title: Osteoprotegerin and bone turnover markers in heavily pretreated HIV-infected patients.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Infectious Diseases Department, San Raffaele Scientific Institute, Milan, Italy. elena.seminari@hsr.it
authors.forename: E
authors.initials: E
authors.lastname: Seminari
authors.forename: A
authors.initials: A
authors.lastname: Castagna
authors.forename: A
authors.initials: A
authors.lastname: Soldarini
authors.forename: L
authors.initials: L
authors.lastname: Galli
authors.forename: G
authors.initials: G
authors.lastname: Fusetti
authors.forename: F
authors.initials: F
authors.lastname: Dorigatti
authors.forename: H
authors.initials: H
authors.lastname: Hasson
authors.forename: A
authors.initials: A
authors.lastname: Danise
authors.forename: M
authors.initials: M
authors.lastname: Guffanti
authors.forename: A
authors.initials: A
authors.lastname: Lazzarin
authors.forename: A
authors.initials: A
authors.lastname: Rubinacci
mesh_terms: D000328:Adult; D000367:Age Factors; D000469:Alkaline Phosphatase / Q000097:blood; D019380:Anti-HIV Agents / Q000627:therapeutic use*; D023241:Antiretroviral Therapy, Highly Active; D015415:Biomarkers / Q000097:blood; D015992:Body Mass Index; D001851:Bone Diseases, Metabolic / Q000097:blood / Q000821:virology; D016723:Bone Remodeling; D003401:Creatine / Q000097:blood; D003430:Cross-Sectional Studies; D005260:Female; D006023:Glycoproteins / Q000097:blood*; D015658:HIV Infections / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology*; D006801:Humans; D006962:Hyperparathyroidism, Secondary / Q000097:blood / Q000821:virology; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D015675:Osteocalcin / Q000097:blood; D010024:Osteoporosis / Q000097:blood / Q000821:virology; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear / Q000097:blood*; D018124:Receptors, Tumor Necrosis Factor / Q000097:blood*; D013601:T-Lymphocytes / Q000276:immunology; D013997:Time Factors; D014808:Vitamin D Deficiency / Q000097:blood / Q000821:virology
chemical_list: D019380:Anti-HIV Agents; D015415:Biomarkers; D006023:Glycoproteins; D053244:Osteoprotegerin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506030:TNFRSF11B protein, human; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D003401:Creatine