title: Biochemical and histological assessment of alkali therapy during high animal protein intake in the rat.
abstract: The Westernized diet is acidogenic due to the high content of sulfur-containing amino acids and relative deficiency of potassium organic anions. Chronic acid loads result in hypercalciuria and negative calcium balance often associated with loss of bone mineral. Alkali therapy tends to reverse the hypercalciuria but little is known regarding its effect on bone as assessed by bone histomorphometry. The present study utilized dynamic bone histomorphometry to evaluate the effects of alkali therapy on acid-induced changes in bone turnover. Serum and urine analyses and bone histomorphometry were assessed in adult rats after 2 months of either a low casein (LC) or high casein (HC) diet supplemented with either potassium chloride (KCl) or potassium citrate (KCit). Compared to animals on LC-KCl diet, HC-KCl diet delivered a substantial acid load as shown by significant increases in urinary sulfate, ammonium, and net acid excretion, and a lower urinary pH and citrate excretion without detectable changes in serum parameters. The acid load also resulted in hypercalciuria. Dynamic and static bone histomorphometry disclosed a significant reduction in cancellous bone volume and trabecular number associated with a 2.5-fold increase in eroded and a 3.5-fold increase in osteoclastic surfaces. There was also a near 2-fold increase in bone formation rate in rats on the HC-KCl diet. When animals on the HC diet were given KCit instead of KCl, all of the aforementioned changes in urine biochemistry and bone turnover were significantly attenuated or entirely prevented. These findings underscore the deleterious effects of high animal protein intake in promoting hypercalciuria and increasing bone turnover. Co-administration of potassium alkali attenuates or prevents these changes. In this animal model of high dietary animal protein intake, the major skeletal effect of alkali therapy is to reduce bone resorption, with little or no effect on bone formation.
authors: Department of Internal Medicine, Center for Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-8885, USA. Joseph.Zerwekh@utsouthwestern.edu
authors: Joseph E
authors: JE
authors: Zerwekh
authors: Lixian
authors: L
authors: Zou
authors: Charles Y C
authors: CY
authors: Pak
authors: Orson W
authors: OW
authors: Moe
authors: Patricia A
authors: PA
authors: Preisig
mesh_terms: D000468:Alkalies / Q000494:pharmacology*; D000818:Animals; D001774:Blood Chemical Analysis; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism*; D005247:Feeding Behavior / Q000187:drug effects*; D008297:Male; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016482:Urinalysis; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000468:Alkalies; D011506:Proteins