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Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 11 - 11
1 Dec 2022
Tolgyesi A Huang C Akens M Hardisty M Whyne C
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Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality


Orthopaedic Proceedings
Vol. 104-B, Issue SUPP_12 | Pages 15 - 15
1 Dec 2022
Tolgyesi A Huang C Akens M Hardisty M Whyne C
Full Access

Bone turnover and the accumulation of microdamage are impacted by the presence of skeletal metastases which can contribute to increased fracture risk. Treatments for metastatic disease may further impact bone quality. The present study aims to establish a preliminary understanding of microdamage accumulation and load to failure in osteolytic vertebrae following stereotactic body radiotherapy (SBRT), zoledronic acid (ZA), or docetaxel (DTX) treatment. Twenty-two six-week old athymic female rats (Hsd:RH-Foxn1rnu, Envigo, USA) were inoculated with HeLa cervical cancer cells through intracardiac injection (day 0). Institutional approval was obtained for this work and the ARRIVE guidelines were followed. Animals were randomly assigned to four groups: untreated (n=6), spine stereotactic body radiotherapy (SBRT) administered on day 14 (n=6), zoledronic acid (ZA) administered on day 7 (n=5), and docetaxel (DTX) administered on day 14 (n=5). Animals were euthanized on day 21. T13-L3 vertebral segments were collected immediately after sacrifice and stored in −20°C wrapped in saline soaked gauze until testing. µCT scans (µCT100, Scanco, Switzerland) of the T13-L3 segment confirmed tumour burden in all T13 and L2 vertebrae prior to testing. T13 was stained with BaSO. 4. to label microdamage. High resolution µCT scans were obtained (90kVp, 44uA, 4W, 4.9µm voxel size) to visualize stain location and volume. Segmentations of bone and BaSO. 4. were created using intensity thresholding at 3000HU (~736mgHA/cm. 3. ) and 10000HU (~2420mgHA/cm. 3. ), respectively. Non-specific BaSO. 4. was removed from the outer edge of the cortical shell by shrinking the segmentation by 105mm in 3D. Stain volume fraction was calculated as the ratio of BaSO. 4. volume to the sum of BaSO. 4. and bone volume. The L1-L3 motion segments were loaded under axial compression to failure using a µCT compatible loading device (Scanco) and force-displacement data was recorded. µCT scans were acquired unloaded, at 1500µm displacement and post-failure. Stereological analysis was performed on the L2 vertebrae in the unloaded µCT scans. Differences in mean stain volume fraction, mean load to failure, and mean bone volume/total volume (BV/TV) were compared between treatment groups using one-way ANOVAs. Pearson's correlation between stain volume fraction and load to failure by treatment was calculated using an adjusted load to failure divided by BV/TV. Stained damage fraction was significantly different between treatment groups (p=0.0029). Tukey post-hoc analysis showed untreated samples to have higher stain volume fraction (16.25±2.54%) than all treatment groups (p<0.05). The ZA group had the highest mean load to failure (195.60±84.49N), followed by untreated (142.33±53.08N), DTX (126.60±48.75N), and SBRT (95.50±44.96N), but differences did not reach significance (p=0.075). BV/TV was significantly higher in the ZA group (49.28±3.56%) compared to all others. The SBRT group had significantly lower BV/TV than the untreated group (p=0.018). Load divided by BV/TV was not significantly different between groups (p=0.24), but relative load to failure results were consistent (ZA>Untreated>DTX>SBRT). No correlations were found between stain volume fraction and load to failure. Focal and systemic cancer treatments effect microdamage accumulation and load to failure in osteolytic vertebrae. Current testing of healthy controls will help to further separate the effects of the tumour and cancer treatments on bone quality


Orthopaedic Proceedings
Vol. 103-B, Issue SUPP_1 | Pages 3 - 3
1 Feb 2021
Hwang E Braly H Ismaily S Noble P
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INTRODUCTION. The increasing incidence of periprosthetic femoral fractures (PFF) after total hip arthroplasty presents growing concerns due to challenges in treatment and increased mortality. PFF are often observed when the prosthesis is implanted in varus, especially with blade-type stems. To help elucidate its impact on the PFF risk, the specific research question is: What is the effect of misalignment of a blade-type stem (resulting in down-sized prosthesis) on 1)the distribution and magnitude of cortical stresses and 2)implant-bone micromotion. METHOD. We developed two finite element models consisting of an average female femur implanted within a generic blade-type stem prosthesis, (i)in neutral alignment, and (ii)oriented in 5° of varus, coupled with corresponding down-sizing of the prosthesis. Each model consisted of 1.1million elements, while the average mesh length at the implant-bone interface was 0.4mm. Elastic moduli of 15GPa(cortex), 150MPa(trabecular bone), and 121GPa(implant), and Poisson's ratio of 0.3 were assumed. The distal end was fixed and the interface was defined as a surface-to-surface contact with friction coefficients (dynamic 0.3; static 0.4). Walking and stair-climbing were simulated by loading the joint contact and muscle forces after scaling to the subjects’ body weight. The peak von Mises stress and the average stress within the surface having 1cm diameter and the center at where the peak stress occurred at each contacting area, the interfacial micromotion along medial, lateral side were analyzed. For statistical analysis, two-tailed t-test was performed between the neutral and varus cases over four loading cycles with significance level of p<0.05. RESULTS. Neutral alignment led to three areas of cortical/implant contact with focal load transfer via those areas, whereas varus placement limited to two areas (Figure 1). In both simulations, the greatest stress was observed at the proximal medial contact. With varus, average and peak stresses increased by 39% and 65% during walking and 28% and 35% during stair-climbing, respectively (Table 1). Micromotion was greatest over the proximal third of the interface, especially along lateral side (Figure 2). The 90. th. percentile values with the varus exceeded the neutral by 35% with walking and 28% with stair-climbing over the lateral interface. DISCUSSION. The proximal medial location of the greatest stress correlates well with clinical observations in PFF involving a posteromedial calcar fragment. Based on current lesser stress than the reported yield stress, loading during daily living activities may result in microdamage rather than an immediate PFF. However, impact loading such as hammering for stem insertion may introduce PFF at the location, especially with in varus. The increase in interfacial micromotion is expected to lead to increase in the risk for implant loosening, also leading to PFF. Further study is needed to confirm the validity and generalizability of these findings. SIGNIFICANCE/CLINICAL RELEVANCE. This study demonstrates the importance of proper alignment of femoral stems of a blade-type design. The misalignment (resulting in down-sizing) increased stress up to 65% and micromotion up to 35% around prosthesis, even during daily activities, thus increased attention to proper implant alignment and sizing is suggested when using components of this design. For any figures or tables, please contact the authors directly


Orthopaedic Proceedings
Vol. 95-B, Issue SUPP_34 | Pages 480 - 480
1 Dec 2013
Pienkowski D Porter D Monier-Faugere M Malluche H
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Advances in the performance and longevity of total joint arthroplasty (TJA) have been enabled by related progress in implant materials, device designs, and surgical techniques. Successful TJA also depends upon adequate bone quality to provide an enduring mechanical foundation. Bone quality can be defined as the ability to repetitively withstand physiologically-relevant loads without excess deformation or fracture. It is now recognized that bone quality encompasses more than just material quantity, i.e. densitometrically-measured bone mass. Bone quality is also determined by: material composition and arrangement, cortical and cancellous structure, and extent of microdamage. These properties, together with the appropriate mass, confer bone with the biomechanical competence needed to meet the repetitive load-bearing demands imposed by total joint implants. The need for TJA continues to increase in the aging global baby-boomer population. Unfortunately, this group is also experiencing increases in related comorbidities including: osteoporosis, kidney dysfunction, and diabetes, among others. Collectively these three comorbidities afflict more than 74 million Americans, and each is increasing at 2–8% annually. More importantly, each of these comorbidities negatively affects bone quality through alterations in bone turnover independent of bone mass changes commonly associated with these diseases. Specifically, alterations in bone turnover result in abnormal mineral-to-matrix ratios as measured by Fourier transform infra-red (FTIR) spectroscopy (Fig. 1) and altered Young's moduli (shape-independent resistance to deformation) as measured by nanoindentation (Fig. 2). These parameters are related to bones' fracture toughness and load-bearing capabilities, respectively. Also, low bone turnover is associated with mechanically important structural changes, i.e., decreased trabecular thickness (Fig. 3), cortical thickness and cancellous volume. Furthermore, low bone turnover may result in reducing the repair rate of physiologically – induced bone microdamage. This may lead to increases in the number or length of bone cracks, crack coalescence, and ultimately reduced energy needed for fracture. Therefore, patients needing TJA who also have comorbidities associated with abnormal bone quality are at risk for inferior arthroplasty results. Recognition and treatment of the TJA-relevant biomechanical implications of these comorbidities may help improve outcomes


Orthopaedic Proceedings
Vol. 94-B, Issue SUPP_XXIII | Pages 129 - 129
1 May 2012
Findlay D
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Osteocytes (OCY) are the end stage differentiation cells of the osteoblast lineage, and are incorporated in the bone matrix during bone formation. In doing so, OCY control the mineralisation of osteoid. OCY form a dense inter-connected network of cell bodies and cell processes throughout the mineralised matrix of bone. OCY viability depends on interstitial fluid flow along the OCY canaliculi, driven by pulsatile blood flow and loading of the skeleton. Maintenance of the density and viability of OCY are essential for bone health because OCY perform many important functions in bone. Firstly, OCY appear to initiate bone repair of bone microdamage. Secondly, OCY are almost certainly the cells, which initiate new bone formation in response to increased loading of bone. Thirdly, OCY are able to regulate the amount of new bone formation in bone remodelling cycles, at least in part by the production of a molecule called sclerostin (SCL). Mutations in the SCL gene, or deletion of the SCL gene in transgenic mice, are associated with particularly dense, fracture resistant bones. This information has led to development of anti-SCL antibodies as a potential anabolic therapy for bones. Bone loss in ovariectomised aged rats was shown recently to be reversed by treatment with neutralising SCL antibodies. There is also some data to suggest that these antibodies may promote fracture healing. Reduced OCY viability and/or density have been reported in association with osteoporotic fracture. OCY viability seems to be dependent on skeletal loading, adequate skeletal blood flow and estrogen in females. OCY viability is adversely affected by hypoxia, unloading of the skeleton and pharmacobiology, such as chronic exposure to glucocorticoids. Both micro and macro-fractures result in disruption of the OCY network, as do procedures such as drilling and cutting of bone. Because of the important roles of OCY in bone, new approaches to bone health may require the identification of agents to protect these cells from harmful influences in disease and ageing