Randomized Trial of Risedronate to Prevent Bone Loss in Renal Transplant Recipients.

Randomized Trial of Risedronate to Prevent Bone Loss in Renal Transplant

Patients with kidney failure have underlying bone disease at the time of transplant. Fractures of various bones can be as high as 22%. Medication required for the transplant plays a role in bone loss.

Bisphosphonates are used in the general population to treat bone loss of osteoporosis and steroid-induced bone loss. While previous studies, using various bisphosphonates, have shown preservation of bone mineral density in renal transplant recipients, we have demonstrated that pamidronate, a second generation bisphosphonate, is associated with low bone turnover while still preserving bone mineral density. Improved bone mineral density is associated with decreased fracture risk in the general population, while low bone turnover may be associated with increased fracture in dialysis patients.

The purpose of this study is to determine whether risedronate, a third generation bisphosphonate, is effective in preserving bone density when given prophylactically following renal transplantation and whether it is associated with low bone turnover at one year following renal transplantation.

Study Overview

• Status: Completed
• Conditions: Renal Transplant Osteodystrophy
• Intervention / Treatment: Drug: Risedronate; Drug: Placebo

Detailed Description

Participants who receive a living donor kidney transplant undergo a bone biopsy at the time of kidney transplant and after one year of protocol. Once adequate kidney function is established, both groups take by mouth a weekly capsule (the control group has a placebo; the treatment group has risedronate 35 mg). Both groups undergo baseline, 6 month and 12 month dual energy x-ray absorptiometry (DEXA) bone mineral density scans. Both groups undergo bone hormonal studies at regular intervals.

• Study Type: Interventional
• Enrollment (Actual): 60
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• United States
  • New York
    • Bronx, New York, United States, 10467
      • Montefiore Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Adults with end stage renal disease who are undergoing living donor kidney transplantation

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Risedronate; subjects received Risedronate for one year	Drug: Risedronate; risedronate 35 mg weekly; Other Names: bisphosphonate
Placebo Comparator: subjects received placebo; subjects received placebo for 1 year	Drug: Placebo; Risedronate Placebo 35 mg weekly; Other Names: Risedronate placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Mineral Density of Spine at 6 Months	Bone Mineral Density (BMD) measurements were of the vertebral spine (L1-L4) measured using the Hologic 4500 QDC scanner.	month 6 of the treatment
Bone Mineral Density of Spine at 12 Months	Bone Mineral Density (BMD) measurements were of the vertebral spine (L1-L4) measured using same Hologic 4500 QDC scanner.	month 12 of treatment
Bone Mineral Density of the Hip at 6 Months	Bone mineral density (BMD) of the total hip were measured using the Hologic 4500 QDC scanner.	month 6 of the treatment
Bone Mineral Density of the Hip at 12 Months	Bone mineral density (BMD) of the total hip were measured using the Hologic 4500 QDC scanner.	month 12 of the treatment
Bone Mineral Density of Forearm at 6 Months	Bone mineral density (BMD) of the distal third of the nondialysis access forearm were measured using the Hologic 4500 QDC scanner.	month 6 of the treatment
Bone Mineral Density of Forearm at 12 Months	Bone mineral density (BMD) of the distal third of the nondialysis access forearm were measured using the Hologic 4500 QDC scanner.	month 12 of the treatment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Bone Histomorphometry - Percent Bone Volume (BV/TV)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Percent Bone Volume is the percentage of total volume occupied by calcified bone. Percent Bone volume is calculated as Bone Volume (BV) divided by Tissue Volume (TV), where TV is bone plus marrow.	Baseline and month 12 of the treatment
Bone Histomorphometry - Trabecular Thickness (TbTh)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. The ends of certain bones, known as cancellous bones, are actually not solid but are full of holes that are connected to each other by thin rods and plates of bone tissue known as trabeculae. Trabeculae of bone provide structural support to the spongy bone found at the ends of long bones. Trabeculae Trabecular Thickness (TbTh), a structural parameter, is the distance across individual trabecula.	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Mineralized Bone Volume (MdV/BV)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Percent Mineralized Bone Volume is the percentage of Bone Volume consisting of mineralized bone. Percent Mineralized Bone Volume is calculated as Mineralized Bone Volume (MdV) divided by Bone Volume (BV).	Baseline and month 12 of the treatment
Bone Histomorphometry - Mineralized Bone Volume (MdV)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Bone mineralization is the process of laying down minerals on the matrix of the bone, with calcium and phosphorus as the most abundant minerals. Mineralized Bone Volume (MdV) is the percentage of mineralized bone tissue.	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Osteoid Volume Relative to Bone Volume(OV/BV)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. The reported values indicates the percent of a given volume of bone that consists of unmineralized bone. It is equal to Osteoid Volume (OV) divided by Bone Volume (BV).	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Osteoid Volume Relative to Tissue Volume (OV/TV)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. The reported values indicates the percent of a given volume of tissue (bone + marrow) that consists of unmineralized bone. It is equal to Osteoid Volume (OV) divided by Tissue Volume (TV).	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Osteoid Surface Relative to Bone Surface (OS/BS)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. The reported values indicates the percent of bone surface that consists of unmineralized bone. It is equal to Osteoid Surface (OS) divided by Bone Surface (BS).	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Osteoblasts Relative to Bone Surface (OB/BS)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoblasts (OB) are cells that make bones by producing a matrix that becomes mineralized. Bone mass is a balance between the osteoblasts (OB) that form the bone and cells called osteoclasts (OC) that break down the bone. The reported values indicate the percent of bone surface (BS) that is made up of osteoblasts (OB).	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Osteoclasts Relative to Bone Surface (OC/BS)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoclasts (OC) are cells responsible for bone resorption, which is the breaking down of bones. Osteoclasts make and secrete digestive enzymes that break up or dissolve the bone tissue. Bone mass is a balance between the osteoblasts (OB) cells that form the bone and the osteoclasts (OC) cells that break down the bone. The reported values indicate the percent of bone surface (BS) that consists of osteoclasts (OC).	Baseline and month 12 of the treatment
Bone Histomorphometry - Percent Eroded Surface Relative to Bone Surface (ES/BS)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoclasts (OC) are cells responsible for bone resorption, which is the breaking down of bones. Osteoclasts make and secret digestive enzymes tha break up or dissolve the bone tissue. An eroded surface (ES) is the surface of the lacuna ( a cavity or depression in the bone) generated by an active OC. The reported values indicate the percent of eroded surface relative to bone surface (BS).	Baseline and month 12 of the treatment
Bone Histomorphometry - Bone Formation Rate	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoblasts (OB) are cells that make bones by producing a matrix that becomes mineralized. Bone formation rate (BFR) indicates how much of the bone is actively mineralizing; it is determined by the number of active OB and the average work of each OB.	Baseline and month 12 of the treatment
Bone Histomorphometry - Osteoid Volume (OV)	Bone histomorphometry is quantitative information on bone remodeling and structure, obtained through examination of an undecalcified bone biopsy. Osteoid is the unmineralized, organic portion of the bone matrix that forms prior to the maturation of bone tissue. The reported values indicates the Osteoid Volume (OV), the volume of bone that consists of unmineralized bone.	Baseline and month 12 of the treatment

Collaborators and Investigators

• Sponsor: Montefiore Medical Center
• Investigators: Principal Investigator: Maria Coco, MD, MS, Montefiore Medical Center

Publications and helpful links

General Publications

• Coco M, Pullman J, Cohen HW, Lee S, Shapiro C, Solorzano C, Greenstein S, Glicklich D. Effect of risedronate on bone in renal transplant recipients. J Am Soc Nephrol. 2012 Aug;23(8):1426-37. doi: 10.1681/ASN.2011060623. Epub 2012 Jul 12.

Study record dates

Study Major Dates

• Study Start: October 1, 2002
• Primary Completion (Actual): July 1, 2008
• Study Completion (Actual): July 1, 2008

Study Registration Dates

• First Submitted: December 15, 2005
• First Submitted That Met QC Criteria: December 15, 2005
• First Posted (Estimate): December 19, 2005

Study Record Updates

• Last Update Posted (Actual): March 1, 2019
• Last Update Submitted That Met QC Criteria: February 5, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: renal transplant; post-transplant osteoporosis
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Membrane Transport Modulators; Bone Density Conservation Agents; Calcium-Regulating Hormones and Agents; Calcium Channel Blockers; Risedronic Acid; Etidronic Acid; Diphosphonates
• Other Study ID Numbers: 02-08-224

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes