Effect of systemic glucocorticoid therapy on bone metabolism and the osteoprotegerin system in patients with active Crohn’s disease.
Abstract
BACKGROUND AND AIMS: Osteoporosis may occur in 25-30% of patients with Crohn's disease. Its pathogenesis is not completely understood. Both systemic inflammation in acute disease and treatment with systemic glucocorticoids have been implicated. The aim of the present study was to investigate changes in bone density and biochemical markers of bone metabolism before and during a 3-month period of high-dose glucocorticoid treatment for acute flare-up of Crohn's disease. METHODS: Twenty-five patients with active Crohn's disease requiring systemic glucocorticoid treatment (prednisolone, 60 mg/day) were investigated. Lumbar spine and femoral neck bone mineral densitometry was performed at baseline and again after 3 months. Clinical examinations including evaluation of the Crohn's disease activity index and measurement of the biochemical markers osteocalcin, deoxypyridinoline, osteoprotegerin and the soluble receptor activator of NF-kappaB ligand were performed prior to, and at 1, 2 and 12 weeks following steroid administration. RESULTS Median lumbar bone mineral density decreased significantly during the observation period by 1.04% from -0.84 (t score; range, -2.8 to +0.57) to -0.95 (range, -3.1 to +0.40; P = 0.022), while bone density of the total femur decreased by 2.9% from -0.83 (range, -2.61 to +1.86) to -0.90 (range, -2.65 to +0.19; P = 0.01). Serum levels of osteocalcin, a bone formation marker, and osteoprotegerin, an anti-resorptive cytokine produced by osteoblasts, decreased after the first 2 weeks of treatment and reached baseline levels after 3 months. No significant change was found for the bone resorption marker deoxypyridinoline, while soluble receptor activator of NF-kappaB ligand, a cytokine promoting bone resorption, tended to increase during steroid treatment. CONCLUSION: A decrease in bone mineral density in patients with Crohn's disease appears to result, at least in part, from a short-term effect of systemic glucocorticoid. Modulation of osteoclastogenesis by the receptor activator of NF-kappaB ligand/osteoprotegerin cytokine system and decreased osteoblastic function may be the underlying molecular basis.
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The skeletal response to prednisolone in these rats shared similarities to humans, including decreased BMD, histological evidence of increased bone resorption, and biochemical evidence of suppressed bone formation.
“the skeletal response to prednisolone in these rats shared several similarities to changes observed in humans, including significantly decreased BMD (243), histological evidence of increased bone resorption (194), and biochemical evidence of suppressed bone formation (244, 267, 268).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [244]
The most universally described skeletal consequence of glucocorticoid therapy is reduction in BMD, which can lead to increased fracture risk.
“The most universally described skeletal consequence of glucocorticoid therapy is a reduction in BMD, which can lead to increased fracture risk (243-245).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [244]
In patients with Crohn's disease, serum OPG levels decreased and RANKL tended to increase with glucocorticoid therapy compared with baseline.
“In a study of patients with Crohn's disease, serum OPG levels decreased, whereas RANKL tended to increase with glucocorticoid therapy compared with baseline (244).”
From Receptor Activator of Nuclear Factor κB Ligand and Osteoprotegerin Regulation of Bone Remodeling in Health and Disease (2008) · cites this paper as [244]
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dos Santos, D. C., Corrêa, G. C. D. S., Lealchang, G. W.-T., Serrati, N., Guzman, S. G. G., Costa, S. C., de Souza, K. C., Orlando, N., Fragoso, V. D. L. A. L., Su, P. D. W., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.03
Fraturas na infância associada ao uso frequente de glicocorticóides
da Silva, E. F., de Sousa, I. T., da Silva, I. B. C., Silva, J. V. B., Neiva, L. M., Su, P. D. W., Orlando, N., Costa, S. C., Fragoso, V. D. L. A. L., de Souza, T. G. M., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.13
Ribeiro, J. S., de Matos, T. D. P., DIAS, G. C. D. S., Marques, J. P. S. G., Monteiro, S. C., de Alencar, A. C. C., de Abreu, E. L., de Souza, K. C., Orlando, N., Su, P. D. W., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.08
Fraturas do rádio e tipos de tratamento: Cirúrgico e não cirúrgico
Fadul, M. R., PORTELA, M. G. S. A., Monteiro, R. A. L. D. S., de Sousa, S. M., OLÍMPIO, Y. M. T., Costa, S. C., de Souza, K. C., Orlando, N., Fragoso, V. D. L. A. L., Su, P. D. W., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.15
Traumas pediátricos: Fraturas supracondilianas do úmero na criança
Santos, E. B., Vieira, M. C. A., Tiradentes, A. C. S., Justiniano, G. L. B., da Graça, P. K. B., Costa, S. C., de Souza, K. C., Alecrim, M. D. G. C., Orlando, N., Fragoso, V. D. L. A. L., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.11
Fraturas pediátricas em galho verde: Revisão de literatura
de Moraes, A. C. M., Filho, A. N. A. C., Neto, G. J. R. D. F., Revoredo, J. B. L. R., Frota, M. E., Su, P. D. W., de Abreu, E. L., de Souza, K. C., de Alencar, A. C. C., Orlando, N., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.06
Fraturas em crianças com sobrepeso e obesidade na idade pré-escolar
Melo, A. L., Fernandes, G. M. L., de Araújo, G. P., Müller, L. D. C., Paludo, M., Costa, S. C., de Souza, K. C., Orlando, N., Fragoso, V. D. L. A. L., Su, P. D. W., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.14
Fraturas em antebraços de crianças: Uma revisão integrativa da literatura
dos Santos, A. H. S., Sampaio, F. L. D. A., Santana, N. R., Barros, P. R. C., Lacerda, R. M., de Souza, K. C., Su, P. D. W., de Alencar, A. C. C., Orlando, N., de Abreu, E. L., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.05
Desenvolvimento motor em criança: Benefícios e prejuízos da atividade física
Martins, B. S., Bastos, D. B., de Oliveira, J. J., Neto, J. M. H. P., Maquiné, J. V. S., Costa, S. C., de Souza, K. C., Orlando, N., Fragoso, V. D. L. A. L., & Su, P. D. W. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.10
Traumas ortopédicos pediátricos na fase escolar: Um estudo epidemiológico
da Fonseca, I. A., dos Santos, S. E. M., Modesto, V. D., Monteiro, V. M., dos Santos, V. P., Su, P. D. W., Orlando, N., Costa, S. C., de Alencar, A. C. C., Fragoso, V. D. L. A. L., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.09
Tópicos em Ortopedia Pediátrica - Volume 1
(2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6
Perfil de fraturas pela ocorrência de maus tratos em crianças
Salla, A. A. R., da Silva, C. D. F., Coutinho, M. A. F., da Cunha, S. J. S., Lima, V. K. O., de Alencar, A. C. C., de Abreu, E. L., de Souza, K. C., Orlando, N., Su, P. D. W., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.07
Fatores associados à fratura de clavícula na distócia de ombro: Uma revisão integrativa
de Lima, A. E. M., Feitosa, A. P. S., Feitoza, L. P. G. D. C., Toledo, F. T., Saleh, S. W. A., Costa, S. C., de Souza, K. C., Orlando, N., Fragoso, V. D. L. A. L., Su, P. D. W., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.01
Alagia, A. L. N., da Silva, J. C., GOMES, M. L. L., Almeida, R. G., de Souza, K. C., Alecrim, M. D. G. C., Orlando, N., Su, P. D. W., Costa, S. C., & Fragoso, V. D. L. A. L. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.12
Efeitos da atividade física na infância sobre o desenvolvimento ósseo
Marques, L. W. M., Zortéa, L. B., RODRIGUES, T. T., Siqueira, L. M., Monteiro, P. S., Su, P. D. W., de Souza, K. C., Orlando, N., Costa, S. C., Fragoso, V. D. L. A. L., et al. (2023) · Editora Poisson eBooks · doi:10.36229/978-65-5866-297-6.cap.17
- Authors
- von Tirpitz, C., Epp, S., Klaus, J., Mason, R., Hawa, G., Brinskelle-Schmal, N., Hofbauer, L. C., Adler, G., Kratzer, W., & Reinshagen, M.
- Affiliations
- Universität Ulm (DE)
- Philipps University of Marburg (DE)
- Venue
- European Journal of Gastroenterology & Hepatology
- Published
- 2003-11
- Volume
- 15
- Issue
- 11
- Pages
- 1165-1170
- ISSN
- 0954-691X (ISSN-L)
- OpenAlex
- W2049696732
- Cited by
- 69
- References
- 40
- Citations by year
- 2024: 1 · 2023: 16 · 2021: 2 · 2020: 2 · 2017: 4 · 2016: 2 · 2015: 1 · 2014: 1 · 2013: 3 · 2012: 4
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- European Journal of Gastroenterology & Hepatology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Orthopedics and Sports Medicine › Bone health and osteoporosis research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Bone Metabolism and Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Inflammatory Bowel Disease
- Keywords
- Crohn's disease, glucocorticoid therapy, prednisolone, osteoporosis, bone mineral density, osteoprotegerin, RANKL, bone metabolism, osteocalcin, deoxypyridinoline, bone resorption, bone formation, osteoclastogenesis, lumbar spine, femoral neck, CDAI, steroid-induced bone loss
- MeSH terms
- Acute Disease, Adult, Alkaline Phosphatase, Bone and Bones, Crohn Disease, Drug Administration Schedule, Female, Glucocorticoids, Glycoproteins, Humans, Male, Pilot Projects, Prednisolone, Prospective Studies, Biomarkers, Bone Density, Osteocalcin, Receptors, Tumor Necrosis Factor, Receptors, Cytoplasmic and Nuclear, Osteoprotegerin
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