Osteopenia following total gastrectomy in the rat--state of mineral metabolism and bone histomorphometry

Abstract

Total gastrectomy (GX) in humans is frequently followed by osteopenia, but the details are unclear. The present investigations in the rat were aimed at elucidating its pathogenesis. Seventeen weeks after GX, we evaluated Ca, Mg and P metabolism as well as bone parameters, including fluorochrome-based bone histomorphometry. In GX rats, fecal Mg was increased, but intestinal absorption of P, Ca, and Mg was within normal limits, as was the urinary excretion of Ca, Mg, hydroxyproline and the pyridinium cross-links. In contrast, urinary P as well as cyclic AMP were significantly increased. In serum of GX rats, gastrin and 25-hydroxyvitamin D (25-OHD) were decreased, and Ca, Mg, P, parathyroid hormone (PTH), calcitonin, and the bone marker osteocalcin were normal, whereas 1,25-dihydroxyvitamin D [1,25(OH)2D] was significantly increased. GX rats had significantly reduced bone density and mineral content, severe high-turnover osteopenia, characterized by normal width but significantly decreased maturation time of osteoid, increased bone formation rate, and increased numbers of osteoclasts. We concluded that after GX (1) there is high-turnover osteopenia with normal mineralization and other histomorphometric features resembling those seen in states with hyperphosphaturia and subsequent hypervitaminosis D; (2) normal serum PTH levels and several indirect indicators of parathyroid gland function argue against the presence of (secondary) hyperparathyroidism, whereas increased bone mobilization due to elevated 1,25(OH)2D explains the maintenance of homeostasis of serum minerals, especially Ca, at the expense of bone mineral; (3) a complex interplay of mineral-metabolic effectors exists, among which low 25-OHD-PTH-independent renal phosphate losses, and high 1,25(OH)2D are prominent features. The presented animal model is recommended for future research in this area.