Rümenapf G, Schwille P O, Erben R G, Schreiber M, Bergé B, Fries W, Schmiedl A, Koroma S, Hohenberger W
Department of Surgery, Friedrich-Alexander University, Erlangen, Germany.
Calcif Tissue Int. 1998 Nov;63(5):433-41. doi: 10.1007/s002239900553.
In humans, gastric surgery results in in osteopenia via mechanisms that are insufficiently understood; surgery-induced changes in the hormonal axes involving the stomach, thyroid, and the parathyroids may play a role. To study this in more detail, we evaluated calcium (Ca), magnesium (Mg), and phosphorus (P) metabolism as well as physical, chemical, and histomorphometric bone parameters in rats rendered hypergastrinemic by fundectomy (FX). In independent experiments, the response to an oral Ca challenge was investigated in intact rats versus FX, and in thyroidectomized versus thyroid-intact FX rats. Sixteen weeks following FX, body weight was approximately 80% that of sham-operated controls. In urine, P excretion was elevated fivefold, the pH was significantly decreased, and cAMP excretion was elevated as compared with controls; serum parathyroid hormone (PTH), calcitonin, 25OHD, Ca, Mg, and P were normal; gastrin and 1,25(OH)2D were elevated. On the basis of bone ash mineral content, FX rats developed significant osteopenia, and histomorphometry indicated only slightly elevated bone turnover and mineralization. Following oral Ca, thyroid-intact FX rats developed hypercalcemia, serum gastrin decreased, and calcitonin increased significantly; in thyroidectomized FX rats, calcitonin remained at baseline levels although there was a similar degree of hypercalcemia; PTH decreased during the hypercalcemic period in both groups. Serum gastrin did not correlate with calcitonin or PTH, and in multivariate regression analysis the only predictor of serum 1, 25(OH)2D was urinary phosphorus. It was concluded that in the FX rat (1) osteopenia is not caused by intestinal Ca malabsorption, vitamin D, Ca deficiency, or secondary hyperparathyroidism; (2) osteopenia may be related to PTH-independent urinary hyperexcretion of P, followed by a rise of serum 1,25(OH)2D; (3) the existence of endocrine axes among gastrin, calcitonin, and PTH cannot be substantiated. FX osteopenia appears to be related to gastric acid abolition, and the reactive hypergastrinemia probably stabilizes the mass and turnover of bone.
在人类中，胃手术会通过一些尚未完全了解的机制导致骨质减少；手术引起的涉及胃、甲状腺和甲状旁腺的激素轴变化可能起了作用。为了更详细地研究这一问题，我们评估了通过胃底切除术（FX）使胃泌素血症增加的大鼠的钙（Ca）、镁（Mg）和磷（P）代谢以及物理、化学和组织形态计量学骨参数。在独立实验中，研究了完整大鼠与FX大鼠以及甲状腺切除的FX大鼠与甲状腺完整的FX大鼠对口服钙刺激的反应。FX术后16周，体重约为假手术对照组的80%。与对照组相比，尿液中P排泄量增加了五倍，pH值显著降低，cAMP排泄量增加；血清甲状旁腺激素（PTH）、降钙素、25OHD、Ca、Mg和P均正常；胃泌素和1,25(OH)2D升高。基于骨灰矿物质含量，FX大鼠出现了明显的骨质减少，组织形态计量学表明骨转换和矿化仅略有升高。口服钙后，甲状腺完整的FX大鼠出现高钙血症，血清胃泌素降低，降钙素显著增加；在甲状腺切除的FX大鼠中，尽管高钙血症程度相似，但降钙素仍保持在基线水平；两组在高钙血症期间PTH均降低。血清胃泌素与降钙素或PTH无相关性，多变量回归分析中血清1,25(OH)2D的唯一预测因子是尿磷。得出的结论是，在FX大鼠中：（1）骨质减少不是由肠道钙吸收不良、维生素D、钙缺乏或继发性甲状旁腺功能亢进引起的；（2）骨质减少可能与PTH非依赖性的尿P过度排泄有关，随后血清1,25(OH)2D升高；（3）胃泌素、降钙素和PTH之间内分泌轴的存在无法得到证实。FX骨质减少似乎与胃酸消除有关，反应性高胃泌素血症可能稳定了骨量和骨转换。
