Rix Marianne, Eskildsen Peter, Olgaard Klaus
Nephrological Dept P 2132, Rigshospitalet, University of Copenhagen, Blegdamsvej 9, DK-2100 Copenhagen, Denmark.
Nephrol Dial Transplant. 2004 Apr;19(4):870-6. doi: 10.1093/ndt/gfg595.
The bone abnormalities that lead to symptomatic renal osteodystrophy commence early in the course of renal failure, but the optimal time to start treatment needs clarifying. The present study examined the effect of alfacalcidol treatment on bone metabolism and bone density in patients with pre-dialysis chronic renal failure (CRF) in a prospective, randomized, placebo-controlled double blind design.
Repetitive measures of bone mineral density (BMD) estimated by dual energy X-ray absorptiometry and plasma levels of biochemical markers of bone turnover [osteocalcin, bone alkaline phosphatase, propeptide of type-I collagen (PICP) and telopeptide of type-I collagen] and parameters of calcium homeostasis were performed in 36 patients with a glomerular filtration rate (GFR) of 6-60 ml/min.
A significant difference in BMD between the treatment groups in favour of the alfacalcidol-treated patients was found in the spine (4.2%), the femoral neck (4.9%) and the total femur (3.0%) (P<0.05). In the alfacalcidol group, plasma levels of parathyroid hormone 1-84 decreased from baseline values by 47+/-9%, and p-osteocalcin and bone alkaline phosphatase decreased by 24+/-9% and 48+/-8%, respectively (P<0.05). In the placebo group, PICP increased by 32+/-26% (P<0.05). No significant changes were found in plasma levels of vitamin D metabolites. GFR decreased significantly from baseline values in the alfacalcidol group (by 28+/-4 ml/min) and in the placebo group (by 26+/-5 ml/min) (P<0.05), with no difference being detected between the groups.
Long-term treatment with alfacalcidol is safe and might be beneficial for the preservation of bone mass in the pre-dialysis stages of CRF, most likely through a reduction in bone turnover as estimated from the changes of the biochemical bone markers.
导致有症状性肾性骨营养不良的骨骼异常在肾衰竭病程早期就已开始，但开始治疗的最佳时机仍需明确。本研究采用前瞻性、随机、安慰剂对照双盲设计，探讨阿法骨化醇治疗对透析前慢性肾衰竭（CRF）患者骨代谢和骨密度的影响。
对36例肾小球滤过率（GFR）为6 - 60 ml/min的患者，采用双能X线吸收法重复测量骨密度（BMD），并检测骨转换生化标志物[骨钙素、骨碱性磷酸酶、I型胶原前肽（PICP）和I型胶原端肽]的血浆水平以及钙稳态参数。
治疗组之间在脊柱（4.2%）、股骨颈（4.9%）和全股骨（3.0%）的骨密度存在显著差异，阿法骨化醇治疗的患者占优势（P<0.05）。在阿法骨化醇组，甲状旁腺激素1 - 84的血浆水平较基线值下降了47±9%，骨钙素和骨碱性磷酸酶分别下降了24±9%和48±8%（P<0.05）。在安慰剂组，PICP升高了32±26%（P<0.05）。维生素D代谢产物的血浆水平未发现显著变化。阿法骨化醇组和安慰剂组的GFR均较基线值显著下降（分别下降28±4 ml/min和26±5 ml/min）（P<0.05），两组之间未检测到差异。
阿法骨化醇长期治疗是安全的，可能有利于在CRF透析前阶段维持骨量，最可能是通过根据骨生化标志物变化估计的骨转换减少来实现。
