title: Reduced bone formation and relatively increased bone resorption in absorptive hypercalciuria.
abstract: Absorptive hypercalciuria (AH), a common stone-forming condition characterized biochemically by intestinal hyperabsorption of calcium and hypercalciuria may be associated with bone loss. In AH type I (AH-1), hypercalciuria persists despite restriction in dietary calcium intake. We therefore hypothesized that the skeleton may contribute to the hypercalciuria in this subgroup of patients. Histomorphometric analysis of iliac crest biopsies were performed on nine stone-formers with AH-1 and on nine matched normal subjects. After stabilization on a stone-prevention diet, calcium homeostasis in the stone formers was then evaluated on inpatient constant metabolic diet before and after short-term blockade of bone resorption by alendronate (10 mg daily, 17 days total). Compared with controls, the stone-formers had lower indices of bone formation (osteoblast surface/bone surface 1.8+/-2.1 vs 3.0+/-1.5%, P=0.04; wall thickness 35.8+/-6.9 vs 47.2+/-7.6%, P=0.001) and relatively higher bone resorption (osteoclast surface/bone surface 0.4+/-0.2 vs 0.2+/-0.2%, P=0.05). In the stone-formers, a short-term course of alendronate treatment corrected fasting urinary calcium (0.14+/-0.06 to 0.06+/-0.04 mg Ca/mg Cr, P=0.001) and marginally reduced 24-h urinary calcium by 48 mg/day (P=0.06). Increased intestinal calcium absorption and hypercalciuria persisted, but estimated calcium balance improved (P=0.007). Our results suggest that the hypercalciuria of AH-1 originates primarily from intestinal hyperabsorption of calcium, but bone resorption in excess of bone formation may contribute.
authors.affiliation: Department of Internal Medicine, UT Southwestern Medical Center at Dallas, Center for Mineral Metabolism and Clinical Research, Dallas, Texas, USA.
authors.forename: H J
authors.initials: HJ
authors.lastname: Heller
authors.forename: J E
authors.initials: JE
authors.lastname: Zerwekh
authors.forename: F A
authors.initials: FA
authors.lastname: Gottschalk
authors.forename: C Y C
authors.initials: CY
authors.lastname: Pak
mesh_terms: D000328:Adult; D019386:Alendronate / Q000627:therapeutic use; D015519:Bone Density / Q000502:physiology; D050071:Bone Density Conservation Agents / Q000627:therapeutic use; D001862:Bone Resorption / Q000188:drug therapy / Q000503:physiopathology*; D001842:Bone and Bones / Q000473:pathology* / Q000502:physiology; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D053565:Hypercalciuria / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D008875:Middle Aged; D010012:Osteogenesis / Q000502:physiology*
chemical_list: D050071:Bone Density Conservation Agents; D019386:Alendronate