title: Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: A Paired Transiliac Biopsy Study.
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.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Barbara M
authors.initials: BM
authors.lastname: Misof
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Paul
authors.initials: P
authors.lastname: Roschger
authors.affiliation: Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Hugh J
authors.initials: HJ
authors.lastname: McMillan
authors.affiliation: School of Epidemiology, Public Health and Preventive Medicine, University of Ottawa, Children's Hospital of Eastern Ontario Research Institute, Ottawa, Canada.
authors.forename: Jinhui
authors.initials: J
authors.lastname: Ma
authors.affiliation: Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria.
authors.forename: Klaus
authors.initials: K
authors.lastname: Klaushofer
authors.affiliation: Department of Pediatrics, McGill University, Shriners Hospital of Montreal, Montreal, Canada.
authors.forename: Frank
authors.initials: F
authors.lastname: Rauch
authors.affiliation: Department of Pediatrics, University of Ottawa, Children's Hospital of Eastern Ontario, Ottawa, Canada.
authors.forename: Leanne M
authors.initials: LM
authors.lastname: Ward
mesh_terms: D000293:Adolescent; D000818:Animals; D001416:Back Pain / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D001706:Biopsy; D015519:Bone Density / Q000187:drug effects*; D002648:Child; D004164:Diphosphonates / Q000008:administration & dosage*; D006801:Humans; D008297:Male; D020388:Muscular Dystrophy, Duchenne / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D013131:Spine / Q000378:metabolism / Q000473:pathology
chemical_list: D004164:Diphosphonates
keywords: BONE MINERALIZATION DENSITY DISTRIBUTION (BMDD); DUCHENNE MUSCULAR DYSTROPHY; HISTOMORPHOMETRY; INTRAVENOUS BISPHOSPHONATE TREATMENT; PAIRED TRANSILIAC BONE BIOPSY; QUANTITATIVE BACKSCATTER ELECTRON IMAGING