Renal Osteodystrophy: An Individual Management Approach

Conditions:Renal Impairment / Chronic Kidney Disease, Renal Impairment / Chronic Kidney Disease
Therapuetic Areas:Nephrology / Urology
Age Range:21 - Any
Start Date:July 2015
End Date:June 2020
Contact:Hartmut Malluche, MD

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Renal Osteodystrophy: A Fresh Approach

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 chronic kidney disease (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 because of
challenges related to racially specific bone turnover states. Therefore, 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 also retard progression of vascular calcifications. Blood tests
measuring FGF23, indicators of Wnt pathway activity, bone resorption and formation 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 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, bone
pain, and cardiovascular risk, while greatly improving their quality of life. These
improvements will also convey major socioeconomic benefits by decreasing the high associated
treatment costs. The proposed study is highly relevant to the National Institute of Diabetes
and Digestive and Kidney Diseases' mission of disseminating science-based information to
improve the health and quality of life for patients with endocrine, metabolic and kidney

Inclusion Criteria:

- Aged 21 years or older;

- Chronic maintenance dialysis of at least 3 months' duration;

- Osteoporotic by DXA of either spine or total hip (Women: post-menopausal or age ≥ 50
with T-score ≤ -2.5; Men: age ≥ 50 with T-score ≤ -2.5; All others, Z-score ≤ -2.5);

- Mental competence;

- Willingness to participate in the study;

- Normal serum calcium.

Exclusion Criteria:

- Pregnancy or breast feeding;

- Incarceration;

- Systemic illnesses or organ diseases that may affect bone (except type 1 or type 2
diabetes mellitus);

- Clinical condition that may limit study participation (e.g., unstable angina,
respiratory distress, infections).

- Chronic alcoholism and/or drug addiction;

- Known Paget 's disease of bone;

- Prior external beam or implant radiation therapy involving the skeleton;

- More than 3 computed tomography (CT) scans in the prior 12 months (to avoid excessive
radiation exposure);

- Participation in a study of an investigational drug during the past 90 days;

- Planning to move out of the area within 1 year of the study;

- On active transplant list;

- BMD t-score of the radius less than -3.5 by DXA (to avoid the known potential negative
effects of teriparatide treatment on BMD of the radius);

- Planned or anticipated oral surgery within the next 12 months;

- Inability to stand or sit upright for at least 30 minutes;

- Abnormalities of the esophagus which delay esophageal emptying such as stricture or

- Treatment within last 6 months with drugs that may affect bone metabolism including
bisphosphonates and teriparatide (except for treatment with calcitriol, vitamin D
analogs and/or calcimimetics);

- Current treatment with medicines containing digoxin or warfarin;

- Calcidiol level below the normal range. (The current routine clinical practice in our
dialysis clinics is to check calcidiol status twice yearly and supplement with vitamin
D according to serum calcidiol levels. It is therefore unlikely that a substantial
number of patients will be excluded due to this exclusion criterion.)
We found this trial at
Lexington, Kentucky
859) 257-9000
Phone: 859-218-1509
University of Kentucky The University of Kentucky is a public, land grant university dedicated to...
Lexington, KY
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