Chlorthalidone improves vertebral bone quality in genetic hypercalciuric stone-forming rats
| Autor: | Christopher D. Culbertson, Sara P Y Che, Thomas L. Willett, David A. Bushinsky, John R. Asplin, Marc D. Grynpas |
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| Rok vydání: | 2011 |
| Předmět: |
Calcium Phosphates
medicine.medical_specialty Bone density Endocrinology Diabetes and Metabolism Hypercalciuria environment and public health Bone resorption Article Rats Sprague-Dawley Kidney Calculi Calcification Physiologic Bone Density Internal medicine medicine Animals Orthopedics and Sports Medicine Femur Thiazide Bone mineral Calcium Oxalate Chemistry fungi Chlorthalidone medicine.disease Spine Biomechanical Phenomena Femoral Neck Fractures Rats enzymes and coenzymes (carbohydrates) Endocrinology CTD medicine.drug Calcification |
| Zdroj: | Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 26(8) |
| ISSN: | 1523-4681 |
| Popis: | We have bred a strain of rats to maximize urine (u) calcium (Ca) excretion and model hypercalciuric nephrolithiasis. These genetic hypercalciuric stone-forming (GHS) rats excrete more uCa than control Sprague-Dawley rats, uniformly form kidney stones, and similar to patients, demonstrate lower bone mineral density. Clinically, thiazide diuretics reduce uCa and prevent stone formation; however, whether they benefit bone is not clear. We used GHS rats to test the hypothesis that the thiazide diuretic chlorthalidone (CTD) would have a favorable effect on bone density and quality. Twenty GHS rats received a fixed amount of a 1.2% Ca diet, and half also were fed CTD (4 to 5 mg/kg/d). Rats fed CTD had a marked reduction in uCa. The axial and appendicular skeletons were studied. An increase in trabecular mineralization was observed with CTD compared with controls. CTD also improved the architecture of trabecular bone. Using micro-computed tomography (µCT), trabecular bone volume (BV/TV), trabecular thickness, and trabecular number were increased with CTD. A significant increase in trabecular thickness with CTD was confirmed by static histomorphometry. CTD also improved the connectivity of trabecular bone. Significant improvements in vertebral strength and stiffness were measured by vertebral compression. Conversely, a slight loss of bending strength was detected in the femoral diaphysis with CTD. Thus results obtained in hypercalciuric rats suggest that CTD can favorably influence vertebral fracture risk. CTD did not alter formation parameters, suggesting that the improved vertebral bone strength was due to decreased bone resorption and retention of bone structure. |
| Databáze: | OpenAIRE |
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