Renal Osteodystrophy: An Individual Management Approach

• Alendronate (Drug)
• Teriparatide (Drug)
• Cinacalcet (Drug)

Primary outcomes

• Change in Quantitative Computed Tomography (QCT) Bone Mineral Density of the Hip [One Year (at baseline and one year)]: At one year the investigators will asses bone mass using QCT of the total hip and compare one year changes in bone mass between the treatment and control groups.

Secondary outcomes

• Change in Coronary Artery Calcifications by Multiple Detector Computed Tomography (MDCT) [One year (at baseline and one year)]: At one year the investigators will asses differences between the treatment and control groups in changes in Coronary Artery Calcifications by MDCT. 1 Yr. Change in Sqrt CAC Vol.
• Change in Serum Biochemical Bone Markers of Bone Activity - Parathyroid Hormone (PTH) [1 Year (at baseline and one year)]: Bone markers of bone activity tracked over time for changes.1 Yr. Change in PTH
• Change in Serum Biochemical Bone Markers of Bone Activity - Bone-specific Alkaline Phosphatase (BSAP) [1 year (at baseline and one year)]: Bone markers of bone activity tracked over time for changes.1 Yr. Change in BSAP
• Change in Serum Biochemical Bone Markers of Bone Activity - Fibroblast Growth Factor 23 (FGF23) [1 Year (at baseline and 1 year)]: Bone markers of bone activity tracked over time for changes. 1 Yr. Change in FGF-23

Sex: All, ages: 21 Years to any

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 achalasia;
* 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.)

Participant flow

Outcome results

• Change in Quantitative Computed Tomography (QCT) Bone Mineral Density of the Hip (Primary), Mean, g/cm^3: Control, Low Turnover -10.71 +/- 4.73; Treatment, Low Turnover 5.72 +/- 4.74; Control, High Turnover -3.52 +/- 3.36; Treatment, High Turnover .2 +/- 5.67 (p .443)
• Change in Coronary Artery Calcifications by Multiple Detector Computed Tomography (MDCT) (Secondary), Mean, Hounsfield Unit: Control, Low Turnover 2.78 +/- 1.51; Treatment, Low Turnover 4.48 +/- 1.83; Control, High Turnover 4.97 +/- 1.89; Treatment, High Turnover 3.47 +/- 1.28 (p .490)
• Change in Serum Biochemical Bone Markers of Bone Activity - Parathyroid Hormone (PTH) (Secondary), Mean, pg/ml: Control, Low Turnover 89 +/- 32.3; Treatment, Low Turnover 379 +/- 118.6; Control, High Turnover -125 +/- 81.2; Treatment, High Turnover -240 +/- 126.5 (p <.001)
• Change in Serum Biochemical Bone Markers of Bone Activity - Bone-specific Alkaline Phosphatase (BSAP) (Secondary), Mean, pg/ml: Control, Low Turnover .61 +/- 3.683; Treatment, Low Turnover -1.01 +/- 4.616; Control, High Turnover -8.92 +/- 6.121; Treatment, High Turnover -10.36 +/- 5.522 (p .083)
• Change in Serum Biochemical Bone Markers of Bone Activity - Fibroblast Growth Factor 23 (FGF23) (Secondary), Mean, pg/ml: Control, Low Turnover 985 +/- 1611; Treatment, Low Turnover 326 +/- 1114; Control, High Turnover 3337 +/- 1427; Treatment, High Turnover 607 +/- 467 (p .283)

Adverse events

Time frame: Years 1-5

Serious adverse events by term

19 more terms not shown.

Other adverse events by term

63 more terms not shown.

• Results publication: Hara T, Hijikata Y, Matsubara Y, Watanabe N. Pharmacological interventions versus placebo, no treatment or usual care for osteoporosis in people with chronic kidney disease stages 3-5D. Cochrane Database Syst Rev. 2021 Jul 7;7(7):CD013424. doi: 10.1002/14651858.CD013424.pub2. PMID 34231877

• Study Protocol, Statistical Analysis Plan, and Informed Consent Form (PDF, 2020-03-13)

• Hartmut Malluche, MD, Principal investigator, University of Kentucky

NIH grants: R01DK080770