Tartrate-resistant acid phosphate as biomarker of bone turnover over the lifespan and different physiologic stages in sheep

Currently, the best resources for assessment of bone tissue using imaging techniques are expensive and available in few medical facilities, thus serum or urinary bone turnover biomarkers could be useful as early indicators of prognosis. However, there is a wide range of variability in bone turnover markers due to several factors, such as different ages and metabolic stages, thus it is important to have as much data published on the subject as possible. The aim of this study was therefore to generate a reference range for alkaline phosphatase (ALP) and tartrate-resistant acid phosphatase (TRAP) and validate the already published data.National Council for Scientific and Technological Development (CNPq - Brazil) PhD scholarship 202248/2015–1.info:eu-repo/semantics/publishedVersio

Evaluation of bone turnover markers and serum minerals variations for predicting fracture healing versus non-union processes in adult sheep as a model for orthopedic research

Bone turnover markers (BTMs) have been considered as an auxiliary method of following the fracture healing process and for early prediction of impaired bone healing. A better understanding of the potential of BTMs in this application could allow for earlier interventions and improved patient care. The aim of this study with a large animal experimental model was to assess the variation of bone formation markers SOH namely the total alkaline phosphatase (ALP) and its bone-specific isoform (BALP), serum concentration of intact osteocalcin (OC), N-terminal propeptide type III procollagen (PIIINP) and of bone resorption markers â  namely tartrate resistant acid phosphatase (TRAP) and deoxypyridinoline crosslink (DPD) during the first stages of a normal fracture healing process and of a segmental critical size defect (CSD), which progresses to a non-union process. Thirty healthy female sheep (Portuguese Churra-da-Terra- Quente breed), approximately 4-years-old, were enrolled in this study. Jugular venous blood samples were collected pre-operatively and at 1, 2, 3, 4, 6, 8, 10 and 12 post-operative weeks. The animals of the CSD group showed significant lower serum levels of BALP, OC and significant higher serum PIIINP levels at early stages of the fracture healing process, compared with animals that progressed in a normal fracture healing process. Serum BALP, OC and PIIINP levels could be useful as non-invasive auxiliary tools with other complementary methods for predicting the outcome of traumatic bone fractures.Cristina P. Sousa acknowledges the Portuguese Foundation for Science and Technology (FCT) for her PhD scholarship (Grant No SFRH/BD/45018/2008).info:eu-repo/semantics/publishedVersio

Bone turnover markers for early detection of fracture healing disturbances: A review of the scientific literature

Imaging techniques are the standard method for assessment of fracture healing processes. However, these methods are perhaps not entirely reliable for early detection of complications, the most frequent of these being delayed union and non-union. A prompt diagnosis of such disorders could prevent prolonged patient distress and disability. Efforts should be directed towards the development of new technologies for improving accuracy in diagnosing complications following bone fractures. The variation in the levels of bone turnover markers (BTMs) have been assessed with regard to there ability to predict impaired fracture healing at an early stage, nevertheless the conclusions of some studies are not consensual. In this article the authors have revised the potential of BTMs as early predictors of prognosis in adult patients presenting traumatic bone fractures but who did not suffer from osteopenia or postmenopausal osteoporosis. The available information from the different studies performed in this field was systematized in order to highlight the most promising BTMs for the assessment of fracture healing outcome.As técnicas imagiológicas são o método convencional para a avaliação dos processos de cicatrização das fraturas. No entanto, estes métodos não são talvez totalmente confiáveis para a deteção precoce de complicações, as mais frequentes destas sendo o atraso da união e a não-união. Um diagnóstico eficaz destas desordens poderia prevenir a dor e a incapacidade prolongada do paciente. Esforços devem ser dirigidos no sentido do desenvolvimento de novas tecnologias para melhorar a exatidão no diagnóstico de complicações após fraturas ósseas. A variação nos níveis dos marcadores do turnover ósseo (BTMs) têm sido avaliados com vista à sua capacidade para prever o comprometimento da cicatrização das fraturas numa fase inicial, no entanto, as conclusões de alguns estudos não são consensuais. Neste artigo os autores fizeram uma revisão do potencial dos BTMs como fatores de previsibilidade precoce do prognóstico em doentes adultos que apresentavam fraturas ósseas traumáticas mas que não sofriam de osteopenia ou osteoporose pós-menopausa. A informação disponível nos diferentes estudos realizados neste campo foi sistematizada com vista a evidenciar-se os BTMs mais promissores para a avaliação da evolução da cicatrização das fraturas.SFRH/BD/45018/200

Bone turnover markers in sheep and goat: a review of the scientific literature

Bone turnover markers (BTMs) are product of bone cell activity and are generally divided in bone formation and bone resorption markers. The purpose of this review was to structure the available information on the use of BTMs in studies on small ruminants, especially for monitoring their variations related to diet, exercise, gestation and metabolic lactation state, circadian and seasonal variations, and also during skeletal growth. Pre-clinical and translational studies using BTMs with sheep and goats as animal models in orthopaedic research studies to help in the evaluation of the fracture healing process and osteoporosis research are also described in this review. The available information from the reviewed studies was systematically organized in order to highlight the most promising BTMs in small ruminant research, as well as provide a wide view of the use of sheep and goat as animal models in orthopaedic research, type of markers and commercial assay kits with cross-reactivity in sheep and goat, method of sample and storage of serum and urine for bone turnover markers determination and the usefulness and limitations of bone turnover markers in the different studies, therefore an effective tool for researchers that seek answers to different questions while using BTMs in small ruminants.José Arthur de A. Camassa acknowledges to the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), Brazil, for his PhD scholarship 202248/2015-1.info:eu-repo/semantics/publishedVersio

A Comparison of Two-Dimensional and Three-Dimensional Techniques for Kinematic Analysis of the Sagittal Motion of Sheep Hindlimbs During Walking on a Treadmill

Compared to rodents, sheep offer several attractive features as an experimental model for testing different medical and surgical interventions related to pathological gait caused by neurological diseases and injuries. To use sheep for development of novel treatment strategies in the field of neuroscience, it is key to establish the relevant kinematic features of locomotion in this species. To use sheep for development of novel treatment strategies in the field of neuroscience, it is crucial to understand fundamental baseline characteristics of locomotion in this species. Despite their relevance for medical research, little is known about the locomotion in the ovine model, and next to nothing about the three-dimensional (3D) kinematics of the hindlimb. This study is the first to perform and compare two-dimensional (2D) and 3D hindlimb kinematics of the sagittal motion during treadmill walking in the ovine model. Our results show that the most significant differences took place throughout the swing phase of the gait cycle were for the distal joints, ankle and metatarsophalangeal joint, whereas the hip and knee joints were much less affected. The results provide evidence of the inadequacy of a 2D approach to the computation of joint kinematics in clinically normal sheep during treadmill walking when the interest is centered on the hoof's joints. The findings from the present investigation are likely to be useful for an accurate, quantitative and objective assessment of functionally altered gait and its underlying neuronal mechanisms and biomechanical consequences.</jats:p

Assessment of Lumbar Vertebrae L1&ndash;L7 and Proximal Femur Microstructure in Sheep as a Large Animal Model for Osteoporosis Research

Sheep have been widely used as a model for osteoporosis research. This study aimed to characterise changes in microstructure and composition in lumbar vertebrae L1&ndash;L7 and the proximal femur after implementation of a bone loss induction protocol (in this species). A sham control and experimental group (glucocorticoid-treated ovariectomized sheep) were used (n = 6/group), with a study duration up to the 24th postoperative week. Through micro-computed tomography, vertebrae and femoral head trabecular bones from the experimental group presented a consistent decrease in bone volume fraction (BV/TV), trabecular thickness (Tb.Th), and trabecular number (Tb.N) and an increase in trabecular separation (Tb.Sp) and total porosity (p &gt; 0.05). The mineral density of the femoral heads from the experimental group showed a statistically significant decrease (p &#706; 0.05). The entire histomorphometric analysis of the vertebrae in the experimental group showed an increase in cortical porosity (Ct.Po) and a decrease in cortical thickness (Ct.Th) (p &#706; 0.0001 and p &#706; 0.001, respectively). Vertebrae L6 and L7 were the most affected, showing a significant increase in Ct.Po (p &lt; 0.05) and a significant decrease in Ct.Th at the L6 level (p &lt; 0.05). Regarding the trabecular bone at the vertebral level, only L4 showed a significant increase in Tb.Sp (p &#706; 0.05). In the femoral heads&rsquo; subchondral cortical layer, the Ct.Po increased significantly and Ct.Th decreased (p &lt; 0.01), and at the trabecular level, the BV/TV, Tb.Th, and Tb.N decreased significantly, while Tb.Sp increased (p &lt; 0.05). In conclusion, the L4, L6 and L7 vertebrae seem the most suitable for further preclinical and translational studies of vertebral augmentation or spinal fusion in this animal model

Photoelastic Analysis of Two Different Cementless Femoral Stems for Total Hip Arthroplasty in a Canine Model

Objectives The aim of this article was to analyse and compare internal stress generated at different points of a femoral photoelastic model after insertion and axial load application using two different cementless femoral stems for total hip arthroplasty in dogs: a collared stem combined with limited textured surface and absence of grooves and a collarless stem with fully textured surface and grooves. Methods Ten femoral photoelastic models, divided into two groups, were created using two different designs of cementless femoral stems. The models were submitted to axial loading on the femoral head in a universal test machine. The internal stress (kPa) around the femoral stems was evaluated at seven predetermined points using a transmission polariscope. Results The internal stress at the femoral calcar was larger in the models with collared stem combined with limited textured surface and absence of grooves (p &lt; 0.05). No differences were identified between the groups in the other points (p &gt; 0.05), corresponding to the tip of the stems and proximal lateral region of the femur. Conclusions The collar of femoral stem combined with the absence of grooves and more limited textured surface increase the axial load transmission to the femoral calcar, and in vivo, it may act to reduce complications, such as subsidence and stress shielding. However, other biomechanical tests and clinical evaluations must be performed to determine other important aspects for the implantation of these prostheses.</jats:p

Evaluation of hematology, general serum biochemistry, bone turnover markers and bone marrow cytology in a glucocorticoid treated ovariectomized sheep model for osteoporosis research

Osteoporosis is a metabolic disorder characterized by a loss of bone mass and structure and increasing the risk of fragility fractures, mostly among postmenopausal women. Sheep is a recognized large animal model for osteoporosis research. An experimental group of ewes (3-4 years old) was subjected to ovariectomy (OVX) and weekly glucocorticoid (GC) application for 24 weeks and compared with a sham control group. Blood and bone marrow parameters were analyzed before and 24 weeks after OVX and GC administration. Osteopenia was confirmed through micro-computed tomography and histomorphometric analysis of L4 vertebra in the study end. A statistically significant increase was observed in mean corpuscular volume, mean cell hemoglobin and monocytes and a decrease in red blood count and eosinophils (p<0.05). Alkaline phosphatase (ALP), gamma-glutamyl transpeptidase, magnesium and α1-globulin increased, and creatinine, albumin, sodium and estradiol decreased (p<0.05). A slight decrease of bone formation markers (bone ALP and osteocalcin) and an increase of bone resorption markers (C-terminal telopeptides of collagen type 1 and tartrate-resistant acid phosphatase) were observed, but without statistical significance. This study aims to contribute to better knowledge of sheep as a model for osteoporosis research and the consequences that a performed induction protocol may impose on organic metabolism.This work is funded by national funds through Portuguese Foundation for Science and Technology (FCT) under the projects UlDB/AGR/04033/2020 and UIDB/CVT/00772/2020, and, under the Scientific Employment Stimulus -Institutional Call -CEECINS/00127/2018

Video_1_A Comparison of Two-Dimensional and Three-Dimensional Techniques for Kinematic Analysis of the Sagittal Motion of Sheep Hindlimbs During Walking on a Treadmill.MP4

Compared to rodents, sheep offer several attractive features as an experimental model for testing different medical and surgical interventions related to pathological gait caused by neurological diseases and injuries. To use sheep for development of novel treatment strategies in the field of neuroscience, it is key to establish the relevant kinematic features of locomotion in this species. To use sheep for development of novel treatment strategies in the field of neuroscience, it is crucial to understand fundamental baseline characteristics of locomotion in this species. Despite their relevance for medical research, little is known about the locomotion in the ovine model, and next to nothing about the three-dimensional (3D) kinematics of the hindlimb. This study is the first to perform and compare two-dimensional (2D) and 3D hindlimb kinematics of the sagittal motion during treadmill walking in the ovine model. Our results show that the most significant differences took place throughout the swing phase of the gait cycle were for the distal joints, ankle and metatarsophalangeal joint, whereas the hip and knee joints were much less affected. The results provide evidence of the inadequacy of a 2D approach to the computation of joint kinematics in clinically normal sheep during treadmill walking when the interest is centered on the hoof's joints. The findings from the present investigation are likely to be useful for an accurate, quantitative and objective assessment of functionally altered gait and its underlying neuronal mechanisms and biomechanical consequences.</p