title: Genetic hypercalciuric stone-forming rats have a primary decrease in BMD and strength.
abstract: Kidney stone patients often have a decrease in BMD. It is unclear if reduced BMD is caused by a primary disorder of bone or dietary factors. To study the independent effects of hypercalciuria on bone, we used genetic hypercalciuric stone-forming (GHS) rats. GHS and control (Ctl) rats were fed a low Ca (0.02% Ca, LCD) or a high Ca (1.2% Ca, HCD) diet for 6 wk in metabolic cages. All comparisons are to Ctl rats. Urine Ca was greater in the GHS rats on both diets. GHS fed HCD had reduced cortical (humerus) and trabecular (L(1)-L(5) vertebrae) BMD, whereas GHS rats fed LCD had a reduction in BMD similar to Ctl. GHS rats fed HCD had a decrease in trabecular volume and thickness, whereas LCD led to a approximately 20-fold increase in both osteoid surface and volume. GHS rats fed HCD had no change in vertebral strength (failure stress), ductibility (failure strain), stiffness (modulus), or toughness, whereas in the humerus, there was reduced ductibility and toughness and an increase in modulus, indicating that the defect in mechanical properties is mainly manifested in cortical, rather than trabecular, bone. GHS rat cortical bone is more mineralized than trabecular bone and LCD led to a decrease in the mineralization profile. Thus, the GHS rats, fed an ample Ca diet, have reduced BMD with reduced trabecular volume, mineralized volume, and thickness, and their bones are more brittle and fracture prone, indicating that GHS rats have an intrinsic disorder of bone that is not secondary to diet.
authors.affiliation: Laboratory Medicine and Pathobiology Department, University of Toronto, Ontario, Canada.
authors.forename: Marc
authors.initials: M
authors.lastname: Grynpas
authors.forename: Stephen
authors.initials: S
authors.lastname: Waldman
authors.forename: Douglas
authors.initials: D
authors.lastname: Holmyard
authors.forename: David A
authors.initials: DA
authors.lastname: Bushinsky
mesh_terms: D015502:Absorptiometry, Photon; D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000503:physiopathology*; D053565:Hypercalciuria / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D007669:Kidney Calculi / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D008855:Microscopy, Electron, Scanning; D051381:Rats; D017207:Rats, Sprague-Dawley