Effectiveness of combined chain exercises on pain and function in patients with knee osteoarthritis

Objective: This randomized controlled trial was designed to investigate and compare the effectiveness of twelve-week open, closed and combined kinetic-chain exercises (OKCEs, CKCEs and CCEs) on pain and physical function (PF) in the management of knee osteoarthritis. Method: Ninety-six consecutive patients with knee OA were randomly assigned to one of OKCE, CKCE and CCE groups. Participants’ average daily pain (ADP), pain before and after walking (PBW and PAW), were evaluated using Visual Analogue Scale while PF was assessed using Ibadan Knee/Hip Osteoarthritis Outcome Measure. Results: Seventy-nine participants completed the study but data of another 4 participants who completed only 8week treatment were included in data analysis (total=83; mean age = 61.10±13.75 years). The groups’ demographic and dependent variables were comparable at baseline but CCE group demonstrated significantly more reductions (p < 0.05) in ADP, PBW and PAW than OKCE and CKCE groups at weeks 4, 8 and 12 of the study. However, there were significant within group improvements (p < 0.05) in all four variables for the three groups. Conclusion: CCEs are better than OKCEs and CKCEs for pain reduction in though all three exercise regimens are singly effective. CCEs are recommended for improving treatment outcome for pain in patients with knee osteoarthritis.


Introduction
Knee osteoarthritis (OA) is a major public health issue because it causes chronic pain, reduces physical function and diminishes quality of life 1 .Ageing of the population and increased global prevalence of obesity are anticipated to dramatically increase the prevalence of knee OA and its associated impairments 1,2 .The disease imposes a significant healthcare burden and accounts for high annual hospitalizations in the developed world 2,3,4,5 .Ultimately, chronic OA of the lower limb joints leads to reduced physical fitness with resultant increased risk of cardio metabolic co-morbidity 6,7,8 and early mortality 9 .Osteoarthritis (OA) is characterized by complex multifactorial joint pathology 10 and is the most common form of joint disorder in the world 4 .It has been estimated that about 40% to 80% of people with radiographic changes will have symptomatic knee OA which is highly prevalent among older people worldwide (10% to 30%), especially in rural regions, where people are involved in heavy occupational tasks 11 .The prevalence of OA increases with age and majority of individuals over the age of 65 have radiographic and/or clinical evidence of OA 12,13,14,15 .Reports from community and hospital based studies conducted in some geographical sections of Nigeria also suggest considerable number of adult in the country are affected OA 16,17,18 although data on general prevalence of OA in Nigeria is scarce.The knee is the most frequently involved joint in OA 19 .It has been demonstrated that muscle strength and functional capacity are reduced in patients suffering from this disease 20,21 ,and the functional consequences of knee OA are associated with lower extremity mobility limitations 22,23 .Deterioration in quadriceps function may cause impaired balance and gait, thus reducing mobility and function in patients with knee OA 24 .Though, pain is the most important symptom that often makes individuals with OA to seek medical attention 25,26,27 ,the patient may present with such symptoms as limitation of joint motion, muscle atrophy and weakness, joint instability, progressive functional limitation and associated disability, depending on the severity and stage of the disease 28 .There is no known cure for knee OA but exercise therapy is among the dominant non-pharmacological interventions recommended by international guidelinesfor amelioration of symptoms [1].Evidence from systematic reviews and metaanalyses of randomized controlled trials have shown that muscle strengthening and aerobic exercises are effective in reducing pain and disability, improving quality of life in patients with mild to moderate OA of the knee 5,29,3031,32,33 .A systematicreview by Lange et al 34 particularly reported that resistance training for patients with knee OAimproved muscle strength and self-reported measures of pain and physical function in over 50-75%of the studies reviewed.Quadriceps muscle weakness and atrophy have been reported to contribute to functional impairment and pain in patients with knee OA 35 and quadriceps strengthening can be achieved through closed kinetic chain or open kinetic chain exercises (OKCEs or CKCEs) 13,36 .CKCEs are modeled as closed linkages, in which a movement in a joint simultaneously produces movements in other joints of the extremity while OKCEsisolate one link of the kinetic chain and the distal segment is free to move 13,37 .The two forms of exercises have been shown to be individually effective for improving pain and function in patients with knee OA 38,39,40,41 and there seems no consensus on the comparative efficacy of OKCEs and CKCEs.On the other hand, combined chain exercises (CCEs) have been anecdotally used among physiotherapists but their effects on knee OA have not been reported in literature.This study was hence designed to evaluate and compare the effects of quadriceps strengthening twelve-week OKCEs, CKCEs and CCEs on pain and physical functionin patients with OA of the knee and the following questions were answered: (1) What would be the effects of a12-week each of open and closed kinetic chain quadriceps strengthening exercises (OKCE) on average daily pain and pain associated with walkingin patients with knee OA?
(2) Would the effects of 12-week OKCEs, CKCEs and CCEs on average daily pain, pain associatedwith walking and physical functionin patients with knee OA be comparable?Materials and Methods A-single-blind randomized controlled trial involving patients with knee OA was performed.The study was approved by the Health Research Ethics Committee of the University of Ibadan and University College Hospital (Ref no: UI/ EC/13/0013), the permission of the management of the Federal Medical Centre (FMC), Owo, Nigeria was also sought and obtained before the commencement of the study.All participants gave their informed consent before being included.The participants were patients with mild to moderate knee OA attending the Physiotherapy Department, FMC, Owo between January 2013 and December 2014; they have been diagnosed according to the radiographic assessment of their knee joints by the orthopaedic surgeons and family physicians.They were male and females with knee OA of one or both knees with grade IIKell gren and Lawrence classification system based on plain x-rays 42 .They also satisfied the American College of Rheumatology Criteria for classification of knee OA [10] and were placed on 3000mg Paracetamol daily.Patients with knee OA who also had neurological diseases of the lower limb (such as post stroke muscle weakness and poliomyelitis), severe systemic disease such as hypertension, kidney failure and severe diabetic condition, psychiatric disorder, and those unable to walk were excluded from the study 10 Computer generated random numbers were used to assign participants to one of three intervention groups: Open Kinetic Chain Exercise (OKCE), Closed Kinetic Chain Exercise (CKCE) and Combined Chain Exercise (CCE) Groups (by a physiotherapist who did not partake in assessment and treatment).A minimum sample size of 78 (26 per group was estimated for the study at α = 0.05, power = 80% and effect size = 0.8 using the Cohen's table 43 .A total of 105 patients were enrolled in this study.Of these, 9 subjects did not meet the inclusion criteria.The remaining 96 participants were randomly assigned into the three intervention groups.Thirteen participants did not complete the first four weeks of intervention and their data were not included in final analysis.Seventy-nine participants (OKCE = 26, CKCE = 26 and CCE = 27) completed the study; however, four participants who completed 8weeks of the exercise programmes but dropped out at the ninth week had their data included in the analysis making a total of 83 participants (OKCE = 28, CKCE = 27, CCE = 28).A total of 17.7% (OKCE = 6.25%,CKCE = 6.25%,CCE = 5.20%), attrition rate was hence observed in the study.

Assessment of average daily pain and pain during walking
Visual Analogue Scale (VAS) was used for assessment of pain.Average daily pain (ADP) was assessed by asking the participant to mark the point on the VAS that corresponded to the intensity of the average pain he/she felt every day which was recorded as the participant's average daily pain (ADP) 44,45 .Pain before walking(PBW)was assessed using VAS at rest before the participants commenced waking on a 50-foot walkway 10 .Pain after walking (PBW) was assessed using VAS immediately after the participant completed walking the 50-foot distance 10 .The validated Yoruba version was administered on participants who only understood the local language 46 .

Assessment of Physical Function (PF)
The participants completed the self-administered part of Ibadan Knee/Hip Osteoarthritis Outcome Measure (IKHOAM) while the researcher filled the clinician administered section after the participants performed the required physical tasks.The IKHOAM is a scale that assesses PF and treatment outcomes in patients with knee and/or hip OA.It was developed to reflect the Nigerian environment and culture 47 and is a three-part 33 items questionnaire that is both patient (self) and clinician administered, taking approximately 15 minutes to complete.The score range is 0-232; a higher score indicates higher functioning.The sum of scores in all three parts of the questionnaire was converted to a value over 100 using appropriate formula.The IKHOAM is available in English and three main Nigerian languages (Yoruba, Igbo and Hausa), along with evidence of psychometric properties.The Yoruba version which was administered to Yoruba speaking participants was developed and validated to encourage the use of the IKHOAM in Southwestern region of Nigeria 48 .The instrument has been shown to have high validity, reliability and responsiveness in measuring function in Nigerians with knee/hip OA 48,49,50,51 .ADP, PBW, PAW and PF were assessed at baseline and at the end of weeks 4, 8 and 12 of study.Intervention Participants were required not to alter their normal activities of daily living or take part in any additional form of physical activity or physiotherapywhile the study lasted. (1) Open Kinetic Chain Exercise(OKCE) Group Participants in this group were treated individually and performed the following exercises:

Quadriceps setting
The participant in a supine position isometrically contracted the quadriceps muscle of the affected lower extremity by drawing up his patella while maintaining the knee in extension.He held the contraction for a count of 10, relaxed and repeated the exercise 10 times 13,52 .This exercise was carried out by the participants throughout the duration of the study.

Straight leg raising (SLR)
The participant in a supine position isometrically contracted his quadriceps (quadriceps setting) and lifted the lower extremity up to achieve about 45° of hip flexion while maintaining the knee in extension.He held the position to a count of 10, and then lowered the limb; repeating the exercise 10 times.The contralateral knee and hip were flexed to about 90 0 and 45° respectively to avoid undue stress on the low back 13 .From third week SLR with weight was commenced by strapping an ankle weight equivalent to his/her 10RM to the ankle region, the Participant then lifted the lower extremity to about 45° of hip flexion while maintaining the knee in extension.The contralateral knee and hip were also each flexed to 45°1 3,52 .

Full-arc extension
The participant in a high sitting position had a weight corresponding to his 10RM strapped to the leg of the affected lower extremity just above the ankle.The popliteal space was protected with a roll of towel.He then lifted the load slowly through the range of 90° to 0° of knee flexion (full extension).He held the position for a count of 5 and then lowered the load 13 .He/she performed three bouts of ten repetitions of this exercise per session but the foot was rested on a stool between the bouts 13,52 .This exercise was carried out from the fourth week to the end of the study.

Cycling in the air
The participant in supine lying position on the gym mat raised his legs with the hip joints flexed to about 90 degrees and knees bent to about 90 0 in the air.With slow and steady balance, he then performed the cycling movements of the lower limbs in the air continuously for a period of two minutes 53 .During the air cycling of the legs, the hands were placed along the sides of the body and resting on the gym mat.This exercise was for the entire twelve week. (2) Closed Chain Kinetic Chain Exercise Group Participants in CKCE Group individually underwent the following exercises:

Quadriceps Setting Exercise
The participant sat on a chair with his back supported, knee extended and heel on the floor.The participants then pressed their heel against the floor and thigh against the seat of the chair.The position was held for a count of 10 after which the participant relaxed.The exercise was repeated ten times 13 .This exercise was performed throughout the duration of the study.

Wall slides
In a standing position, the participant positioned his back up against the wall with hips and knees flexed to about 60 0 as if he was preparing to sit on a chair 13,54 .The position was held for 10 seconds, after which the participant returned to the starting position and relaxed for 5 seconds.Ten repetitions of wall slides were carried out per exercise session 55 .From week 3, participants commenced wall slides with weight by holding dumbbells in both hands.This was initiated with a weight equivalent to his 10RM and progressed by determining a new 10RM at the beginning of each week of study 52 Step-up and step-down The participant performed forward, backward and lateral step-ups and step-downs using a 5cm -high sturdy wooden box 52 .The participant's trunk was kept upright and he/she ensured that his/her heel was the last to leave the floor and the last to return in order to emphasize the activities of the quadriceps muscle 13 .The participant performed 10 repetitions of each component of the exercise.This exercise was carried out during the sixth week of the study only 52 .From week 7, ankle weight was strapped to participants' ankle region for step-ups and step-downs with weight

Discussion Effects of open, closed and combined chain exercises on average daily pain, pain during gait and function in knee ostearthritis
The significant effects of the three exercise programmes on ADP is consistent with reports from previous studies regarding the effect of muscle strengthening exercise regimens on pain in patients with knee OA 10,53,56,57 .Reduction in pain and consequent improvement in function following quadriceps strengthening exercise have been attributed to increased stability of the knee joint which is enhanced by improvement in quadriceps muscle strength 58,59 .Evidence from literature also suggests that quadriceps strengthening may activate the pain-suppressing β-endorphin system 60 , favourably alter sensory input to the central nervous system and the gate control mechanism (regulating pain perception) 61 and as well improve blood flow and cartilage nutrition 62 .In a more recent study by Anwer and Alghadir 59 , a five -week isometric quadriceps exercise programme brought about a significant reduction in knee pain and improvement in function in the of patients with knee OA; the finding seems to compare favourably with the results of the present study as the three intervention groups in this study had significant reduction in pain as early as fourth week of treatment.The within-group comparisons conducted revealed that 12 -week OKCEs, CKCEs and CCEs) had significant effects on PBW and PAW from the fourth week of the study.The findings are in agreement with the reports of previous related randomized controlled trials on the effects of strengthening exercises on pain associated with walking in knee OA 10,63 40,53,65,66 .The similarity between the findings of these researchers and that of the present study may be attributed to significant pain reduction observed in present study which was also reported by these authors; a significant inverse relationship between pain and physical function has been previously reported in literature 67 .Despite differences in sample sizes and duration of treatment among the aforementioned studies; the strength training protocols were commonly progressive in nature as in the present study.

Comparative effectiveness of open, closed and combined chain exercises on average daily pain, pain during walking and function
The three groups were comparable at baseline in their anthropometric and clinical variables; hence, any subsequent difference between them can be attributed to the difference in the effects of the interventions.The combined chain exercise (CCE) Alghamdi and his colleagues 68 submitted further that the use of OKCEs alone in managing knee OA compromises the specificity and selectivity principles of training which state that optimal gains in a motor activity are made when the exercise most closely resembles the activity 13,68 .Some other researchers have earlier opined that exercise intervention for OA should involve considerations of joint stability, joint motion, joint effusion, synovial fluid level, position sense, balance, and conduct of daily activities 69,70,71 .Improvements in daily function would be best served by exercise resembling the daily activity 68 .The specificity of such exercises (OKCE) must also be geared toward mainly strengthening instead of improving a specific functional activity; while issues relating to exercise extend beyond simple consideration of cartilage wear and tear.The superiority of combined CCE exercises over CKCE and OKCE exercises in terms of reduction of average daily pain and pain associated with walking of participants in this present study may be evidence in support of such viewpoints.
Studies on the effectiveness of CCEs in the management of knee OA are rather scarce, though they have been anecdotally used among     Nigerian Physiotherapists, the effectiveness of such intervention in some related knee pathologies such as post anterior cruciate ligament (ACL) reconstruction 72 and patellofemoral pain syndrome (PPS) 73 have been reported in literature.The findings of this study regarding significantly more reduction in pain for the CCE group appears consistent with the reports of Minoonejad et al 73 who also reported significantly more reduction in pain intensity for participants with PPS in the CCE group than the controls although the extent to which their findings can be compared with the results of this study is limited because the controlsdid not undergo any exercise training.Mikkelsen et al 72 found that addition of isokinetic OKCEs to CKCEs for one study group at the sixth week after both groups commenced CKCEs produced significantly higher isokinetic quadriceps strength than the group that had CKCEs alone; their finding are not really comparable with that of this study because pain was not assessed by Mikkelsen et al 72 Unlike CCEs, the comparative effects of OKCE and CKCE exercises on pain in knee OA have been largely studied in the past two decades 38,39,40,41,52,63,65 although some of the authors did not report significant difference in the effect s of OKCEs and CKCEs.The result of this study on ADP is hence consistent with the reports of this aforementioned authors.CKCE group had significantly lower PAW than OKCE group at the end of weeks 4, 8 and 12 of this study.It has been opined that CKCEs resemble functional activities 13,37 and constitute about 65% of human gait 74 , this may have accounted for the observed difference since walking a form of functional activity.

Clinical Implication of Study
The study's outcome indicated that OKCEs, CKCEs and CCEs are all effective for improving treatment outcomes for average daily pain and pain during walking and physical function in patients with knee OA.However, CCEs are more effective than OKCEs and CKCEs on three of the four tested variables.Addition of CKCEs to the more popular OKCEs in the management of patients with knee OA may help physiotherapists to achieve better treatment outcome for pain and consequent reduction in disability.Specifically, the study has demonstrated the effectiveness of CCEs for pain reduction in patients with knee OA and pain has been identified as the major reason why this category of patients seek medical assistance 27 .

Conclusion
The

Figure 1 :
Figure 1: Trends of average daily pain for the OKCE, CKCE and CCE groups at the 4 time points of the study.

Figure 2 :
Figure 2: Trends of pain before walking for the OKCE, CKCE and CCE groups at the 4 time points of the study.

Figure 3 :
Figure 3: Trends of pain after walking for the OKCE, CKCE and CCE groups at the 4 time points of the study.

Figure 4 :
Figure 4: Trends of physical function scores for the OKCE, CKCE and CCE groups at the 4 time points of the study.
also had significantly lower mean PAW than OKCE group.The trends of ADP, PBW, PAW and PF across the four time points of the study are presented in figures 1-4.
OKCE group at the end of week 8 whileCKCE and CCE groups had significantly lower mean PAW than the OKCE group at the end of week 4 and 8 of study.At the end of week 12, participants in the CCE groups had significantly lower mean PAW than those in either OKCE or CKCE groups while the CKCE group

Table 3 :Across groupcomparison of participants' pain and physical function scores at baseline and at the end of weeks 4, 8 and 12 of the study
findings of this study have shown that OKCEs, CKCEs and CCEs are all effective for reducing painand disability in patients with knee OA but CCEs are more effective than either CKCEs or OKCEs for pain relief while CKCEs are more effective than OKCEs for reducing pain during walking.Physiotherapists are encouraged by the findings from this study to combine open and closed kinetic chain exercises for pain relief and improvement of function in patients with mild to moderate OA.Future studies should investigate the effects of combined chain exercises on other clinical and psychosocial variables in knee OA.The efficacy of CCEs in osteoarthritis of other joints such as the hip may also be investigated.