High resolution pQCT micro architectureal parameters to predict bone failure in the case of forward fall

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Influence of Loading Conditions in Finite Element Analysis Assessed by HR-pQCT on Ex Vivo Fracture Prediction

Many fractures occur in individuals with normal areal Bone Mineral Density (aBMD) measured by Dual X-ray Absorptiometry (DXA). High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) allows for non-invasive evaluation of bone stiffness and strength through micro finite element (?FE) analysis at the tibia and radius. These ?FE outcomes are strongly associated with fragility fractures but do not provide clear enhancement compared with DXA measurements. The objective of this study was to establish whether a change in loading conditions in standard ?FE analysis assessed by HR-pQCT enhance the discrimination of low-trauma fractured radii (n = 11) from non-fractured radii (n = 16) obtained experimentally throughout a mechanical test reproducing a forward fall. Micro finite element models were created using HR-pQCT images, and linear analyses were performed using four different types of loading conditions (axial, non-axial with two orientations and torsion). No significant differences were found between the failure load assessed with the axial and non-axial models. The different loading conditions tested presented the same area under the receiver operating characteristic (ROC) curves of 0.79 when classifying radius fractures with an accuracy of 81.5%. In comparison, the area under the curve (AUC) is 0.77 from DXA-derived ultra-distal aBMD of the forearm with an accuracy of 85.2%. These results suggest that the restricted HR-pQCT scanned region seems not sensitive to loading conditions for the prediction of radius fracture risk based on ex vivo experiments (n = 27)

High Resolution pQCT micro-architectural parameters to predict bone failure in the case of a forward fall

8th World Congress of Biomechanics, DUBLIN, IRLANDE, 08-/07/2018 - 12/07/2018The gold standard for the diagnosis of osteoporosis is the measurement of areal bone mineral density by Dual X-ray absorptiometry. But the assessment of the bone fracture risk is still not sufficiently discriminant. Indeed, half of the patient considered non-osteoporotic will fracture. In this context, the objective of this study is to evaluate whether bone micro-architecture of distal radius assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) manage to discriminate fractured from non-fractured bones obtained in a previous ex vivo experimental study reproducing a forward fall under dynamic loading conditions

Measuring Hubble Constant with Dark Neutron Star-Black Hole Mergers

Detection of gravitational waves (GWs) from neutron star-black hole (NSBH) standard sirens can provide local measurements of the Hubble constant ($H_0$), regardless of the detection of an electromagnetic (EM) counterpart: The presence of matter terms in GWs breaks the degeneracy between mass parameters and redshift, allowing simultaneous measurement of both the luminosity distance and redshift. Although the tidally disrupted NSBH systems can have EM emission, the detection prospects of an EM counterpart will be limited to $z < 0.8$ in the optical, in the era of the next generation GW detectors. However, the distinctive merger morphology and the high redshift detectability of tidally-disrupted NSBH makes them promising standard siren candidates for this method. Using recent constraints on the equation-of-state of NSs from multi-messenger observations of NICER and LIGO/Virgo/KAGRA, we show the prospects of measuring $H_{0}$ solely from GW observation of NSBH systems, achievable by Einstein Telescope (ET) and Cosmic Explorer (CE) detectors. We first analyze individual events to quantify the effect of high-frequency ($\ge$ 500 Hz) tidal distortions on the inference of NS tidal deformability parameter ($\Lambda$) and hence on $H_0$. We find that disruptive mergers can constrain $\Lambda$ up to $\mathcal{O}(60\%)$ more precisely than non-disruptive ones. However, this precision is not sufficient to place stringent constraints on the $H_0$ for individual events. By performing Bayesian analysis on different sets of simulated NSBH data (up to $N=100$ events, corresponding to a timescale from several hours to a day observation) in the ET+CE detectors, we find that NSBH systems enable unbiased 4% - 13% precision on the estimate of $H_0$ (68% credible interval). This is a similar measurement precision found in studies analyzing populations of NSBH mergers with EM counterparts in the LVKC O5 era

Expression of the type 1 lysophosphatidic acid receptor in osteoblastic cell lineage controls both bone mineralization and osteocyte specification.

International audienceLysphosphatidic acid (LPA) is a major natural bioactive lipid mediator whose biological functions affect multiple organs. These include bone as demonstrated by global Lpar1-knockout mice (Lpar1-/-) which present a bone growth defect. LPA acts on all bone cells including osteoblasts, that are responsible for bone formation, and osteoclasts, which are specialized cells that resorb bone. LPA appears as a potential new coupling molecule during bone remodeling. LPA1 is the most ubiquitous LPA receptor among the six LPA receptor family members (LPA1-6). To better understand the specific role of LPA via its receptor LPA1 in osteoblastic cell lineage we generated osteoblast-specific Lpar1 knockout mice (Lpar1-∆Ob) by crossing Lpar1flox/flox and Osx:Cre+ mouse lines. Lpar1-∆Ob mice do not recapitulate the bone defects of Lpar1-/- mice but revealed reduced bone mineralization and decreased cortical thickness, as well as increased bone porosity associated with an augmentation in the lacunae areas of osteocyte and their apoptotic yield. In vitro, primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts revealed a remarkable premature expression of alkaline phosphatase, reduced cell proliferation associated with decreased YAP-P nuclear accumulation, and reduced mineralization activity. Osteocyte specification is markedly impaired as demonstrated by reduced expression of early (E11) and late (DMP1, DKK1, SOST) osteocyte markers ex vivo in enriched osteocytic fractions of Lpar1-∆Ob mouse bone explants. In addition, E11 expression and dendrite formation induced by FGF2 are markedly impaired in both primary Lpar1-∆Ob and immortalized cl1-Ob-Lpar1-/- osteoblasts. Taken together these results suggest a new role for LPA in bone mass control via bone mineralization and osteocyte function