Schmitt C P, Hessing S, Oh J, Weber L, Ochlich P, Mehls O
Division of Pediatric Nephrology, University Children's Hospital, Heidelberg, Germany.
Kidney Int. 2000 Apr;57(4):1484-92. doi: 10.1046/j.1523-1755.2000.00993.x.
Parathyroid hormone (PTH) is secreted in a pulsatile fashion. Continuous infusion of PTH(1-84) resulted in a net decrease in trabecular bone volume. Differential effects have been reported following an intermittent application of PTH. We investigated the effects of a continuous infusion and of an intermittent (2 times daily subcutaneously) administration of PTH(1-37) on growth and bone mineral density (BMD) in healthy and uremic rats.
Two-stage subtotal nephrectomy was performed on 130 g female Sprague-Dawley rats. PTH(1-37) or solvent was administered through minipumps in sham-operated and uremic rats (60 microg/kg x day for 2 weeks). The effect of intermittent administration was tested with a subcutaneous injection of solvent: 30 microg/kg PTH(1-37) two times per day, 100 pmol calcitriol (C)/kg two times per day, or both. The length (snout-tailtip) and BMD were measured at the start of uremia and at sacrifice. BMD was measured by peripheral quantitative computer tomography at the proximal tibia, 6 and 12 mm distal of the kneejoint space. Femur bone morphology was assessed by x-rays, and calcium content was measured by atomic absorption spectrophotometry.
Length gain was not altered by the continuous infusion of PTH. In contrast, it was significantly increased by intermittent PTH (control solvent 5.35 +/- 0.37 cm vs. control PTH 6.19 +/- 0.47 cm; uremia solvent 4.78 +/- 0.20 cm vs. uremia PTH 6.17 +/- 0.36 cm; P < 0.05). Intermittent PTH but not C increased BMD in uremic rats (Delta total BMD 134 + 13.3 vs. 76.3 +/- 11.5 mg/mL; P < 0.05). X-rays revealed increased bone mass following treatment with PTH but not with C. Uremia decreased bone calcium content (64 +/- 0.3 vs. 73. 3 +/- 2.5 mg/mL), which was normalized by PTH (80 +/- 3.6 mg/mL, P < 0.05) but not by C (69 +/- 1.9 mg/mL).
Pulsatile administration of PTH does not adversely affect, but improves longitudinal growth independent of concomitant treatment with C. At the same time PTH increases BMD and the calcium content of bone.
甲状旁腺激素（PTH）以脉冲方式分泌。持续输注PTH（1-84）导致小梁骨体积净减少。间歇性应用PTH后有不同的作用报道。我们研究了持续输注和间歇性（每日皮下注射2次）给予PTH（1-37）对健康和尿毒症大鼠生长及骨矿物质密度（BMD）的影响。
对130 g雌性Sprague-Dawley大鼠进行两阶段次全肾切除术。在假手术和尿毒症大鼠中通过微型泵给予PTH（1-37）或溶剂（60 μg/kg·天，共2周）。通过皮下注射溶剂、每天2次30 μg/kg PTH（1-37）、每天2次100 pmol骨化三醇（C）或两者联合来测试间歇性给药的效果。在尿毒症开始时和处死时测量体长（鼻尖至尾尖）和BMD。通过外周定量计算机断层扫描在膝关节间隙远端6 mm和12 mm处测量近端胫骨的BMD。通过X线评估股骨骨形态，通过原子吸收分光光度法测量钙含量。
持续输注PTH未改变体长增加。相比之下，间歇性PTH显著增加体长（对照溶剂组5.35±0.37 cm vs.对照PTH组6.19±0.47 cm；尿毒症溶剂组4.78±0.20 cm vs.尿毒症PTH组6.17±0.36 cm；P<0.05）。间歇性PTH而非C增加了尿毒症大鼠的BMD（总BMD变化134±13.3 vs. 76.3±11.5 mg/mL；P<0.05）。X线显示PTH治疗后骨量增加，而C治疗后未增加。尿毒症降低了骨钙含量（64±0.3 vs. 73.3±2.5 mg/mL），PTH使其恢复正常（80±3.6 mg/mL，P<0.05），而C未使其恢复正常（69±1.9 mg/mL）。
脉冲式给予PTH不会产生不利影响，反而可改善纵向生长，且与同时给予C无关。同时，PTH增加BMD和骨钙含量。
