title: 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.
authors.affiliation: Department of Surgery, Friedrich-Alexander University, Erlangen, Germany.
authors.forename: G
authors.initials: G
authors.lastname: Rümenapf
authors.forename: P O
authors.initials: PO
authors.lastname: Schwille
authors.forename: R G
authors.initials: RG
authors.lastname: Erben
authors.forename: M
authors.initials: M
authors.lastname: Schreiber
authors.forename: B
authors.initials: B
authors.lastname: Bergé
authors.forename: W
authors.initials: W
authors.lastname: Fries
authors.forename: A
authors.initials: A
authors.lastname: Schmiedl
authors.forename: S
authors.initials: S
authors.lastname: Koroma
authors.forename: W
authors.initials: W
authors.lastname: Hohenberger
mesh_terms: D000818:Animals; D001835:Body Weight; D001842:Bone and Bones / Q000378:metabolism*; D002116:Calcitonin / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D002136:Calcium, Dietary; D002149:Energy Intake; D005743:Gastrectomy; D005748:Gastric Fundus; D005753:Gastric Mucosa / Q000737:chemistry / Q000378:metabolism; D005755:Gastrins / Q000502:physiology*; D006801:Humans; D008274:Magnesium / Q000378:metabolism; D008297:Male; D008903:Minerals / Q000378:metabolism*; D010281:Parathyroid Hormone / Q000502:physiology*; D010758:Phosphorus / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013270:Stomach / Q000502:physiology*; D013965:Thyroidectomy; D014807:Vitamin D / Q000502:physiology*
chemical_list: D002136:Calcium, Dietary; D005755:Gastrins; D008903:Minerals; D010281:Parathyroid Hormone; D014807:Vitamin D; D010758:Phosphorus; D002116:Calcitonin; D008274:Magnesium; D002118:Calcium