Medial Scapular Body (MSB) Goutallier Classification - MRI based reliability and validity of evaluation of the Goutallier classification for grading fatty infiltration of the rotator cuff.

INTRODUCTION: The degree of atrophy and fatty infiltration of rotator cuff muscle belly is a key predictor for cuff repairability. Traditionally, Goutallier grading of fatty infiltration is assessed at sagittal scapular Y-view. Massive rotator cuff tears are associated with tendon retraction and medial retraction of cuff musculature, resulting in medialization of the muscle bulk. Thus, standard Y-view can misrepresent the region of interest and may misguide clinicians when assessing repairability. It is hypothesized that by assessing the muscle belly with multiple medial sagittal MRI sections at medial scapular body, the Medial Scapular Body - Goutallier Classification (MSB-GC) will improve reliability and repeatability giving a more representative approximation to the degree of fatty infiltration, as compared with original Y-view. METHODS: Fatty infiltration of the rotator cuff muscles were classified based on the Goutallier grade (0 to 4) at three defined sections section 1: original Y-view; section 2: level of suprascapular notch; section 3: three cm medial to suprascapular notch on MRI scans. Six sub-specialist fellowship trained shoulder surgeons, and three musculoskeletal radiologists independently evaluated deidentified MRI scans of included patients. RESULTS: Out of 80 scans, 78% (n=62) were massive cuff tears involving supraspinatus, infraspinatus and subscapularis tendon. Inter-observer reliability (consistency between observers) for Goutallier grade was excellent for all three predefined sections (range:0.87-0.95). Intra-observer reliability (repeatability) for Goutallier grade was excellent for all three sections and four rotator cuff muscles (range:0.83-0.97). There was a moderate to strong positive correlation of Goutallier grades between sections 1 and 3 and between sections 2 and 3 and these were statistically significant (p<0.001). There was a reduction in the severity of fatty infiltration on the Goutallier classification from sections 1 to 3 across all muscles. 42.5% of both supraspinatus and infraspinatus were downgraded by one, 20% of supraspinatus and 3.8% of infraspinatus were downgraded by 2 and 2.5% of supraspinatus were downgraded by 3. CONCLUSION: This study found that applying the Goutallier classification to more medial MRI sections (MSB-GC) resulted in assignment of lower grades for all rotator cuff muscles. Additionally, this method demonstrated excellent test-retest reliability and repeatability. Inclusion of a more medial view or whole scapula on MRI, especially in advanced levels of tear retraction, could be more reliable and representative for assessment of the degree of fatty infiltration within the muscle bulk that could help predict tear repairability and therefore improve clinical decision-making which should be studied further in clinical studies.

Anterior deltoid muscle reflection using a deltopectoral approach is safe and does not influence outcome of reverse shoulder arthroplasty.

BACKGROUND: The deltopectoral approach is well accepted for shoulder arthroplasty procedures. The extended deltopectoral approach with detachment of the anterior deltoid from the clavicle allows increased joint exposure and can protect the anterior deltoid from traction injury. The efficacy of this extended approach has been demonstrated in anatomic total shoulder replacement surgery. However, this has not been shown in reverse shoulder arthroplasty (RSA). The primary aim of this study was to evaluate the safety of the extended deltopectoral approach in RSA. The secondary aim was to evaluate the performance of the deltoid reflection approach in terms of complications and surgical, functional, and radiologic outcomes up to 24 months after surgery. METHODS: A prospective, nonrandomized comparative study was performed between January 2012 and October 2020 including 77 patients in the deltoid reflection group and 73 patients in the comparative group. The decision for inclusion was based on patient and surgeon factors. Complications were recorded. Patients were followed up for ≥24 months to evaluate their shoulder function and undergo ultrasound evaluation. Functional outcome measures included the Oxford Shoulder Score, Disabilities of the Arm, Shoulder and Hand score, American Shoulder and Elbow Surgeons score, pain intensity (rated on visual analog scale [VAS] from 0 to 100), and range of motion (forward flexion, abduction, and external rotation). A regression analysis was performed to evaluate any factors of influence on the VAS score. RESULTS: There were no significant differences in the complication rate between the 2 groups (14.5% in deltoid reflection group and 13.8% in comparative group, P = .915). Ultrasound evaluation was available in 64 patients (83.1%), and no proximal detachment was observed. In addition, there were no significant differences in functional outcome measures both preoperatively and at 24 months after surgery between the groups assessed based on the mean VAS pain score, Oxford Shoulder Score, Disabilities of the Arm, Shoulder and Hand score, American Shoulder and Elbow Surgeons score, forward flexion, abduction, and external rotation. Adjustment for possible confounders in a regression model indicated that only prior surgery significantly influenced the VAS pain score after surgery (P = .031; 95% confidence interval, 0.574-11.67). Deltoid reflection (P = .068), age (P = .466), sex (P = .936), use of glenoid graft (P = .091), prosthesis manufacturer (P = .382), and preoperative VAS score (P = .362) were not of influence. DISCUSSION: The results of this study show that an extended deltopectoral approach for RSA is safe. Selected reflection of the anterior deltoid muscle improved exposure and prevented anterior deltoid muscle injury followed by reattachment. Patients had similar functional scores preoperatively and at 24 months postoperatively compared with a comparative group. Furthermore, ultrasound evaluation showed intact reattachments.

A biomechanical analysis of double-screw, double-button, and screw-button fixation constructs in patient-specific instrument-guided Latarjet procedure.

BACKGROUND: The Latarjet coracoid transfer procedure reliably stabilizes the glenohumeral joint for shoulder instability. However, complications such as graft osteolysis, nonunion and fracture continue to affect patient clinical outcomes. The double-screw (SS) construct is regarded as the gold standard method of fixation. SS constructs are associated with graft osteolysis. More recently, a double-button technique (BB) has been suggested to minimize graft-related complications. However, BB constructs are associated with fibrous nonunion. To mitigate this risk, a single screw combined with a single button (SB) construct has been proposed. It is thought that this technique incorporates the strength of the SS construct and allows micromotion superiorly to mitigate stress shielding-related graft osteolysis. AIMS: The primary aim of this study was to compare the failure load of SS, BB, and SB constructs under a standardized biomechanical loading protocol. The secondary aim was to characterize the displacement of each construct throughout testing. METHODS: Computed tomography scans of 20 matched-pair cadaveric scapulae were performed. Specimens were harvested and dissected free of soft tissue. SS and BB techniques were randomly assigned to specimens for matched-pair comparison with SB trials. A patient-specific instrument (PSI)-guided Latarjet procedure was performed on each scapula. Specimens were tested using a uniaxial mechanical testing device under cyclic loading (100 cycles, 1 Hz, 200 N/s) followed by a load-to-failure protocol (0.5 mm/s). Construct failure was defined by graft fracture, screw avulsion, and/or graft displacement of more than 5 mm. RESULTS: Forty scapulae from 20 fresh frozen cadavers with a mean age of 69.3 years underwent testing. On average, SS constructs failed at 537.8 N (SD 296.8), whereas BB constructs failed at 135.1 N (SD 71.4). SB constructs required a significantly greater load to fail compared with BB constructs (283.5 N, SD 162.8, P = .039). Additionally, SS (1.9 mm, IQR 0.87) had a significantly lower maximum total graft displacement during the cyclic loading protocol compared with SB (3.8 mm, IQR 2.4, P = .007) and BB (7.4 mm, IQR 3.1, P < .001) constructs. CONCLUSION: These findings support the potential of the SB fixation technique as a viable alternative to SS and BB constructs. Clinically, the SB technique could reduce the incidence of loading-related graft complications seen in the first 3 months of BB Latarjet cases. The study is limited to time-specific results and does not account for bone union or osteolysis.

Modelling Human Locomotion to Inform Exercise Prescription for Osteoporosis.

PURPOSE OF REVIEW: We review the literature on hip fracture mechanics and models of hip strain during exercise to postulate the exercise regimen for best promoting hip strength. RECENT FINDINGS: The superior neck is a common location for hip fracture and a relevant exercise target for osteoporosis. Current modelling studies showed that fast walking and stair ambulation, but not necessarily running, optimally load the femoral neck and therefore theoretically would mitigate the natural age-related bone decline, being easily integrated into routine daily activity. High intensity jumps and hopping have been shown to promote anabolic response by inducing high strain in the superior anterior neck. Multidirectional exercises may cause beneficial non-habitual strain patterns across the entire femoral neck. Resistance knee flexion and hip extension exercises can induce high strain in the superior neck when performed using maximal resistance loadings in the average population. Exercise can stimulate an anabolic response of the femoral neck either by causing higher than normal bone strain over the entire hip region or by causing bending of the neck and localized strain in the superior cortex. Digital technologies have enabled studying interdependences between anatomy, bone distribution, exercise, strain and metabolism and may soon enable personalized prescription of exercise for optimal hip strength.

Muscular Coordination of Single-Leg Hop Landing in Uninjured and Anterior Cruciate Ligament-Reconstructed Individuals.

This study compared lower-limb muscle function, defined as the contributions of muscles to center-of-mass support and braking, during a single-leg hopping task in anterior cruciate ligament-reconstructed (ACLR) individuals and uninjured controls. In total, 65 ACLR individuals and 32 controls underwent a standardized anticipated single-leg forward hop. Kinematics and ground reaction force data were input into musculoskeletal models to calculate muscle forces and to quantify muscle function by decomposing the vertical (support) and fore-aft (braking) ground reaction force components into contributions by individual lower-limb muscles. Four major muscles, the vasti, soleus, gluteus medius, and gluteus maximus, were primarily involved in support and braking in both ACLR and uninjured groups. However, although the ACLR group demonstrated lower peak forces for these muscles (all Ps < .001, except gluteus maximus, P = .767), magnitude differences in these muscles' contributions to support and braking were not significant. ACLR individuals demonstrated higher erector spinae (P = .012) and hamstrings forces (P = .085) to maintain a straighter, stiffer landing posture with more forward lumbar flexion. This altered landing posture may have enabled the ACLR group to achieve similar muscle function to controls, despite muscle force deficits. Our findings may benefit rehabilitation and the development of interventions to enable faster and safer return to sport.

Computational model of the dual action of PTH - Application to a rat model of osteoporosis.

This paper presents a pharmacokinetic/pharmacodynamic (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.

Effect of Polyester and Plaster of Paris Casts on Determination of Volumetric Bone Mineral Density Assessed by Peripheral Quantitative Computed Tomography (pQCT).

Peripheral quantitative computed tomography (pQCT) is a non-invasive, low-radiation tool for measuring volumetric bone mineral density. It has potential for use in fracture healing applications; however, the unknown attenuation effects of cast material on peripheral quantitative computed tomography have contributed to its limited use in this area. The effect of two common cast materials, polyester and Plaster of Paris was investigated by performing both in vitro and in vivo studies. The in vitro study tested the effect of increasing layers of cast material on bone density measurements performed on a hydroxyapatite phantom. Cast thickness was directly associated with a reduction in bone mineral density, with twelve layers of polyester and Plaster of Paris resulting in a 0.55 and 2.21 % decrease in bone density measurements. Precision error in situ with polyester cast material was 0.71 %, and 2.31 % with Plaster of Paris cast material. The in vivo study comprised a prospective trial with 28 healthy adult participants to evaluate the effect of the two cast materials. Trabecular bone mineral density was increased by 0.5 % in the presence of a polyester cast and decreased by 4.22 % in the presence of a Plaster of Paris cast. Cortical bone mineral density was decreased by 3.46 and 5.54 % for polyester and Plaster of Paris, respectively. This study quantified the effects of orthopaedic casts on pQCT-derived bone parameters. The results suggest applicability of commonly utilised cast materials in combination with pQCT to assess fracture healing.

Bone turnover and mineralisation kinetics control trabecular BMDD and apparent bone density: insights from a discrete statistical bone remodelling model.

The mechanical quality of trabecular bone is influenced by its mineral content and spatial distribution, which is controlled by bone remodelling and mineralisation. Mineralisation kinetics occur in two phases: a fast primary mineralisation and a secondary mineralisation that can last from several months to years. Variations in bone turnover and mineralisation kinetics can be observed in the bone mineral density distribution (BMDD). Here, we propose a statistical spatio-temporal bone remodelling model to study the effects of bone turnover (associated with the activation frequency Ac . f ) and mineralisation kinetics (associated with secondary mineralisation T sec ) on BMDD. In this model, individual basic multicellular units (BMUs) are activated discretely on trabecular surfaces that undergo typical bone remodelling periods. Our results highlight that trabecular BMDD is strongly regulated by Ac . f and T sec in a coupled way. Ca wt% increases with lower Ac . f and short T sec . For example, a Ac . f = 4 BMU/year/mm 3 and T sec = 8 years result in a mean Ca wt% of 25, which is in accordance with Ca wt% values reported in quantitative backscattered electron imaging (qBEI) experiments. However, for lower Ac . f and shorter T sec (from 0.5 to 4 years) one obtains a high Ca wt% and a very narrow skew BMDD to the right. This close link between Ac . f and T sec highlights the importance of considering both characteristics to draw meaningful conclusion about bone quality. Overall, this model represents a new approach to modelling healthy and diseased bone and can aid in developing deeper insights into disease states like osteoporosis.

Advances in mechanobiological pharmacokinetic-pharmacodynamic models of osteoporosis treatment - Pathways to optimise and exploit existing therapies.

Osteoporosis (OP) is a chronic progressive bone disease which is characterised by reduction of bone matrix volume and changes in the bone matrix properties which can ultimately lead to bone fracture. The two major forms of OP are related to aging and/or menopause. With the worldwide increase of the elderly population, particularly age-related OP poses a serious health issue which puts large pressure on health care systems. A major challenge for development of new drug treatments for OP and comparison of drug efficacy with existing treatments is due to current regulatory requirements which demand testing of drugs based on bone mineral density (BMD) in phase 2 trials and fracture risk in phase 3 trials. This requires large clinical trials to be conducted and to be run for long time periods, which is very costly. This, together with the fact that there are already many drugs available for treatment of OP, makes the development of new drugs inhibitive. Furthermore, an increased trend of the use of different sequential drug therapies has been observed in OP management, such as sequential anabolic-anticatabolic drug treatment or switching from one anticatabolic drug to another. Running clinical trials for concurrent and sequential therapies is neither feasible nor practical due to large number of combinatorial possibilities. In silico mechanobiological pharmacokinetic-pharmacodynamic (PK-PD) models of OP treatments allow predictions beyond BMD, i.e. bone microdamage and degree of mineralisation can also be monitored. This will help to inform clinical drug usage and development by identifying the most promising scenarios to be tested clinically (confirmatory trials rather than exploratory only trials), optimise trial design and identify subgroups of the population that show benefit-risk profiles (both good and bad) that are different from the average patient. In this review, we provide examples of the predictive capabilities of mechanobiological PK-PD models. These include simulation results of PMO treatment with denosumab, implications of denosumab drug holidays and coupling of bone remodelling models with calcium and phosphate systems models that allows to investigate the effects of co-morbidities such as hyperparathyroidism and chronic kidney disease together with calcium and vitamin D status on drug efficacy.

Cortical bone adaptation response is region specific, but not peak load dependent: insights from µ CT image analysis and mechanostat simulations of the mouse tibia loading model.

The two major aims of the present study were: (i) quantify localised cortical bone adaptation at the surface level using contralateral endpoint imaging data and image analysis techniques, and (ii) investigate whether cortical bone adaptation responses are universal or region specific and dependent on the respective peak load. For this purpose, we re-analyse previously published µ CT data of the mouse tibia loading model that investigated bone adaptation in response to sciatic neurectomy and various peak load magnitudes (F = 0, 2, 4, 6, 8, 10, 12 N). A beam theory-based approach was developed to simulate cortical bone adaptation in different sections of the tibia, using longitudinal strains as the adaptive stimuli. We developed four mechanostat models: universal, surface-based, strain directional-based, and combined surface and strain direction-based. Rates of bone adaptation in these mechanostat models were computed using an optimisation procedure (131,606 total simulations), performed on a single load case (F = 10 N). Subsequently, the models were validated against the remaining six peak loads. Our findings indicate that local bone adaptation responses are quasi-linear and bone region specific. The mechanostat model which accounted for differences in endosteal and periosteal regions and strain directions (i.e. tensile versus compressive) produced the lowest root mean squared error between simulated and experimental data for all loads, with a combined prediction accuracy of 76.6, 55.0 and 80.7% for periosteal, endosteal, and cortical thickness measurements (in the midshaft of the tibia). The largest root mean squared errors were observed in the transitional loads, i.e. F = 2 to 6 N, where inter-animal variability was highest. Finally, while endpoint imaging studies provide great insights into organ level bone adaptation responses, the between animal and loaded versus control limb variability make simulations of local surface-based adaptation responses challenging.

An in silico approach to elucidate the pathways leading to primary osteoporosis: age-related vs. postmenopausal.

Numerical models of bone remodelling have traditionally been used to perform in silico tests of bone loss in postmenopausal women and also to simulate the response to different drug treatments. These models simulate the menopausal oestrogen decline by altering certain signalling pathways. However, they do not consider the simultaneous effect that ageing can have on cell function and bone remodelling, and thus on bone loss. Considering ageing and oestrogen decline together is important for designing osteoporosis treatments that can selectively counteract one or the other disease mechanism. A previously developed bone cell population model was adapted to consider the effect of ageing through: (1) the decrease of TGF- ß contained in the bone matrix and (2) an increased production of sclerostin by non-skeletal cells. Oestrogen deficiency is simulated in three different ways: (a) an increase in RANKL expression, (b) a decrease in OPG production, and (c) an increase in the responsiveness of osteoclasts to RANKL. The effect of ageing was validated using the cross-sectional study of (Riggs et al. in J Bone Miner Res 19: 1945-1954, 2004) on BMD of trabecular bone of the vertebral body of men. The joint effect of ageing and oestrogen deficiency was validated using these same clinical results but in women. In ageing, the effect of the increasing production of sclerostin is more important than the decrease of TGF- ß , while the three mechanisms used to simulate the effect of oestrogen deficiency produce almost identical responses. The results show that an early menopause leads to a lower average density in the fifth decade, but after the sixth decade the average density is independent of the age at menopause. Treatment of osteoporosis with denosumab was also simulated to conclude that the drug is not very effective if started before 10 years after menopause or before age 60.

Glucocorticoids disrupt longitudinal advance of cortical bone basic multicellular units in the rabbit distal tibia.

Glucocorticoids (GCs) are the leading cause of secondary osteoporosis. The emerging perspective, derived primarily from 2D histological study of trabecular bone, is that GC-induced bone loss arises through the uncoupling of bone formation and resorption at the level of the basic multicellular unit (BMU), which carries out bone remodeling. Here we explore the impact of GCs on cortical bone remodeling in the rabbit model. Based upon the rapid reduction of bone formation and initial elevation of resorption caused by GCs, we hypothesized that the rate of advance (longitudinal erosion rate; LER) of cortical BMUs would be increased. To test this hypothesis we divided 20 female New Zealand White rabbits into four experimental groups: ovariohysterectomy (OVH), glucocorticoid (GC), OVH + GC and SHAM controls (n = 5 animals each). Ten weeks post-surgery (OVH or sham), and two weeks after the initiation of dosing (daily subcutaneous injections of 1.5 mg/kg of methylprednisolone sodium succinate in the GC-treated groups and 1 ml of saline for the others), the right tibiae were scanned in vivo using Synchrotron Radiation (SR) in-line phase contrast micro-CT at the Canadian Light Source. After an additional 2 weeks of dosing, the rabbits were euthanized and ex vivo images were collected using desktop micro-CT. The datasets were co-registered in 3D and LER was calculated as the distance traversed by BMU cutting-cones in the 14-day interval between scans. Counter to our hypothesis, LER was greatly reduced in GC-treated rabbits. Mean LER was lower in GC (4.27 µm/d; p < 0.001) and OVH + GC (4.19 µm/d; p < 0.001), while similar in OVH (40.13 µm/d; p = 0.990), compared to SHAM (40.44 µm/d). This approximately 90 % reduction in LER with GCs was also associated with an overall disruption of BMU progression, with radial expansion of the remodeling space occurring in all directions. This unexpected outcome suggests that GCs do not simply uncouple formation and resorption within cortical BMUs and highlights the value of the time-lapsed 4D approach employed.

Achieving maximal voluntary contraction of paraspinal muscles requires two tasks: Insight from an EMG study of females with and without adolescent idiopathic scoliosis.

An accurate estimation of maximal voluntary muscle activation is critical for normalisation in scientific studies. Only a handful of studies appropriately normalise muscle activation data when investigating paraspinal muscle activity in populations such as adolescent idiopathic scoliosis (AIS). This neglect compromises the ability to interpret data. The aim of this study was to determine the type of trunk extension task that reliably achieves peak paraspinal muscle activation in participants with and without AIS. Adolescent females with typically developing spines (controls: n = 20, mean[SD] age 13.1[1.8]years), or primary right thoracic AIS (n = 24, age: 13.8[1.5]years, Cobb angle thoracic: 39.5[16.4]°, lumbar: 28.0[11.6]°) performed a series of 3x unresisted and 3x resisted maximal voluntary trunk extensions in prone. Paraspinal muscle activation was recorded bilaterally at two thoracic levels and one lumbar level using surface electromyography (EMG). Muscle activation was highly repeatable within task [ICC 0.77-0.95, all p < 0.01]. At group level, there were no differences in peak muscle activation between tasks irrespective of side (left/right) or vertebral level (Estimate 0.98, 95%CI 0.36 to 2.65, p=0.97). Peak activation was achieved with the unresisted task in 40.5%, and resisted task in 59.5% of the total outcomes (6 recording locations, 44 participants). Individual participant maximum amplitude varied up to 64% (mean[SD]:18[13]%) between the unresisted and resisted tasks. We recommend that both the resisted and unresisted trunk extension tasks are used to increase confidence that a maximum voluntary activation of paraspinal muscles is achieved. Failure to do so could introduce large error in the estimations of muscle activation.

Cortical thickness adaptation to combined mechanical loading and parathyroid hormone treatments is site specific and synergistic in the mouse tibia model.

In this study, we aimed to quantify the localised effects of mechanical loading (ML), low (20 µg/kg/day), moderate (40 µg/kg/day) or high (80 µg/kg/day) dosages of parathyroid hormone (PTH), and combined (PTHML) treatments on cortical bone adaptation in healthy 19-week old female C57BL/6 mice. To this end, we utilise a previously reported image analysis algorithm on µCT data of the mouse tibia published by Sugiyama et al. (2008) to measure changes in cortical area, marrow cavity area and local cortical thickness measures (ΔCt.Ar, ΔMa.Ar, ΔCt.Th respectively), evaluated at two cross-sections within the mouse tibia (proximal-middle (37 %) and middle (50 %)), and are compared to a superposed summation (P + M) of individual treatments to determine the effectiveness of combining treatments in vivo. ΔCt.Ar analysis revealed a non-linear, synergistic interactions between PTH and ML in the 37 % cross-section that saturates at higher PTH dosages, whereas the 50 % cross-section experiences an approximately linear, additive adaptation response. This coincided with an increase in ΔMa.Ar (indicating resorption of the endosteal surface), which was only counteracted by combined high dose PTH with ML in the middle cross-section. Regional analysis of ΔCt.Th changes reveal localised cortical thinning in response to low dose PTH treatment in the posteromedial region of the middle cross-section, signifying that PTH does not provide a homogeneous adaptation response around the cortical perimeter. We observe a synergistic response in the proximal-middle cross-section, with regions of compressive strain experiencing the greatest adaptation response to PTHML treatments, (peak ΔCt.Th of 189.32, 213.78 and 239.30 µm for low, moderate and high PTHML groups respectively). In contrast, PTHML treatments in the middle cross-section show a similar response to the superposed P + M group, with the exception of the combined high dose PTHML treatment which shows a synergistic interaction. These analyses suggest that, in mice, adding mechanical loading to PTH treatments leads to region specific bone responses; synergism of PTHML is only achieved in some regions experiencing high loading, while other regions respond additively to this combined treatment.

The loading direction dramatically affects the mechanical properties of the mouse tibia.

Introduction: The in vivo tibial loading mouse model has been extensively used to evaluate bone adaptation in the tibia after mechanical loading treatment. However, there is a prevailing assumption that the load is applied axially to the tibia. The aim of this in silico study was to evaluate how much the apparent mechanical properties of the mouse tibia are affected by the loading direction, by using a validated micro-finite element (micro-FE) model of mice which have been ovariectomized and exposed to external mechanical loading over a two-week period. Methods: Longitudinal micro-computed tomography (micro-CT) images were taken of the tibiae of eleven ovariectomized mice at ages 18 and 20 weeks. Six of the mice underwent a mechanical loading treatment at age 19 weeks. Micro-FE models were generated, based on the segmented micro-CT images. Three models using unitary loads were linearly combined to simulate a range of loading directions, generated as a function of the angle from the inferior-superior axis (θ, 0°-30° range, 5° steps) and the angle from the anterior-posterior axis (ϕ, 0°: anterior axis, positive anticlockwise, 0°-355° range, 5° steps). The minimum principal strain was calculated and used to estimate the failure load, by linearly scaling the strain until 10% of the nodes reached the critical strain level of -14,420 µÎµ. The apparent bone stiffness was calculated as the ratio between the axial applied force and the average displacement along the longitudinal direction, for the loaded nodes. Results: The results demonstrated a high sensitivity of the mouse tibia to the loading direction across all groups and time points. Higher failure loads were found for several loading directions (θ = 10°, ϕ 205°-210°) than for the nominal axial case (θ = 0°, ϕ = 0°), highlighting adaptation of the bone for loading directions far from the nominal axial one. Conclusion: These results suggest that in studies which use mouse tibia, the loading direction can significantly impact the failure load. Thus, the magnitude and direction of the applied load should be well controlled during the experiments.

Assessment of thoracic spinal curvatures in static postures using spatially tracked 3D ultrasound volumes: a proof-of-concept study.

The assessment of spinal posture is a difficult endeavour given the lack of identifiable bony landmarks for placement of skin markers. Moreover, potentially significant soft tissue artefacts along the spine further affect the accuracy of marker-based approaches. The objective of this proof-of-concept study was to develop an experimental framework to assess spinal postures by using three-dimensional (3D) ultrasound (US) imaging. A phantom spine model immersed in water was scanned using 3D US in a neutral and two curved postures mimicking a forward flexion in the sagittal plane while the US probe was localised by three electromagnetic tracking sensors attached to the probe head. The obtained anatomical 'coarse' registrations were further refined using an automatic registration algorithm and validated by an experienced sonographer. Spinal landmarks were selected in the US images and validated against magnetic resonance imaging data of the same phantom through image registration. Their position was then related to the location of the tracking sensors identified in the acquired US volumes, enabling the localisation of landmarks in the global coordinate system of the tracking device. Results of this study show that localised 3D US enables US-based anatomical reconstructions comparable to clinical standards and the identification of spinal landmarks in different postures of the spine. The accuracy in sensor identification was 0.49 mm on average while the intra- and inter-observer reliability in sensor identification was strongly correlated with a maximum deviation of 0.8 mm. Mapping of landmarks had a small relative distance error of 0.21 mm (SD = ± 0.16) on average. This study implies that localised 3D US holds the potential for the assessment of full spinal posture by accurately and non-invasively localising vertebrae in space.

Effect of neglecting passive spinal structures: a quantitative investigation using the forward-dynamics and inverse-dynamics musculoskeletal approach.

Purpose: Inverse-dynamics (ID) analysis is an approach widely used for studying spine biomechanics and the estimation of muscle forces. Despite the increasing structural complexity of spine models, ID analysis results substantially rely on accurate kinematic data that most of the current technologies are not capable to provide. For this reason, the model complexity is drastically reduced by assuming three degrees of freedom spherical joints and generic kinematic coupling constraints. Moreover, the majority of current ID spine models neglect the contribution of passive structures. The aim of this ID analysis study was to determine the impact of modelled passive structures (i.e., ligaments and intervertebral discs) on remaining joint forces and torques that muscles must balance in the functional spinal unit. Methods: For this purpose, an existing generic spine model developed for the use in the demoa software environment was transferred into the musculoskeletal modelling platform OpenSim. The thoracolumbar spine model previously used in forward-dynamics (FD) simulations provided a full kinematic description of a flexion-extension movement. By using the obtained in silico kinematics, ID analysis was performed. The individual contribution of passive elements to the generalised net joint forces and torques was evaluated in a step-wise approach increasing the model complexity by adding individual biological structures of the spine. Results: The implementation of intervertebral discs and ligaments has significantly reduced compressive loading and anterior torque that is attributed to the acting net muscle forces by -200% and -75%, respectively. The ID model kinematics and kinetics were cross-validated against the FD simulation results. Conclusion: This study clearly shows the importance of incorporating passive spinal structures on the accurate computation of remaining joint loads. Furthermore, for the first time, a generic spine model was used and cross-validated in two different musculoskeletal modelling platforms, i.e., demoa and OpenSim, respectively. In future, a comparison of neuromuscular control strategies for spinal movement can be investigated using both approaches.

Spatio-temporal simulations of bone remodelling using a bone cell population model based on cell availability.

Here we developed a spatio-temporal bone remodeling model to simulate the action of Basic Multicelluar Units (BMUs). This model is based on two major extensions of a temporal-only bone cell population model (BCPM). First, the differentiation into mature resorbing osteoclasts and mature forming osteoblasts from their respective precursor cells was modelled as an intermittent process based on precursor cells availability. Second, the interaction between neighbouring BMUs was considered based on a "metabolic cost" argument which warrants that no new BMU will be activated in the neighbourhood of an existing BMU. With the proposed model we have simulated the phases of the remodelling process obtaining average periods similar to those found in the literature: resorption ( ∼ 22 days)-reversal (∼8 days)-formation (∼65 days)-quiescence (560-600 days) and an average BMU activation frequency of ∼1.6 BMUs/year/mm3. We further show here that the resorption and formation phases of the BMU become coordinated only by the presence of TGF-ß (transforming growth factor ß), i.e., a major coupling factor stored in the bone matrix. TGF-ß is released through resorption so upregulating osteoclast apoptosis and accumulation of osteoblast precursors, i.e., facilitating the transition from the resorption to the formation phase at a given remodelling site. Finally, we demonstrate that this model can explain targeted bone remodelling as the BMUs are steered towards damaged bone areas in order to commence bone matrix repair.

Engineering the perfect mattress: The influence of substrate mechanics on deep tissue stresses in supine.

BACKGROUND: With increasing global interest in sleep hygiene, sleep ergonomics is an area that has been largely understudied. During sleep individuals turn over during the night to restore blood flow in occluded blood vessels, indicating that control of local tissue pressure may play a role in improving sleep comfort. This study investigates the influence of mattress stiffness on tissue compressive stresses during supine lying. METHODS: A subject-specific 3D finite element (FE) model of the pelvis area has been developed to simulate supine lying on substrates of varying firmness. Constitutive parameters for the adipose-skin tissue and muscle-organ tissue were calibrated using a novel application of the inverse finite element method. FINDINGS: The compressive stress was consistently greatest in the muscle interfacing the sacrum at 18.5 kPa on the soft foam, and 30.9 kPa on the firm foam. From soft to firm, the compressive stress increased by 67% at the sacrum, 20% at the ischium, 42% at the lesser trochanter, and 50% at the skin. INTERPRETATION: The non-linearity of the foam substrate had a pressure distributing effect, relieving the peak compressive stresses at the sacrum, indicating that it may be possible to design arrays of foam substrates that can provide most efficient pressure relief.

Geometry and bone mineral density determinants of femoral neck strength changes following exercise.

Physical exercise induces spatially heterogeneous adaptation in bone. However, it remains unclear where the changes in BMD and geometry have the greatest impact on femoral neck strength. The aim of this study was to determine the principal BMD-and-geometry changes induced by exercise that have the greatest effect on femoral neck strength. Pre- and post-exercise 3D-DXA images of the proximal femur were collected of male participants from the LIFTMOR-M exercise intervention trial. Meshes with element-by-element correspondence were generated by morphing a template mesh to each bone to calculate changes in BMD and geometry. Finite element (FE) models predicted femoral neck strength changes under single-leg stance and sideways fall load. Partial least squares regression (PLSR) models were developed with BMD-only, geometry-only, and BMD-and-geometry changes to determine the principal modes that explained the greatest variation in neck strength changes. The PLSR models explained over 90% of the strength variation with 3 PLS components using BMD-only (R2 > 0.92, RMSE < 0.06 N) and 8 PLS components with geometry-only (R2 > 0.93, RMSE < 0.06 N). Changes in the superior neck and distal cortex were most important during single-leg stance while the superior neck, medial head, and lateral trochanter were most important during a sideways fall. Local changes in femoral neck and head geometry could differentiate the exercise groups from the control group. Exercise interventions may target BMD changes in the superior neck, inferior neck, and greater trochanter for improved femoral neck strength in single-leg stance and sideways fall.