Analysis of bone quality in the elderly: effects of immobilization and type 2 diabetes mellitus as age-related risk factors
Final Report Abstract
1) Immoblization and bone quality investigations led to the verification that the mechanosensory network in a load bearing bone, i.e. the human femur is detrimentally affected by immobilization. Lower osteocyte lacunar density, micropetrosis of lacunae, and lower canalicular connectivity were determined as hypothesized. However, changes in osteocyte lacunar size were not found in the cortex of these bones. In addition, a further deterioration of cortical porosity compared to osteoporotic bone was also found, suggesting a more detrimental effect of long-term lack of mechanical loading on bones. Further studies on the biomechanical properties of the tissues have not yet been completed and findings might be incorporated in larger upcoming publications. 2) T2DM changes of bone quality were multiple in nature and several studies resulted from this part of the proposal. In set of multiscale investigations, a subset of bones from T2DM individuals were determined that presented with elevated endocortical microporosity in both femora and tibia bones. In terms of bone quality, it was the T2DM group without elevated porosity that presented with higher mineral-to-matrix ratio and elevated levels of non-enzymatic crosslinks e.g. carboxymethyl lysine (CML). While the cortical bone from the T2DM group with elevated porosity showed a lower tissue mineral density (TMD) and impaired mechanical properties with Reference Point Indentation. Our work also suggested that AGEs might contribute to lowered biomechanical properties of bones from T2DM individuals. However, the in vitro glycation studies to tease out the direct effect of AGE presence and mechanical behavior of bone matrix is currently under review with the BONE Journal. Also, we did not determine any effect on osteocyte or lacuno-canalicular characteristics in long bones, yet found that when looking at jaw bones, T2DM presence led to a lower osteocyte lacunar size within the trabecular bone compartment.
Publications
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Dimorphic Mechanisms of Fragility in Diabetes Mellitus: the Role of Reduced Collagen Fibril Deformation. Journal of Bone and Mineral Research, 37(11), 2259-2276.
Wölfel, Eva M.; Schmidt, Felix N.; vom Scheidt, Annika; Siebels, Anna K.; Wulff, Birgit; Mushumba, Herbert; Ondruschka, Benjamin; Püschel, Klaus; Scheijen, Jean; Schalkwijk, Casper G.; Vettorazzi, Eik; Jähn-Rickert, Katharina; Gludovatz, Bernd; Schaible, Eric; Amling, Michael; Rauner, Martina; Hofbauer, Lorenz C.; Zimmermann, Elizabeth A. & Busse, Björn
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Individuals with type 2 diabetes mellitus show dimorphic and heterogeneous patterns of loss in femoral bone quality. Bone, 140, 115556.
Wölfel, Eva M.; Jähn-Rickert, Katharina; Schmidt, Felix N.; Wulff, Birgit; Mushumba, Herbert; Sroga, Grazyna E.; Püschel, Klaus; Milovanovic, Petar; Amling, Michael; Campbell, Graeme M.; Vashishth, Deepak & Busse, Björn
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Long-Term Immobilization in Elderly Females Causes a Specific Pattern of Cortical Bone and Osteocyte Deterioration Different From Postmenopausal Osteoporosis. Journal of Bone and Mineral Research, 35(7), 1343-1351.
Rolvien, Tim; Milovanovic, Petar; Schmidt, Felix N.; von Kroge, Simon; Wölfel, Eva M.; Krause, Matthias; Wulff, Birgit; Püschel, Klaus; Ritchie, Robert O.; Amling, Michael & Busse, Björn
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Bone loss recovery in mice following microgravity with concurrent bone-compartment-specific osteocyte characteristics. European Cells and Materials, 42, 220-231.
von Kroge, S.; Wölfel, E.M.; Buravkova, L.B.; Atiakshin, D.A.; Markina, E.A.; Schinke, T.; Rolvien, T.; Busse, B. & Jähn-Rickert, K.
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Bone quality analysis of jaw bones in individuals with type 2 diabetes mellitus—post mortem anatomical and microstructural evaluation. Clinical Oral Investigations, 25(7), 4377-4400.
Rodic, Teodora; Wölfel, Eva Maria; Milovanovic, Petar; Fiedler, Imke A. K.; Cvetkovic, Danica; Jähn, Katharina; Amling, Michael; Sopta, Jelena; Nikolic, Slobodan; Zivkovic, Vladimir; Busse, Björn & Djuric, Marija
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Bone fragility in diabetes: novel concepts and clinical implications. The Lancet Diabetes & Endocrinology, 10(3), 207-220.
Hofbauer, Lorenz C.; Busse, Björn; Eastell, Richard; Ferrari, Serge; Frost, Morten; Müller, Ralph; Burden, Andrea M.; Rivadeneira, Fernando; Napoli, Nicola & Rauner, Martina
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Human tibial cortical bone with high porosity in type 2 diabetes mellitus is accompanied by distinctive bone material properties. Bone, 165, 116546.
Wölfel, Eva M.; Fiedler, Imke A.K.; Dragoun, Kolibova Sofie; Krug, Johannes; Lin, Mei-Chun; Yazigi, Bashar; Siebels, Anna K.; Mushumba, Herbert; Wulff, Birgit; Ondruschka, Benjamin; Püschel, Klaus; Glüer, Claus C.; Jähn-Rickert, Katharina & Busse, Björn
