Kinai Ei, Gatanaga Hiroyuki, Mizushima Daisuke, Nishijima Takeshi, Aoki Takahiro, Genka Ikumi, Teruya Katsuji, Tsukada Kunihisa, Kikuchi Yoshimi, Oka Shinichi
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
AIDS Clinical Center, National Center for Global Health and Medicine, Tokyo, Japan.
J Infect Chemother. 2017 May;23(5):259-264. doi: 10.1016/j.jiac.2016.10.009. Epub 2017 Mar 6.
Clinical and experiments evidence indicate that protease inhibitors (PI) can cause bone mineral density (BMD) loss. However, the mechanism of such loss remains obscure.
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.
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).
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.
临床和实验证据表明，蛋白酶抑制剂（PI）可导致骨密度（BMD）降低。然而，这种降低的机制仍不清楚。
这项单中心横断面研究纳入了184例接受PI治疗的HIV感染患者，这些患者均接受了双能X线吸收测定扫描。检测血清磷、肾小管磷重吸收率（%TRP）、甲状腺和甲状旁腺功能（iPTH）、维生素D、骨钙素（OC）、尿脱氧吡啶啉（DPD）以及尿I型胶原交联N末端肽（u-NTx）。
使用PI的患者中甲状腺功能减退的发生率[32/117（27%）]是非PI使用者[8/67（12%）]的两倍（p = 0.016），在多变量分析中与PI的使用显著相关[比值比（OR）11.37，95%置信区间（CI）1.358 - 95.17，p = 0.025]。无论是在总体人群中（-1.37 vs. -1.00，p = 0.041）还是PI使用者中（-1.56 vs. -1.13，p = 0.029），甲状腺功能减退患者的脊柱骨密度均显著低于甲状腺功能正常者。多变量回归分析确定甲状腺功能减退与脊柱骨密度呈负相关[估计值-0.437，95% CI -0.858至-0.024，p = 0.042]。PI使用者的OC、DPD和u-NTx显著高于非PI使用者（分别为p = 0.01、0.05和0.01）。
使用PI与甲状腺功能减退以及骨转换加速有关，这会加重PI相关的骨密度降低。在接受PI治疗的患者中，有必要进行甲状腺功能检查以防止PI相关骨密度降低的进一步进展。
