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

BackgroundClinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure.MethodsThis 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.ResultsThe 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).ConclusionsPI 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.