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Browsing by Author "Lang, Thomas F."
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Item Heterogeneous Spatial and Strength Adaptation of the Proximal Femur to Physical Activity: A Within-Subject Controlled Cross-Sectional Study(Wiley, 2020-04) Warden, Stuart J.; Carballido-Gamio, Julio; Weatherholt, Alyssa M.; Keyak, Joyce H.; Yan, Chenxi; Kersh, Mariana E.; Lang, Thomas F.; Fuchs, Robyn K.; Physical Therapy, School of Health and Human SciencesPhysical activity (PA) enhances proximal femur bone mass, as assessed using projectional imaging techniques. However, these techniques average data over large volumes obscuring spatially heterogeneous adaptations. The current study used quantitative computed tomography, statistical parameter mapping, and subject-specific finite element (FE) modeling to explore spatial adaptation of the proximal femur to PA. In particular, we were interested in adaptation occurring at the superior femoral neck and improving strength under loading from a fall onto the greater trochanter. High/long jump athletes (n=16) and baseball pitchers (n=16) were utilized as within-subject controlled models as they preferentially load their takeoff leg and leg contralateral to their throwing arm, respectively. Controls (n=15) were included, but did not show any dominant-to-nondominant (D-to-ND) leg differences. Jumping athletes showed some D-to-ND leg differences, but less than pitchers. Pitchers had 5.8% (95% CI, 3.9–7.6%) D-to-ND leg differences in total hip volumetric bone mineral density (vBMD), with increased vBMD in the cortical compartment of the femoral neck, and trochanteric cortical and trabecular compartments. Voxel-based morphometry analyses and cortical bone mapping showed pitchers had D-to-ND leg differences within the regions of the primary compressive trabeculae, inferior femoral neck, and greater trochanter, but not the superior femoral neck. FE modeling revealed pitchers had 4.1% (95%CI, 1.4–6.7%) D-to-ND leg differences in ultimate strength under single-leg stance loading, but no differences in ultimate strength to a fall onto the greater trochanter. These data indicate the asymmetrical loading associated with baseball induces proximal femur adaptation in regions associated with weight bearing and muscle contractile forces, and increases strength under single-leg stance loading. However, there were no benefits evident at the superior femoral neck and no measurable improvement in ultimate strength to common injurious loading during aging (i.e. fall onto the greater trochanter) raising questions as to how to better target these variables with PA.Item Osteocyte-Intrinsic TGF-β Signaling Regulates Bone Quality through Perilacunar/Canalicular Remodeling(Elsevier, 2017-11-28) Dole, Neha S.; Mazur, Courtney M.; Acevedo, Claire; Lopez, Justin P.; Monteiro, David A.; Fowler, Tristan W.; Gludovatz, Bernd; Walsh, Flynn; Regan, Jenna N.; Messina, Sara; Evans, Daniel S.; Lang, Thomas F.; Zhang, Bin; Ritchie, Robert O.; Mohammad, Khalid S.; Alliston, Tamara; Medicine, School of MedicineSummary Poor bone quality contributes to bone fragility in diabetes, aging, and osteogenesis imperfecta. However, the mechanisms controlling bone quality are not well understood, contributing to the current lack of strategies to diagnose or treat bone quality deficits. Transforming growth factor beta (TGF-β) signaling is a crucial mechanism known to regulate the material quality of bone, but its cellular target in this regulation is unknown. Studies showing that osteocytes directly remodel their perilacunar/canalicular matrix led us to hypothesize that TGF-β controls bone quality through perilacunar/canalicular remodeling (PLR). Using inhibitors and mice with an osteocyte-intrinsic defect in TGF-β signaling (TβRIIocy−/−), we show that TGF-β regulates PLR in a cell-intrinsic manner to control bone quality. Altogether, this study emphasizes that osteocytes are key in executing the biological control of bone quality through PLR, thereby highlighting the fundamental role of osteocyte-mediated PLR in bone homeostasis and fragility.