Alterations in lumbar spine mechanics due to degenerative disc disease

2010 Fall.Includes bibliographical references.Degenerative disc disease is a major source of low back pain. It is hypothesized to significantly alter the biomechanics of the lumbar spine both at the tissue and motion segment (multi-vertebral) levels. However, explicit correlations between the former and the latter has not been established, and this critical link is only possible through modeling the intervertebral disc tissue behavior within a constitutive framework and implementing it in a finite element model of the lumbar spine. In order to develop a better appreciation of the biomechanics of disc degeneration, the main objectives of this dissertation work were to investigate the degenerative disease related mechanical alterations on lumbar spine through finite element modeling and experimentation, and evaluate the contemporary treatment strategies. To meet this objective, a finite element model of the healthy human lumbar spine was generated based on computed tomography (CT) imagery. Mesh convergence was verified based on strain energy density predictions. Kinematic and mechanical predictions of clinical interest, including range of motion and intradiscal nuclear pressure, were validated under pure moment loading. The mechanical properties of healthy and degenerated annulus fibrosus tissue were quantified using an orthotropic continuum model, with empirical determination of the requisite material coefficients derived from biaxial and uniaxial tension tests. The resultant material models were implemented into the validated finite element model in order to simulate disc degeneration at the L3-L4 level. At the tissue level, degeneration was found to significantly increase the dispersion in the collagen fiber orientation and the nonlinearity of the fiber mechanical behavior. At the motion segment level, degeneration increased the mobility of the spine, with concomitant increases in the local stress predictions in the annulus and facet force transmission. Our results were in good agreement with the clinical findings of instability and injury to the intervertebral disc due to degeneration. Total disc replacement was also considered as a treatment option within the aforementioned finite element framework. The model predictions indicated that single and two-level disc replacement restored motion at the treated levels, while linearizing the kinematic response and increasing the facet force transmission. The data reflect that the successful surgical outcome is most likely obtained when maximum preservation of native disc tissue is achieved during implantation of the prosthetic device

Volume depletion provided by blood donation alters twist mechanics of the heart: Preload dependency of left ventricular torsion

Objectives: The crucial role of twisting motion on both left ventricular (LV) contraction and relaxation has been clearly identified. However, the reports studying the association between LV torsion and loading conditions have revealed conflicting outcomes. Previously normal saline infusion was shown to increase LV rotation. Our aim was to test this phenomenon after volume depletion in healthy volunteer blood donors. Design: A total of 26 healthy male volunteers were included in the study. LV end-diastolic and end-systolic diameter, LV ejection fraction, LV diastolic parameters, LV apical and basal rotation and peak systolic LV torsion were measured by speckle-tracking echocardiography before and after 450 mL blood donation. Results: Blood donation led to a significant decrease in end-diastolic LV internal diameter (48.7 +/- 0.4 versus 46.4 +/- 0.4mm; p<0.001) and cardiac output (6.2 +/- 1.0 versus 5.1 +/- 0.7 L/min; p<0.001). There was a significant decrease in the magnitude of peak systolic apical rotation (4.4 +/- 1.9 degrees versus 2.9 +/- 1.5 degrees; p<0.001) but no change in basal rotation (2.6 +/- 1.4 degrees versus 2.7 +/- 1.6 degrees; p=0.81). Peak systolic LV Torsion decreased after blood donation (6.9 +/- 1.9 degrees versus 5.7 +/- 2.1 degrees; p=0.028). Conclusions: LV apical rotation and peak systolic LV torsion seem to be preload dependent. Preload reduction provided by 450-mL blood donation decreased LV torsion in healthy male volunteers. Volume dynamics should be taken into account in the evaluation of LV torsion

Salt-inducible kinases dictate parathyroid hormone 1 receptor action in bone development and remodeling

International audienceThe parathyroid hormone 1 receptor (PTH1R) mediates the biologic actions of parathyroid hormone (PTH) and parathyroid hormone-related protein (PTHrP). Here, we showed that salt-inducible kinases (SIKs) are key kinases that control the skeletal actions downstream of PTH1R and that this GPCR, when activated, inhibited cellular SIK activity. Sik gene deletion led to phenotypic changes that were remarkably similar to models of increased PTH1R signaling. In growth plate chondrocytes, PTHrP inhibited SIK3, and ablation of this kinase in proliferating chondrocytes rescued perinatal lethality of PTHrP-null mice. Combined deletion of Sik2 and Sik3 in osteoblasts and osteocytes led to a dramatic increase in bone mass that closely resembled the skeletal and molecular phenotypes observed when these bone cells express a constitutively active PTH1R that causes Jansen's metaphyseal chondrodysplasia. Finally, genetic evidence demonstrated that class IIa histone deacetylases were key PTH1R-regulated SIK substrates in both chondrocytes and osteocytes. Taken together, our findings establish that SIK inhibition is central to PTH1R action in bone development and remodeling. Furthermore, this work highlights the key role of cAMP-regulated SIKs downstream of GPCR action