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Hazel R. C. Screen - One of the best experts on this subject based on the ideXlab platform.
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TENDON FASCICLES SHOW AN AGE-SPECIFIC RESPONSE TO Cyclic Fatigue Loading
2018Co-Authors: Chavaunne T. Thorpe, Graham P. Riley, Helen L. Birch, Peter D. Clegg, Hazel R. C. ScreenAbstract:Summary StatementFatigue Loading has an age-specific effect on tendon fascicle micro-mechanics, with greater fibre sliding in aged samples indicating a decreased mechanical integrity, and a reduced...
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TENDON FASCICLES SHOW AN AGE-SPECIFIC RESPONSE TO Cyclic Fatigue Loading
Journal of Bone and Joint Surgery-british Volume, 2014Co-Authors: Chavaunne T. Thorpe, Graham P. Riley, Helen L. Birch, Peter D. Clegg, Hazel R. C. ScreenAbstract:Summary Statement Fatigue Loading has an age-specific effect on tendon fascicle micro-mechanics, with greater fibre sliding in aged samples indicating a decreased mechanical integrity, and a reduced ability to withstand Cyclic Loading, which may partially explain the age-related risk of tendon injury. Introduction The human Achilles and equine superficial digital flexor (SDFT) tendons function as energy stores, experiencing large, repetitive stresses and strains 1 and are therefore highly susceptible to injury, particularly in aged individuals. We have previously observed rotation within SDFT fascicles in response to applied strain, which indicates the presence of helical sub-structures within this tendon. Further, we have shown that this rotation decreases with ageing, suggesting alterations to the helix sub-structure and a difference in the extension mechanisms in aged tendons. We therefore hypothesise that Cyclic Fatigue Loading (FL) will result in alterations in fascicle extension mechanisms which are age specific. Methods Fascicles (n= 6–8/tendon) were dissected from the forelimb SDFTs of 6 young (aged 3–6 years) and 5 old horses (aged 18–20 years). Half the fascicles underwent 1800 cycles of FL to 60% of their predicted failure stress, while the remaining fascicles acted as unloaded controls. Following FL, fascicles were stained with 5-dicholorotriazynl fluorescein, secured in a straining rig and viewed under a confocal microscope. A grid was photobleached onto each fascicle and images were taken at 2% strain increments up to 10%. Deformation of the grid was quantified by measuring changes in longitudinal strain, deviation from the vertical gridline and rotation of the horizontal gridline. Statistical significance was set at p Results In agreement with previous studies, local longitudinal strains were smaller than the overall applied strain, and did not differ between FL and control groups or with ageing. Deviation of the vertical gridline, representing fibre sliding, did not differ between FL and control samples from young horses, but there was a significant increase in fibre sliding in FL samples from old horses (p Discussion The results support the hypothesis, showing that FL causes age-specific alterations in fascicle extension mechanisms. Our previous findings suggest that, in samples from young horses, extension is facilitated by the unwinding of helical sub-structures, which is indicated by the grid rotation observed. The results of the current study show that FL causes a significant decrease in this rotation, suggesting the helix sub-structures are altered by FL, which may reduce the ability of fascicles to extend and recoil. By contrast, in aged samples this rotation decreased, indicating ageing also causes alterations to the helical sub-structures. FL of aged samples resulted in increased fibre sliding, indicating that damage may be occurring between the collagen fibres, which is likely to decrease the mechanical integrity of the fascicles. The observed age-specific alterations in extension mechanisms after FL suggest that fascicles from aged tendons, where structure of the helix is already compromised, suffer increased fibre sliding. Fibre sliding may initiate a cell response predisposing aged tendons to degenerative changes and subsequent injury.
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Fascicles from energy-storing tendons show an age-specific response to Cyclic Fatigue Loading
Journal of the Royal Society Interface, 2014Co-Authors: Chavaunne T. Thorpe, Graham P. Riley, Helen L. Birch, Peter D. Clegg, Hazel R. C. ScreenAbstract:Some tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), act as energy stores, stretching and recoiling to increase efficiency during locomotion. Our previous observations of rotation in response to applied strain in SDFT fascicles suggest a helical structure, which may provide energy-storing tendons with a greater ability to extend and recoil efficiently. Despite this specialization, energy-storing tendons are prone to age-related tendinopathy. The aim of this study was to assess the effect of Cyclic Fatigue Loading (FL) on the microstructural strain response of SDFT fascicles from young and old horses. The data demonstrate two independent age-related mechanisms of Fatigue failure; in young horses, FL caused low levels of matrix damage and decreased rotation. This suggests that Loading causes alterations to the helix substructure, which may reduce their ability to recoil and recover. By contrast, fascicles from old horses, in which the helix is already compromised, showed greater evidence of matrix damage and suffer increased fibre sliding after FL, which may partially explain the age-related increase in tendinopathy. Elucidation of helix structure and the precise alterations occurring owing to both ageing and FL will help to develop appropriate preventative and repair strategies for tendinopathy.
Peter Muir - One of the best experts on this subject based on the ideXlab platform.
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Role of calcitonin gene-related peptide in bone repair after Cyclic Fatigue Loading.
PloS one, 2011Co-Authors: Susannah J. Sample, Zhengling Hao, Aliya P. Wilson, Peter MuirAbstract:Background Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone Loading, particularly Fatigue Loading. Methodology/Principal Findings We used the rat ulna end-Loading model to induce Fatigue damage in the ulna unilaterally during Cyclic Loading. We postulated that CGRP would influence skeletal responses to Cyclic Fatigue Loading. Rats were Fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP8–37, for a 10 day study period. Ten days after Fatigue Loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and Fatigue-induced skeletal responses were quantified. We found that Cyclic Fatigue Loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP8–37 was associated with increased targeted remodeling in the Fatigue-loaded ulna. Administration of CGRP or CGRP8–37 both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP8–37 administration. Conclusions CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone Fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton.
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effect of short term treatment with alendronate on ulnar bone adaptation to Cyclic Fatigue Loading in rats
Journal of Orthopaedic Research, 2007Co-Authors: Jennifer G. Barrett, Susannah J. Sample, Peter Muir, Jenna Mccarthy, Vicki L. Kalscheur, Laura ProkuskiAbstract:Targeted remodeling of Fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to Cyclic Fatigue. The ulnae of 140 rats were Cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before Fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to Fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before Fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before Fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before Fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in Fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during Fatigue. After Fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the Fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from Fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
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Effect of short‐term treatment with alendronate on ulnar bone adaptation to Cyclic Fatigue Loading in rats
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2007Co-Authors: Jennifer G. Barrett, Susannah J. Sample, Peter Muir, Jenna Mccarthy, Vicki L. Kalscheur, Laura ProkuskiAbstract:Targeted remodeling of Fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to Cyclic Fatigue. The ulnae of 140 rats were Cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before Fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to Fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before Fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before Fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before Fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in Fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during Fatigue. After Fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the Fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from Fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
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response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to Cyclic Fatigue Loading
Bone, 2004Co-Authors: Sara A Colopy, Susannah J. Sample, Jennifer G. Barrett, Vicki L. Kalscheur, J Benzdean, Yan Lu, Nichole A Danova, Ray Vanderby, Mark D Markel, Peter MuirAbstract:Abstract Cyclic Loading induces Fatigue in bone and initiates a complex, functionally adaptive response. We investigated the effect of a single period of Fatigue on the histologic structure and biomechanical properties of bone. The ulnae of 40 rats were subjected to Cyclic Fatigue (−6000 μe) unilaterally until 40% loss of stiffness developed, followed by 14 days of adaptation. The contralateral ulna served as a treatment control (n = 20 rats), and a baseline loaded/non-loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were examined histologically and the remaining bones (10 rats/group) were tested mechanically. The following measurements were collected: volumetric bone mineral density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U); cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN). Using confocal microscopy, the bones were examined for diffuse matrix injury, canalicular disruption, and osteocyte disruption. The adapted bones had increased B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue Loading decreased structural properties and induced linear microcracking. At 14 days, adaptation restored structural properties and microcracking was partially repaired. There was a significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during adaptation. Disruption of osteocytes was observed adjacent to microcracks immediately after Fatigue Loading, and this did not change after the period of adaptation. In Fatigue-loaded bone distant from microcracks, diffuse matrix injury and canalicular disruption were often co-localized and were increased in the lateral (tension) cortex. These changes were partially reversed after adaptation. Loss of canalicular staining and the presence of blind-ends in regions with matrix injury were suggestive of rupture of dendritic cell processes. Taken together, these data support the general hypothesis that the osteocyte syncytium can respond to Cyclic Loading and influence targeted remodeling during functional adaptation. Changes in the appearance of the osteocyte syncytium were found in Fatigue-loaded bone with and without linear microcracks. We hypothesize that the number of dendritic cell processes that experience load-related disruption may determine osteocyte metabolic responses to Loading and influence targeted remodeling.
Chavaunne T. Thorpe - One of the best experts on this subject based on the ideXlab platform.
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TENDON FASCICLES SHOW AN AGE-SPECIFIC RESPONSE TO Cyclic Fatigue Loading
2018Co-Authors: Chavaunne T. Thorpe, Graham P. Riley, Helen L. Birch, Peter D. Clegg, Hazel R. C. ScreenAbstract:Summary StatementFatigue Loading has an age-specific effect on tendon fascicle micro-mechanics, with greater fibre sliding in aged samples indicating a decreased mechanical integrity, and a reduced...
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TENDON FASCICLES SHOW AN AGE-SPECIFIC RESPONSE TO Cyclic Fatigue Loading
Journal of Bone and Joint Surgery-british Volume, 2014Co-Authors: Chavaunne T. Thorpe, Graham P. Riley, Helen L. Birch, Peter D. Clegg, Hazel R. C. ScreenAbstract:Summary Statement Fatigue Loading has an age-specific effect on tendon fascicle micro-mechanics, with greater fibre sliding in aged samples indicating a decreased mechanical integrity, and a reduced ability to withstand Cyclic Loading, which may partially explain the age-related risk of tendon injury. Introduction The human Achilles and equine superficial digital flexor (SDFT) tendons function as energy stores, experiencing large, repetitive stresses and strains 1 and are therefore highly susceptible to injury, particularly in aged individuals. We have previously observed rotation within SDFT fascicles in response to applied strain, which indicates the presence of helical sub-structures within this tendon. Further, we have shown that this rotation decreases with ageing, suggesting alterations to the helix sub-structure and a difference in the extension mechanisms in aged tendons. We therefore hypothesise that Cyclic Fatigue Loading (FL) will result in alterations in fascicle extension mechanisms which are age specific. Methods Fascicles (n= 6–8/tendon) were dissected from the forelimb SDFTs of 6 young (aged 3–6 years) and 5 old horses (aged 18–20 years). Half the fascicles underwent 1800 cycles of FL to 60% of their predicted failure stress, while the remaining fascicles acted as unloaded controls. Following FL, fascicles were stained with 5-dicholorotriazynl fluorescein, secured in a straining rig and viewed under a confocal microscope. A grid was photobleached onto each fascicle and images were taken at 2% strain increments up to 10%. Deformation of the grid was quantified by measuring changes in longitudinal strain, deviation from the vertical gridline and rotation of the horizontal gridline. Statistical significance was set at p Results In agreement with previous studies, local longitudinal strains were smaller than the overall applied strain, and did not differ between FL and control groups or with ageing. Deviation of the vertical gridline, representing fibre sliding, did not differ between FL and control samples from young horses, but there was a significant increase in fibre sliding in FL samples from old horses (p Discussion The results support the hypothesis, showing that FL causes age-specific alterations in fascicle extension mechanisms. Our previous findings suggest that, in samples from young horses, extension is facilitated by the unwinding of helical sub-structures, which is indicated by the grid rotation observed. The results of the current study show that FL causes a significant decrease in this rotation, suggesting the helix sub-structures are altered by FL, which may reduce the ability of fascicles to extend and recoil. By contrast, in aged samples this rotation decreased, indicating ageing also causes alterations to the helical sub-structures. FL of aged samples resulted in increased fibre sliding, indicating that damage may be occurring between the collagen fibres, which is likely to decrease the mechanical integrity of the fascicles. The observed age-specific alterations in extension mechanisms after FL suggest that fascicles from aged tendons, where structure of the helix is already compromised, suffer increased fibre sliding. Fibre sliding may initiate a cell response predisposing aged tendons to degenerative changes and subsequent injury.
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Fascicles from energy-storing tendons show an age-specific response to Cyclic Fatigue Loading
Journal of the Royal Society Interface, 2014Co-Authors: Chavaunne T. Thorpe, Graham P. Riley, Helen L. Birch, Peter D. Clegg, Hazel R. C. ScreenAbstract:Some tendons, such as the human Achilles and equine superficial digital flexor tendon (SDFT), act as energy stores, stretching and recoiling to increase efficiency during locomotion. Our previous observations of rotation in response to applied strain in SDFT fascicles suggest a helical structure, which may provide energy-storing tendons with a greater ability to extend and recoil efficiently. Despite this specialization, energy-storing tendons are prone to age-related tendinopathy. The aim of this study was to assess the effect of Cyclic Fatigue Loading (FL) on the microstructural strain response of SDFT fascicles from young and old horses. The data demonstrate two independent age-related mechanisms of Fatigue failure; in young horses, FL caused low levels of matrix damage and decreased rotation. This suggests that Loading causes alterations to the helix substructure, which may reduce their ability to recoil and recover. By contrast, fascicles from old horses, in which the helix is already compromised, showed greater evidence of matrix damage and suffer increased fibre sliding after FL, which may partially explain the age-related increase in tendinopathy. Elucidation of helix structure and the precise alterations occurring owing to both ageing and FL will help to develop appropriate preventative and repair strategies for tendinopathy.
Susannah J. Sample - One of the best experts on this subject based on the ideXlab platform.
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Role of calcitonin gene-related peptide in bone repair after Cyclic Fatigue Loading.
PloS one, 2011Co-Authors: Susannah J. Sample, Zhengling Hao, Aliya P. Wilson, Peter MuirAbstract:Background Calcitonin gene related peptide (CGRP) is a neuropeptide that is abundant in the sensory neurons which innervate bone. The effects of CGRP on isolated bone cells have been widely studied, and CGRP is currently considered to be an osteoanabolic peptide that has effects on both osteoclasts and osteoblasts. However, relatively little is known about the physiological role of CGRP in-vivo in the skeletal responses to bone Loading, particularly Fatigue Loading. Methodology/Principal Findings We used the rat ulna end-Loading model to induce Fatigue damage in the ulna unilaterally during Cyclic Loading. We postulated that CGRP would influence skeletal responses to Cyclic Fatigue Loading. Rats were Fatigue loaded and groups of rats were infused systemically with 0.9% saline, CGRP, or the receptor antagonist, CGRP8–37, for a 10 day study period. Ten days after Fatigue Loading, bone and serum CGRP concentrations, serum tartrate-resistant acid phosphatase 5b (TRAP5b) concentrations, and Fatigue-induced skeletal responses were quantified. We found that Cyclic Fatigue Loading led to increased CGRP concentrations in both loaded and contralateral ulnae. Administration of CGRP8–37 was associated with increased targeted remodeling in the Fatigue-loaded ulna. Administration of CGRP or CGRP8–37 both increased reparative bone formation over the study period. Plasma concentration of TRAP5b was not significantly influenced by either CGRP or CGRP8–37 administration. Conclusions CGRP signaling modulates targeted remodeling of microdamage and reparative new bone formation after bone Fatigue, and may be part of a neuronal signaling pathway which has regulatory effects on load-induced repair responses within the skeleton.
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effect of short term treatment with alendronate on ulnar bone adaptation to Cyclic Fatigue Loading in rats
Journal of Orthopaedic Research, 2007Co-Authors: Jennifer G. Barrett, Susannah J. Sample, Peter Muir, Jenna Mccarthy, Vicki L. Kalscheur, Laura ProkuskiAbstract:Targeted remodeling of Fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to Cyclic Fatigue. The ulnae of 140 rats were Cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before Fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to Fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before Fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before Fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before Fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in Fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during Fatigue. After Fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the Fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from Fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
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Effect of short‐term treatment with alendronate on ulnar bone adaptation to Cyclic Fatigue Loading in rats
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2007Co-Authors: Jennifer G. Barrett, Susannah J. Sample, Peter Muir, Jenna Mccarthy, Vicki L. Kalscheur, Laura ProkuskiAbstract:Targeted remodeling of Fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to Cyclic Fatigue. The ulnae of 140 rats were Cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before Fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to Fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before Fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before Fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before Fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in Fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during Fatigue. After Fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the Fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from Fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
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response of the osteocyte syncytium adjacent to and distant from linear microcracks during adaptation to Cyclic Fatigue Loading
Bone, 2004Co-Authors: Sara A Colopy, Susannah J. Sample, Jennifer G. Barrett, Vicki L. Kalscheur, J Benzdean, Yan Lu, Nichole A Danova, Ray Vanderby, Mark D Markel, Peter MuirAbstract:Abstract Cyclic Loading induces Fatigue in bone and initiates a complex, functionally adaptive response. We investigated the effect of a single period of Fatigue on the histologic structure and biomechanical properties of bone. The ulnae of 40 rats were subjected to Cyclic Fatigue (−6000 μe) unilaterally until 40% loss of stiffness developed, followed by 14 days of adaptation. The contralateral ulna served as a treatment control (n = 20 rats), and a baseline loaded/non-loaded group (n = 20 rats/group) was included. Bones from 10 rats/group were examined histologically and the remaining bones (10 rats/group) were tested mechanically. The following measurements were collected: volumetric bone mineral density (vBMD); ultimate force (Fu); stiffness (S); energy-to-failure (U); cortical area (Ct.Ar); microcrack density (Cr.Dn); microcrack mean length (Cr.Le); microcrack surface density (Cr.S.Dn); osteocyte density (Ot.N/T.Ar and Ot.N/TV); bone volume fraction (B.Ar/T.Ar); resorption space density (Rs.N/Ct.Ar); and maximum and minimum area moments of inertia (IMAX and IMIN). Using confocal microscopy, the bones were examined for diffuse matrix injury, canalicular disruption, and osteocyte disruption. The adapted bones had increased B.Ar, IMAX, and IMIN in the mid-diaphysis. Fatigue Loading decreased structural properties and induced linear microcracking. At 14 days, adaptation restored structural properties and microcracking was partially repaired. There was a significant nonlinear relationship between Ot.N/T.Ar and B.Ar/T.Ar during adaptation. Disruption of osteocytes was observed adjacent to microcracks immediately after Fatigue Loading, and this did not change after the period of adaptation. In Fatigue-loaded bone distant from microcracks, diffuse matrix injury and canalicular disruption were often co-localized and were increased in the lateral (tension) cortex. These changes were partially reversed after adaptation. Loss of canalicular staining and the presence of blind-ends in regions with matrix injury were suggestive of rupture of dendritic cell processes. Taken together, these data support the general hypothesis that the osteocyte syncytium can respond to Cyclic Loading and influence targeted remodeling during functional adaptation. Changes in the appearance of the osteocyte syncytium were found in Fatigue-loaded bone with and without linear microcracks. We hypothesize that the number of dendritic cell processes that experience load-related disruption may determine osteocyte metabolic responses to Loading and influence targeted remodeling.
Laura Prokuski - One of the best experts on this subject based on the ideXlab platform.
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effect of short term treatment with alendronate on ulnar bone adaptation to Cyclic Fatigue Loading in rats
Journal of Orthopaedic Research, 2007Co-Authors: Jennifer G. Barrett, Susannah J. Sample, Peter Muir, Jenna Mccarthy, Vicki L. Kalscheur, Laura ProkuskiAbstract:Targeted remodeling of Fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to Cyclic Fatigue. The ulnae of 140 rats were Cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before Fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to Fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before Fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before Fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before Fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in Fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during Fatigue. After Fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the Fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from Fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
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Effect of short‐term treatment with alendronate on ulnar bone adaptation to Cyclic Fatigue Loading in rats
Journal of orthopaedic research : official publication of the Orthopaedic Research Society, 2007Co-Authors: Jennifer G. Barrett, Susannah J. Sample, Peter Muir, Jenna Mccarthy, Vicki L. Kalscheur, Laura ProkuskiAbstract:Targeted remodeling of Fatigue-injured bone involves activation of osteoclastic resorption followed by local bone formation by osteoblasts. We studied the effect of parenteral alendronate (ALN) on bone adaptation to Cyclic Fatigue. The ulnae of 140 rats were Cyclically loaded unilaterally until 40% loss of stiffness developed. We used eight treatment groups: (1) baseline control; (2) vehicle (sterile saline) and (3) alendronate before Fatigue, no adaptation (Pre-VEH, Pre-ALN, respectively); (4) vehicle and (5) alendronate during adaptation to Fatigue (Post-VEH, Post-ALN, respectively); (6) vehicle before Fatigue and during adaptation (Pre-VEH/Post-VEH); (7) alendronate before Fatigue and vehicle during adaptation (Pre-ALN/Post-VEH); (8) alendronate before Fatigue and during adaptation (Pre-ALN/Post-ALN). Bones from half the rats/group were tested mechanically; remaining bones were examined histologically. The following variables were quantified: volumetric bone mineral density (vBMD); ultimate force (F(u)); stiffness (S); work-to-failure (U); cortical area (Ct.Ar); new woven bone tissue area (Ne.Wo.B.T.Ar); resorption space density (Rs.N/T.Ar). Microcracking was only seen in Fatigue-loaded ulnae. A significant effect of alendronate on vBMD was not found. Preemptive treatment with alendronate did not protect the ulna from structural degradation during Fatigue. After Fatigue, recovery of mechanical properties by adaptation occurred; here a significant alendronate effect was not found. An alendronate-specific effect on adaptive Ne.Wo.B.T.Ar was not found. In the Fatigue-loaded ulna, Rs.N/T.Ar was increased in vehicle-treated adapted groups, but not alendronate-treated adapted groups, when compared with baseline control. These data suggest that short-term alendronate treatment does not protect bone from Fatigue in this model. Inhibition of remodeling may reduce microcrack repair over time.
