Protease inhibitor-associated bone mineral density loss is related to hypothyroidism and related bone turnover acceleration

J Infect Chemother. 2017 May;23(5):259-264. doi: 10.1016/j.jiac.2016.10.009. Epub 2017 Mar 6.

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.

Keywords: Bone mineral density loss; Bone turnover; HIV; Hypothyroidism; Protease inhibitors.

MeSH terms

  • Adolescent
  • Adult
  • Amino Acids / metabolism
  • Bone Density / drug effects*
  • Bone Remodeling / drug effects*
  • Collagen Type I / metabolism
  • Cross-Sectional Studies
  • Humans
  • Hypothyroidism / blood
  • Hypothyroidism / metabolism
  • Hypothyroidism / physiopathology*
  • Osteocalcin / metabolism
  • Parathyroid Glands / physiopathology
  • Peptides / metabolism
  • Phosphates / metabolism
  • Phosphorus / blood
  • Protease Inhibitors / pharmacology*
  • Thyroid Gland / physiopathology
  • Vitamin D / metabolism
  • Young Adult

Substances

  • Amino Acids
  • Collagen Type I
  • Peptides
  • Phosphates
  • Protease Inhibitors
  • collagen type I trimeric cross-linked peptide
  • Osteocalcin
  • Vitamin D
  • Phosphorus
  • deoxypyridinoline