The effects of metabolic acidosis on bone formation and bone resorption in the rat

Abstract

Metabolic acidosis (MA) has been implicated in the pathogenesis of both osteomalacia and osteopenia. Alterations in the secretion of parathyroid hormone and in the metabolism of vitamin D may contribute to such skeletal changes. To minimize the influence of these factors, quantitative bone histology and measurements of bone formation using double tetracycline labeling were done in thyroparathyroidectomized (TPTX) rats with MA induced by ammonium chloride (TPTX-A), and in both non-acidotic TPTX (TPTX-C) and intact (C) controls. To evaluate the response of both cortical and trabecular bone to MA, histologic studies were done at three separate sites in the tibia, cortical bone from the mid-shaft, and trabecular bone from the epiphysis and from the metaphysis. Plasma pH was lower in TPTX-A, 7.24 +/- 0.10, than in either TPTX-C, 7.39 +/- 0.03, or C, 7.43 +/- 0.04, P less than 0.01, and urinary hydroxyproline excretion increased from 89.8 +/- 8.7 in TPTX-C to 150.2 +/- 25.9 micrograms/mg/creatinine in TPTX-A, P less than 0.01. Resorption surface at the epiphysis increased from 1.8 +/- 0.6% in TPTX-C to 4.0 +/- 1.6% in TPTX-A, P less than 0.05, values not different from those in C, 3.1 +/- 1.1%. Resorption surface was unchanged at other skeletal sites, but total bone volume at the metaphysis fell from 15.5 +/- 5.6% in TPTX-C to 9.0 +/- 4.3% in TPTX-A, P less than 0.05. Bone formation was reduced at each skeletal site in TPTX-A vs. TPTX-C, P less than 0.05 for all values, but histologic evidence of osteomalacia was not observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Influence of benzoic acid and phytase in low-phosphorus diets on bone characteristics in growing-finishing pigs1

“…Benzoic acid is the only organic acid in pig nutrition which reduces urinary pH through its metabolic end product hippuric acid. This acidification is why more Ca is excreted in urine to re-establish the acid-base balance of the body as it is reported in rats (Kraut et al, 1986). In this study, this effect was observed in the reduced Ca content in MT of the younger pigs.…”

“…Benzoic acid as a feed additive has been authorized in the European Union since May 2003 [Commission Regulation (EC) 877/2003;European Union, 2003] and is now listed in the group of zootechnical additives (EC 1138(EC /2007European Union, 2007). The acidification of diet and gastrointestinal tract can cause an increased renal mineral excretion and, thus, reduce bone mineralization (Kraut et al, 1986). It is unclear whether 4 these effects can be avoided with the addition of Phy but results in the study by Radcliffe et al (1998) indicate such a protective effect.…”

Contribution of Intestine, Bone, Kidney, and Dialysis to Extracellular Fluid Calcium Content

“…Indeed, bone mineral, especially carbonate, has been reported to decrease during metabolic acidosis (66,71,72), and provision of bicarbonate increases bone mineral (73,74). In vitro metabolic acidosis increases Ca efflux from bone both by promoting physicochemical mineral dissolution within hours (13), especially of CaCO 3 (21), and by enhancing osteoclastic bone resorption over longer periods (13).…”

Sevelamer carbonate increases serum bicarbonate in pediatric dialysis patients

“…It is well recognized that children with chronic metabolic acidosis and normal renal function have poor growth, and in vitro studies have shown that metabolic acidosis is associated with a decrease in bone mineralization [16]. Thus, current Kidney Disease Outcomes Quality Initiative (K/DOQI) nutritional guidelines for children recommend maintaining a serum bicarbonate level >22 mmol/L [17].…”