title: Different impact of NNRTI and PI-including HAART on bone mineral density loss in HIV-infected patients.
abstract: OBJECTIVE
  To evaluate the changes in Bone Mineral Density (BMD) and bone remodelling markers in a group of HIV patients treated with HAART and controlled in a long follow-up and to identify possible risk factors for accelerated bone mass loss.
  
  
  METHODS
  In a series of 172 HIV patients treated with HAART a total of 67 patients (44 males and 33 females) underwent repeated bone mineral density measurement by DEXA in lumbar spine and in femur; the patients were classified according to T-score WHO criteria. Serum bone alkaline phosphatase (BAP), by IRMA, and urine pyridinoline/deoxypyridinoline (PYD&DPD), by EIA, were also assayed in all cases.
  
  
  RESULTS
  At baseline, 62/67 patients were on HAART, while 5 were naïve; 44.8% were previous intravenous drug users (IVDU), 46.3% heterosexual and 8.9% homosexual, mean age being 40.2 ± 6.5 years, and 23.9% had previous AIDS diagnosis. Fifteen/67 (22.4%) of treated patients had osteoporosis and 25/67 (37.3%) osteopenia in spine and/or femur including 3 naïve, 27/67 (40.3%), including 2 naïve, had normal BMD in both sites. Fifty-one/67 patients were monitored during follow-up (56.8 ± 5.3 months); 27 (52.9%) of these (Group 1), received protease inhibitors (PI) and 24 (47.1%), including naïve, (Group 2) received not nucleoside reverse transcriptase inhibitors (NNRTI) for > 50% of follow-up period. In Group 1 patients, BMD reduction was observed after follow-up in respect of basal condition in both spine and femur, but significantly (p = 0.011) only for the latter. However, mean BMD values remained stable in both sites in Group 2 patients. Basal BAP and PYD&DPD levels were higher in Group 1 than Group 2, but not significantly. Moreover, only PYD&DPD levels at the follow-up evaluation were significantly (p = 0.031) higher in Group 1 than Group 2. Of the remaining 16/67 patients with osteoporosis/osteopenia, 10 received PI and 6 NNRTI and were treated with therapies that could increase bone density, in particular, 9 with Alendronate/Vitamin D/Calcium and 7 with only vitamin D/calcium; these patients were excluded from statistical analysis of 51 Group 1/Group 2 cases. In the 16 patients, after these specific treatments, mean spine and femur BMD increased over time, but significantly only in those cases including alendronate in their protocol.
  
  
  CONCLUSIONS
  The study showed that in HIV patients on HAART BMD decrease, even osteoporosis, can be present persisting over time, particularly in PI in respect of NNRTI treated patients. The pathogenesis is probably multifactorial, the different antiviral drugs seeming to differently affect bone metabolism. Alendronate/Vitamin D/Calcium therapy can be useful to slow down bone mass loss and also improve osteoporosis/osteopenia conditions, thus, reducing fracture risk also continuing HAART.
authors.affiliation: Unit of Infectious Diseases, Department of Clinical and Experimental Medicine, University of Sassari, Sassari, Italy. giordano.madeddu@uniss.it.
authors.forename: G
authors.initials: G
authors.lastname: Madeddu
authors.forename: A
authors.initials: A
authors.lastname: Spanu
authors.forename: P
authors.initials: P
authors.lastname: Solinas
authors.forename: S
authors.initials: S
authors.lastname: Babudieri
authors.forename: G M
authors.initials: GM
authors.lastname: Calia
authors.forename: C
authors.initials: C
authors.lastname: Lovigu
authors.forename: M
authors.initials: M
authors.lastname: Mannazzu
authors.forename: S
authors.initials: S
authors.lastname: Nuvoli
authors.forename: B
authors.initials: B
authors.lastname: Piras
authors.forename: P
authors.initials: P
authors.lastname: Bagella
authors.forename: M S
authors.initials: MS
authors.lastname: Mura
authors.forename: G
authors.initials: G
authors.lastname: Madeddu
mesh_terms: D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D023241:Antiretroviral Therapy, Highly Active / Q000009:adverse effects / Q000379:methods*; D015519:Bone Density / Q000187:drug effects*; D001851:Bone Diseases, Metabolic / Q000139:chemically induced / Q000453:epidemiology*; D016723:Bone Remodeling / Q000187:drug effects; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000453:epidemiology*; D015497:HIV-1; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000139:chemically induced / Q000453:epidemiology*; D011480:Protease Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D012189:Retrospective Studies; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D055815:Young Adult
chemical_list: D011480:Protease Inhibitors; D018894:Reverse Transcriptase Inhibitors; D000469:Alkaline Phosphatase