Casado José L, Santiuste Carmen, Vazquez Monica, Bañón Sara, Rosillo Marta, Gomez Ana, Perez-Elías María J, Caballero Carmen, Rey José M, Moreno Santiago
aDepartment of Infectious Diseases bDepartment of Biochemistry cDepartment of Rheumatology dDepartment of Nuclear Medicine, Ramon y Cajal Hospital, Madrid, Spain.
AIDS. 2016 Jun 1;30(9):1423-31. doi: 10.1097/QAD.0000000000001067.
The mechanisms underlying the effect of tenofovir disoproxil fumarate (TDF) on the decline of bone mineral density (BMD) have not been established, especially the effect of renal tubular dysfunction.
Longitudinal study of 90 patients with two successive dual X-ray absorptiometry scans after evaluation of serum and urinary parameters (proteinuria, albuminuria, phosphaturia, uricosuria, glycosuria, β-2-microglobulin, and retinol-binding protein).
After a median of 38 months on TDF, osteopenia at spine and hip was observed in 49 and 48%, and osteoporosis in 9 and 2%, respectively. There was a lineal correlation between BMD at femoral neck and time on TDF (Spearman's rho = -0.27; P = 0.01). One or more tubular abnormalities were observed in 80% of cases (hyperphosphaturia, 50%). A lower BMD correlated with phosphaturia (r = -0.25; P = 0.03), even with phosphataemia within normal limits. In fact, patients with previous improvement in phosphaturia had better BMD at inclusion (Spearman's rho = -0.33; P < 0.01). A second dual X-ray absorptiometry, after a median of 40.8 months (33.8-45.1; 627.7 patients-year on TDF), showed additional BMD reduction at hip in 50% of cases (36% with bone loss >3%), a decline associated with phosphaturia (β, -0.31; P = 0.01) or number of tubular abnormalities (β, -0.41; P = 0.01), but also with use of boosted protease inhibitors (β, -0.47; P = 0.03) and BMD at inclusion (β, -0.33; P = 0.03).
Chronic abnormal phosphaturia explains, at least in part, progressive bone loss during TDF therapy. These data suggest that tubular dysfunction leads to an altered equilibrium between phosphataemia, phosphaturia, and bone as mechanism of progressive BMD decline.
富马酸替诺福韦二吡呋酯（TDF）对骨密度（BMD）下降影响的潜在机制尚未明确，尤其是肾小管功能障碍的影响。
对90例患者进行纵向研究，在评估血清和尿液参数（蛋白尿、白蛋白尿、磷酸盐尿、尿酸尿、糖尿、β-2微球蛋白和视黄醇结合蛋白）后进行连续两次双能X线吸收测定扫描。
在接受TDF治疗的中位时间为38个月后，脊柱和髋部骨质减少的发生率分别为49%和48%，骨质疏松的发生率分别为9%和2%。股骨颈骨密度与TDF治疗时间呈线性相关（Spearman等级相关系数ρ=-0.27；P=0.01）。80%的病例观察到一种或多种肾小管异常（高磷酸盐尿，50%）。较低的骨密度与磷酸盐尿相关（r=-0.25；P=0.03），即使血磷水平在正常范围内。事实上，先前磷酸盐尿有所改善的患者在纳入研究时骨密度更好（Spearman等级相关系数ρ=-0.33；P<0.01）。在中位时间为40.8个月（33.8 - 45.1；627.7患者-年的TDF治疗）后进行的第二次双能X线吸收测定显示，50%的病例髋部骨密度进一步降低（36%骨量丢失>3%），这种下降与磷酸盐尿（β，-0.31；P=0.01）或肾小管异常数量（β，-0.41；P=0.01）相关，但也与使用增强型蛋白酶抑制剂（β，-0.47；P=0.03）和纳入研究时的骨密度（β，-0.33；P=0.03）相关。
慢性异常磷酸盐尿至少部分解释了TDF治疗期间的进行性骨质流失。这些数据表明，肾小管功能障碍导致血磷、磷酸盐尿和骨骼之间的平衡改变，这是骨密度进行性下降的机制。
