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

Randomized Trial of Risedronate to Prevent Bone Loss in Renal Transplant

Status

Completed

Phases

Phase 1Phase 2

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT00266708

Enrollment

Registered

2005-12-19

Start date

2002-10-31

Completion date

2008-07-31

Last updated

2019-03-01

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Renal Transplant Osteodystrophy

Keywords

renal transplant, post-transplant osteoporosis

Brief summary

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.

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.

Interventions

DRUGRisedronate

risedronate 35 mg weekly

DRUGPlacebo

Risedronate Placebo 35 mg weekly

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

TRIPLE (Subject, Caregiver, Investigator)

Eligibility

Sex/Gender

ALL

Age

18 Years to No maximum

Healthy volunteers

Inclusion criteria

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

Design outcomes

Primary

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

Secondary

Measure	Time frame	Description
Bone Histomorphometry - Percent Osteoid Surface Relative to Bone Surface (OS/BS)	Baseline and month 12 of the treatment	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).
Bone Histomorphometry - Percent Osteoblasts Relative to Bone Surface (OB/BS)	Baseline and month 12 of the treatment	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).
Bone Histomorphometry - Percent Osteoclasts Relative to Bone Surface (OC/BS)	Baseline and month 12 of the treatment	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).
Bone Histomorphometry - Percent Bone Volume (BV/TV)	Baseline and month 12 of the treatment	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.
Bone Histomorphometry - Bone Formation Rate	Baseline and month 12 of the treatment	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.
Bone Histomorphometry - Osteoid Volume (OV)	Baseline and month 12 of the treatment	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.
Bone Histomorphometry - Percent Eroded Surface Relative to Bone Surface (ES/BS)	Baseline and month 12 of the treatment	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).
Bone Histomorphometry - Trabecular Thickness (TbTh)	Baseline and month 12 of the treatment	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.
Bone Histomorphometry - Percent Mineralized Bone Volume (MdV/BV)	Baseline and month 12 of the treatment	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).
Bone Histomorphometry - Mineralized Bone Volume (MdV)	Baseline and month 12 of the treatment	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.
Bone Histomorphometry - Percent Osteoid Volume Relative to Bone Volume(OV/BV)	Baseline and month 12 of the treatment	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).
Bone Histomorphometry - Percent Osteoid Volume Relative to Tissue Volume (OV/TV)	Baseline and month 12 of the treatment	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).

Countries

United States

Participant flow

Recruitment details

Transplant candidates from Montefiore Medical Centre were recruited for the study.

Pre-assignment details

117 transplant candidates were identified as potentially eligible for the study. 57 of the 117 refused to participate and 60 of the candidates signed consent forms. Of the 60 who signed, 18 were either not transplanted or lost to follow-up so only 42 were randomized.

Participants by arm

Arm	Count
Risedronate subjects received Risedronate for one year Risedronate 35 Mg: risedronate 35 mg weekly	20
Placebo subjects received placebo for 1 year Placebo weekly	22
Total	42

Withdrawals & dropouts

Period	Reason	FG000	FG001
Overall Study	Asthma	0	2
Overall Study	No renal function	1	1
Overall Study	Refused biopsy	3	6

Baseline characteristics

Characteristic	Risedronate	Placebo	Total
Age, Continuous	42 years STANDARD_DEVIATION 11	48 years STANDARD_DEVIATION 14	44.7 years STANDARD_DEVIATION 12.42
BMD Calcium - Forearm	0.54 gm/cm^2 STANDARD_DEVIATION 0.09	0.61 gm/cm^2 STANDARD_DEVIATION 0.09	0.57 gm/cm^2 STANDARD_DEVIATION 0.09
BMD Calcium - Hip	0.90 gm/cm^2 STANDARD_DEVIATION 0.15	0.92 gm/cm^2 STANDARD_DEVIATION 0.17	0.909 gm/cm^2 STANDARD_DEVIATION 0.16
BMD Calcium - Spine	1.01 gm/cm^2 STANDARD_DEVIATION 0.17	1.01 gm/cm^2 STANDARD_DEVIATION 0.17	1.01 gm/cm^2 STANDARD_DEVIATION 0.17
Race/Ethnicity, Customized African American	3 Participants	3 Participants	6 Participants
Race/Ethnicity, Customized Hispanic	10 Participants	11 Participants	21 Participants
Race/Ethnicity, Customized Other	2 Participants	2 Participants	4 Participants
Race/Ethnicity, Customized White	5 Participants	6 Participants	11 Participants
Region of Enrollment United States	20 participants	22 participants	42 participants
Sex: Female, Male Female	9 Participants	6 Participants	15 Participants
Sex: Female, Male Male	11 Participants	16 Participants	27 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk
deaths Total, all-cause mortality	0 / 20	0 / 22
other Total, other adverse events	0 / 20	0 / 22
serious Total, serious adverse events	1 / 20	0 / 20

Outcome results

Primary

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.

Time frame: month 12 of the treatment