title: Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration.
abstract: BACKGROUND
  Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure.
  
  
  METHODS
  This single-center, cross-sectional study included 184 HIV-infected patients treated with PI who underwent dual-energy X-ray absorptiometry scan. Serum phosphorus, percentage of tubular reabsorption of phosphate (%TRP), thyroid and parathyroid function (iPTH), vitamin D, osteocalcin (OC), urinary deoxypyridinoline (DPD), and urinary cross-linked N-telopeptide of type I collagen (u-NTx) were measured.
  
  
  RESULTS
  The rate of hypothyroidism in PI-users [32/117 (27%)] was double that in non-PI users [8/67 (12%), p = 0.016] and was significantly associated with PI use in multivariate analysis [odds ratio (OR) 11.37, 95% confidence interval (CI) 1.358-95.17, p = 0.025]. Spine BMD was significantly lower in hypothyroid patients than euthyroid, for both total population (-1.37 vs. -1.00, p = 0.041) and PI users (-1.56 vs. -1.13, p = 0.029). Multivariate regression analysis identified inverse correlation between hypothyroidism and spine BMD [estimate -0.437, 95% CI -0.858 to -0.024, p = 0.042]. OC, DPD and u-NTx were significantly higher in PI users than in non-PI users (p = 0.01, 0.05, and 0.01, respectively).
  
  
  CONCLUSIONS
  PI use is associated with hypothyroidism as well as bone turnover acceleration, which worsens PI-associated BMD loss. In PI-treated patients, thyroid function tests are warranted to prevent further progression of PI-associated BMD loss.
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan. Electronic address: ekinai@acc.ncgm.go.jp.
authors.forename: Ei
authors.initials: E
authors.lastname: Kinai
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Gatanaga
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Mizushima
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Nishijima
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Aoki
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Ikumi
authors.initials: I
authors.lastname: Genka
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Katsuji
authors.initials: K
authors.lastname: Teruya
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Kunihisa
authors.initials: K
authors.lastname: Tsukada
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Kikuchi
authors.affiliation: AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Oka
mesh_terms: D000293:Adolescent; D000328:Adult; D000596:Amino Acids / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D016723:Bone Remodeling / Q000187:drug effects*; D024042:Collagen Type I / Q000378:metabolism; D003430:Cross-Sectional Studies; D006801:Humans; D007037:Hypothyroidism / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D015675:Osteocalcin / Q000378:metabolism; D010280:Parathyroid Glands / Q000503:physiopathology; D010455:Peptides / Q000378:metabolism; D010710:Phosphates / Q000378:metabolism; D010758:Phosphorus / Q000097:blood; D011480:Protease Inhibitors / Q000494:pharmacology*; D013961:Thyroid Gland / Q000503:physiopathology; D014807:Vitamin D / Q000378:metabolism; D055815:Young Adult
chemical_list: D000596:Amino Acids; D024042:Collagen Type I; D010455:Peptides; D010710:Phosphates; D011480:Protease Inhibitors; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D014807:Vitamin D; D010758:Phosphorus; C036020:deoxypyridinoline
keywords: Bone mineral density loss; Bone turnover; HIV; Hypothyroidism; Protease inhibitors