Bone Quality: The Mechanical Effects of Microarchitecture and Matrix Properties

In this body of work we have examined some of the current concepts pertaining to the relation between bone mass, bone quality and the mechanical properties of bone. In our first series of studies we used a model of human osteoarthritis to investigate the implications of changes in the effective tissue modulus. Having established that the material properties of the trabecular bone were altered in the earliest stages of osteoarthritis, we then investigated a possible cause, namely the breakdown or denaturation of bone collagen. Our original hypothesis was that damage at the micro scale originates at the molecular scale and that an assay of denatured collagen would refl ect the first stages of the accumulation of microdamage in bone. Although we found a significant increase in the amount of denatured collagen in early osteoarthritis, our hypothesis regarding its mechanical origin turned out to be unlikely. This points to two alternate possibilities; that either the breakdown of collagen was of an enzymatic nature, or that the quality of the original collagen was poor. In the final investigation of this series we studied the implications of a reduction of the effective tissue modulus in the presence of a normal adaptive bone response. In this study we found that when local bone strain was used as the stimulus for the mechanosensory system a reduction of the local stiffness of the bone material would result in stiffening of the bone material at the organ level. Put in a simpler way, we determined that sclerotic thickening of the subchondral bone plate could result in a stiffer plate, even if the bone material was inferior. In our second series, we investigated the effects of high dose bisphosphonate treatment in a canine model. This was part of a larger effort to quantify the effects of bisphosphonates on bone quality (150, 164, 250). Our original hypothesis was that, in addition to increasing bone mass and architectural quality, bisphosphonate treatment would result in a more mature (i.e. highly mineralized) bone matrix. This higher level of mineralization would then result in a stiffer material with improved matrix qualities. Again, we were surprised by our results! We found that any improvements in the stiffness that we could detect were due to changes in bone mass and micro-architecture alone. We also found a large, but expected, increase in the amount of microdamage present. It remains to be seen whether a similar accumulation of microdamage will occur in humans treated at clinical dosages. As is often the case in medicine, there is no easy way to improve the quality of the bone, and when not considered carefully, side effects of a treatment could be detrimental to its effi cacy. In our third series of studies we focused on the contributions of micro-architecture to bone mechanics. First we evaluated some of the morphometric tools used to quantify architecture. We found that use of the parallel plate model led to volume fraction dependant biases and recommend that direct three dimensional methods should be used whenever possible. Through the BIOMED 1 project and the Gift of Hope Organ and Tissue Donor network (not to mention the generosity of the donor’s families and the staff members who collected these specimens) Summary we acquired a unique selection of trabecular bone specimens. We used these specimens to quantify how bone architecture varied both between people and locations in the body. First, we examined the relation between bone mass and architecture. The general question that we asked could be expressed as; “If you have a certain amount of bone, in how many ways is it typically arranged?” We quantifi ed the arrangement of this bone using microCT in conjunction with standard three-dimensional morphometric measures. By using finite element models of the trabecular structure we could fully characterize the influence of microarchitecture on mechanics without considering possibly confounding matrix-level effects. In the BIOMED dataset we had samples from multiple clinically relevant sites and a wide range of donors. This provided an ideal data set to examine the effect of skeletal site. In the GOH dataset we had a large number of specimens from a small number of sites and a moderately large number of donors (this was particularly true with regards to the proximal tibia). This data set was well suited for investigating how the structure of trabecular bone varied between different people. In this analysis we found that even after correcting for the amount of bone present (BV/TV) there were indeed particular aspects of the architecture that were site specifi c. We concluded that this was probably due to differences in the mechanical function of the bone at these different sites. We also saw large differences in the bone architecture between people with equal bone mass. We could supply a striking visual representation of this by choosing 4 extreme donors from our data. For these donors, at this anatomic site, it seems that having a highly connected bone structure comes at the expense of having thin trabeculae. A small supplemental study of these four donors led us, once again, to some surprising results. Although the structure of the bone varied widely between these donors, the relation between the amount of bone present and the stiffness in the main loading direction was unaffected. It was only in the minor loading directions and in shear that the differences in architecture seemed to affect the mechanics. It had been previously demonstrated that including a morphometric measure of anisotropy improves the estimation of mechanical properties as opposed to using density alone (38, 171, 189). In our supplemental study, the differences that we observed on the minor axes as opposed to the main loading axis indicate different levels of mechanical anisotropy between these donors. If these differences could be quantified using a measure of morphometric anisotropy alone we should have been able to derive a general constitutive relation for our population i.e. by using a predictive model based on both bone mass and morphometric anisotropy we should be able to predict the mechanical properties for any donor. We tested this hypothesis by evaluating 3 different relations between the morphology and the bone’s elastic properties. Although adding anisotropy resulted in strong increases in the predictive power of the models, there were still strong site-dependant and donor-dependant differences. Unsatisfied with this result we decided to extend the one of the current models to include additional morphometric parameters. A principal components analysis demonstrated the morphology could generally be described by 3 components; one related to bone mass, one to connectivity and the last to anisotropy. We found that by including parameters such as trabecular spacing or connectivity density in the model we could improve the prediction of the model by about 20% and eliminate much of the residual error that was associated with donor and anatomic site. Although the observed improvement in predicting the mechanical properties was small, it was sufficient to validate the concept that microarchitecture does indeed influence bone mechanics. Concluding this portion of the thesis, we have demonstrated that inter-site and inter-individual differences exist in bone quality as measured by trabecular micro-architecture and that these differences can be, for a large part, quantified using existing morphometric parameters

Parallel plate model for trabecular bone exhibits volume fraction-dependent bias

Unbiased stereological methods were used in conjunction with microcomputed tomographic (micro-CT) scans of human and animal bone to investigate errors created when the parallel plate model was used to calculate morphometric parameters. Bone samples were obtained from the human proximal tibia, canine distal femur, rat tail, and pig spine and scanned in a micro-CT scanner. Trabecular thickness, trabecular spacing, and trabecular number were calculated using the parallel plate model. Direct thickness, and spacing and connectivity density were calculated using unbiased three-dimensional methods. Both thickness and spacing calculated using the plate model were well correlated to the direct three-dimensional measures (r(2) = 0. 77-0.92). The correlation between trabecular number and connectivity density varied greatly (r(2) = 0.41-0.94). Whereas trabecular thickness was consistently underestimated using the plate model, trabecular spacing was underestimated at low volume fractions and overestimated at high volume fractions. Use of the plate model resulted in a volume-dependent bias in measures of thickness and spacing (p < 0.001). This was a result of the fact that samples of low volume fraction were much more "rod-like" than those of the higher volume fraction. Our findings indicate that the plate model provides biased results, especially when populations with different volume fractions are compared. Therefore, we recommend direct thickness measures when three-dimensional data sets are available

Navigating environmental, economic, and technological trade-offs in the design and operation of submerged anaerobic membrane bioreactors (AnMBRs)

Anaerobic membrane bioreactors (AnMBRs) enable energy recovery from wastewater while simultaneously achieving high levels of treatment. The objective of this study was to elucidate how detailed design and operational decisions of submerged AnMBRs influence the technological, environmental, and economic sustainability of the system across its life cycle. Specific design and operational decisions evaluated included: solids retention time (SRT), mixed liquor suspended solids (MLSS) concentration, sludge recycling ratio (r), flux (J), and specific gas demand per membrane area (SGD). The possibility of methane recovery (both as biogas and as soluble methane in reactor effluent) and bioenergy production, nutrient recovery, and final destination of the sludge (land application, landfill, or incineration) were also evaluated. The implications of these design and operational decisions were characterized by leveraging a quantitative sustainable design (QSD) framework which integrated steady-state performance modeling across seasonal temperatures (using pilot-scale experimental data and the simulating software DESASS), life cycle cost (LCC) analysis, and life cycle assessment (LCA). Sensitivity and uncertainty analyses were used to characterize the relative importance of individual design decisions, and to navigate trade-offs across environmental, economic, and technological criteria. Based on this analysis, there are design and operational conditions under which submerged AnMBRs could be net energy positive and contribute to the pursuit of carbon negative wastewater treatment.This research work was possible thanks to project CTM2011-28595-C02-01/02 (funded by the Spanish Ministry of Economy and Competitiveness jointly with the European Regional Development Fund and Generalitat Valenciana GVA-ACOMP2013/203), and by the King Abdullah University of Science and Technology (KAUST) Academic Partnership Program (UIeRA 2012-06291), which are gratefully acknowledged. The authors would like also to acknowledge the Jack Kent Cooke Foundation for partial funding for B.D. Shoener.Pretel-Jolis, R.; Shoener, BD.; Ferrer, J.; Guest, J. (2015). Navigating environmental, economic, and technological trade-offs in the design and operation of submerged anaerobic membrane bioreactors (AnMBRs). Water Research. (87):531-541. https://doi.org/10.1016/j.watres.2015.07.002S5315418

Single Spin Asymmetry ANA_N in Polarized Proton-Proton Elastic Scattering at s=200\sqrt{s}=200 GeV

We report a high precision measurement of the transverse single spin asymmetry $A_N$ at the center of mass energy $\sqrt{s}=200$ GeV in elastic proton-proton scattering by the STAR experiment at RHIC. The $A_N$ was measured in the four-momentum transfer squared $t$ range $0.003 \leqslant |t| \leqslant 0.035$ \GeVcSq, the region of a significant interference between the electromagnetic and hadronic scattering amplitudes. The measured values of $A_N$ and its $t$-dependence are consistent with a vanishing hadronic spin-flip amplitude, thus providing strong constraints on the ratio of the single spin-flip to the non-flip amplitudes. Since the hadronic amplitude is dominated by the Pomeron amplitude at this $\sqrt{s}$, we conclude that this measurement addresses the question about the presence of a hadronic spin flip due to the Pomeron exchange in polarized proton-proton elastic scattering.Comment: 12 pages, 6 figure

Longitudinal double-spin asymmetry and cross section for inclusive neutral pion production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV

We report a measurement of the longitudinal double-spin asymmetry A_LL and the differential cross section for inclusive Pi0 production at midrapidity in polarized proton collisions at sqrt(s) = 200 GeV. The cross section was measured over a transverse momentum range of 1 < p_T < 17 GeV/c and found to be in good agreement with a next-to-leading order perturbative QCD calculation. The longitudinal double-spin asymmetry was measured in the range of 3.7 < p_T < 11 GeV/c and excludes a maximal positive gluon polarization in the proton. The mean transverse momentum fraction of Pi0's in their parent jets was found to be around 0.7 for electromagnetically triggered events.Comment: 6 pages, 3 figures, submitted to Phys. Rev. D (RC

Partonic flow and ϕ\phi-meson production in Au+Au collisions at sNN\sqrt{s_{NN}} = 200 GeV

We present first measurements of the $\phi$-meson elliptic flow ($v_{2}(p_{T})$) and high statistics $p_{T}$ distributions for different centralities from $\sqrt{s_{NN}}$ = 200 GeV Au+Au collisions at RHIC. In minimum bias collisions the $v_{2}$ of the $\phi$ meson is consistent with the trend observed for mesons. The ratio of the yields of the $\Omega$ to those of the $\phi$ as a function of transverse momentum is consistent with a model based on the recombination of thermal $s$ quarks up to $p_{T}\sim 4$ GeV/$c$, but disagrees at higher momenta. The nuclear modification factor ($R_{CP}$) of $\phi$ follows the trend observed in the $K^{0}_{S}$ mesons rather than in $\Lambda$ baryons, supporting baryon-meson scaling. Since $\phi$-mesons are made via coalescence of seemingly thermalized $s$ quarks in central Au+Au collisions, the observations imply hot and dense matter with partonic collectivity has been formed at RHIC.Comment: 6 pages, 4 figures, submit to PR

Plasma Wakefield Acceleration with a Modulated Proton Bunch

The plasma wakefield amplitudes which could be achieved via the modulation of a long proton bunch are investigated. We find that in the limit of long bunches compared to the plasma wavelength, the strength of the accelerating fields is directly proportional to the number of particles in the drive bunch and inversely proportional to the square of the transverse bunch size. The scaling laws were tested and verified in detailed simulations using parameters of existing proton accelerators, and large electric fields were achieved, reaching 1 GV/m for LHC bunches. Energy gains for test electrons beyond 6 TeV were found in this case.Comment: 9 pages, 7 figure

High pTp_{T} non-photonic electron production in pp+pp collisions at s\sqrt{s} = 200 GeV

We present the measurement of non-photonic electron production at high transverse momentum ($p_T >$ 2.5 GeV/$c$) in $p$ + $p$ collisions at $\sqrt{s}$ = 200 GeV using data recorded during 2005 and 2008 by the STAR experiment at the Relativistic Heavy Ion Collider (RHIC). The measured cross-sections from the two runs are consistent with each other despite a large difference in photonic background levels due to different detector configurations. We compare the measured non-photonic electron cross-sections with previously published RHIC data and pQCD calculations. Using the relative contributions of B and D mesons to non-photonic electrons, we determine the integrated cross sections of electrons ($\frac{e^++e^-}{2}$) at 3 GeV/$c < p_T <~$10 GeV/$c$ from bottom and charm meson decays to be ${d\sigma_{(B\to e)+(B\to D \to e)} \over dy_e}|_{y_e=0}$ = 4.0$\pm0.5$({\rm stat.})$\pm1.1$({\rm syst.}) nb and ${d\sigma_{D\to e} \over dy_e}|_{y_e=0}$ = 6.2$\pm0.7$({\rm stat.})$\pm1.5$({\rm syst.}) nb, respectively.Comment: 17 pages, 17 figure