Abstract
Gastrectomy (GX) is thought to result in osteomalacia due to deficiencies in Vitamin D and Ca. Using a GX rat model, we showed that GX induced high turnover of bone with hyperosteoidosis, prominent increase of mineralization and increased mRNA expression of both osteoclast-derived tartrate-resistant acid phosphatase 5b and osteocalcin. The increased 1, 25(OH)2D3 level and unchanged PTH and calcitonin levels suggested that conventional bone and Ca metabolic pathways were not involved or changed in compensation. Thus, GX-induced bone pathology was different from a typical osteomalacia. Gene expression profiles through microarray analysis and data mining using Ingenuity Pathway Analysis indicated that 612 genes were up-regulated and 1,097 genes were down-regulated in the GX bone. These genes were related functionally to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes. Network analysis indicated 9 genes (Aldehyde dehydrogenase 1 family, member A1; Aquaporin 9; Interleukin 1 receptor accessory protein; Very low density lipoprotein receptor; Periostin, osteoblast specific factor; Aggrecan; Gremlin 1; Angiopoietin-like 4; Wingless-type MMTV integration site family, member 10B) were hubs connected with tissue development and immunological diseases. These results suggest that chronic systemic inflammation might underlie the GX-induced pathological changes in bone.
Highlights
Gastrectomy (GX) reduces bone mineral content in humans [1,2,3], and the condition has been designated as osteomalacia due to deficiencies in vitamin D (VD) and calcium (Ca) as described in textbooks of orthopedics and endocrinology
We found that the GX-induced high turnover of bone with hyperosteoidosis and the increased mineralization were associated with an alteration in the expression of thousands of genes in bone, and that these were functionally related to connective tissue development, skeletal and muscular system development and function, Ca signaling and the role of osteoblasts, osteoclasts and chondrocytes
There were no significant differences in body weights between sham and GX
Summary
Gastrectomy (GX) reduces bone mineral content in humans [1,2,3], and the condition has been designated as osteomalacia due to deficiencies in vitamin D (VD) and calcium (Ca) as described in textbooks of orthopedics and endocrinology. The aims of this study were to re-evaluate the histological, biochemical and molecular changes in GX-induced bone using animal models and more advanced procedures. These conditions can be reproduced in rats by GX or fundectomy (FX), the resection of the acid-producing part of the stomach [4,5,6]. GX or FX in rats induced a marked and rapid reduction in bone mineral density and trabecular bone volume [4]. Treatment with a proton pump inhibitor (PPI) had no effects on the decrease in bone mineral density, suggesting that lack of gastric acid seemed not to contribute to the bone loss after GX [4]. The gastric fundus, the acid-producing part of the stomach was critical for bone metabolism [7,8,9], since osteopenia could be preserved by retaining 10,30% of the fundic mucosa [8]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
