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Description
Renal osteodystrophy (ROD) represents the bone histologic abnormalities resulting from loss of renal function.
It starts early during the loss of kidney function and is seen in virtually all chronic end stage kidney disease
patients on dialysis (CKD-5D). A major component of ROD is bone loss leading to CKD-associated
osteoporosis. Debilitating hip fractures occur in patients with CKD at a rate 4.4 times higher than in the general
population, with associated high costs, morbidity and an annual mortality of 64%. CKD osteoporosis is
distinctly different from post-menopausal osteoporosis. Presently, no uniformly accepted CKD osteoporosis
treatment protocol exists, and most physicians are reluctant to treat this disorder despite the profound impact
on health and quality of life, and its association with vascular calcifications. These vascular calcifications confer
an increased risk for cardiovascular events which are the major cause of the over 20% annual mortality rate in
CKD-5D patients.
The goal of the proposed controlled randomized study is to test the concept that CKD osteoporosis can be
successfully treated when treatment is individualized by patients’ turnover status. The study will demonstrate
that reversal of bone loss can be achieved by increasing bone formation in low turnover patients, and by
reducing bone resorption in normal or high turnover patients. A second aim of this study is to provide new
information whether these treatments will not only improve bone mass, but also retard progression of vascular
calcifications. Novel blood tests will be followed to understand potential mechanisms and to evaluate their
usefulness for prediction of changes in bone mass and vascular calcifications.
CKD-5D patients with established osteoporosis will be enrolled into one of two treatment arms based on bone
turnover status. Each arm will be adaptively randomized by race, age and gender into treatment or control
groups. In the low turnover arm, teriparatide combined with cinacalcet will be given, and in the normal or high
turnover arm, alendronate will be administered. Bone mineral density will be measured at baseline and after
one year of treatment by dual X-ray absoptiometry and quantitative computed tomography. Calcifications of the
coronaries, aorta and heart valves will also be measured at the same times by multi-detector computed
tomography.
If this proof-of-concept study is successful, it will offer a heretofore unavailable treatment for osteoporosis in
CKD-5D patients thus changing the prevailing clinical practice paradigm. This will provide immediate benefit to
CKD patients by reducing fracture risk and bone pain, while greatly improving their quality of life. Reduction in
fractures will convey a major socioeconomic benefit by decreasing the high associated treatment costs. These
benefits are highly relevant to the NIDDK’s mission of disseminating science-based information to improve the
health and quality of life for patients with endocrine, metabolic and kidney diseases.
Status | Finished |
---|---|
Effective start/end date | 4/1/08 → 6/30/21 |
Funding
- National Institute Diabetes & Digestive & Kidney: $3,165,353.00
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Projects
- 1 Finished
-
Renal Osteodystrophy: A Fresh Approach
Malluche, H. (PI), Davenport, D. (CoI), Blomquist, G. (Former CoI), Kryscio, R. (Former CoI), Lima, F. (Former CoI), Lowry, C. (Former CoI) & Montgomery, J. (Former CoI)
National Institute Diabetes & Digestive & Kidney
4/1/08 → 6/30/21
Project: Research project