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Effect of denosumab on peripheral compartmental bone density, microarchitecture and estimated bone strength in de novo kidney transplant recipients


Bonani, Marco; Meyer, Ursina; Frey, Diana; Graf, Nicole; Bischoff-Ferrari, Heike A; Wüthrich, Rudolf P (2016). Effect of denosumab on peripheral compartmental bone density, microarchitecture and estimated bone strength in de novo kidney transplant recipients. Kidney & Blood Pressure Research, 41(5):614-622.

Abstract

BACKGROUND/AIMS: In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known.
METHODS: The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14).
RESULTS: Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336).
CONCLUSIONS: These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis.

Abstract

BACKGROUND/AIMS: In a randomized controlled clinical trial in kidney transplant recipients (NCT01377467) we have recently shown that RANKL inhibition with denosumab significantly improved areal bone mineral density (aBMD) when given during the first year after transplantation. The effect of denosumab on skeletal microstructure and bone strength in kidney transplant recipients is not known.
METHODS: The purpose of the present bone microarchitecture ancillary study was to investigate high-resolution peripheral quantitative computed tomography (HRpQCT) data from the distal tibia and distal radius in 24 study patients that had been randomized to receive either two injections of denosumab 60 mg at baseline and after 6 months (n=10) or no treatment (n=14).
RESULTS: Consistent with the full trial findings, denosumab reduced biomarkers of bone turnover, and significantly increased aBMD at the lumbar spine (median difference of 4.7%; 95% confidence interval [CI] 2.6 - 7.8; p<0.001). Bone quality as assessed by total and cortical volumetric bone mineral density (Tot. vBMD, Ct.vBMD) and cortical thickness (Ct.Th) increased significantly at the tibia, while changes at the radius were less pronounced. The trabecular volumetric BMD (Tb.vBMD), thickness (Tb. Th), separation (Tb.Sp) and number (Tb.N) and the cortical porosity (Ct.Po) at the tibia and the radius did not significantly change in both treatment groups. Micro-finite element analysis (µFEA) showed that bone stiffness increased significantly at the tibia (median difference 5.6%; 95% CI 1.8% - 9.2%; p=0.002) but not at the radius (median difference 2.9%, 95% CI -3.7% - 9.1%; p=0.369). Likewise, failure load increased significantly at the tibia (median difference 5.1%; 95% CI 2.1% - 8.1%; p=0.002) but not at the radius (median difference 2.4%, 95% CI -3.2% - 8.5%; p=0.336).
CONCLUSIONS: These findings demonstrate that denosumab improves bone density and bone quality in first-year kidney transplant recipients at risk to develop osteoporosis.

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Additional indexing

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > University Hospital Zurich > Rheumatology Clinic and Institute of Physical Medicine
04 Faculty of Medicine > University Hospital Zurich > Clinic for Geriatric Medicine
Dewey Decimal Classification:610 Medicine & health
Language:English
Date:2016
Deposited On:06 Jan 2017 10:50
Last Modified:07 Mar 2017 09:35
Publisher:Karger
ISSN:1420-4096
Free access at:Publisher DOI. An embargo period may apply.
Publisher DOI:https://doi.org/10.1159/000447930
PubMed ID:27622692

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