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Osteoporosis Therapy With Denosumab in Organ Transplant Recipients

OBJECTIVE: Osteoporosis and fragility fractures represent serious complications for the solid organ transplant population. The recommended osteoporosis therapy for organ recipients involves supplementation with calcium and vitamin D and bisphosphonate administration. However, these options can prove...

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Autores principales: Brunova, Jana, Kratochvilova, Simona, Stepankova, Jitka
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915642/
https://www.ncbi.nlm.nih.gov/pubmed/29720961
http://dx.doi.org/10.3389/fendo.2018.00162
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author Brunova, Jana
Kratochvilova, Simona
Stepankova, Jitka
author_facet Brunova, Jana
Kratochvilova, Simona
Stepankova, Jitka
author_sort Brunova, Jana
collection PubMed
description OBJECTIVE: Osteoporosis and fragility fractures represent serious complications for the solid organ transplant population. The recommended osteoporosis therapy for organ recipients involves supplementation with calcium and vitamin D and bisphosphonate administration. However, these options can prove limited for patients with impaired renal function. An alternative therapy option is offered by denosumab, a monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand. PATIENTS AND METHODS: We evaluated 63 patients with osteoporosis (23 males and 40 females, age 56.4 ± 13.1 years) following solid organ transplantation (15 diabetic patients after simultaneous transplantation of the kidney and pancreas, 34 patients after kidney transplantation, and 14 patients with liver grafts). Osteoporosis was diagnosed according to standard DEXA examination using the Lunar Prodigy apparatus. Transplanted patients with impaired renal function were treated for osteoporosis of the lumbar spine (L-spine) and/or proximal femur with calcium and vitamin D supplementation and 60 mg of denosumab every 6 months between the years 2012 and 2017. The mean duration of the therapy was 1.65 ± 0.7 years. RESULTS: After denosumab therapy, L-spine T-scores improved across the whole group, ranging from −2.7 ± 0.09 to −1.8 ± 1.0 (p < 0.001). T-score values for the proximal femur increased from −2.5 ± 0.8 to −2.0 ± 0.7 after the therapy (p < 0.01). We observed only a mild, statistically insignificant improvement in distal forearm T-scores. The mean increase in L-spine bone mineral density (BMD) was 11.5 ± 6.2% in subjects with osteoporosis at this site and 10.4 ± 6.1% in the case of all patients. BMD of the proximal femur increased by 10.4 ± 8.3% in patients with osteoporosis and by 7.5 ± 7.3% in all patients. Denosumab therapy decreased the prevalence of osteoporosis in the L-spine from 75 to 27% (p < 0.001) and proximal femur osteoporosis from 54 to 36% (p < 0.05). Denosumab therapy reduced elevated levels of osteocalcin and beta-crosslaps (βCTX) in comparison with baseline levels (p < 0.001) across the whole group of graft recipients. CONCLUSION: Denosumab therapy was well-tolerated and improved bone density in our group of solid organ transplant recipients. The indications are that denosumab could be a viable therapeutic option for transplanted patients with osteoporosis, especially in those with renal function impairment or bisphosphonate intolerance.
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spelling pubmed-59156422018-05-02 Osteoporosis Therapy With Denosumab in Organ Transplant Recipients Brunova, Jana Kratochvilova, Simona Stepankova, Jitka Front Endocrinol (Lausanne) Endocrinology OBJECTIVE: Osteoporosis and fragility fractures represent serious complications for the solid organ transplant population. The recommended osteoporosis therapy for organ recipients involves supplementation with calcium and vitamin D and bisphosphonate administration. However, these options can prove limited for patients with impaired renal function. An alternative therapy option is offered by denosumab, a monoclonal antibody that targets receptor activator of nuclear factor kappa-B ligand. PATIENTS AND METHODS: We evaluated 63 patients with osteoporosis (23 males and 40 females, age 56.4 ± 13.1 years) following solid organ transplantation (15 diabetic patients after simultaneous transplantation of the kidney and pancreas, 34 patients after kidney transplantation, and 14 patients with liver grafts). Osteoporosis was diagnosed according to standard DEXA examination using the Lunar Prodigy apparatus. Transplanted patients with impaired renal function were treated for osteoporosis of the lumbar spine (L-spine) and/or proximal femur with calcium and vitamin D supplementation and 60 mg of denosumab every 6 months between the years 2012 and 2017. The mean duration of the therapy was 1.65 ± 0.7 years. RESULTS: After denosumab therapy, L-spine T-scores improved across the whole group, ranging from −2.7 ± 0.09 to −1.8 ± 1.0 (p < 0.001). T-score values for the proximal femur increased from −2.5 ± 0.8 to −2.0 ± 0.7 after the therapy (p < 0.01). We observed only a mild, statistically insignificant improvement in distal forearm T-scores. The mean increase in L-spine bone mineral density (BMD) was 11.5 ± 6.2% in subjects with osteoporosis at this site and 10.4 ± 6.1% in the case of all patients. BMD of the proximal femur increased by 10.4 ± 8.3% in patients with osteoporosis and by 7.5 ± 7.3% in all patients. Denosumab therapy decreased the prevalence of osteoporosis in the L-spine from 75 to 27% (p < 0.001) and proximal femur osteoporosis from 54 to 36% (p < 0.05). Denosumab therapy reduced elevated levels of osteocalcin and beta-crosslaps (βCTX) in comparison with baseline levels (p < 0.001) across the whole group of graft recipients. CONCLUSION: Denosumab therapy was well-tolerated and improved bone density in our group of solid organ transplant recipients. The indications are that denosumab could be a viable therapeutic option for transplanted patients with osteoporosis, especially in those with renal function impairment or bisphosphonate intolerance. Frontiers Media S.A. 2018-04-17 /pmc/articles/PMC5915642/ /pubmed/29720961 http://dx.doi.org/10.3389/fendo.2018.00162 Text en Copyright © 2018 Brunova, Kratochvilova and Stepankova. https://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Endocrinology
Brunova, Jana
Kratochvilova, Simona
Stepankova, Jitka
Osteoporosis Therapy With Denosumab in Organ Transplant Recipients
title Osteoporosis Therapy With Denosumab in Organ Transplant Recipients
title_full Osteoporosis Therapy With Denosumab in Organ Transplant Recipients
title_fullStr Osteoporosis Therapy With Denosumab in Organ Transplant Recipients
title_full_unstemmed Osteoporosis Therapy With Denosumab in Organ Transplant Recipients
title_short Osteoporosis Therapy With Denosumab in Organ Transplant Recipients
title_sort osteoporosis therapy with denosumab in organ transplant recipients
topic Endocrinology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5915642/
https://www.ncbi.nlm.nih.gov/pubmed/29720961
http://dx.doi.org/10.3389/fendo.2018.00162
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