Early Acceleration Phase and Late Stationary Phase of Remodeling Imbalance in Long Bones of Male Rats Exposed to Long-Standing Acidemia: A 10-Month Longitudinal Study Using Bone Histomorphometry

Abstract

Chronic metabolic acidosis (CMA) is known to have a detrimental effect on bone metabolism as a result of accelerated bone resorption and impaired bone formation. Typically, a number of compensatory adaptations must have occurred which may help palliate negative calcium balance and acidemia, e.g., increased intestinal calcium and phosphorus absorption. The final outcome with respect to bone remodeling after exposure to CMA for several months was, therefore, elusive. Herein, we investigated bone changes in male rats fed 1.5% NH(4)Cl in drinking water for up to 10 months to induce CMA with plasma pH of 7.2-7.3. Significant decreases in bone mineral density and content were detected by dual-energy X-ray absorptiometry after 6 months of CMA, whereas histomorphometric analysis revealed a significant decrease in bone volume already at week 2 after CMA induction. Exposure to CMA longer than 2 weeks also decreased trabecular number, trabecular thickness, osteoblast surface, mineral apposition rate, and bone formation rate, while increasing trabecular separation, osteoclast surface, and eroded surface. Bone resorption was rapid during weeks 2-16 (acceleration phase) and thereafter persisted at a slower rate (stationary phase) until week 40. Furthermore, CMA markedly reduced the total calcium content in bone and enhanced urinary calcium excretion as measured by atomic absorption spectrophotometry. It could be concluded that, after exposure to a long-standing acidemia, the enhanced bone resorption and suppressed bone formation led to osteopenia throughout the 10-month period, with accelerated bone loss seen only during the first 6 months. Thereafter, the compensatory adaptations appeared to help stabilize bone mass at a subnormal level.