Histomorphometry and Bone Matrix Mineralization Before and After Bisphosphonate Treatment in Boys With Duchenne Muscular Dystrophy: A Paired Transiliac Biopsy Study

摘要

Duclienne muscular dystrophy (DMD) is a genetic disorder causing progressive muscle weakness. To prolong independent ambulation, DMD patients are treated with glucocorticaids, 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.Calilean) 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. (C) 2015 American Society for Bone and Mineral Research.