ORCID Profile
0000-0002-3175-9170
Current Organisation
University of Saskatchewan
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Biomechanical engineering | Biomedical engineering | Numerical modelling and mechanical characterisation
Publisher: Wiley
Date: 03-11-2003
DOI: 10.1002/AJPA.10365
Abstract: We examined the composition of the founding population of Iceland through the study of morphological traits in skeletons from Iceland, Ireland, Norway, and Greenland. This is the first study to address this issue from the Settlement Period of Iceland and contemporary s les from Ireland. We pose the following questions: 1) Was the founding population of Iceland of mixed or homogeneous origin? 2) Is there evidence for a significant Irish cohort in the founding population, as suggested in medieval Icelandic literature? Analysis of biodistance revealed that both Settlement Age and later s les from Iceland showed a greater degree of phenetic similarity to contemporary Viking Age Norwegians than to s les obtained from early medieval Ireland. Analysis of among-in idual morphological variation showed that the Settlement Age population of Iceland did not exhibit an increase in variation in comparison to other populations in the s le, suggesting a relatively homogenous origin. However, estimation of admixture between the Irish and Norwegian populations indicated that 66% of the Icelandic settlers were of Norwegian origin. Comparison of the Icelandic s les to hybrid s les produced by res ling the Viking Age Norwegian and early medieval Irish s les revealed that the Icelandic s les are much closer to the Norwegian s les than expected, based on a 66:34 mixture of Norwegian and Irish settlers. We conclude that the Settlement Age population of Iceland was predominantly (60-90%) of Norwegian origin. Although this population was relatively homogenous, our results do not preclude significant contributions from Ireland as well as other sources not represented in our analysis.
Publisher: Springer Science and Business Media LLC
Date: 25-02-2020
Publisher: Elsevier BV
Date: 04-2020
DOI: 10.1016/J.BONE.2020.115223
Abstract: This paper introduces a theoretical framework for the study of the efficacy of romosozumab, a humanized monoclonal antibody targeting sclerostin for the treatment of osteoporosis. We developed a comprehensive mechanistic pharmacokinetic-pharmacodynamic (PK-PD) model of the effect of drug treatment on bone remodeling in postmenopausal osteoporosis (PMO). We utilized a one-compartment PK model to represent subcutaneous injections of romosozumab and subsequent absorption into serum. The PD model is based on a recently-developed bone cell population model describing the bone remodeling process at the tissue scale. The latter accounts for mechanical feedback by incorporating nitric oxide (NO) and sclerostin (Scl) as biochemical feedback molecules. Utilizing a competitive binding model, where Wnt and Scl compete for binding to LRP5/6, allows to regulate anabolic bone remodeling responses. Here, we extended this model with respect to romosozumab binding to sclerostin. For the currently approved monthly injections of 210 mg, the model predicted a 6.59%, 10.38% and 15.25% increase in BMD at the lumbar spine after 6, 12 and 24 months, respectively. These results are in good agreement with the data reported in the literature. Our model is also able to distinguish the bone-site specific drug effects. For instance, at the femoral neck, our model predicts a BMD increase of 3.85% after 12 months of 210 mg injections, which is consistent with literature observations. Finally, our simulations indicate rapid bone loss after treatment discontinuation, indicating that some additional interventions such as use of bisphosphonates are required to maintain bone mass.
Publisher: Elsevier BV
Date: 07-2019
DOI: 10.1016/J.JTBI.2019.04.020
Abstract: This paper presents a pharmacokinetic harmacodynamic (PK/PD) model of the action of PTH(1-34) on bone modelling and remodelling, developed for quantitatively investigating the dose- and administration pattern-dependency of the bone tissue response to this drug. Firstly, a PK model of PTH(1-34) was developed, accounting for administration via subcutaneous injections. Subsequently, the PK model was coupled to a (mechanistic) bone cell population model of bone modelling and remodelling, taking into account the effects of PTH(1-34) on the differentiation of lining cells into active osteoblasts, on the apoptosis of active osteoblasts, and on proliferation of osteoblast precursors, as well as on the key regulatory pathways of bone cell activities. Numerical simulations show that the coupled PK/PD model is able to distinguish between continuous and intermittent administration patterns of PTH(1-34), in terms of yielding both catabolic bone responses (if drug administration is carried out continuously) and anabolic bone responses (if drug administration is carried out intermittently). The model also features a non-linear relation between bone gain and drug dose (as known from experiments) doubling the dose from 80 μg/kg/day to 160 μg/kg/day induced a 1.3-fold increase of the bone volume-to-total volume ratio. Furthermore, the model presented in this paper confirmed that bone modelling represents an essential mechanism of the anabolic response of bone to PTH(1-34) administration in rat models, and that the large amount of bone formation observed in such models cannot be explained via remodelling alone.
Publisher: Wiley
Date: 17-01-2014
DOI: 10.1002/JBMR.2055
Abstract: The long-term benefits of habitual physical activity during adolescence on adult bone structure and strength are poorly understood. We investigated whether physically active adolescents had greater bone size, density, content, and estimated bone strength in young adulthood when compared to their peers who were inactive during adolescence. Peripheral quantitative computed tomography (pQCT) was used to measure the tibia and radius of 122 (73 females) participants (age mean ± SD, 29.3 ± 2.3 years) of the Saskatchewan Pediatric Bone Mineral Accrual Study (PBMAS). Total bone area (ToA), cortical density (CoD), cortical area (CoA), cortical content (CoC), and estimated bone strength in torsion (SSIp ) and muscle area (MuA) were measured at the diaphyses (66% tibia and 65% radius). Total density (ToD), trabecular density (TrD), trabecular content (TrC), and estimated bone strength in compression (BSIc ) were measured at the distal ends (4%). Participants were grouped by their adolescent physical activity (PA) levels (inactive, average, and active) based on mean PA Z-scores obtained from serial questionnaire assessments completed during adolescence. We compared adult bone outcomes across adolescent PA groups in each sex using analysis of covariance followed by post hoc pairwise comparisons with Bonferroni adjustments. When adjusted for adult height, MuA, and PA, adult males who were more physically active than their peers in adolescence had 13% greater adjusted torsional bone strength (SSIp , p < 0.05) and 10% greater adjusted ToA (p < 0.05) at the tibia diaphysis. Females who were more active in adolescence had 10% larger adjusted CoA (p < 0.05), 12% greater adjusted CoC (p < 0.05) at the tibia diaphysis, and 3% greater adjusted TrC (p < 0.05) at the distal tibia when compared to their inactive peers. Benefits to tibia bone size, content, and strength in those who were more active during adolescence seemed to persist into young adulthood, with greater ToA and SSIp in males, and greater CoA, CoC, and TrC in females.
Publisher: Wiley
Date: 22-09-2020
DOI: 10.1002/JBMR.4124
Publisher: Routledge
Date: 27-02-2011
Publisher: Elsevier
Date: 2018
Publisher: Elsevier BV
Date: 12-2017
Publisher: Wiley
Date: 03-01-2022
DOI: 10.1002/JBMR.4700
Abstract: Cortical bone remodeling is carried out by basic multicellular units (BMUs), which couple resorption to formation. Although fluorochrome labeling has facilitated study of BMU formative parameters since the 1960s, some resorptive parameters, including the longitudinal erosion rate (LER), have remained beyond reach of direct measurement. Indeed, our only insights into this spatiotemporal parameter of BMU behavior come from classical studies that indirectly inferred LER. Here, we demonstrate a 4D in vivo method to directly measure LER through in‐line phase contrast synchrotron imaging. The tibias of rabbits ( n = 15) dosed daily with parathyroid hormone were first imaged in vivo (synchrotron micro‐CT day 15) and then ex vivo 14 days later (conventional micro‐CT day 29). Mean LER assessed by landmarking the co‐registered scans was 23.69 ± 1.73 μm/d. This novel approach holds great promise for the direct study of the spatiotemporal coordination of bone remodeling, its role in diseases such as osteoporosis, as well as related treatments. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
Publisher: Springer Science and Business Media LLC
Date: 13-05-2019
DOI: 10.1007/S10237-019-01158-W
Abstract: Significant progress has been made to identify the cells and signaling molecules involved in the mechanobiological regulation of bone remodeling. It is now well accepted that osteocytes act as mechanosensory cells in bone expressing several signaling molecules such as nitric oxide (NO) and sclerostin (Scl) which are able to control bone remodeling responses. In this paper, we present a comprehensive multiscale computational model of bone remodeling which incorporates biochemical osteocyte feedback. The mechanostat theory is quantitatively incorporated into the model using mechanical feedback to control expression levels of NO and Scl. The catabolic signaling pathway RANK-RANKL-OPG is co-regulated via (continuous) PTH and NO, while the anabolic Wnt signaling pathway is described via competitive binding reactions between Wnt, Scl and the Wnt receptors LRP5/6. Using this novel model of bone remodeling, we investigate the effects of changes in the mechanical loading and hormonal environment on bone balance. Our numerical simulations show that we can calibrate the mechanostat anabolic and catabolic regulatory mechanisms so that they are mutually exclusive. This is consistent with previous models that use a Wolff-type law to regulate bone resorption and formation separately. Furthermore, mechanical feedback provides an effective mechanism to obtain physiological bone loss responses due to mechanical disuse and/or osteoporosis.
Publisher: American Chemical Society (ACS)
Date: 27-11-2017
DOI: 10.1021/ACS.LANGMUIR.7B01350
Abstract: The nature of trapped air on submersed ultra-water-repellent interfaces has been investigated. These gaseous layers (plastrons) can last from hours to, in some ex les such as the Salvinia molesta fern, months. The interface of submerged superhydrophobic surfaces with carefully controlled micropatterned surface roughness has been probed using synchrotron-based high-resolution X-ray phase tomography. This technique looks in situ, through the aqueous/gas interface in three dimensions. Long-term plastron stability appears to correlate with the appearance of scattered microdroplets <20 μm in diameter that are sandwiched within the 30 μm thick gaseous interfacial layer. These microdroplets are centered on defects or damaged sections within the substrate surface approximately 20-50 μm apart. Such irregularities represent heterogeneous micro/nano-hierarchical structures with varying surface structures and chemistry. The stability of microdroplets is governed by a combination of electrostatic repulsion, contact angle limitations, and a saturated vapor pressure, the latter of which reduces the rate of diffusion of gas out of the air layer, thus increasing underwater longevity. Homogenous surfaces exhibiting purely nano- or micro-regularity do not support such microdroplets, and, as a consequence, plastrons can disappear in 160 h for surfaces with scattered microdroplets. Such behavior may be a requirement for long-term nonwetting in any system.
Start Date: 10-2023
End Date: 09-2026
Amount: $397,000.00
Funder: Australian Research Council
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