Rix M, Andreassen H, Eskildsen P, Langdahl B, Olgaard K
Medical Department C, Roskilde County Hospital Koge, Denmark.
Kidney Int. 1999 Sep;56(3):1084-93. doi: 10.1046/j.1523-1755.1999.00617.x.
Metabolic bone disease might commence early in the course of renal failure. This study therefore examined the frequency and severity of the skeletal changes in predialysis chronic renal failure by measurements of bone mineral density (BMD), biochemical markers of bone turnover (osteocalcin, bone-specific alkaline phosphatase, carboxy terminal propeptide of type I collagen, and carboxy-terminal telopeptide of type I collagen), parathyroid hormone (PTH), ionized calcium (Ca++), phosphate (P), and vitamin D metabolites.
The study was performed in 113 patients (male/female: 82/31) with chronic renal diseases [mean glomerular filtration rate (GFR) of 37 ml/min] and in 89 matched, normal control subjects.
The patients had significantly (P<0.05) reduced BMD in the spine (-6.3%), the femur (-12.1%), the forearm (-5.7%), and the total body (-4.2%) as compared with the control subjects. Dividing the patients into quartiles according to GFR revealed that BMD decreased with the gradual decline in renal function at all the measured skeletal sites, but was most pronounced in the femur: 0.63+/-0.03, 0.74+/-0.02, 0.77+/-0.02, and 0.82+/-0.03 g/cm2 in each quartile from lowest to highest GFR compared with 0.82+/-0.02 g/cm2 in the control group (P<0.0001). All of the measured bone markers showed increasing plasma levels with the more advanced stages of renal failure. Serum PTH and serum P levels increased, whereas serum Ca++ and 1,25-dihydroxyvitamin D decreased. BMD Z-scores of the femur and of the forearm correlated to the biochemical markers and to PTH (P<0.05 to P<0.0001). The biochemical markers all showed strong correlations to PTH, also when corrected for the effect of the decline in GFR (r = 0.40 to 0.92, P<0.01 to P< 0.0001).
Skeletal changes are initiated at an early stage of chronic renal failure, as estimated from reduced BMD and elevated levels of PTH and from the biochemical markers of both bone formation and bone resorption.
代谢性骨病可能在肾衰竭病程早期就已开始。因此,本研究通过测量骨密度(BMD)、骨转换的生化标志物(骨钙素、骨特异性碱性磷酸酶、I型胶原羧基末端前肽和I型胶原羧基末端端肽)、甲状旁腺激素(PTH)、离子钙(Ca++)、磷酸盐(P)和维生素D代谢物,来检测透析前慢性肾衰竭患者骨骼变化的频率和严重程度。
本研究纳入了113例慢性肾病患者(男/女:82/31)[平均肾小球滤过率(GFR)为37 ml/min],并选取了89例匹配的正常对照者。
与对照组相比,患者的脊柱(-6.3%)、股骨(-12.1%)、前臂(-5.7%)和全身(-4.2%)骨密度显著降低(P<0.05)。根据GFR将患者分为四分位数,结果显示,在所有测量的骨骼部位,骨密度均随着肾功能的逐渐下降而降低,其中以股骨最为明显:从最低到最高GFR的每个四分位数中,骨密度分别为0.63±0.03、0.74±0.02、0.77±0.02和0.82±0.03 g/cm2,而对照组为0.82±0.02 g/cm2(P<0.0001)。所有测量的骨标志物血浆水平均随着肾衰竭的进展而升高。血清PTH和血清P水平升高,而血清Ca++和1,25-二羟维生素D降低。股骨和前臂的BMD Z评分与生化标志物及PTH相关(P<0.05至P<0.0001)。即使校正了GFR下降的影响,生化标志物与PTH之间仍均显示出强相关性(r = 0.40至0.92,P<0.01至P<0.0001)。
根据降低的骨密度、升高的PTH水平以及骨形成和骨吸收的生化标志物估计,慢性肾衰竭早期即已出现骨骼变化。