- Email: [email protected]
Strength Training of the Quadriceps Muscles Following ACL Loss: Effects on Strength and Joint Integrity
WISSENSCHAFTLICHER BEITRAG
Orthop€adie Traumatologie
SportOrthoTrauma 28, 266–273 (2012) Elsevier – Urban&Fischer www.elsevier.de/SportOrthoTrauma http://dx.doi.org/10.1016/j.orthtr.2012.10.006
WISSENSCHAFTLICHER BEITRAG E. Szabo et al.
Krafttraining des M. quadriceps nach VKBRuptur: Effekt auf Kraft und Gelenksintegrit€ at Zusammenfassung Hintergrund: Verletzungen des vorderen Kreuzbandes (VKB) geh€oren zu den h€aufigsten Knieverletzungen und sind ein etablierter Risikofaktor f€ur Gelenkarthrose. Als Folge sind Muskelatrophie, Kraftminderung und verz€ogerte Muskelaktivierung h€aufig mit dieser Verletzung verbunden und gelten als eigenst€andige Risikofaktoren f€ur Gelenkarthrose. Muskelaufbautraining, wird als therapeutische Maßnahmen praktiziert um die Kniestabilit€at zu verbessern und neuromuskul€arer Hemmung entgegenzuwirken. Allerdings sind die positiven Effekte von Muskelaufbautraining abh€angig von Intensit€at, Dosierung und Dauer. Das Ziel dieser Studie war es, den Einfluss verschiedener Trainingsprotokolle auf die Entwicklung von Gelenkarthrose in Knien mit rupturierten VKB’s zu quantifizieren. Methoden: 15 ausgewachsene New Zealand White Rabbits (NZW) wurden in drei experimentelle Gruppen eingeteilt: (i) VKB-Durchtrennung gefolgt von einem maximalen Muskeltraining, (ii) VKB-Durchtrennung gefolgt von einem submaximalen Muskeltraining und (iii) VKB-Ruptur ohne Aufbautraining. Das maximale Extensor-Drehmoment des Knies wurde in jeder Trainingssession gemessen. Nach dem finalen Experiment wurden die Kniegelenke histologisch analysiert. Resultate: Tiere in beiden Muskelaufbaugruppen zeigten einen signifikanten Anstieg des maximalen Drehmomentes sowie eine signifikant weiter fortgeschrittene Knorpelsch€adigung als die untrainierte Gruppe. Die maximal trainierte und nicht trainierte Kontrollgruppe zeigte eine signifikant reduzierte Quadrizepskraft auf der experimentellen Seite verglichen mit der
266
E. Szabo et al.
Strength Training of the Quadriceps Muscles Following ACL Loss: Effects on Strength and Joint Integrity Eva Szabo, Christian Egloff, Ruth Seerattan, Tim Leonard, Walter Herzog Eingegangen am 3. September 2012; akzeptiert am 15. Oktober 2012
Introduction
As the main knee extensor muscles,
the quadriceps group has a number of important functional roles. However, following anterior cruciate ligament (ACL) injury, the quadriceps group atrophies [3,13,23,24], becomes weaker [3,9,13,20,21,24] and activation patterns are altered and reduced [6,22,24]. Quadriceps strength has been linked with function and improved gait patterns after ACL loss [1,12,24] and reconstruction [10,12]. Nonetheless, quadriceps weakness often remains despite corrective surgery and aggressive rehabilitation programs aimed at improving muscle strength [3,12,22]. In order to maximize function and quality of life for subjects with ACL injury, this loss of quadriceps mass, strength and activation must be understood so that measures can be taken to avoid it and safely build strength. Rehabilitation following loss of the ACL is further complicated by a complex relationship between injury, exercise and osteoarthritis (OA). Quadriceps weakness alone is considered a risk factor for the development of OA [18], and exercise is often prescribed as a mean of OA treatment [15,17,25]. In addition,
effective quadriceps strength training has been linked to increased function and decreased disability in human subjects with OA. Nonetheless, several studies in animal models have shown that the effect of exercise is dosedependent, and can have detrimental effects. Galois et al. [5] found that slight to moderate exercise slowed the development of OA in rats which had undergone ACL transection compared to sedentary rats or rats which underwent ‘‘intense’’ exercise. Other studies also provide evidence that an ‘‘excessive’’ amount of exercise on its own [16] or in conjunction with an injury model [2] increases osteoarthritic changes in rat knees. This leads to a difficult balance between the apparently beneficial effects of quadriceps strength, and the need to keep exercise within a safe level for joint health. The aim of this study was to develop a greater understanding of the interactions between joint injury, muscle training, and the development of OA. To achieve this, we asked two specific questions: (i) can a muscle stimulation regime applied shortly after ACL injury prevent quadriceps weakness and atrophy; and (ii) what effect does such a
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
kontralateralen Seite. Die submaximale Trainingsgruppe zeigte keine signifikanten Seitenunterschiede in der Muskelkraft. Diskussion: Unsere Resultate weisen darauf hin, dass Muskelaufbautraining in hoher Intensit€at und h€aufigen Repetitionen zu erh€ohtem Muskelaufbau wie auch zu akzelerierten Knorpelsch€aden f€uhrt. Obwohl die vorliegenden Resultate aus dem Tiermodell stammen, sehen wir dennoch große € Ahnlichkeiten des Kniegelenkes in der muskul€aren und oss€aren Biomechanik, weshalb die beobachteten Effekte auch beim Menschen gelten k€onnten; sie sollten daher bei der Anwendung von Quadrizeps-Rehabilitations-Strategien sorgf€altig ber€ucksichtigt werden. Schlussfolgerung: Obwohl Muskelaufbautraining insbesondere der Quadrizepsmuskulatur im Falle einer VKBRuptur einen wichtiger Pfeiler im therapeutischen Rehabilitationsprogramm darstellt, zeigen unsere Ergebnisse, dass die Dosierung und Intensit€at solcher Trainingseinheiten mit Vorsicht vorgenommen werden sollten, um nachteilige Folgen zu vermeiden.
Experimental Design Skeletally mature New Zealand White rabbits were used in accord with the experimental protocol approved by the University of Calgary Animal Care Committee. The left limb of all rabbits was used as the experimental limb while the right limb was used as an intact control. The experimental groups were:
ACL Transection Surgery ACL transections were performed as described previously [13]. Briefly, the joint capsule was opened through a lateral incision and the ACL was identified, hooked and then cut. The transection was verified visually as well as by manual assessment of the changes in anterior and medial-lateral laxity. The joint capsule and subcuticular layer were closed with 3.0 Monosyn (Jorgensen Laboratories Inc.) or 3.0 Vicryl sutures (Johnson and Johnson), and the skin was closed with 3.0 Braunamid sutures (Jorgensen Laboratories Inc.).
1. ACL Transected (ACLT), Maximal Training (n = 6): All six rabbits in the ACLT, maximally trained group underwent ACL transection on the experimental hind limb. Shortly after the transection surgery, they underwent a fourweek training program consisting of electrical stimulation of the quadriceps muscles of the experimental limb. Each session consisted of sets of maximal contractions. 2. ACLT, Sub-maximal Training (n = 5): All five rabbits in the ACLT, sub-maximally trained group underwent ACL transection on the experimental hind limb. Shortly after the transection surgery, they underwent a four-week training program consisting of electrical stimulation of the quadriceps muscles of the experimental limb. Each session consisted of a single long set of repeated sub-maximal contractions. 3. ACLT, Untrained (n = 4): All four rabbits in the ACLT, untrained group underwent ACL transection on the experimental hind limb. Following the transection surgery, they were allowed to recover for 4.5 weeks.
Training Protocols For rabbits in the muscle training groups, the training sessions began 4 days following the ACL transection surgery. Each rabbit underwent a total of 12 training sessions, with three sessions a week for 4 weeks. For both training protocols, in each training session, rabbits were anesthetized using a 3.5% isoflurane (Benson Medical) to oxygen mixture. An area of skin over the quadriceps muscle was prepared for electrode placement by shaving and cleaning with alcohol. The anesthetized rabbit was placed on its back in a sling with a warm waterheating pad. The left hind limb was bluntly constrained in a stereotactic frame with the knee at 90˚ of flexion. Forces were measured using a strain bar placed over the rabbit’s tibia just proximal to the ankle and oriented in the direction of knee extensor force (Figure 1). The strain bar was instrumented with strain gauges and an amplifier in a Wheatstone half-bridge configuration and data were recorded using Windaq data collection software (DATAQ Instruments, 2000). The distance from the strain bar to the knee (most prominent point of
stimulation regime have on knee joint integrity?
Methods
E. Szabo et al.
Strength Training of the Quadriceps Muscles Following ACL Loss
267
WISSENSCHAFTLICHER BEITRAG
Figure 1 Training set-up. The animal’s leg is rigidly fixed in a custom build stereotactic frame through bony pins in the hips and femoral condyles. The tibia is taped to a restraining bar, which is connected to the motor. Electrical stimulation is performed with cutaneous electrodes.
the lateral femoral condyle) was measured and recorded. Knee extensor torque was calculated by multiplying the force measured with the tibial restraining bar by the distance of that bar to the knee. The quadriceps group was identified and selfadhesive electrodes were attached and held in place at mid-belly. All contractions were induced using a Grass S8800 Stimulator (Grass Instruments). For the maximal training sessions, supra-maximal contractions were induced with 0.4 ms pulse duration, 150 Hz frequency and 500 ms train duration. Each session consisted of 5 sets of 10 contractions with
268
E. Szabo et al.
500 ms of rest between contractions and 2 minutes of rest between sets [4]. In order to evaluate the data from the training sessions, the average torque from each set in each session was considered (Figure 2). The average torque from the first set of each session was then considered the maximum session torque, and was used to rate improvement in strength over the course of the training sessions. For the sub-maximal training sessions, one maximal contraction was elicited at the beginning of the session followed by 15 minutes of sub-maximal contractions at approximately 20% of the maximum
(Figure 3). The sub-maximal contractions were 500 ms long with 1500 ms of rest. The intensity of the sub-maximal contractions was maintained by adjusting the voltage and frequency of stimulation. Although the actual voltages and frequencies varied considerably between rabbits and sessions, they ranged from around 45 Hz and 20 V at the beginning of the session, to around 80 Hz and 80 V at the end of the session. This variance is due to physiological differences in between animals and of the experimental setup. Therefore a slight difference in electrode placement, skin impedance, muscle geometry and size, or electrode pressure would require different stimulation parameters to achieve the target level of 20% of the maximum force. Also this increase in stimulation parameters (voltage and frequency) from the beginning to the end of the training protocol was necessary, as the quadriceps muscles became fatigued and increased stimulation ensured that the force was kept constant at 20% of maximum throughout the entire 15 minute training protocol. Following completion of the exercise, anesthesia was reversed and rabbits were removed from the frame and allowed to recover on a heating pad. All rabbits were given a subcutaneous injection of 0.05 mL Hydromorphone (Sandoz Canada) as an analgesic. Strain Bar Calibration The strain bar used for force measurements was calibrated at the beginning of the training period, and before the terminal experiments. A series of seven calibrated weights were hung from the strain bar covering the range of experimentally observed knee extensor forces. Linearity of the
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
Rabbits were sacrificed by an intravenous injection of Euthanyl (Bimeda-MTC).
Figure 2 Raw data from a training session of a typical rabbit from the maximal training group.
force bar was confirmed and a calibration equation relating force to voltage was obtained using linear regression (r > 0.99). Terminal Experiment The terminal experiments were performed 4.5 weeks following the ACL transection surgery for all experimental groups. The isometric knee extensor torque of both hind limbs of all rabbits was measured following the general procedure described by Longino et al. [13]. Briefly, rabbits were anaesthetized and femoral nerve cuffs were implanted in order to directly stimulate the quadriceps.
The hind limb was fixed in a stereotactic frame using pointed metal rods at the pelvis and femoral condyles to maintain a constant hip angle of 1408. Tests were conducted on both hind limbs of each rabbit at knee angles of 80˚, 100˚ and 120˚. Maximum isometric knee extensor contractions were induced using a stimulation frequency of 100 Hz. For analysis, strength was defined as the average torque over the three angles. Two repeat trials were performed at each knee angle. Weakness was defined as the percent difference between the torques produced by the control and the experimental limbs.
Histological analysis Following sacrifice, both knees of all rabbits were prepared for histological analysis using standard procedures for Mankin scoring. Briefly, joint surfaces were isolated from the surrounding tissue. The joints were then decalcified and divided into six sections: the medial and lateral tibia, the medial and lateral femoral condyles, the femoral groove, and the patella. These sections were processed and embedded in paraffin blocks. The blocks were cut into 12 mm slices and every eighth slice was used for histological analysis. The joints were rated using a standard Mankin scoring system [14] on each of the six areas of the knees. Statistical Analysis For analysis of the trends over the training period, linear regression and correlation analysis were used within experimental groups. For final strength, the average of the torques across the three angles tested was used for each rabbit and paired comparisons were made using the Wilcoxon rank sum and signed-rank tests. Mankin scores from experimental and contralateral joints were similarly compared using the Wilcoxon rank sum and signed-rank tests. For all statistical tests, a significance level of a = 0.05 was used.
Results
Figure 3 Raw data from a typical training session for a rabbit from the 20% training group.
E. Szabo et al.
Training Over the course of the training sessions, despite a large amount of variation in actual daily torques, the rabbits in the maximally trained group showed a significant increase in knee extensor strength (Figure 4).
Strength Training of the Quadriceps Muscles Following ACL Loss
269
WISSENSCHAFTLICHER BEITRAG
strength was significantly lower on the ACLT side compared to the contralateral control side. In the sub-maximally trained rabbits, there was no significant difference in strength between the experimental and control hind limbs (Table 1, Figure 6). The sub-maximally trained rabbits were found to have significantly greater strength in their experimental limb as well as significantly lower side-to-side weakness than the untrained rabbits (Table 1, Figure 6). Figure 4 Maximum training session torques and fitted improvement curve for all rabbits in the maximal training group.
Similarly, rabbits in the submaximal training group showed a significant strength increase throughout the training period (r2 = 0.33), and this increase in strength was particularly consistent
from the first training session onward (r2 = 0.90; Figure 5). Strength Differences In the maximally trained and untrained rabbits, quadriceps
Figure 5 Maximum torques for all rabbits in the sub-maximal training group. Following an initial decline, knee extensor torques from the 3rd training session on increased steadily throughout the training period (r2 = 0.9; p = 0.05). The red line shows the linear regression including the pre-training measurement and all 12 training sessions (r2 = 0.33; p = 0.05).
270
E. Szabo et al.
Histology The Mankin scores for the medial tibial plateau, the medial femoral condyle and the lateral femoral condyle were significantly greater in the experimental knees than the control knees of the maximally trained rabbits (p < 0.05). In the sub-maximally trained rabbits, the Mankin scores were higher in the experimental limb on the medial femoral condyle (p < 0.05), while in the untrained rabbits, there were no significant side-to-side differences (p > 0.05) (Table 1). Figure 7 shows the averages of the worst scores for the three groups. Between group comparisons were not made because of age differences between rabbits in the different groups. For example, it appears that the Mankin scores are higher in the sub-maximal training group rabbits compared to the normal controls and the maximally trained group rabbits. However, rabbits in the sub-maximal group were also on average 6 months older than rabbits in the other groups, and we believe that this difference may reflect the age of the rabbits rather than the specific training protocol, as supported by the increase in the control side values in the sub-maximally trained group rabbits compared to the other two groups.
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
Table 1. Average knee extensor torques and Mankin Scores shown with corresponding standard deviations (SD). Please note that the values presented are considered as percentage difference of the averages of the strength and torques, respectively. Differences in Torque
Untrained
Maximal
sub-maximal
Average torque (Nm) control (SD) Average torque (Nm) experimental (SD) Percent Difference
3.17 (0.38) 2.14 (0.08) 32.5%
3.1(0.49) 2.28(0.68) 26.5%
3.34 (0.63) 2.67(0.24) 20%
Differences in Mankin Score
Untrained
Maximal
sub-maximal
Average Mankin Score, control (SD) Average Mankin Score, experimental (SD) Percent Difference
8.25 (0.89) 9.5 (0.44) 13.20%
7.8 (0.95) 9.4 (1.7) 17.1%
10.4 (0.89) 12 (1.22) 13.33%
Discussion Effect of Training on Quadriceps Muscles Following ACL rupture in humans, quadriceps muscles atrophy and
become weaker [3,9,21,23,24], thereby creating asymmetries between the ACL-deficient and the intact leg [3,9,24]. Some of the strength loss in the ACL-deficient leg has been associated with muscle inhibition; that is an inability to
Figure 6 Average knee extensor torques. In the maximally trained and untrained group there was a significantly lower strength on the experimental side (ACLT) compared to the contralateral control.
Figure 7 Histological scoring (Mankin) for three groups. The maximal and submaximal testing showed significant higher scores compared to the contralateral limb, p = 0.031 and p = 0.063, respectively.
E. Szabo et al.
maximally contract the knee extensors [8,22,24]. In this animal model, we used electrical stimulation of the knee extensors to avoid any possible effects associated with muscle inhibition [19]. The maximal training protocol mimicked a powerful resistance exercise program that would normally be associated with strength gains and increased muscle mass. The maximal training regime produced increases in strength in the ACL-deficient leg (Figure 4), but did not alleviate the side-to-side differences between ACL-deficient and intact leg which were also observed in the control group rabbits (Figure 6). The submaximal training protocol was designed to mimic endurance training and large strength gains were not expected. Nonetheless, submaximally trained rabbits showed a modest increase in quadriceps strength (Figure 5), but unlike the maximally trained rabbits, we were unable to detect any side-to-side strength differences (Figure 6). It is unclear why the side-to-side weakness observed in the untrained group rabbits was not alleviated in the maximal training group rabbits but was below significance in the sub-maximal training group rabbits. A contralateral training effect may have contributed to this result and could have been induced in a number of ways. First, with the instability in the injured knee, the
Strength Training of the Quadriceps Muscles Following ACL Loss
271
WISSENSCHAFTLICHER BEITRAG
contralateral hind limb may have been used to compensate for the loss of functionality of the ACLdeficient leg, therefore becoming overloaded and trained during daily activities. This idea is supported by previous work in this animal model which showed that push off forces in hopping rabbits were substantially greater in the intact contralateral compared to the ACL-deficient hind limb [13]. Though this likely added to the difficulty of achieving balanced strength and it is possible that this effect was compounded by fatigue in the experimental leg following the training protocol, this explanation does not seem adequate to explain the difference between the training protocols. Second, previous studies have shown that unilateral strength training can have a direct strengthening effect on the contralateral limb [7,11]. It is possible that this effect was greater in the maximally than the sub-maximally trained rabbits. Third, the sub-maximally trained group consisted of 5 animals and although we did see a trend towards side-to-side differences in this group, a lack of statistical power may have prevented to show a statistically significant result. Training had a detrimental effect on the cartilages of the ACL-transected knees. Both maximal and submaximal training resulted in increased Mankin scores in some parts of the knee indicating that the cartilage was significantly more degenerated in the experimental compared to the control limbs (Figure 7). These results are similar to the findings by Appleton et al. [2] who showed that forced mobilization of ACLT rats resulted in accelerated OA development. In those experiments, the exercise protocol was designed to involve weight bearing through the knees’ full range of motion. Here, we showed
272
E. Szabo et al.
that OA is similarly accelerated by both high intensity and high repetition isometric strength training protocols. A limitation in this experimental setup was the relatively short recovery time (4 days) after ACL transection compared to the untreated group. It might be that in the beginning of the training sessions the knee joints were still in a posttraumatic inflammatory state, which could have led to accelerated cartilage degradation. Comparisons of the results of this study to humans have to be made with utmost caution. Since this study was based on an anaesthetized animal model, pain, which is considered an important limiting factor in voluntary training, was not integrated in the experimental protocol. However, we demonstrated that a maximal training regime is detrimental to articular cartilage integrity and that sub-maximal training protocols might be better and healthier options for the ACLinjured knee.
Conclusions Although muscle strength gains were seen over the course of the training sessions for both a maximal and a sub-maximal training protocol in ACLT rabbits, only the submaximal protocol eliminated the side-to-side strength imbalances characteristic in ACL deficiency. Both protocols, however, resulted in an increase in OA development and progression in the experimental knees. Thus, the results of this study suggest that therapeutic interventions involving quadriceps strengthening in legs with unstable knees must be performed with caution, as strengthening will lead to loading of the knee and may have a
negative effect on the articular cartilage.
Conflict of interests There is no conflict of interests.
Acknowledgments Canadian Institutes for Health Research, Alberta Innovates-Health Solutions Team Grant on Osteoarthritis, The Canada Research Chair Programme, The Killam Foundation.
References [1] E. Ageberg, Consequences of a ligament injury on neuromuscular function and relevance to rehabilitation using the anterior cruciate ligamentinjured knee as model, J. Electromyogr. Kinesiol. 12 (3) (2002) 205–212. [2] C.T. Appleton, et al., Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis, Arthritis Res. Ther. 9 (1) (2007) pR13. [3] G.A. Arangio, et al., Thigh muscle size and strength after anterior cruciate ligament reconstruction and rehabilitation, J. Orthop. Sports Phys. Ther. 26 (5) (1997) 238–243. [4] T.A. Butterfield, W. Herzog, Is the force-length relationship a useful indicator of contractile element damage following eccentric exercise? J. Biomech. 38 (9) (2005) 1932–1937. [5] L. Galois, et al., Dose-response relationship for exercise on severity of experimental osteoarthritis in rats: a pilot study, Osteoarthritis Cartilage 12 (10) (2004) 779–786. [6] E.M. Hasler, et al., In vivo knee joint loading and kinematics before and after ACL transection in an animal model, J. Biomech. 31 (3) (1998) 253–262. [7] T. Hortobagyi, et al., Cross-education of muscle strength is greater with stimulated than voluntary contractions, Motor Control 3 (2) (1999) 205–219. [8] M.V. Hurley, The effects of joint damage on muscle function,
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
[9]
[10]
[11]
[12]
[13]
[14]
proprioception and rehabilitation, Man Ther. 2 (1) (1997) 11–17. H. Ikeda, H. Kurosawa, S.G. Kim, Quadriceps torque curve pattern in patients with anterior cruciate ligament injury, Int. Orthop. 26 (6) (2002) 374–376. S.L. Keays, et al., The relationship between knee strength and functional stability before and after anterior cruciate ligament reconstruction, J. Orthop. Res. 21 (2) (2003) 231–237. P.V. Komi, et al., Effect of isometric strength training of mechanical, electrical, and metabolic aspects of muscle function, Eur. J. Appl. Physiol. Occup. Physiol. 40 (1) (1978) 45–55. M. Lewek, et al., The effect of insufficient quadriceps strength on gait after anterior cruciate ligament reconstruction, Clin. Biomech. 17 (1) (2002) 56– 63 (Bristol, Avon). D. Longino, C. Frank, W. Herzog, Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-deficient rabbit, J. Orthop. Res. 23 (6) (2005) 1404–1410. H.J. Mankin, et al., Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data, J. Bone Joint Surg. Am. 53 (3) (1971) 523–537.
[15] A.E. Mikesky, et al., Effects of strength training on the incidence and progression of knee osteoarthritis, Arthritis Rheum. 55 (5) (2006) 690– 699. [16] G. Pap, et al., Development of osteoarthritis in the knee joints of Wistar rats after strenuous running exercise in a running wheel by intracranial selfstimulation, Pathol. Res. Pract. 194 (1) (1998) 41–47. [17] S. Poitras, et al., A critical appraisal of guidelines for the management of knee osteoarthritis using Appraisal of Guidelines Research and Evaluation criteria, Arthritis Res. Ther. 9 (6) (2007) pR126. [18] E.M. Roos, et al., Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis, Nat. Rev. Rheumatol. 7 (1) (2011) 57–63. [19] M.H. Trimble, R.M. Enoka, Mechanisms underlying the training effects associated with neuromuscular electrical stimulation, Phys. Ther. 71 (4) (1991) 273–280, discussion 280-2. [20] E. Tsepis, et al., Hamstring weakness as an indicator of poor knee function in ACL-deficient patients, Knee Surg. Sports Traumatol. Arthrosc. 12 (1) (2004) 22–29. [21] E. Tsepis, et al., Thigh muscle weakness in ACL-deficient knees persists without structured rehabilitation, Clin. Orthop. Relat. Res. 450 (2006) 211–218.
[22] D. Urbach, et al., Bilateral deficit of voluntary quadriceps muscle activation after unilateral ACL tear, Med. Sci. Sports Exerc. 31 (12) (1999) 1691–1696. [23] G.N. Williams, et al., Quadriceps femoris muscle morphology and function after ACL injury: a differential response in copers versus non-copers, J. Biomech. 38 (4) (2005) 685–693. [24] G.N. Williams, et al., Quadriceps weakness, atrophy, and activation failure in predicted noncopers after anterior cruciate ligament injury, Am. J. Sports Med. 33 (3) (2005) 402–407. [25] W. Zhang, et al., OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines, Osteoarthritis Cartilage 16 (2) (2008) 137–162.
Correspondence to: Prof. Walter Herzog University of Calgary Faculty of Kinesiology 2500 University Drive N.W. Calgary, AB Canada T2N 1N4 Tel.: 1-403-220-8525 Fax: 1-403-220-2070. E-Mail: [email protected]
Available online at www.sciencedirect.com
E. Szabo et al.
Strength Training of the Quadriceps Muscles Following ACL Loss
273
Orthop€adie Traumatologie
SportOrthoTrauma 28, 266–273 (2012) Elsevier – Urban&Fischer www.elsevier.de/SportOrthoTrauma http://dx.doi.org/10.1016/j.orthtr.2012.10.006
WISSENSCHAFTLICHER BEITRAG E. Szabo et al.
Krafttraining des M. quadriceps nach VKBRuptur: Effekt auf Kraft und Gelenksintegrit€ at Zusammenfassung Hintergrund: Verletzungen des vorderen Kreuzbandes (VKB) geh€oren zu den h€aufigsten Knieverletzungen und sind ein etablierter Risikofaktor f€ur Gelenkarthrose. Als Folge sind Muskelatrophie, Kraftminderung und verz€ogerte Muskelaktivierung h€aufig mit dieser Verletzung verbunden und gelten als eigenst€andige Risikofaktoren f€ur Gelenkarthrose. Muskelaufbautraining, wird als therapeutische Maßnahmen praktiziert um die Kniestabilit€at zu verbessern und neuromuskul€arer Hemmung entgegenzuwirken. Allerdings sind die positiven Effekte von Muskelaufbautraining abh€angig von Intensit€at, Dosierung und Dauer. Das Ziel dieser Studie war es, den Einfluss verschiedener Trainingsprotokolle auf die Entwicklung von Gelenkarthrose in Knien mit rupturierten VKB’s zu quantifizieren. Methoden: 15 ausgewachsene New Zealand White Rabbits (NZW) wurden in drei experimentelle Gruppen eingeteilt: (i) VKB-Durchtrennung gefolgt von einem maximalen Muskeltraining, (ii) VKB-Durchtrennung gefolgt von einem submaximalen Muskeltraining und (iii) VKB-Ruptur ohne Aufbautraining. Das maximale Extensor-Drehmoment des Knies wurde in jeder Trainingssession gemessen. Nach dem finalen Experiment wurden die Kniegelenke histologisch analysiert. Resultate: Tiere in beiden Muskelaufbaugruppen zeigten einen signifikanten Anstieg des maximalen Drehmomentes sowie eine signifikant weiter fortgeschrittene Knorpelsch€adigung als die untrainierte Gruppe. Die maximal trainierte und nicht trainierte Kontrollgruppe zeigte eine signifikant reduzierte Quadrizepskraft auf der experimentellen Seite verglichen mit der
266
E. Szabo et al.
Strength Training of the Quadriceps Muscles Following ACL Loss: Effects on Strength and Joint Integrity Eva Szabo, Christian Egloff, Ruth Seerattan, Tim Leonard, Walter Herzog Eingegangen am 3. September 2012; akzeptiert am 15. Oktober 2012
Introduction
As the main knee extensor muscles,
the quadriceps group has a number of important functional roles. However, following anterior cruciate ligament (ACL) injury, the quadriceps group atrophies [3,13,23,24], becomes weaker [3,9,13,20,21,24] and activation patterns are altered and reduced [6,22,24]. Quadriceps strength has been linked with function and improved gait patterns after ACL loss [1,12,24] and reconstruction [10,12]. Nonetheless, quadriceps weakness often remains despite corrective surgery and aggressive rehabilitation programs aimed at improving muscle strength [3,12,22]. In order to maximize function and quality of life for subjects with ACL injury, this loss of quadriceps mass, strength and activation must be understood so that measures can be taken to avoid it and safely build strength. Rehabilitation following loss of the ACL is further complicated by a complex relationship between injury, exercise and osteoarthritis (OA). Quadriceps weakness alone is considered a risk factor for the development of OA [18], and exercise is often prescribed as a mean of OA treatment [15,17,25]. In addition,
effective quadriceps strength training has been linked to increased function and decreased disability in human subjects with OA. Nonetheless, several studies in animal models have shown that the effect of exercise is dosedependent, and can have detrimental effects. Galois et al. [5] found that slight to moderate exercise slowed the development of OA in rats which had undergone ACL transection compared to sedentary rats or rats which underwent ‘‘intense’’ exercise. Other studies also provide evidence that an ‘‘excessive’’ amount of exercise on its own [16] or in conjunction with an injury model [2] increases osteoarthritic changes in rat knees. This leads to a difficult balance between the apparently beneficial effects of quadriceps strength, and the need to keep exercise within a safe level for joint health. The aim of this study was to develop a greater understanding of the interactions between joint injury, muscle training, and the development of OA. To achieve this, we asked two specific questions: (i) can a muscle stimulation regime applied shortly after ACL injury prevent quadriceps weakness and atrophy; and (ii) what effect does such a
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
kontralateralen Seite. Die submaximale Trainingsgruppe zeigte keine signifikanten Seitenunterschiede in der Muskelkraft. Diskussion: Unsere Resultate weisen darauf hin, dass Muskelaufbautraining in hoher Intensit€at und h€aufigen Repetitionen zu erh€ohtem Muskelaufbau wie auch zu akzelerierten Knorpelsch€aden f€uhrt. Obwohl die vorliegenden Resultate aus dem Tiermodell stammen, sehen wir dennoch große € Ahnlichkeiten des Kniegelenkes in der muskul€aren und oss€aren Biomechanik, weshalb die beobachteten Effekte auch beim Menschen gelten k€onnten; sie sollten daher bei der Anwendung von Quadrizeps-Rehabilitations-Strategien sorgf€altig ber€ucksichtigt werden. Schlussfolgerung: Obwohl Muskelaufbautraining insbesondere der Quadrizepsmuskulatur im Falle einer VKBRuptur einen wichtiger Pfeiler im therapeutischen Rehabilitationsprogramm darstellt, zeigen unsere Ergebnisse, dass die Dosierung und Intensit€at solcher Trainingseinheiten mit Vorsicht vorgenommen werden sollten, um nachteilige Folgen zu vermeiden.
Experimental Design Skeletally mature New Zealand White rabbits were used in accord with the experimental protocol approved by the University of Calgary Animal Care Committee. The left limb of all rabbits was used as the experimental limb while the right limb was used as an intact control. The experimental groups were:
ACL Transection Surgery ACL transections were performed as described previously [13]. Briefly, the joint capsule was opened through a lateral incision and the ACL was identified, hooked and then cut. The transection was verified visually as well as by manual assessment of the changes in anterior and medial-lateral laxity. The joint capsule and subcuticular layer were closed with 3.0 Monosyn (Jorgensen Laboratories Inc.) or 3.0 Vicryl sutures (Johnson and Johnson), and the skin was closed with 3.0 Braunamid sutures (Jorgensen Laboratories Inc.).
1. ACL Transected (ACLT), Maximal Training (n = 6): All six rabbits in the ACLT, maximally trained group underwent ACL transection on the experimental hind limb. Shortly after the transection surgery, they underwent a fourweek training program consisting of electrical stimulation of the quadriceps muscles of the experimental limb. Each session consisted of sets of maximal contractions. 2. ACLT, Sub-maximal Training (n = 5): All five rabbits in the ACLT, sub-maximally trained group underwent ACL transection on the experimental hind limb. Shortly after the transection surgery, they underwent a four-week training program consisting of electrical stimulation of the quadriceps muscles of the experimental limb. Each session consisted of a single long set of repeated sub-maximal contractions. 3. ACLT, Untrained (n = 4): All four rabbits in the ACLT, untrained group underwent ACL transection on the experimental hind limb. Following the transection surgery, they were allowed to recover for 4.5 weeks.
Training Protocols For rabbits in the muscle training groups, the training sessions began 4 days following the ACL transection surgery. Each rabbit underwent a total of 12 training sessions, with three sessions a week for 4 weeks. For both training protocols, in each training session, rabbits were anesthetized using a 3.5% isoflurane (Benson Medical) to oxygen mixture. An area of skin over the quadriceps muscle was prepared for electrode placement by shaving and cleaning with alcohol. The anesthetized rabbit was placed on its back in a sling with a warm waterheating pad. The left hind limb was bluntly constrained in a stereotactic frame with the knee at 90˚ of flexion. Forces were measured using a strain bar placed over the rabbit’s tibia just proximal to the ankle and oriented in the direction of knee extensor force (Figure 1). The strain bar was instrumented with strain gauges and an amplifier in a Wheatstone half-bridge configuration and data were recorded using Windaq data collection software (DATAQ Instruments, 2000). The distance from the strain bar to the knee (most prominent point of
stimulation regime have on knee joint integrity?
Methods
E. Szabo et al.
Strength Training of the Quadriceps Muscles Following ACL Loss
267
WISSENSCHAFTLICHER BEITRAG
Figure 1 Training set-up. The animal’s leg is rigidly fixed in a custom build stereotactic frame through bony pins in the hips and femoral condyles. The tibia is taped to a restraining bar, which is connected to the motor. Electrical stimulation is performed with cutaneous electrodes.
the lateral femoral condyle) was measured and recorded. Knee extensor torque was calculated by multiplying the force measured with the tibial restraining bar by the distance of that bar to the knee. The quadriceps group was identified and selfadhesive electrodes were attached and held in place at mid-belly. All contractions were induced using a Grass S8800 Stimulator (Grass Instruments). For the maximal training sessions, supra-maximal contractions were induced with 0.4 ms pulse duration, 150 Hz frequency and 500 ms train duration. Each session consisted of 5 sets of 10 contractions with
268
E. Szabo et al.
500 ms of rest between contractions and 2 minutes of rest between sets [4]. In order to evaluate the data from the training sessions, the average torque from each set in each session was considered (Figure 2). The average torque from the first set of each session was then considered the maximum session torque, and was used to rate improvement in strength over the course of the training sessions. For the sub-maximal training sessions, one maximal contraction was elicited at the beginning of the session followed by 15 minutes of sub-maximal contractions at approximately 20% of the maximum
(Figure 3). The sub-maximal contractions were 500 ms long with 1500 ms of rest. The intensity of the sub-maximal contractions was maintained by adjusting the voltage and frequency of stimulation. Although the actual voltages and frequencies varied considerably between rabbits and sessions, they ranged from around 45 Hz and 20 V at the beginning of the session, to around 80 Hz and 80 V at the end of the session. This variance is due to physiological differences in between animals and of the experimental setup. Therefore a slight difference in electrode placement, skin impedance, muscle geometry and size, or electrode pressure would require different stimulation parameters to achieve the target level of 20% of the maximum force. Also this increase in stimulation parameters (voltage and frequency) from the beginning to the end of the training protocol was necessary, as the quadriceps muscles became fatigued and increased stimulation ensured that the force was kept constant at 20% of maximum throughout the entire 15 minute training protocol. Following completion of the exercise, anesthesia was reversed and rabbits were removed from the frame and allowed to recover on a heating pad. All rabbits were given a subcutaneous injection of 0.05 mL Hydromorphone (Sandoz Canada) as an analgesic. Strain Bar Calibration The strain bar used for force measurements was calibrated at the beginning of the training period, and before the terminal experiments. A series of seven calibrated weights were hung from the strain bar covering the range of experimentally observed knee extensor forces. Linearity of the
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
Rabbits were sacrificed by an intravenous injection of Euthanyl (Bimeda-MTC).
Figure 2 Raw data from a training session of a typical rabbit from the maximal training group.
force bar was confirmed and a calibration equation relating force to voltage was obtained using linear regression (r > 0.99). Terminal Experiment The terminal experiments were performed 4.5 weeks following the ACL transection surgery for all experimental groups. The isometric knee extensor torque of both hind limbs of all rabbits was measured following the general procedure described by Longino et al. [13]. Briefly, rabbits were anaesthetized and femoral nerve cuffs were implanted in order to directly stimulate the quadriceps.
The hind limb was fixed in a stereotactic frame using pointed metal rods at the pelvis and femoral condyles to maintain a constant hip angle of 1408. Tests were conducted on both hind limbs of each rabbit at knee angles of 80˚, 100˚ and 120˚. Maximum isometric knee extensor contractions were induced using a stimulation frequency of 100 Hz. For analysis, strength was defined as the average torque over the three angles. Two repeat trials were performed at each knee angle. Weakness was defined as the percent difference between the torques produced by the control and the experimental limbs.
Histological analysis Following sacrifice, both knees of all rabbits were prepared for histological analysis using standard procedures for Mankin scoring. Briefly, joint surfaces were isolated from the surrounding tissue. The joints were then decalcified and divided into six sections: the medial and lateral tibia, the medial and lateral femoral condyles, the femoral groove, and the patella. These sections were processed and embedded in paraffin blocks. The blocks were cut into 12 mm slices and every eighth slice was used for histological analysis. The joints were rated using a standard Mankin scoring system [14] on each of the six areas of the knees. Statistical Analysis For analysis of the trends over the training period, linear regression and correlation analysis were used within experimental groups. For final strength, the average of the torques across the three angles tested was used for each rabbit and paired comparisons were made using the Wilcoxon rank sum and signed-rank tests. Mankin scores from experimental and contralateral joints were similarly compared using the Wilcoxon rank sum and signed-rank tests. For all statistical tests, a significance level of a = 0.05 was used.
Results
Figure 3 Raw data from a typical training session for a rabbit from the 20% training group.
E. Szabo et al.
Training Over the course of the training sessions, despite a large amount of variation in actual daily torques, the rabbits in the maximally trained group showed a significant increase in knee extensor strength (Figure 4).
Strength Training of the Quadriceps Muscles Following ACL Loss
269
WISSENSCHAFTLICHER BEITRAG
strength was significantly lower on the ACLT side compared to the contralateral control side. In the sub-maximally trained rabbits, there was no significant difference in strength between the experimental and control hind limbs (Table 1, Figure 6). The sub-maximally trained rabbits were found to have significantly greater strength in their experimental limb as well as significantly lower side-to-side weakness than the untrained rabbits (Table 1, Figure 6). Figure 4 Maximum training session torques and fitted improvement curve for all rabbits in the maximal training group.
Similarly, rabbits in the submaximal training group showed a significant strength increase throughout the training period (r2 = 0.33), and this increase in strength was particularly consistent
from the first training session onward (r2 = 0.90; Figure 5). Strength Differences In the maximally trained and untrained rabbits, quadriceps
Figure 5 Maximum torques for all rabbits in the sub-maximal training group. Following an initial decline, knee extensor torques from the 3rd training session on increased steadily throughout the training period (r2 = 0.9; p = 0.05). The red line shows the linear regression including the pre-training measurement and all 12 training sessions (r2 = 0.33; p = 0.05).
270
E. Szabo et al.
Histology The Mankin scores for the medial tibial plateau, the medial femoral condyle and the lateral femoral condyle were significantly greater in the experimental knees than the control knees of the maximally trained rabbits (p < 0.05). In the sub-maximally trained rabbits, the Mankin scores were higher in the experimental limb on the medial femoral condyle (p < 0.05), while in the untrained rabbits, there were no significant side-to-side differences (p > 0.05) (Table 1). Figure 7 shows the averages of the worst scores for the three groups. Between group comparisons were not made because of age differences between rabbits in the different groups. For example, it appears that the Mankin scores are higher in the sub-maximal training group rabbits compared to the normal controls and the maximally trained group rabbits. However, rabbits in the sub-maximal group were also on average 6 months older than rabbits in the other groups, and we believe that this difference may reflect the age of the rabbits rather than the specific training protocol, as supported by the increase in the control side values in the sub-maximally trained group rabbits compared to the other two groups.
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
Table 1. Average knee extensor torques and Mankin Scores shown with corresponding standard deviations (SD). Please note that the values presented are considered as percentage difference of the averages of the strength and torques, respectively. Differences in Torque
Untrained
Maximal
sub-maximal
Average torque (Nm) control (SD) Average torque (Nm) experimental (SD) Percent Difference
3.17 (0.38) 2.14 (0.08) 32.5%
3.1(0.49) 2.28(0.68) 26.5%
3.34 (0.63) 2.67(0.24) 20%
Differences in Mankin Score
Untrained
Maximal
sub-maximal
Average Mankin Score, control (SD) Average Mankin Score, experimental (SD) Percent Difference
8.25 (0.89) 9.5 (0.44) 13.20%
7.8 (0.95) 9.4 (1.7) 17.1%
10.4 (0.89) 12 (1.22) 13.33%
Discussion Effect of Training on Quadriceps Muscles Following ACL rupture in humans, quadriceps muscles atrophy and
become weaker [3,9,21,23,24], thereby creating asymmetries between the ACL-deficient and the intact leg [3,9,24]. Some of the strength loss in the ACL-deficient leg has been associated with muscle inhibition; that is an inability to
Figure 6 Average knee extensor torques. In the maximally trained and untrained group there was a significantly lower strength on the experimental side (ACLT) compared to the contralateral control.
Figure 7 Histological scoring (Mankin) for three groups. The maximal and submaximal testing showed significant higher scores compared to the contralateral limb, p = 0.031 and p = 0.063, respectively.
E. Szabo et al.
maximally contract the knee extensors [8,22,24]. In this animal model, we used electrical stimulation of the knee extensors to avoid any possible effects associated with muscle inhibition [19]. The maximal training protocol mimicked a powerful resistance exercise program that would normally be associated with strength gains and increased muscle mass. The maximal training regime produced increases in strength in the ACL-deficient leg (Figure 4), but did not alleviate the side-to-side differences between ACL-deficient and intact leg which were also observed in the control group rabbits (Figure 6). The submaximal training protocol was designed to mimic endurance training and large strength gains were not expected. Nonetheless, submaximally trained rabbits showed a modest increase in quadriceps strength (Figure 5), but unlike the maximally trained rabbits, we were unable to detect any side-to-side strength differences (Figure 6). It is unclear why the side-to-side weakness observed in the untrained group rabbits was not alleviated in the maximal training group rabbits but was below significance in the sub-maximal training group rabbits. A contralateral training effect may have contributed to this result and could have been induced in a number of ways. First, with the instability in the injured knee, the
Strength Training of the Quadriceps Muscles Following ACL Loss
271
WISSENSCHAFTLICHER BEITRAG
contralateral hind limb may have been used to compensate for the loss of functionality of the ACLdeficient leg, therefore becoming overloaded and trained during daily activities. This idea is supported by previous work in this animal model which showed that push off forces in hopping rabbits were substantially greater in the intact contralateral compared to the ACL-deficient hind limb [13]. Though this likely added to the difficulty of achieving balanced strength and it is possible that this effect was compounded by fatigue in the experimental leg following the training protocol, this explanation does not seem adequate to explain the difference between the training protocols. Second, previous studies have shown that unilateral strength training can have a direct strengthening effect on the contralateral limb [7,11]. It is possible that this effect was greater in the maximally than the sub-maximally trained rabbits. Third, the sub-maximally trained group consisted of 5 animals and although we did see a trend towards side-to-side differences in this group, a lack of statistical power may have prevented to show a statistically significant result. Training had a detrimental effect on the cartilages of the ACL-transected knees. Both maximal and submaximal training resulted in increased Mankin scores in some parts of the knee indicating that the cartilage was significantly more degenerated in the experimental compared to the control limbs (Figure 7). These results are similar to the findings by Appleton et al. [2] who showed that forced mobilization of ACLT rats resulted in accelerated OA development. In those experiments, the exercise protocol was designed to involve weight bearing through the knees’ full range of motion. Here, we showed
272
E. Szabo et al.
that OA is similarly accelerated by both high intensity and high repetition isometric strength training protocols. A limitation in this experimental setup was the relatively short recovery time (4 days) after ACL transection compared to the untreated group. It might be that in the beginning of the training sessions the knee joints were still in a posttraumatic inflammatory state, which could have led to accelerated cartilage degradation. Comparisons of the results of this study to humans have to be made with utmost caution. Since this study was based on an anaesthetized animal model, pain, which is considered an important limiting factor in voluntary training, was not integrated in the experimental protocol. However, we demonstrated that a maximal training regime is detrimental to articular cartilage integrity and that sub-maximal training protocols might be better and healthier options for the ACLinjured knee.
Conclusions Although muscle strength gains were seen over the course of the training sessions for both a maximal and a sub-maximal training protocol in ACLT rabbits, only the submaximal protocol eliminated the side-to-side strength imbalances characteristic in ACL deficiency. Both protocols, however, resulted in an increase in OA development and progression in the experimental knees. Thus, the results of this study suggest that therapeutic interventions involving quadriceps strengthening in legs with unstable knees must be performed with caution, as strengthening will lead to loading of the knee and may have a
negative effect on the articular cartilage.
Conflict of interests There is no conflict of interests.
Acknowledgments Canadian Institutes for Health Research, Alberta Innovates-Health Solutions Team Grant on Osteoarthritis, The Canada Research Chair Programme, The Killam Foundation.
References [1] E. Ageberg, Consequences of a ligament injury on neuromuscular function and relevance to rehabilitation using the anterior cruciate ligamentinjured knee as model, J. Electromyogr. Kinesiol. 12 (3) (2002) 205–212. [2] C.T. Appleton, et al., Forced mobilization accelerates pathogenesis: characterization of a preclinical surgical model of osteoarthritis, Arthritis Res. Ther. 9 (1) (2007) pR13. [3] G.A. Arangio, et al., Thigh muscle size and strength after anterior cruciate ligament reconstruction and rehabilitation, J. Orthop. Sports Phys. Ther. 26 (5) (1997) 238–243. [4] T.A. Butterfield, W. Herzog, Is the force-length relationship a useful indicator of contractile element damage following eccentric exercise? J. Biomech. 38 (9) (2005) 1932–1937. [5] L. Galois, et al., Dose-response relationship for exercise on severity of experimental osteoarthritis in rats: a pilot study, Osteoarthritis Cartilage 12 (10) (2004) 779–786. [6] E.M. Hasler, et al., In vivo knee joint loading and kinematics before and after ACL transection in an animal model, J. Biomech. 31 (3) (1998) 253–262. [7] T. Hortobagyi, et al., Cross-education of muscle strength is greater with stimulated than voluntary contractions, Motor Control 3 (2) (1999) 205–219. [8] M.V. Hurley, The effects of joint damage on muscle function,
Strength Training of the Quadriceps Muscles Following ACL Loss
WISSENSCHAFTLICHER BEITRAG
[9]
[10]
[11]
[12]
[13]
[14]
proprioception and rehabilitation, Man Ther. 2 (1) (1997) 11–17. H. Ikeda, H. Kurosawa, S.G. Kim, Quadriceps torque curve pattern in patients with anterior cruciate ligament injury, Int. Orthop. 26 (6) (2002) 374–376. S.L. Keays, et al., The relationship between knee strength and functional stability before and after anterior cruciate ligament reconstruction, J. Orthop. Res. 21 (2) (2003) 231–237. P.V. Komi, et al., Effect of isometric strength training of mechanical, electrical, and metabolic aspects of muscle function, Eur. J. Appl. Physiol. Occup. Physiol. 40 (1) (1978) 45–55. M. Lewek, et al., The effect of insufficient quadriceps strength on gait after anterior cruciate ligament reconstruction, Clin. Biomech. 17 (1) (2002) 56– 63 (Bristol, Avon). D. Longino, C. Frank, W. Herzog, Acute botulinum toxin-induced muscle weakness in the anterior cruciate ligament-deficient rabbit, J. Orthop. Res. 23 (6) (2005) 1404–1410. H.J. Mankin, et al., Biochemical and metabolic abnormalities in articular cartilage from osteo-arthritic human hips. II. Correlation of morphology with biochemical and metabolic data, J. Bone Joint Surg. Am. 53 (3) (1971) 523–537.
[15] A.E. Mikesky, et al., Effects of strength training on the incidence and progression of knee osteoarthritis, Arthritis Rheum. 55 (5) (2006) 690– 699. [16] G. Pap, et al., Development of osteoarthritis in the knee joints of Wistar rats after strenuous running exercise in a running wheel by intracranial selfstimulation, Pathol. Res. Pract. 194 (1) (1998) 41–47. [17] S. Poitras, et al., A critical appraisal of guidelines for the management of knee osteoarthritis using Appraisal of Guidelines Research and Evaluation criteria, Arthritis Res. Ther. 9 (6) (2007) pR126. [18] E.M. Roos, et al., Muscle weakness, afferent sensory dysfunction and exercise in knee osteoarthritis, Nat. Rev. Rheumatol. 7 (1) (2011) 57–63. [19] M.H. Trimble, R.M. Enoka, Mechanisms underlying the training effects associated with neuromuscular electrical stimulation, Phys. Ther. 71 (4) (1991) 273–280, discussion 280-2. [20] E. Tsepis, et al., Hamstring weakness as an indicator of poor knee function in ACL-deficient patients, Knee Surg. Sports Traumatol. Arthrosc. 12 (1) (2004) 22–29. [21] E. Tsepis, et al., Thigh muscle weakness in ACL-deficient knees persists without structured rehabilitation, Clin. Orthop. Relat. Res. 450 (2006) 211–218.
[22] D. Urbach, et al., Bilateral deficit of voluntary quadriceps muscle activation after unilateral ACL tear, Med. Sci. Sports Exerc. 31 (12) (1999) 1691–1696. [23] G.N. Williams, et al., Quadriceps femoris muscle morphology and function after ACL injury: a differential response in copers versus non-copers, J. Biomech. 38 (4) (2005) 685–693. [24] G.N. Williams, et al., Quadriceps weakness, atrophy, and activation failure in predicted noncopers after anterior cruciate ligament injury, Am. J. Sports Med. 33 (3) (2005) 402–407. [25] W. Zhang, et al., OARSI recommendations for the management of hip and knee osteoarthritis, Part II: OARSI evidence-based, expert consensus guidelines, Osteoarthritis Cartilage 16 (2) (2008) 137–162.
Correspondence to: Prof. Walter Herzog University of Calgary Faculty of Kinesiology 2500 University Drive N.W. Calgary, AB Canada T2N 1N4 Tel.: 1-403-220-8525 Fax: 1-403-220-2070. E-Mail: [email protected]
Available online at www.sciencedirect.com
E. Szabo et al.
Strength Training of the Quadriceps Muscles Following ACL Loss
273