Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism
Abstract Background Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease and at end-stage are associated with increased risk of fragility fractures. The disruption of phosphorus homeostasis leads to secondary hyperparathyroidism, a common complicatio...
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-02-01
|
| Series: | BMC Nephrology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12882-018-0822-8 |
| _version_ | 1818528954503397376 |
|---|---|
| author | Nikita M. Bajwa Cheryl P. Sanchez Richard C. Lindsey Heather Watt Subburaman Mohan |
| author_facet | Nikita M. Bajwa Cheryl P. Sanchez Richard C. Lindsey Heather Watt Subburaman Mohan |
| author_sort | Nikita M. Bajwa |
| collection | DOAJ |
| description | Abstract Background Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease and at end-stage are associated with increased risk of fragility fractures. The disruption of phosphorus homeostasis leads to secondary hyperparathyroidism, a common complication of chronic kidney disease. However, the molecular pathways by which high phosphorus influences bone metabolism in the early stages of the disease are not completely understood. We investigated the effects of a high phosphorus diet on bone and mineral metabolism using a 5/6 nephrectomy model of chronic kidney disease. Methods Four-week old rats were randomly assigned into groups: 1) Control with standard diet, 2) Nephrectomy with standard rodent diet, and 3) Nephrectomy with high phosphorus diet. Rats underwent in vivo imaging at baseline, day 14, and day 28, followed by ex vivo imaging. Results Cortical bone density at the femoral mid-diaphysis was reduced in nephrectomy-control and nephrectomy-high phosphorus compared to control rats. In contrast, trabecular bone mass was reduced at both the lumbar vertebrae and the femoral secondary spongiosa in nephrectomy-high phosphorus but not in nephrectomy-control. Reduced trabecular bone volume adjusted for tissue volume was caused by changes in trabecular number and separation at day 35. Histomorphometry revealed increased bone resorption in tibial secondary spongiosa in nephrectomy-control. High phosphorus diet-induced changes in bone microstructure were accompanied by increased serum parathyroid hormone and fibroblast growth factor 23 levels. Conclusion Our study demonstrates that changes in mineral metabolism and hormonal dysfunction contribute to trabecular and cortical bone changes in this model of early chronic kidney disease. |
| first_indexed | 2024-12-11T06:56:48Z |
| format | Article |
| id | doaj.art-ffe9c9b9cd524644b6a5536e7d247235 |
| institution | Directory Open Access Journal |
| issn | 1471-2369 |
| language | English |
| last_indexed | 2024-12-11T06:56:48Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Nephrology |
| spelling | doaj.art-ffe9c9b9cd524644b6a5536e7d2472352022-12-22T01:16:45ZengBMCBMC Nephrology1471-23692018-02-0119111110.1186/s12882-018-0822-8Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidismNikita M. Bajwa0Cheryl P. Sanchez1Richard C. Lindsey2Heather Watt3Subburaman Mohan4Musculoskeletal Disease Center, VA Loma Linda Healthcare SystemDepartment of Pediatrics, Loma Linda UniversityMusculoskeletal Disease Center, VA Loma Linda Healthcare SystemMusculoskeletal Disease Center, VA Loma Linda Healthcare SystemMusculoskeletal Disease Center, VA Loma Linda Healthcare SystemAbstract Background Changes in mineral metabolism and bone structure develop early in the course of chronic kidney disease and at end-stage are associated with increased risk of fragility fractures. The disruption of phosphorus homeostasis leads to secondary hyperparathyroidism, a common complication of chronic kidney disease. However, the molecular pathways by which high phosphorus influences bone metabolism in the early stages of the disease are not completely understood. We investigated the effects of a high phosphorus diet on bone and mineral metabolism using a 5/6 nephrectomy model of chronic kidney disease. Methods Four-week old rats were randomly assigned into groups: 1) Control with standard diet, 2) Nephrectomy with standard rodent diet, and 3) Nephrectomy with high phosphorus diet. Rats underwent in vivo imaging at baseline, day 14, and day 28, followed by ex vivo imaging. Results Cortical bone density at the femoral mid-diaphysis was reduced in nephrectomy-control and nephrectomy-high phosphorus compared to control rats. In contrast, trabecular bone mass was reduced at both the lumbar vertebrae and the femoral secondary spongiosa in nephrectomy-high phosphorus but not in nephrectomy-control. Reduced trabecular bone volume adjusted for tissue volume was caused by changes in trabecular number and separation at day 35. Histomorphometry revealed increased bone resorption in tibial secondary spongiosa in nephrectomy-control. High phosphorus diet-induced changes in bone microstructure were accompanied by increased serum parathyroid hormone and fibroblast growth factor 23 levels. Conclusion Our study demonstrates that changes in mineral metabolism and hormonal dysfunction contribute to trabecular and cortical bone changes in this model of early chronic kidney disease.http://link.springer.com/article/10.1186/s12882-018-0822-8Chronic kidney diseaseBoneRenal pathologyPhosphorusFGF23 |
| spellingShingle | Nikita M. Bajwa Cheryl P. Sanchez Richard C. Lindsey Heather Watt Subburaman Mohan Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism BMC Nephrology Chronic kidney disease Bone Renal pathology Phosphorus FGF23 |
| title | Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism |
| title_full | Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism |
| title_fullStr | Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism |
| title_full_unstemmed | Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism |
| title_short | Cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism |
| title_sort | cortical and trabecular bone are equally affected in rats with renal failure and secondary hyperparathyroidism |
| topic | Chronic kidney disease Bone Renal pathology Phosphorus FGF23 |
| url | http://link.springer.com/article/10.1186/s12882-018-0822-8 |
| work_keys_str_mv | AT nikitambajwa corticalandtrabecularboneareequallyaffectedinratswithrenalfailureandsecondaryhyperparathyroidism AT cherylpsanchez corticalandtrabecularboneareequallyaffectedinratswithrenalfailureandsecondaryhyperparathyroidism AT richardclindsey corticalandtrabecularboneareequallyaffectedinratswithrenalfailureandsecondaryhyperparathyroidism AT heatherwatt corticalandtrabecularboneareequallyaffectedinratswithrenalfailureandsecondaryhyperparathyroidism AT subburamanmohan corticalandtrabecularboneareequallyaffectedinratswithrenalfailureandsecondaryhyperparathyroidism |