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인체의 움직임을 탐구하고,
최적 움직임 회복을 목표로 임상치료를 하다보면 힘줄(tendon)에 스테로이드 주사를 주면 통증은 쉽게 줄어들지만
힘줄의 collagen 붕괴로 약해지면서
그 힘을 회복하기가 매우매우 어렵다는 사실을 알게 된다.
아래 논문 결과는 인대를 스테로이드에 incubation한 것. - 생체실험은 불가능!!
The strength was reduced by 45% after 3 days (95% confidence interval [CI], 17.66-67.71) and by 62% after 7 days (95% CI, 7.22-93.20) compared with the controls.There was also a significant reduction in tensile strength as a result of the LC corticosteroid incubation (P < .05) (Figure 2B). The tensile strength was reduced by 66% after 3 days (95% CI, 43.68-78.86) and 66% after 7 days (95% CI, 26.31-83.81) compared with the controls (Table 1).
다음에는 long term effect에 대한 논문을 찾아야 할듯
panic bird...
Tendon injuries are commonly sustained in both recreational and elite sports and in many working conditions that require repetitive movements. However, despite the considerable incidence of tendinopathy injuries,17,35 the cause of this condition remains elusive. It is generally believed that tendinopathy is related to cumulative mechanical trauma; however, it was recently suggested that stress shielding or compression of the tendon tissue may be an important etiological factor.1
- 힘줄손상은 일반 스포츠활동에서 흔하게 발생하는 질병.
- 하지만 건병증은 그 기전에 대해서 애매한 부분이 많음. 축적되는 기계적 tauma와 연관된다고 믿어지지만 실제로는 힘줄의 압박요소가 가장 중요한 요인이라고 제안되기 시작함.
Local injection with corticosteroid is a common treatment for tendinopathies,16,17,35 although its direct effect on the material properties of the tendon are unknown. In fact, there have been several case reports of tendon rupture after intratendinous corticosteroid administration, in both the upper and the lower extremities.14,20,24,29,32 To what extent such ruptures can be attributed to the steroid treatment itself and/or a progression of the tendinopathy remains unknown. However, it is noteworthy that several animal studies have shown that intratendinous injection of corticosteroids leads to a reduction of tensile strength,23,26,27,33,40,41 although a few studies failed to demonstrate such a corticosteroid-associated reduction in mechanical strength.30,37
- 건병증 치료를 위한 국소적 스테로이드 주사는 가장 흔하게 시행되는 치료임. 스테로이드 주사후 건파열에 대한 많은 보고가있음.
- 많은 연구에서 intratendinous 에 스테로이드 주사는 장력감소를 야기한다는 것을 보여줌.
Many studies concerning the effects of corticosteroids on tendon tissue have been conducted on whole tendon and mostly address the cellular responses and do not, therefore, necessarily relate to the tensile-bearing unit of the tendon.
- 많은 연구에서 건병증에 스테로이드 주사의 효과에 대해 연구하고 있고, 세포반응과 연관된 힘줄의 장력지지와 연관된 탐구가 필요함.
The determination of the mechanical properties of tendons is associated with a number of problems that may introduce considerable variation in the results.9,12 For example, clamping techniques might produce large strain concentrations of the tissue at the clamping site that may lead to premature rupture of the specimen and slippage of the specimen that may distort the actual elongation to failure.10,21
- 힘줄의 기계적 특성은 많은 문제와 관련되어 있음.
- 예를들어 clamping 테크닉은 물린 부위에서 조직의 장력생성을 만들어 탐구가능...
The inherent problems and the considerable variation associated with the testing of isolated whole tendon, in vitro or in situ, may make it difficult to detect if corticosteroids induce small yet clinically meaningful changes in the tensile strength of the tendon. Some of these challenges associated with mechanical testing were recently addressed for testing of single collagen fascicles.21
- 스테로이드로 유발되는 건의 장력강도 변화를 임상적으로 탐구하는 것은 어려움.
The fascicles of tendons consist of multiple collagen fibers made up of collagen molecules that are bound together by covalent intermolecular cross-links.The intermolecular crosslinks are fundamental to the proper behavior and function of the tendon, and lack thereof causes the molecules to slide relative to each other, leaving it extensible and weakened.4,31
- intermolecular crosslink는 힘줄의 적절한 기능에 필수임.
Although intermolecular cross-linking is essential to the mechanical properties of the tendon, there are, to the best of our knowledge, no investigations into the effects of corticosteroids on collagen cross-link amount and tendon strength.
- intermolecular cross-linking이 힘줄의 기계적 특성에 필수이지만, 우리가 아는한, 힘줄의 강도와 콜라겐 교차링크에 대한 스테로이드 주사효과에 대한 탐구는 없음.
The purpose of the present study was to examine the effect of a corticosteroid environment on the tensile strength of isolated collagen fascicles. We hypothesized that incubation in corticosteroids would result in a reduction in the mechanical properties of isolated collagen fascicles. Another objective was to examine the effects of corticosteroids on cross-link density in isolated collagen fascicles, which we expected to decline.
- 이 논문의 목적은 스테로이드 환경에서 힘줄의 인장강도를 조사하는 것임.
- 우리는 스테로이드 incubation가 콜라겐 다발의 기계적 특성을 감소시킬 것이라고 가정함.
- 다른 목적은 스테로이드 incubation가 교차링크 농도가 얼마나 줄어드는가를 알아보는 것임.
RESULTS
There was no difference in fascicle diameter between the intervention groups and the corresponding control groups (Table 1).The HC corticosteroid incubation resulted in a significant reduction in tensile strength compared with the controls (P < .05) (Figure 2A).
- fascicle diameter에는 차이가 없음.
- 스테로이드incubation는 힘줄의 심각한 감소를 야기함.
The strength was reduced by 45% after 3 days (95% confidence interval [CI], 17.66-67.71) and by 62% after 7 days (95% CI, 7.22-93.20) compared with the controls. There was also a significant reduction in tensile strength as a result of the LC corticosteroid incubation (P < .05) (Figure 2B). The tensile strength was reduced by 66% after 3 days (95% CI, 43.68-78.86) and 66% after 7 days (95% CI, 26.31-83.81) compared with the controls (Table 1).
- 3일후 강도의 감소는 45%감소, 7일 후 62% 감소
- 3일후 인장강도는 66%, 7일 후에는 66% 감소
There was no significant difference in the magnitude of strength reduction between the groups. The intermolecular cross-link levels in the samples are shown in Table 2. The corticosteroid incubation did not significantly affect the measures of intermolecular cross-linking.
- 스테로이드 incubation은 intermolecular cross-linking의 수치에 의미심장한 변화없음.
DISCUSSION
The main findings of the present study were that fascicles incubated in corticosteroids in either the HC or the LC for 3 or 7 days had significantly reduced tensile strength compared with the matched controls kept in 9% saline, and there was no difference in the magnitude of strength reduction between the 2 concentrations. Furthermore, the corticosteroid incubation did not influence the intermolecular cross-link amount. It is common clinical practice to use local corticosteroid injection to treat tendinopathies. However, there are several case reports of tendon rupture after intratendinous injections of corticosteroids, in both the upper and the lower extremities.14,20,24,29,32
It is not possible to ascertain to what extent these ruptures were a result of the steroid treatment or a result of the tendinopathy, although it should be noted that several animal studies have shown that corticosteroid treatment is associated with a reduction in tensile
strength.23,26,27,33,40,41 Kennedy and Willis27 showed a decrease in the tensile strength in the rabbit Achilles tendon 2 and 7
days after a single injection of corticosteroids. Others have shown that intra-articular administration of corticosteroids reduces the mechanical properties of ligaments by up to 20% after 15 weeks.33 More recently, it was shown that the tensile strength of rabbit Achilles tendon was reduced by 20% seven weeks after the initial injection of corticosteroids.23
It should be noted that some investigations did not succeed in demonstrating a corticosteroid-associated reduction in mechanical
strength.30,37 However, the present study confirms previous observations of a corticosteroid-associated decline in mechanical properties of tendon and extends this effect to individual tendon fascicles, although the magnitude of the strength reduction in the present study was considerably larger than in previous studies.
Although numerous reports, including the present study, have reported a considerable reduction in tensile strength after corticosteroid treatment, there is currently no explanation for this corticosteroid-associated deleterious effect on the mechanical properties of tendon. It has been suggested that intratendinous injections of corticosteroid may impair the healing process of injured tendons and have a degenerative effect on the tissue.42 Steroid injections have also been shown to be associated with collagen necrosis and incomplete tendon repair.5 Several intratendinous corticosteroid injections(4-10) in rat Achilles tendon have also been shown to be associated with tendon thickening and visible adhesion.39
However, these studies did not examine the mechanical properties of the tissue, and it is not possible to relate morphological changes to changes in the mechanical properties. Mechanical testing of small tendon samples is associated with numerous technical challenges. One important source of variation is the determination of the cross-sectional area of the sample, which in the present study was obtained by multiple diameter measurements along the length of the fascicle.
These measurements yielded a variation of less than 10 μm for an individual specimen and did not differ between the groups. Loading rate may also influence absolute ultimate stress and strain,43,45 although stiffness appears to be largely rate insensitive7,19,22,43,45; however, it would not affect the relative difference between groups. Tissue slippage and stressstrain concentration at the site of tissue clamping,which may lead to premature tissue failure, represent other important challenges during mechanical testing of tendon tissue. These problems may in part be avoided with specialized wedge grips9 and cryo-jaws12; however, these techniques are not well
suited for small-sample testing.
Therefore, in the present study, the tissue samples were glued to the aluminum plates in the testing rig with cyanoacrylate, in accordance with previous studies.44 This permits the stress imposed on the tissue to exceed 100 MPa without any slippage or failure at the fixation site.21 In the present study, tissue rupture occurred in all cases between the end plates.
The concentration of the steroid solution in vitro versus in vivo has to be taken into consideration.When used clinically for the treatment of tendinopathy, corticosteroids are usually diluted with local anesthetics (1 mL steroid/0.5 mL local anesthetics), which corresponds to the concentration of the steroid solution in the HC group in the present study (although the steroid was diluted with saline). Once the solution is injected in the tendon, the collagen fascicles in that area receive the full concentration of the solution, although the solution likely diffuses to the surrounding area shortly thereafter, which prompted us to include the LC group.
It is noteworthy that there was no difference between the concentration groups, which may indicate that a ceiling effect had already been reached in the LC group. Water absorption and diffusion are potential contributing factors; however, the diameters of the fascicles in the intervention groups and the control groups were similar and are therefore unlikely explanations for the results. Furthermore, pH levels need to be considered, and the control experiments (see “Materials and Methods”) demonstrated that they did not influence the outcome.
There are few studies that report on both the mechanical and histological changes in collagen tissue after intratendinous injections with corticosteroids. Kapetanos26 showed that corticosteroid injections yielded a 30% reduction in tensile strength, 13% reduction in tendon weight, 66% reduction in magnitude of adhesion, and 67% reduction in energy to failure compared with the control group. Walsh et al41 showed that the ultimate loads of corticosteroid-treated animal ligaments were inferior compared to those of the controls.
In a follow-up study, Wiggins et al42 showed that the corticosteroids delayed the healing of injured ligaments and reduced the failure strength compared to the nontreated controls.These data suggest that corticosteroid treatment of injured connective tissue negatively influences the healing process and reduces its mechanical properties. Although these studies showed that corticosteroids reduce the tensile strength of the tendon, the authors did not necessarily relate these observations to the tensile-bearing unit of the tendon, namely the fiber.36
Collagen molecules are synthesized by fibroblasts and spontaneously self-assemble into cross-striated fibrils.25 The fibrils are stabilized by covalent cross-links, which are initiated by oxidative deamination of specific lysine and hydroxylysine residues in collagen by lysyl oxidase. The formation of these cross-links contributes to the high tensile strength and relative immunity to chemical degradation.2,8,25 The cross-links have a large influence on the mechanical behavior of collagen, and an increased number of cross-links increases its stiffness.3,13 It was recently shown that crosslink–deficient tendons had a reduced fracture load.38
In the present study, the exposure to corticosteroids markedly affected the strength of the tendon but did not appear to influence the cross-linking or the strain properties (seeTable 2). Thus, factors other than cross-linking have to account for the observed decline in strength. The fibrillar collagen is embedded in a hydrophilic extracellular matrix consisting of proteoglycans, glycoproteins, and glycosaminoglycans. It cannot be discounted that corticosteroid administration somehow influences components of the extracellular matrix and the manner in which these components contribute to the tensile strength of the fibril.15
Clinical Perspectives There are numerous reports14,18,20,24,34 on the pain-relieving effects of corticosteroids in athletes with chronic pain, although the mechanism behind it remains elusive. This clinical pain relief should be weighed against the possible risk of injury due to increased pain-free physical activity on the part of the athlete/patient. Furthermore, most tendons, including the patellar tendon, are subjected to stresses below 30 MPa; however, the Achilles tendon may experience stresses in excess of 70 MPa, which puts it close to the failure stress (approximately 100 MPa).28
Therefore, even a relatively small reduction in mechanical strength of the Achilles tendon may render it dangerously close to its failure limit, whereas the same absolute magnitude of reduction in the patellar tendon may have limited or no clinical effect. This could help explain the larger number of reported Achilles tendon ruptures and the apparent lack thereof in patellar tendon after injection of corticosteroids.
In summary, the present study showed that corticosteroid incubation of 3 and 7 days, with either HC or LC, had a deleterious effect on the mechanical properties of isolated collagen fascicles, whereas the cross-linking was unaffected. However, the magnitude of the observed effect on whole tendon, in vivo, remains unknown.
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