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Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: A Paired Transiliac Biopsy Study.
J Bone Miner Res. 2016 05; 31(5):1060-9.JB

Abstract

Duchenne muscular dystrophy (DMD) is a genetic disorder causing progressive muscle weakness. To prolong independent ambulation, DMD patients are treated with glucocorticoids, which, in turn, can increase bone fragility. In a cohort with vertebral fractures, intravenous bisphosphonate (iv BP) therapy stabilized vertebrae and reduced back pain. To characterize the effects of glucocorticoid therapy and bisphosphonate treatment on bone tissue and material properties, paired transiliac biopsy samples (before and after on average 2.4 years of iv BP) from 9 boys with DMD were studied for histomorphometry and bone mineralization density distribution (BMDD) and compared to reference values. Before iv BP, the boys had low cancellous bone volume (BV/TV) and cortical thickness (Ct.Wi) (both on average 56% of the healthy average, p < 0.001 versus reference), and mineralizing surface (MS/BS) in the lower normal range (on average 74% of the healthy average). The average degree of mineralization of cancellous (Cn.CaMean) and cortical compartments (Ct.CaMean) was 21.48 (20.70, 21.90) wt% and 20.42 (19.32, 21.64) wt%, respectively (median [25th, 75th percentiles]), which was not different from reference. After iv BP, BV/TV and Ct.Wi were, on average, unchanged. However, at the individual patient level, BV/TV Z-scores increased in 2, remained unchanged in 4, and declined in 3 patients. Additionally, on average, MS/BS decreased (-85%, p < 0.001), Cn.CaMean (+2.7%) increased, whereas the heterogeneity of cancellous (Cn.CaWidth -19%) and cortical bone mineralization (Ct.CaWidth -8%, all p < 0.05) decreased versus baseline. The changes in bone mineralization are consistent with the antiresorptive action of iv BP. At the same time, our observations point to the need for novel therapies with less or absent bone turnover suppression, including the fact that bone turnover was low even before bisphosphonate therapy, that bone turnover declined further (as expected) with treatment, and that declines in trabecular bone volume were observed in some boys despite bisphosphonate therapy. © 2015 American Society for Bone and Mineral Research.

Authors+Show Affiliations

Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.Department of Pediatrics, McGill University, Shriners Hospital of Montreal, Montreal, Canada.Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26615086

Citation

Misof, Barbara M., et al. "Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: a Paired Transiliac Biopsy Study." Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, vol. 31, no. 5, 2016, pp. 1060-9.
Misof BM, Roschger P, McMillan HJ, et al. Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: A Paired Transiliac Biopsy Study. J Bone Miner Res. 2016;31(5):1060-9.
Misof, B. M., Roschger, P., McMillan, H. J., Ma, J., Klaushofer, K., Rauch, F., & Ward, L. M. (2016). Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: A Paired Transiliac Biopsy Study. Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research, 31(5), 1060-9. https://doi.org/10.1002/jbmr.2756
Misof BM, et al. Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: a Paired Transiliac Biopsy Study. J Bone Miner Res. 2016;31(5):1060-9. PubMed PMID: 26615086.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: A Paired Transiliac Biopsy Study. AU - Misof,Barbara M, AU - Roschger,Paul, AU - McMillan,Hugh J, AU - Ma,Jinhui, AU - Klaushofer,Klaus, AU - Rauch,Frank, AU - Ward,Leanne M, Y1 - 2016/02/15/ PY - 2015/08/26/received PY - 2015/11/11/revised PY - 2015/11/14/accepted PY - 2015/11/29/entrez PY - 2015/11/29/pubmed PY - 2017/12/16/medline KW - BONE MINERALIZATION DENSITY DISTRIBUTION (BMDD) KW - DUCHENNE MUSCULAR DYSTROPHY KW - HISTOMORPHOMETRY KW - INTRAVENOUS BISPHOSPHONATE TREATMENT KW - PAIRED TRANSILIAC BONE BIOPSY KW - QUANTITATIVE BACKSCATTER ELECTRON IMAGING SP - 1060 EP - 9 JF - Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research JO - J Bone Miner Res VL - 31 IS - 5 N2 - Duchenne muscular dystrophy (DMD) is a genetic disorder causing progressive muscle weakness. To prolong independent ambulation, DMD patients are treated with glucocorticoids, which, in turn, can increase bone fragility. In a cohort with vertebral fractures, intravenous bisphosphonate (iv BP) therapy stabilized vertebrae and reduced back pain. To characterize the effects of glucocorticoid therapy and bisphosphonate treatment on bone tissue and material properties, paired transiliac biopsy samples (before and after on average 2.4 years of iv BP) from 9 boys with DMD were studied for histomorphometry and bone mineralization density distribution (BMDD) and compared to reference values. Before iv BP, the boys had low cancellous bone volume (BV/TV) and cortical thickness (Ct.Wi) (both on average 56% of the healthy average, p < 0.001 versus reference), and mineralizing surface (MS/BS) in the lower normal range (on average 74% of the healthy average). The average degree of mineralization of cancellous (Cn.CaMean) and cortical compartments (Ct.CaMean) was 21.48 (20.70, 21.90) wt% and 20.42 (19.32, 21.64) wt%, respectively (median [25th, 75th percentiles]), which was not different from reference. After iv BP, BV/TV and Ct.Wi were, on average, unchanged. However, at the individual patient level, BV/TV Z-scores increased in 2, remained unchanged in 4, and declined in 3 patients. Additionally, on average, MS/BS decreased (-85%, p < 0.001), Cn.CaMean (+2.7%) increased, whereas the heterogeneity of cancellous (Cn.CaWidth -19%) and cortical bone mineralization (Ct.CaWidth -8%, all p < 0.05) decreased versus baseline. The changes in bone mineralization are consistent with the antiresorptive action of iv BP. At the same time, our observations point to the need for novel therapies with less or absent bone turnover suppression, including the fact that bone turnover was low even before bisphosphonate therapy, that bone turnover declined further (as expected) with treatment, and that declines in trabecular bone volume were observed in some boys despite bisphosphonate therapy. © 2015 American Society for Bone and Mineral Research. SN - 1523-4681 UR - https://www.unboundmedicine.com/medline/citation/26615086/Histomorphometry_and_Bone_Matrix_Mineralization_Before_and_After_Bisphosphonate_Treatment_in_Boys_With_Duchenne_Muscular_Dystrophy:_A_Paired_Transiliac_Biopsy_Study_ L2 - https://doi.org/10.1002/jbmr.2756 DB - PRIME DP - Unbound Medicine ER -