title: The relation between bone and stone formation.
abstract: Hypercalciuria is the most common metabolic abnormality found in patients with calcium-containing kidney stones. Patients with hypercalciuria often excrete more calcium than they absorb, indicating a net loss of total-body calcium. The source of this additional urinary calcium is almost certainly the skeleton, the largest repository of calcium in the body. Hypercalciuric stone formers exhibit decreased bone mineral density (BMD), which is correlated with the increase in urine calcium excretion. The decreased BMD also correlates with an increase in markers of bone turnover as well as increased fractures. In humans, it is difficult to determine the cause of the decreased BMD in hypercalciuric stone formers. To study the effect of hypercalciuria on bone, we utilized our genetic hypercalciuric stone-forming (GHS) rats, which were developed through successive inbreeding of the most hypercalciuric Sprague-Dawley rats. GHS rats excrete significantly more urinary calcium than similarly fed controls, and all the GHS rats form kidney stones while control rats do not. The hypercalciuria is due to a systemic dysregulation of calcium homeostasis, with increased intestinal calcium absorption, enhanced bone mineral resorption, and decreased renal tubule calcium reabsorption associated with an increase in vitamin D receptors in all these target tissues. We recently found that GHS rats fed an ample calcium diet have reduced BMD and that their bones are more fracture-prone, indicating an intrinsic disorder of bone not secondary to diet. Using this model, we should better understand the pathogenesis of hypercalciuria and stone formation in humans to ultimately improve the bone health of patients with kidney stones.
authors.affiliation: Division of Nephrology, Department of Medicine, University of Rochester School of Medicine, 601 Elmwood Ave., Box 675, Rochester, NY, 14642, USA, nancy_krieger@urmc.rochester.edu.
authors.forename: Nancy S
authors.initials: NS
authors.lastname: Krieger
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
mesh_terms: D000042:Absorption; D000818:Animals; D015519:Bone Density; D001862:Bone Resorption; D001842:Bone and Bones / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000378:metabolism; D002129:Calcium Oxalate / Q000378:metabolism / Q000652:urine; D002136:Calcium, Dietary / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006706:Homeostasis; D006801:Humans; D053565:Hypercalciuria / Q000378:metabolism*; D007669:Kidney Calculi / Q000378:metabolism* / Q000503:physiopathology; D007684:Kidney Tubules / Q000378:metabolism; D008297:Male; D053040:Nephrolithiasis / Q000378:metabolism* / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018167:Receptors, Calcitriol / Q000378:metabolism
chemical_list: D002136:Calcium, Dietary; D018167:Receptors, Calcitriol; D002129:Calcium Oxalate; D002118:Calcium