir (n = 28). Here, we present changes at week 48 in bone markers [C-terminal telopeptide of collagen type 1 (CTX), osteocalcin and procollagen type 1 N propeptide (P1NP)] as well as in circulating levels of three proteins involved in bone regulation [osteoprotegerin, receptor activator for NF-κB ligand (RANKL) and sclerostin, a selective regulator of bone formation through the Wnt pathway] in 44 of these patients. χ(2) or Fisher and Student t-tests were performed according to the distribution of the variables.
  
  
  RESULTS
  Bone markers decreased only in the abacavir group [mean (SD) CTX changed from 0.543 (0.495) to 0.301 (0.306) ng/mL; mean (SD) osteocalcin changed from 23.72 (22.20) to 13.95 (12.40) ng/mL; and mean (SD) P1NP changed from 54.68 (54.52) to 28.65 (27.48) ng/mL (P < 0.001 in all cases)], reaching statistical significance between the groups at week 48. Osteoprotegerin did not vary, but sclerostin significantly increased in the abacavir group [from 29.53 (27.91) to 35.56 (34.59) pmol/L, P = 0.002]. No significant differences in osteoprotegerin and sclerostin were detected between the groups at week 48. RANKL values were below the limit of detection in all samples.
  
  
  CONCLUSIONS
  The switch from tenofovir to abacavir seems to induce a positive effect on bone tissue, since bone turnover markers decreased. In addition, circulating sclerostin levels increased, a change associated with improved bone properties.
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Universitat de Vic-Universitat Central de Catalunya, Vic, Barcelona, Spain.
authors.forename: Eugènia
authors.initials: E
authors.lastname: Negredo
authors.affiliation: Institut Hospital del Mar d'Investigació Mèdica (IMIM), Universitat Autònoma de Barcelona and RETICEF, Barcelona, Spain Instituto Carlos III Madrid, Spain.
authors.forename: Adolfo
authors.initials: A
authors.lastname: Diez-Pérez
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain abonjoch@flsida.org.
authors.forename: Anna
authors.initials: A
authors.lastname: Bonjoch
authors.affiliation: Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Pere
authors.initials: P
authors.lastname: Domingo
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Statistics and Operations Research Department, Universitat Politècnica de Catalunya, Barcelona, Spain.
authors.forename: Núria
authors.initials: N
authors.lastname: Pérez-Álvarez
authors.affiliation: Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Mar
authors.initials: M
authors.lastname: Gutierrez
authors.affiliation: Santa Creu i Sant Pau Hospital, Barcelona, Spain.
authors.forename: Gracia
authors.initials: G
authors.lastname: Mateo
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Jordi
authors.initials: J
authors.lastname: Puig
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Patricia
authors.initials: P
authors.lastname: Echeverría
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain.
authors.forename: Roser
authors.initials: R
authors.lastname: Escrig
authors.affiliation: Lluita contra la Sida Foundation, Servicio de Medicina Interna, Germans Trias i Pujol University Hospital, Badalona, Spain Universitat Autònoma de Barcelona, Barcelona, Spain Universitat de Vic-Universitat Central de Catalunya, Vic, Barcelona, Spain Irsicaixa Foundation, Germans Trias i Pujol University Hospital, Badalona, Spain.
authors.forename: Bonaventura
authors.initials: B
authors.lastname: Clotet
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D019380:Anti-HIV Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000032:analysis; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D016723:Bone Remodeling; D015224:Dideoxynucleosides / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005819:Genetic Markers; D015658:HIV Infections / Q000188:drug therapy* / Q000821:virology; D015497:HIV-1 / Q000302:isolation & purification; D006801:Humans; D008297:Male; D008875:Middle Aged; D000068698:Tenofovir / Q000009:adverse effects / Q000627:therapeutic use*; D000099227:Abacavir
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019380:Anti-HIV Agents; D015415:Biomarkers; D019485:Bone Morphogenetic Proteins; D015224:Dideoxynucleosides; D005819:Genetic Markers; D000068698:Tenofovir; D000099227:Abacavir; C422903:SOST protein, human
keywords: HIV-infected patients; RANKL; bone markers; osteoporosis; osteoprotegerin