Browsing by Author "Wulff, Birgit (7004121898)"

Type 2 diabetes mellitus (T2DM), a metabolic disease on the rise, is associated with substantial increase in bone fracture risk. Because individuals with T2DM have normal or high bone mineral density (BMD), osteodensitometric measurements of BMD do not predict fracture risk with T2DM. Here, we aim to identify the underlying mechanism of the diabetes-induced fracture risk using a high-resolution multi-scale analysis of human cortical bone with special emphasis on osseous cellular activity. Specifically, we show increased cortical porosity in a subgroup of T2DM individuals accompanied by changed mineralization patterns and glycoxidative damage to bone protein, caused by non-enzymatic glycation of bone by reducing sugar. Furthermore, the high porosity T2DM subgroup presents with higher regional mineralization heterogeneity and lower mineral maturity, whereas in the T2DM subgroup regional higher mineral-to-matrix ratio was observed. Both T2DM groups show significantly higher carboxymethyl-lysine accumulation. Our results show a dimorphic pattern of cortical bone reorganization in individuals afflicted with T2DM and hence provide new insight into the diabetic bone disease leading to increased fracture risk. © 2020 Elsevier Inc.

Type 2 diabetes mellitus (T2DM), a metabolic disease on the rise, is associated with substantial increase in bone fracture risk. Because individuals with T2DM have normal or high bone mineral density (BMD), osteodensitometric measurements of BMD do not predict fracture risk with T2DM. Here, we aim to identify the underlying mechanism of the diabetes-induced fracture risk using a high-resolution multi-scale analysis of human cortical bone with special emphasis on osseous cellular activity. Specifically, we show increased cortical porosity in a subgroup of T2DM individuals accompanied by changed mineralization patterns and glycoxidative damage to bone protein, caused by non-enzymatic glycation of bone by reducing sugar. Furthermore, the high porosity T2DM subgroup presents with higher regional mineralization heterogeneity and lower mineral maturity, whereas in the T2DM subgroup regional higher mineral-to-matrix ratio was observed. Both T2DM groups show significantly higher carboxymethyl-lysine accumulation. Our results show a dimorphic pattern of cortical bone reorganization in individuals afflicted with T2DM and hence provide new insight into the diabetic bone disease leading to increased fracture risk. © 2020 Elsevier Inc.

Immobilization as a result of long-term bed rest can lead to gradual bone loss. Because of their distribution throughout the bone matrix and remarkable interconnectivity, osteocytes represent the major mechanosensors in bone and translate mechanical into biochemical signals controlling bone remodeling. To test whether immobilization affects the characteristics of the osteocyte network in human cortical bone, femoral diaphyseal bone specimens were analyzed in immobilized female individuals and compared with age-matched postmenopausal individuals with primary osteoporosis. Premenopausal and postmenopausal healthy individuals served as control groups. Cortical porosity, osteocyte number and lacunar area, the frequency of hypermineralized lacunae, as well as cortical bone calcium content (CaMean) were assessed using bone histomorphometry and quantitative backscattered electron imaging (qBEI). Bone matrix properties were further analyzed by Fourier transform infrared spectroscopy (FTIR). In the immobilization group, cortical porosity was significantly higher, and qBEI revealed a trend toward higher matrix mineralization compared with osteoporotic individuals. Osteocyte density and canalicular density showed a declining rate from premenopausal toward healthy postmenopausal and osteoporotic individuals with peculiar reductions in the immobilization group, whereas the number of hypermineralized lacunae accumulated inversely. In conclusion, reduced osteocyte density and impaired connectivity during immobilization are associated with a specific bone loss pattern, reflecting a phenotype clearly distinguishable from postmenopausal osteoporosis. Immobilization periods may lead to a loss of survival signals for osteocytes, provoking bone loss that is even higher than in osteoporosis states, whereas osteocytic osteolysis remains absent. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research