Bones meet competing demands both structurally and metabolically with an ability to “functionally adapt” to the surrounding environment. Diets high in saturated fat and sucrose (HFS) can adversely affect bone by limiting calcium availability. Conversely, applying a mechanical stimulus, appropriate in magnitude, frequency, and rate has been shown to be osteogenic. Thus, we hypothesized that groups subject to a mechanical loading would incur skeletal benefits, whereas exposure to a HFS diet would adversely affect structural integrity. We also proposed that despite the osteogenic potential of loading stimuli, the calcium-limiting effects of a HFS diet would result in a net decrease in bone structural properties, when considered in combination.

Female mice underwent non-invasive exogenous cantilever bending of the right tibia with a 1Hz trapezoidal waveform for 60s, five days per week, for thee weeks. Loading was calibrated to induce peak strain magnitudes of 1000 microstrain. Mice were randomly assigned to one of two dietary cohorts: high-fat-sucrose (HFS, n=36) or adjusted starch diets (n=36). Mice were further subdivided into groups based on loading status: control, sham, or loaded. Upon sacrifice, tibiae were dissected; morphometrical and mechanical properties were assessed and compared.

Control mice fed a HFS diet had significantly reduced cross-sectional area, cortical thickness, maximal load, and energy to failure when compared to control mice fed the starch diet. No changes in material properties were seen. Mice eating a HFS diet as well as experiencing mechanical loading had significantly greater cross-sectional area, energy to failure, and maximal load when compared to control mice fed a HFS diet, but had reduced structural properties when compared with loaded mice within the starch cohort.

To date, bone structural properties, and not material properties were adversely affected as a result of ingesting a HFS diet. A diet effect was observed, between control mice fed a HFS diet and control mice fed a starch diet, with the former group experiencing the negative affects previously associated with HFS diets in rodents. Presently, a load effect was only observed within the HFS cohort.

The purpose of this study was to examine the interactive effects of diet and the aging process on the mechanical and material properties of bone. We investigated how an ad libitum (AL) diet and 40% caloric restriction (CR) with nutrient supplementation, beginning at 3.5 months of age, interacted with the aging process to influence bone development. Diet effects were determined by measuring changes in bone geometry and bone mechanics of the tibia in young adult and senescent Fischer 344 X Brown-Norway Rats (F344 BN) rats.

Male F344 BN rats were divided into two dietary groups, AL or CR. CR commenced at 14 weeks of age, with 40% restriction and micronutrient supplementation. The AL group represented young adult (8 mo) and senescent (30–35 mo) rats. The CR group represented 8 mo and 35–40 mo rats. AL and CR groups were matched together for comparison based on the percentage survival rate. Tibiae were assessed using microcomputed tomography, mechanical testing, and ash analysis.

The results showed that a CR diet resulted in a significant decrease in total body mass when compared to the AL diet group across all ages. With aging, both AL and CR diet groups showed a general increase in structural properties and a decrease in material properties. Furthermore, material and structural properties changed proportionately between both diet groups. Comparisons between diet groups based on percentage survival rate revealed a significant decrease in most structural properties, but no significant changes in material properties with CR. After normalization to body mass, structural properties were significantly greater in the CR group when compared to the AL group.

The significantly greater CR structural properties over the AL diet group after normalization, with no significant changes in material properties, indicated that CR did not adversely affect the appendicular skeleton in F344 BN rats. Therefore, a CR diet with 40% restriction at fourteen weeks, with nutrient supplementation did not negatively impact tibial geometrical and mechanical properties in young and senescent male F344 BN rats.

Purpose: The purpose of this study was to detect any possible prognostic factors which may affect the spinal deformity progression and their relationships in idiopathic scoliosis.

Methods: The stereo-radiograph of whole spine at each visit was reconstructed with two spinal x-ray images in PA 0° and 20° using DLT techniques. Sequential data sets with 3, 4 or 5 successive values of prognostic factors were extracted from 111 consecutive patients (12.3±2.3 yrs, Cobb angle 30.2±12.4°) and separated into the stable and the progressed groups, based on a progression threshold of Cobb angle 5° and 10°. The prognostic factors included gender, curve pattern, age, curve magnitude, apex location, lateral deviation and spinal growth. Effects of those factors were conducted by comparing them between two groups (statistical significances p< 0.05) and the relationships were determined using Pearson’s correlation coefficient (r).

Results: The progressed subjects were predominantly females (50–79%) with double curves. Double curves progressed on both curves RT and LL at the same times and alternatively. There were no significant differences of initial ages and ages with maximum curve magnitudes between two groups. Initial and maximum curve magnitudes were significantly large in the progressed group, but no significantly different between maximum curve magnitudes in the stable group and initial curve magnitude in the progressed group. High curve apex locations were observed in the progressed group. Initial and maximum apex lateral deviations were clearly different in two groups and correlated with curve magnitudes from well to excellent (r = 0.43–0.98). The relationships between the spinal growth and the curve progressing were not consistent (r = −0.6 – +0.6). There were no evidences to show the significant differences of spinal growths between groups and genders.

Conclusions: Scoliosis progression is case dependent. Double curves dynamically progress between curve regions. Initial curve magnitudes have more significant effect on the progression than initial ages. A great progression can be expected from curves with high apex location. Apex lateral deviations are changing with curve magnitudes and spinal growths and, however, the curve magnitudes are not always increased with spinal growths. Funding: 2 Funding Parties: Alberta Provincial CIHR Training Program in Bone and Joint Health

The pathogenesis of scoliosis progression remains poorly understood. Seventy-two subject data sets, consisting of four successive values of Cobb-angle and lateral deviations at apices for six and twelve-months intervals in the coronal plane, were used to train and test an artificial neural network (ANN) to predict spinal deformity progression. The accuracies of the trained ANN (3-4-1) for training and testing data were within 3.64° (±2.58°) and 4.40° (±1.86°) of Cobb angles, and within 3.59 (±3.96) mm and 3.98 (±3.41) mm of lateral deviations, respectively. The adapted technique for predicting the scoliosis deformity progression has promising clinical applications.

Scoliosis is a common and poorly understood three-dimensional spinal deformity. The study purpose is to predict scoliosis progression at six and twelve months intervals in the future using successive spinal indices with an artificial neural network (ANN).

The adapted ANN technique enables earlier detection of scoliosis progression with high accuracy. Improved prediction of scoliosis progression will impact bracing or surgical treatment decisions, and may decrease hazardous X-ray exposure.

Seventy-two data sets from adolescent idiopathic scoliosis subjects recruited at the Alberta Children’s Hospital were used in this study. Data sets composed of four successive values of Cobb angles and lateral deviations at apices for six and twelvemonth intervals (coronal plane) were extracted to train and test a specific ANN for predicting scoliosis progression.

Progression patterns in Cobb angles (n = 10) and lateral deviations (n = 8) were successfully identified. The accuracies of the trained ANN (3-4-1) with the training and testing data sets were 3.64° (±2.58°) and 4.40° (±1.86°) of Cobb angles, 3.59 (±3.96) mm and 3.98 (±3.41) mm of lateral deviations, respectively. These results are in close agreement with those using cubic spline extrapolation techniques (3.49° ± 1.85° and 3.31 ± 4.22 mm) and adaptive neuro-fuzzy inference system (3.92° ±3.53° and 3.37 ±3.95 mm) for the same testing data.

ANN can be a promising technique for prediction of scoliosis progression with substantial improvements in accuracy over current techniques, leading to potentially important implications for scoliosis monitoring and treatment decisions.

Funding: AHFMR, CIHR, Fraternal Order of Eagles, NSERC, GEOIDE.

Spine and torso models were generated concurrently with x-rays for twenty-three patients undergoing scoliosis brace treatment. Clinical indices of spinal deformity and torso surface asymmetry indices were computed from models obtained when patient was first recruited and at approximately one year’s follow-up. Significant correction changes of the torso shape were detected in indices including orientation of cross-sectional principal axes of inertia (p=0.048) and Back Surface Rotation (p=0.08) though spinal corrections were from not significant to subtle (0.20_p_0.88). Trunk asymmetry should be assessed for an objective evaluation and understanding of the effect produced by a specific treatment.

To assess changes in torso geometry and spinal deformity during treatment of idiopathic scoliosis with rigid brace.

Relationship between torso surface geometry and spinal deformity when a rigid brace is applied is essential for better understanding of brace treatment mechanism and optimal application of external forces.

Three-dimensional torso surface models were generated concurrently with postero-anterior x-rays for twenty-three patients undergoing scoliosis brace treatment, when first recruited and at approximately one year’s follow-up. Torso asymmetry indices describing principal axis orientation, back surface rotation, and asymmetry of the centroid line, left and right half-areas and the spinous process line were computed. The statistical paired t-Test (95% CI) was performed to test the probability that no difference exist after one year of treatment in both spinal and torso asymmetry indices.

After one year follow-up patients showed a mean increase of only 2° for the major Cobb angle. This was consistent with not significant to subtle corrections found in clinical (p=0.88) and computed (p=0.75) Cobb angle, lateral deviation (p=0.20), orientation of plane of maximum deformity (p= 0.58) and maximum vertebral axial rotation (p=0.83). Furthermore, significant correction changes of the torso shape were detected in the orientation of cross-sectional principal axes (PAX) of inertia (p=0.048) and Back Surface Rotation (p=0.08).

Here we have shown that we can acquire 3D torso surface and reliably measured a set of indices of transverse torso asymmetry. Future work will look at indication of predictive potential of torso surface indices.

Funding: AHFMR, CIHR, Fraternal Order of Eagles, NSERC, GEOIDE.

Bones can adapt in response to mechanical stimuli; higher rates of loading have been associated with greater bone formation rates. This study determined where bone accretion was localized in response to high loading rates. Non-invasive loads were applied to mice tibiae at one of three rates for four week. It was found, via calcein labels, that adaptation on the periosteal, but not endosteal, surface exhibited a dose-response relation with loading rate; periosteal and endosteal adaptation was localized to regions of high strain gradients. Understanding the stimuli bone responds to may underpin the development of non-pharmacological treatments to enhance bone mass.

Bones can adapt to mechanical stimuli; higher rates of loading have been linked with greater bone formation rates (BFR).

The purpose of this research was to determine if bone accretion associated with higher loading rates occurs in regions of high strain gradients or strain rates and if adaptation is similar on periosteal and endosteal surfaces.

Periosteal but not endosteal surfaces displayed a dose-response relation with loading rate. Adaptation on both periosteal and endosteal surfaces was localized to sectors with high strain gradients.

Understanding the precise stimuli by which bone responds may underpin the development of non-pharmacological treatments to enhance bone mass.

Tibia loaded at the high rate had significantly greater periosteal BFR, relative to tibiae loaded at medium (> 48 %) and low (> 104 %) rates; adaptation was localized to posterior sectors (high strain gradients). Endosteally, adaptation was localized to regions of high strain gradients (anterior sectors), but did not display a dose-response relation with loading rate.

Forty-three skeletally mature C57BL/6 mice were randomly assigned to one of three groups, based on loading rate; low (0.004 ε/s; n = 14), medium (0.020 ε/s; n = 15), and high (0.100 ε/s; n = 14). Loads were applied so that tibiae experienced non-invasive medio-lateral cantilever bending (peak strain = 1000 με) at 1 Hz, 60 s, 5 d/w, for 4 wk. Calcein bone labels were administered on d one and eighteen. A standardized sector of the tibial middiaphyeal shaft was digitally divided into 45° radial sectors, and prepared for histomorphometry.

Funding: Funded in part by NSERC, and CIHR

Studies have shown significantly shorter hospital stays and earlier return to mobilization when epidural analgesia was used in lower extremity surgeries. This study quantified the effects of epidural analgesia on lower extremity kinetics and kinematics during gait. There were no significant differences found in hip, knee, or ankle joint moments or angles between baseline (no drug) and epidural trials, using two different drugs. These findings indicate that epidural analgesia does not alter normal gait in healthy subjects, suggesting that patients requiring epidural analgesia following orthopaedic surgery may also be able to participate in rehabilitation without significant epidural-related changes in gait.

Epidural analgesia has been used post-operatively following chest, abdominal and lower extremity surgery, with significantly shorter hospital stay and earlier return to mobilization demonstrated. This study quantified the effects of epidural analgesia on lower extremity kinetics and kinematics during gait.

Ten healthy volunteers were tested on different days with two drugs. With the catheter (L3-L4 intervertebral space) in place but prior to drug administration, gait was assessed. Testing was repeated 30 min after drug administration. Motion and ground reaction force data were recorded during walking with a four-camera video-based system (Motion Analysis Corp) and force platform (Kistler).

No significant differences existed in 3-D hip, knee, or ankle joint moments or angles among baseline (no drug) and drug trials.

These findings indicate that epidural analgesia does not alter normal gait in healthy subjects, suggesting that patients requiring epidural analgesia following orthopaedic surgery may also be able to participate in rehabilitation without significant epidural-related changes in gait.

It is well documented that early mobilization and rehabilitation following orthopaedic surgery improve healing and shorten hospital stay. However, pain often limits full participation. Epidural analgesia appears to be an appropriate mode of pain relief that, despite somatosensory changes, may allow normal gait.

Epidural analgesia in healthy volunteers does not alter lower extremity kinetics or kinematics, suggesting that it may be an effective mode of pain relief that will allow better participation in therapy following orthopaedic surgery.

Funding: McCaig Professorship Program Development Fund, Wood Professorship, The Foothills Hospital Obstetric Anesthesia Research Fund, The National Science and Engineering Research Council of Canada, and The University of Calgary Biomedical Engineering Program.

Osteochondral allografts (frozen uncontrolled, or cryo-protected with dimethyl sulfoxide) were transplanted into medial femoral condyles of eighteen sheep. Cores from the ipsilateral graft site served as autografts for the contralateral limb. Analysis of graft and host cancellous bone microarchitecture by μCT at three months post transplant demonstrated no significant differences among the treatment groups. Dramatic bone resorption at the graft–host interface, however, occurred in up to 1/3 of condyles from all treatment groups, including fresh autografts suggesting that factors other than donor source or tissue storage played an important role in the bone incorporation of osteochondral grafts.

The purpose of this study was to study the effect of different freezing protocols on periarticular cancellous bone architecture after osteochondral allograft transplantation.

There were no significant differences in graft or host cancellous bone architecture among the groups (autografts, frozen allografts, cryopreserved allografts). Dramatic resorption of graft bone in condyles from all treatment groups suggested that factors other than donor source or tissue storage played important roles during incorporation of osteochondral grafts.

Graft positioning, graft orientation, and recipient bed necrosis may play significant roles during incorporation of osteochondral graft bone.

Osteochondral allografts (10 mm diameter) were transplanted into medial femoral condyles of eighteen skeletally mature Suffolk ewes. Allografts were frozen (–80°C) without cryoprotectant (FROZ) or treated with dimethyl sulfoxide (cryoprotectant) and frozen (–80°C at 1°C · min⁻¹) (CRYO). Osteochondral cores removed from ipsilateral graft sites served as fresh autografts (AUTO) for the contralateral medial femoral condyles. Condyles were harvested at three months and scanned (micro computed tomography –μCT). Three dimensional μCT data of graft and host cancellous bone regions were analyzed for bone volume fraction, trabecular thickness, bone surface–volume ratio, and trabecular anisotropy. No morphological differences were found among treatment groups. Excessive bone resorption of graft and interface precluded analysis of some samples from each group (ALLO — 2/9, CRYO — 3/9, AUTO — 6/18). Dramatic bone loss did not correlate with poor graft orientation, placement, infection, or recipient–bed necrosis, but a combination of these factors may contribute to excessive cancellous bone resorption in osteochondral grafts.

Funding: Medical Research Council of Canada, Canadian Institutes of Health Research, No commercial funding

Please contact author for figures and/or diagrams.

The relations among tissue quality, socket discomfort, gait characteristics, and socket pressures are not well established for the unilateral below-knee amputee population. These relations were evaluated for six amputees at seventeen regions of interest on the residual limb. Pressure sensors were placed directly on the residual limb. Peak dynamic socket pressures were not directly related to peak joint moments. However, increases in ground reaction forces (GRFs) related to increases in socket pressures.

The relations among tissue quality, socket discomfort, gait characteristics, and socket pressures are not well established for the unilateral below-knee amputee population. The purpose of this study was to evaluate these relations for six amputees. A thorough understanding of pressure distribution between the residual limb and prosthetic socket is critical to socket design and limb health. The subjects ranged in age from thirty to seventy-two years of age. The inclusion criteria were male, unilateral transtibial amputation, ability to ambulate independently, non-diabetic, no debilitating health conditions, non-recent amputee. Tissue sensation and socket discomfort were evaluated at seventeen regions of interest on the residual limb. Tissue sensation was assessed using Semmes-Weinstein monofilaments to test light touch/deep pressure sensation, tuning fork to test vibration sensation, and pinprick to test pain sensation. Socket discomfort was assessed using 10 cm Visual Analogue Scale. Gait characteristics were recorded during walking using a Motion Analysis System. Socket pressure measurements were made using F-socket pressure sensors in conjunction with I-Scan software program. Pressure sensors were placed directly on residual limb. Gait characteristics and socket pressures were compared across three different testing days. The site-specific tissue sensitivity scores did not correlate with the socket discomfort scores. In addition, site-specific discomfort scores did not correlate with peak socket pressures recorded at subject’s normal walking speed. Significant day-to-day pressure differences were found at four of the seventeen areas of interest. Peak dynamic socket pressures were not directly related to peak joint moments. Two subjects demonstrated direct relations between ground reaction forces (GRFs) and socket pressure on the different test days.

Funding: NSERC, Workers’ Compensation Board (Alberta), University of Calgary

Recent studies have shown that scoliotic deformity can be estimated accurately from deformity of the full three hundred and sixty degrees torso shape. However, acquisition of these data requires an expensive multi-scanner system. If it was possible to estimate accurately scoliosis from the back surface shape alone, a single scanner and simplified analysis methods could be used. Here, we estimated the Cobb angle within ten degrees in 84% of forty-six patients from back surface data, compared to 99% within ten degrees for a previous, larger study using the entire torso shape. These results suggested that both back-surface and full-torso models for Cobb angle estimation should be pursued for their potential merits.

The surface deformity of scoliosis, often the primary patient complaint, progresses non-linearly with the underlying spinal deformity. If it was possible to estimate reliably the degree of scoliosis from the surface, adolescent patients with non-progressing scoliosis could be spared harmful X-ray radiation. Some of us have previously estimated the scoliotic Cobb angle from three hundred and sixty degrees torso surface deformity. Here, we tested how accurately the Cobb angle could be estimated from back surface data alone, which are easier and less expensive to obtain than full-torso data.

A genetic algorithm selected the clinical parameters to be used by a neural network to estimate scoliosis deformity from back surface deformity. We had forty-six consecutive patients with right-thoracic curves (Cobb angles eleven to ninety-seven degrees), in whom fifteen indices were available including age, height, bracing status, scoliometer reading, back surface rotation, and cosmetic score of landmark asymmetry. Those data were used by a neural network to estimate the Cobb angle within ten degrees in 84% of patients, a 30% improvement over regression-model accuracy, though less accurate than use of the three hundred and sixty degrees torso shape which estimated up to 99% of curves within ten degrees in a previous study.

Neural network predictive accuracy was better when using the full three hundred and sixty degrees torso shape, but the simpler and more economical acquisition of back surface data alone also gave promising results. This pilot comparison study suggested that both models (using back surface data alone vs. using three hundred and sixty degrees torso data) should continue to be developed in attempts to optimize surface estimation of scoliosis.

Osteoarthritis (OA) involves pathology in both articular cartilage and subchondral bone. The osteoprotegerin (OPG)/receptor activator of nuclear factor kappa beta ligand (RANK-L) balance is known to modulate bone turnover. We compared the bony changes in human total knee arthroplasty (TKA) and cadaveric controls. A qualitative increase in subchondral and ligamentous insertional bone mineral density was observed on micro-CT sections of TKA bone compared with cadaveric controls. In-situ hybridization of digoxygenase (DIG)-labelled OPG riboprobes showed selective uptake in osteoblasts but not osteocytes or osteoclasts in TKA bone. Those data suggested that the upregulation of OPG expression by osteoblasts may have precipitated the bony hypertrophy of end-stage OA.

Altered joint mechanics produced by periarticular bone remodelling may precede the cartilage changes of osteoarthritis (OA). Recently, receptor activator of nuclear factor kappa beta (RANK), along with its soluble ligand (RANK-L), have been shown to induce both maturation and activation of bone-degrading osteoclasts. Activation of RANK on osteoclast cells by RANK-L is opposed by another soluble factor, osteoprotegerin (OPG). Thus RANK/OPG balance is important in regulating bone turnover. Here, we compared periarticular bone from patients with end-stage OA undergoing total knee arthroplasty (TKA) with those of cadaveric controls. We assessed bony, histological and molecular changes that are important in the pathogenesis of OA.

Using in-situ hybridization, we found increased staining of digoxygenase (DIG)-labelled OPG in osteoblasts of TKA bone. A corresponding increase in subchondral and insertional bone was seen on micro-CT (μCT) sections from TKA bone in comparison with cadaveric controls. Those changes were accompanied by marked articular cartilage degeneration on histology.

This study is the first of which we are aware that directly assessed the role of OPG in inducing the bony changes seen in human end-stage OA. We used μCT to compare corresponding samples qualitatively from TKA and cadaveric bone. Adjacent sections underwent hybridization of digoxygenase (DIG)-labelled OPG riboprobes to assess gene expression in situ. Finally, samples were stained and analysed for histology.

Bony hypertrophy may be a result of overexpression of OPG that occurs as an important feature of OA pathophysiology.

Funding: This work was supported by a grant from the Hip Hip Hooray Fund of the Canadian Orthopaedic Research Foundation (CORF) and the Wood Professorship in Joint Injury Research. There was no commercial funding for this research project.

Ten New Zealand White rabbits underwent anterior cruciate ligament transection (ACLX), then reconstruction using a mersiline tape graft and mitek mini anchors. Animals were divided into two groups and sacrificed at six and fourteen week after surgery. Medial collateral ligament (MCL)-complexes were evaluated for joint laxity, and periarticular tissues evaluated for changes in vascular volume. Both reconstructed groups showed significantly reduced MCL-complex laxity and inflammatory angiogenesis compared to ACLX controls. This reconstructive method (using an artificial graft) provided transient restabilization out to 6 and 14 wk after ACLX in the rabbit, with a high 80% success rate of intact grafts.

To refine a method of ACL reconstruction in the New Zealand White (NZW) rabbit to study angiogenic adaptations in a restabilized knee joint.

The artificial graft approach provided transient restabilization out to six and fourteen week post ACLX with an 80% success rate, and reduced MCL-complex laxity and inflammatory angiogenesis.

Addressing joint instability after ACLX reduces inflammatory angiogenesis and mechanical deterioration in peri-articular tissues, and delays the progression of OA.

Compared to normal control tissues, loss of the ACL resulted in marked joint instability, and significantly increased vascular volumes in all periarticular tissues examined six and fourteen week post-ACLX. However, following transient restabilization using reconstructive surgery, MCL-complex laxity and periarticular tissue vascular volume were significantly reduced at both the six and fourteen week intervals compared to ACLX controls.

ACL reconstructive surgery was performed on the right knee of ten skeletally mature NZW rabbits using a mersiline tape graft and mitek mini anchors, immediately after the ACL had been transected. MCL-complex laxity was measured in all joints using established biomechanical procedures. To assess the effect of joint restabilization six and fourteen week after ACL reconstruction, limbs were infused with a 5% carmine red dye/5% gelatin solution, and the vascular volume of periarticular tissues was detemined.

The artificial graft approach to rabbit ACL reconstruction resulted in a high success rate of intact grafts 6 and 14 wk post-ACLX. The transient restabilization of an ACLX knee joint results in less inflammatory angio-genesis in periarticular tissues.

Funding: CIHR