DEVELOPMENT, VALIDATION, AND APPLICATION OF A NONINVASIVE SPINAL MOTION MEASUREMENT SYSTEM

Spontaneous vertebral fractures are a large and growing health care problem. Biomechanical factors, specifically, abnormal posture or gait‐related spinal motion may interact with age‐weakened bone to induce altered spinal biomechanics that in turn increase the likelihood of vertebral body fracture. This research takes steps towards the goal of reducing the number of vertebral fractures in two phases: 1) Validation of a noninvasive spinal motion measurement system in cadaver torsos and 2) Application of the measurement system in human subjects. The cadaver study compared vertebral motion at 4 levels (T7,T12,L3,L5) as measured by adhesive skin markers versus motion measured by bone pins implanted into the vertebrae. Cadaver torsos were tested in lateral‐bending, flexion and axialrotation. Mean differences in vertebral body angular motion between skin markers and bone pin markers were \u3c0.5° around the anterior‐posterior and medial‐lateral axes and \u3c0.9° around the superior‐inferior axis. This measurement method was able to accurately quantify vertebral body motion in cadaver torsos thus allowing for application to human subject testing. X‐rays and 3D motion capture were employed to quantify spinal posture and motion parameters during gait in 12 older and 12 younger normal, females. Vertebral motion around 3 axes was measured at 4 levels (T7,T10,T12,L2) using noninvasive retroreflective markers during treadmill gait at 3 speeds (0.5,0.7,0.9m/s). The average angular motion of all gait cycles at each speed was determined for each level. The triplanar ranges of motion and variability of motion were compared as a function of age. Older subjects had 31.7% larger frontal Cobb angles and up to 30.9% and 33.5% smaller ranges of spinal motion in the frontal and sagittal planes. Variability of motion in the sagittal plane was up to 42.9% less in older subjects. Decreased ranges of motion and variability of spinal motion observed in older subjects may imply that vertebral loading in these subjects may not be as uniformly distributed across the vertebrae as in younger subjects. Greater stresses may result from the abnormal motion, thus increasing fracture risk. Confirmation of this hypothesis requires a longitudinal study, but if verified, may lead to the development of inexpensive countermeasures to prevent fractures

Tai Chi for osteopenic women: design and rationale of a pragmatic randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks.</p> <p>Methods/Design</p> <p>A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk.</p> <p>Discussion</p> <p>Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study.</p> <p>Trial registration</p> <p>This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012.</p

Spine Lifting Biomechanics Between Varying Occupational Activity Levels And Recreational Physical Activity Levels

Background: Moderate to vigorous physical activity as the optimum movement patterns for health have continued to be the dominant focus of health and fitness research. Yet, emerging evidence of deleterious, adverse health effects of prolonged inactivity, independent of regular physical activity, presents a new element to establishing the ideal model of movement patterns for health. The musculoskeletal trunk of the body becomes unbalanced as a result of prolonged inactivity, and a biomechanical analysis can help to identify high-risk loading behavior associated with these unbalances. Moreover, poor spine biomechanics can indicate a need for adjustment to present recommendations for optimum movement patterns. Some research of spine biomechanics associated with sedentary occupation or lifestyle exists. However, up to the author’s knowledge, no research exists on sedentary lifestyle independent of recreational physical fitness in respect to spine biomechanics. Purpose: The purpose of this study was to identify biomechanical patterns and significant differences in lifting biomechanics among individuals who are occupationally inactive and active, as well as recreationally active and inactive. Methods: Participants were divided into four groups using the Cambridge EPIC (European Prospective Investigation into Cancer and Nutrition)-Norfolk Physical Activity Questionnaire (EPAQ2): inactive, moderately inactive, moderately active, and active. A total of 23 participants completed the protocol. Spine kinematics of lifting was collected through VICON motion capture system. Additionally, ground reaction forces (GRF) and ground reaction moments (GRM) were collected by forceplate. Kinematic dependent variables were calculated from joint angle curves of trunk segments; included was maximum angular displacement of the middle trunk and lower trunk. Kinetic dependent variables were calculated from the GRF and GRM data, including maximum anterior excursion, maximum anterior velocity, and sway area of the center of pressure (COP) trajectories. Difference of each dependent variable between groups was detected by 1-way ANOVA. When difference existed, post-hoc pair-wise comparisons were conducted and Bonferroni correction was applied to minimize family-wise errors. The significance level was set at α = 0.05. Hypothesis: Participants who maintain an inactive lifestyle, regardless of recreational physical activity, will exhibit significantly different lifting biomechanics when compared to the lifting biomechanics of an active population performing the same lifting tasks. Results: Results indicated a statistically significant difference in flexion range of motion for the inactive group compared to all other groups (p=0.014). The inactive group had a significantly lower degree of flexion range of motion. Joint kinematic data indicated little difference between groups for the reaching phase and lift up phase of straight leg lifts. For bent leg lifts, the active population had significantly greater middle trunk flexion displacement during the reaching phase (p=0.005) and lifting phase (p=0.023) of bent leg lifts. No other significant differences existed between the other groups. Analysis of force platform data produced no significant differences between groups. Percent flexion range of motion was significantly different for the active population during the bent leg reaching phase and lifting phase compared with all other groups. The active population used a much larger degree of their total flexion range of motion to reach and lift up the box from the ground. Discussion: The current study aimed to investigate the effect of a largely inactive lifestyle, independent of regular participation in planned physical exercise, on spine kinematics, center of pressure, and range of motion. Results show evidence of a tendency for greater range of motion and greater flexion displacement of the active sample. Although not statistically significant, the inactive sample findings unexpectedly indicated a tendency for increased flexion displacement compared with the moderately active and moderately inactive groups. The moderately inactive group did not have any significant differences when compare to the moderately active group, which did not support the original hypothesis. However, the inactive group had poorer range of motion compared with all other groups, which supports the initial predictions. In summary, the inactive group presented some evidence of poor biomechanics. The active group shosigns of increased range of motion and flexibility. Finally, the moderately active and moderately inactive groups were very similar among all calculated variables. These findings support previous evidence of regular activity improving range of motion and flexibility. Occupational inactivity coupled with regular recreational activity appears to reduce the risk of developing poor lifting biomechanics

Computational modelling of the scoliotic spine: A literature review

Scoliosis is a deformity of the spine that in severe cases requires surgical treatment. There is still disagreement among clinicians as to what the aim of such treatment is as well as the optimal surgical technique. Numerical models can aid clinical decision-making by estimating the outcome of a given surgical intervention. This paper provided some background information on the modelling of the healthy spine and a review of the literature on scoliotic spine models, their validation, and their application. An overview of the methods and techniques used to construct scoliotic finite element and multibody models was given as well as the boundary conditions used in the simulations. The current limitations of the models were discussed as well as how such limitations are addressed in non-scoliotic spine models. Finally, future directions for the numerical modelling of scoliosis were addressed

Computational modelling of the scoliotic spine: A literature review

open4siScoliosis is a deformity of the spine that in severe cases requires surgical treatment. There is still disagreement among clinicians as to what the aim of such treatment is as well as the optimal surgical technique. Numerical models can aid clinical decision-making by estimating the outcome of a given surgical intervention. This paper provided some background information on the modelling of the healthy spine and a review of the literature on scoliotic spine models, their validation, and their application. An overview of the methods and techniques used to construct scoliotic finite element and multibody models was given as well as the boundary conditions used in the simulations. The current limitations of the models were discussed as well as how such limitations are addressed in non-scoliotic spine models. Finally, future directions for the numerical modelling of scoliosis were addressed.Marco Viceconti and Giorgio Davico were supported by the EU funded project Mobilise-D. The charity Reuse-WithLove is gratefully acknowledged for the financial support to this research.openGould, Samuele L; Cristofolini, Luca; Davico, Giorgio; Viceconti, MarcoGould, Samuele L; Cristofolini, Luca; Davico, Giorgio; Viceconti, Marc

Tai Chi for Osteopenic Women: Design and Rationale of a Pragmatic Randomized Controlled Trial

Background: Post-menopausal osteopenic women are at increased risk for skeletal fractures. Current osteopenia treatment guidelines include exercise, however, optimal exercise regimens for attenuating bone mineral density (BMD) loss, or for addressing other fracture-related risk factors (e.g. poor balance, decreased muscle strength) are not well-defined. Tai Chi is an increasingly popular weight bearing mind-body exercise that has been reported to positively impact BMD dynamics and improve postural control, however, current evidence is inconclusive. This study will determine the effectiveness of Tai Chi in reducing rates of bone turnover in post-menopausal osteopenic women, compared with standard care, and will preliminarily explore biomechanical processes that might inform how Tai Chi impacts BMD and associated fracture risks. Methods/Design: A total of 86 post-menopausal women, aged 45-70y, T-score of the hip and/or spine -1.0 and -2.5, have been recruited from primary care clinics of a large healthcare system based in Boston. They have been randomized to a group-based 9-month Tai Chi program plus standard care or to standard care only. A unique aspect of this trial is its pragmatic design, which allows participants randomized to Tai Chi to choose from a pre-screened list of community-based Tai Chi programs. Interviewers masked to participants' treatment group assess outcomes at baseline and 3 and 9 months after randomization. Primary outcomes are serum markers of bone resorption (C-terminal cross linking telopeptide of type I collagen), bone formation (osteocalcin), and BMD of the lumbar spine and proximal femur (dual-energy X-ray absorptiometry). Secondary outcomes include health-related quality-of-life, exercise behavior, and psychological well-being. In addition, kinetic and kinematic characterization of gait, standing, and rising from a chair are assessed in subset of participants (n = 16) to explore the feasibility of modeling skeletal mechanical loads and postural control as mediators of fracture risk. Discussion: Results of this study will provide preliminary evidence regarding the value of Tai Chi as an intervention for decreasing fracture risk in osteopenic women. They will also inform the feasibility, value and potential limitations related to the use of pragmatic designs for the study of Tai Chi and related mind-body exercise. If the results are positive, this will help focus future, more in-depth, research on the most promising potential mechanisms of action identified by this study. Trial registration: This trial is registered in Clinical Trials.gov, with the ID number of NCT01039012

Marrow fat and perfusion in osteoporosis.

MR allows non-invasive means of evaluating the non-mineralized components of bone, particularly the bone marrow. This thesis focuses on potential changes occurring in bone marrow perfusion and marrow fat in osteoporosis, - changes which may improve our understanding of osteoporosis pathophysiology. We know from histology studies that as osteoporosis develops and bone tissue is lost, it is replaced by fat filling the vacated marrow space. MR allows non-invasive quantification of this fat component. Although fat content may be increasing, it is not known whether any change in fat composition occurs with osteoporosis i.e. does the type of fat within bone change. Epidemiological studies have indicated a link between arterial disease and osteoporosis. It is not known, however, whether any changes occur in bone perfusion in osteoporosis and how these may be related to increasing fat within the marrow.The hypothesis to be tested is that: Advanced magnetic resonance (MR) techniques can be applied to investigate the non-mineralised components of bone tissue in osteoporosis thereby providing more information on bone physiology both in health and diseaseThis thesis is based on a series of eight studies designed to study the relationship between bone marrow perfusion, bone marrow fat content, bone marrow fat composition and bone mineral density. These studies showed that as bone mineral density decreased, bone marrow perfusion decreased. A strong reciprocal relationship was found between decreasing bone marrow perfusion and increasing marrow fat. The reduction in perfusion occurred only with bone and did not affect the extra-osseous tissues alongside bone with the same arterial supply. This indicates that the reduction in bone perfusion is not simply a reflection of a more generalized circulatory impairment in subjects with osteoporosis. This same effect is seen in both males and females and in the proximal femora as well as the spine.In animal-based studies, we found that reduction in bone perfusion was apparent as little as two weeks after orchidectomy or oorphorectomy and closely paralleled features of impaired endothelial function as well as decreased bone mineral density and a hitherto unrecognized reduction in red marrow fraction within the medullary canal. Nitric oxide synthase, produced by the endothelium, is a potent stimulator of angiogenesis and osteoblastic activity. Mesenchymal stem cell differentiation may switch from osteoblastogenesis to adipocytogenesis under hypoxic conditions, while haematopoetic stem cells also supply endothelial stem cells. Potentially endothelial dysfunction, mesenchymal stem cell differentiation and haematopoetic stem cell maturation may be implemented in the development of osteoporosis.In normal subjects, blood perfusion was markedly reduced in the femoral head compared to the femoral neck. In osteoporotic subjects, a further reduction in blood perfusion occurred in both areas. Overall perfusion indices reduced relatively more in the femoral neck than the femoral head region. These changes in bone perfusion help explain why subjects with osteoporosis have impaired healing of femoral neck fractures though do not seem to be at increased risk of avascular necrosis. At a micro-architectural level, reduced bone perfusion may also help explain the impaired healing of microfractures seen in subjects with osteoporosis, a feature likely to contribute to reduce bone strength, microfracture accumulation and eventually clinical insufficiency fracture.Marrow fat was increased in subjects with osteoporosis. Our studies showed that percentage marrow fat content increased even allowing for the quantitative effect increased marrow fat has on the bone densitometry measurements. This effect was shown to be of negligible clinical significance. We found a strong reciprocal relationship between increasing fat and decreasing bone perfusion in both the proximal femur and vertebral body. Although fat content increased, very little difference in marrow fat composition was apparent between normal subjects and those with osteoporosis. We found no difference was apparent in either the N3/N6 marrow fat ratio or the spectrum of individual fatty acids in the marrow of subjects with either normal bone mineral density or osteoporosis. This suggests that alternation of marrow fat composition is not likely to be a direct contributory factor in osteoporosis. Also marrow fat increase was shown to be due to an increase in number rather than size of marrow fat cells. This suggests that marrow fat increases as a result of a switch in mesenchymal cell maturation to adipocytes rather than osteoblasts.Below average perfusion indices in the acetabulum and adductor muscle is predictive of more pronounced bone loss at the femoral neck over the ensuing four years. Perfusion indices can also predict between fast and slow losers with a high sensitivityTo summarise, in the eight studies presented, it was shown that osteoporosis is associated with a significant reduction in bone perfusion and a reciprocal increase in marrow fat content though no change in marrow fat composition. Reduction in bone perfusion is most likely due to an accompanying reduction in functioning marrow fraction. Marrow fat increase is most likely the result of a switch in mesenchymal cell maturation to adipocytes rather than osteoblasts. The studies present in this thesis confirmed the initial hypothesis that “Advanced magnetic resonance techniques can be applied to investigate the non-mineralised components of bone tissue in osteoporosis thereby providing more information on bone physiology both in health and disease.Griffith, James Frances."June 2009."Thesis (M.D.)--Chinese University of Hong Kong, 2012.Includes bibliographical references (leaves 227-250).Appendix includes Chinese.PREFACE AND DECLARATION --- p.1DEDICATION --- p.2ACKNOWLEDGEMENT --- p.3PRECIS --- p.4PUBLICATIONS AND PRESENTATIONS OF STUDIES RELATED TO THIS THESIS --- p.8INTRODUCTION --- p.16Chapter STUDY 1 --- What is the relationship between bone perfusion, marrow fat and bone mineral density? --- p.76Chapter STUDY 2 --- Vertebral marrow fat content, molecular diffusion, and perfusion indices in women with varying bone density, including osteoporosis: MR evaluation --- p.94Chapter STUDY 3 --- Could the results of Study 1 and Study 2 be spurious due to the effect of increasing marrow fat lowering BMD estimation by DEXA? --- p.111Chapter STUDY 4 --- Are the same changes in perfusion and marrow fat seen in the proximal femur as were seen in the lumbar spine (Study 1 & Study 2)? --- p.128Chapter STUDY 5 --- What is the reproducibility of MR perfusion studies and 1H spectroscopy of bone marrow? --- p.150Chapter STUDY 6 --- Marrow fat content increases but does the composition of marrow fat change in osteoporosis? --- p.159Chapter STUDY 7 --- Likely causes of reduced bone perfusion in osteoporosis: novel findings in an ovariectomy rat model --- p.180Chapter STUDY 8 --- Do perfusion indices or marrow fat content predict rate of bone loss? --- p.204SUMMARY --- p.222REFERENCES --- p.227ABBREVIATION LIST --- p.251APPENDIX --- p.25

The safety and efficacy of mesenchymal stem cells for prevention or regeneration of intervertebral disc degeneration: a systematic review

General Posters: abstract no. GP86INTRODUCTION: Mesenchymal stem cells (MSCs) have been used to halt the progression or regenerate the disc with hopes to prevent or treat discogenic back pain. However, the safety and efficacy of the use of MSCs for such treatment in animal and human models at short and long term assessment (i.e. greater than 48 weeks) have not been systematically addressed. This study addressed a systematic review of comparative controlled studies addressing the use of MSCs to that of no treatment/saline for the treatment of disc degeneration. METHODS: Online databases were extensively searched. Controlled trials in animal models and humans were eligible for inclusion. Trial design, MSC characteristics, injection method, disc assessment, outcome intervals, and complication events were assessed. Validity of each study was assessed addressing trial design. Two individuals independently addressed the aforementioned. RESULTS: Twenty-two animal studies were included. No human comparative controlled trials were reported. All three types of MSCs (i.e. derived from bone marrow, synovial and adipose tissue) showed successful inhibition of disc degeneration progression. From three included studies, bone marrow derived MSC showed superior quality of disc repair when compared to other treatments, including TGF-β1, NP bilaminar co-culture and axial distraction regimen. However, osteophyte development was reported in two studies as potential complication of MSC transplantation. CONCLUSIONS: Based on animal models, the current evidence suggests that in the short-term MSC transplantation is safe and effective in halting disc degeneration; however, additional and larger studies are needed to assess the long-term regenerative effects and potential complications. Inconsistency in methodological design and outcome parameters prevent any robust conclusions. In addition, randomized controlled trials in humans are needed to assess the safety and efficacy of such therapy.published_or_final_versio