Gastric Fundectomy in the Rat: Effects on Mineral and Bone Metabolism, with Emphasis on the Gastrin–Calcitonin–Parathyroid Hormone–Vitamin D Axis

Abstract

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.

Drug-induced prevention of gastrectomy- and ovariectomy-induced osteopaenia in the young female rat

“…Elevated levels of 1,25-dihydroxyvitamin D 3 could be caused by secondary hyperparathyroidism. However, there was no evidence of hyperparathyroidism in this study confirming several observations made earlier (Mühlbauer et al 1998, Rümenapf et al 1998, Wojtyczka et al 1998. It may be argued that removal of the acid-producing part of the stomach may cause acidosis with consequences for calcium/bone metabolism.…”

“…Vitamin D deficiency is known to cause impaired absorption and osteomalacia (Imawari et al 1980). This is unlikely to be the cause of the Gx-evoked osteopaenia since the serum concentration of 1,25-dihydroxyvitamin D 3 is raised following Gx (Axelson et al 1991, Rümenapf et al 1998. Elevated levels of 1,25-dihydroxyvitamin D 3 could be caused by secondary hyperparathyroidism.…”

Coupling of porcine bone blood flow and metabolism in high-turnover bone disease measured by [15O]H2O and [18F]fluoride ion positron emission tomography

“…For a detailed description of known changes in bone metabolism after gastrectomy, the reader is referred to the literature [2,15,16,17]. Our previous results as well as a number of other studies support the hypothesis that, owing to disturbances in calcium homeostasis, PTH is increased after gastrectomy, resulting in bone mass loss [2,6,7,18,19].…”

Expression of the cholecystokinin 2-receptor in normal human thyroid gland and medullary thyroid carcinoma

“…Animal models have confirmed the importance of gastrin for calcium and bone homeostasis; in rats, antrectomy and total gastrectomy, both resulting in hypogastrinemia, lead to osteopenia and reduction in bone mineral content (26,27). However, a direct positive correlation between gastrin levels and calcitonin levels could be established neither in these models nor in rats after fundectomy and reflectory hypergastrinemia (28). One explanation might be that gastrin leads to pulsatile calcitonin release in response to enteral stimulation rather than influencing basal secretion of calcitonin from C-cells.…”