Yefta 157 Effect of range of motion and isometric strengthening exercises on grip strength and hand function in rheumatoid arthritis patients October-December, 2008October-December, 2008October-December, 2008October-December, 2008October-December, 2008 Vol.27 - No.4 Vol.27 - No.4 Vol.27 - No.4 Vol.27 - No.4 Vol.27 - No.4 UNIVERSA MEDICINA Yefta Daniel Bastiana,*,**,a, Angela BM Tulaar**, Surjanto Hartono*** and Zuljasri Albar**** *Department of Anatomy, Medical Faculty, Trisakti University **Department of Rehabilitation Medicine, ***Medical Research Unit, ****Rheumatology Division, Department of Internal Medicine, Faculty of Medicine, University of Indonesia Correspondence aDr Yefta Daniel Bastian, SpRM Department of Anatomy, Medical Faculty, Trisakti University, Jl. Kyai Tapa 260 - Grogol Jakarta 11440 Telp 021-5672731 ext.2101 Email: yeftabastian@yahoo.com Univ Med 2008; 27: 157-64 ABSTRACT In previous studies, duration of hand exercises in patients with rheumatoid arthritis (RA) had widely varying ranges, from 3 weeks to 4 months. An experimental study was conducted to evaluate the effect of range of motion (ROM) and muscle strengthening exercises for 6 weeks on grip strength and hand function in RA patients. Seventeen patients with chronic RA were randomly assigned to a treatment group and a control group. The treatment group (n=8) was given muscle strengthening exercises and heat therapy using paraffin baths 3 times a week at the hospital and ROM exercises once a day at home for 6 weeks. The control group (n=9) was given only paraffin baths 3 times a week. After 6 weeks, there were significant differences in hand function (p=0.003), right and left grip strength (p=0.000 and p=0.001) and ROM in the interventional group only. ROM and isometric strengthening exercises significantly improved grip strength and hand function in patients with RA, while no impact was found when the patients were given paraffin baths only. In view of the small size of the study population, there is a need for further studies with larger populations. Keywords: Hand exercise, grip strength, rheumatoid arthritis INTRODUCTION R h e u m a t o i d a r t h r i t i s ( R A ) i s a n inflammatory chronic systemic disease, which i s p a r t i c u l a r l y m a n i f e s t e d a t t h e s y n o v i a l membrane of diarthrodial joints and can result in destruction of the involved joints.(1) It is present in 0.5% to 1% of the general population, twice as often in women, and the age at disease onset is mainly between 45 and 65 years.(2) The clinical picture of RA is characterized by pain, fatigue, disability, and reduced quality of life. 158 Bastian, Tulaar, Hartono, et al Grip strength and hand function The course of the disease is often unpredictable, and the symptoms may vary from day to day. The main goals of treatment for RA are to prevent or control joint damage, prevent loss o f f u n c t i o n , a n d d e c r e a s e p a i n . ( 3 ) D e s p i t e substantial progress in the pharmacological and surgical interventions over the last decade, many patients with RA will still experience disability, pain, psychological distress, fatigue, and poor quality of life.(4) Reduced levels of physical performance has been found to be associated with RA. Patients with RA have been shown to have reduced muscle strength and aerobic capacity. Impairments, disabilities, and h a n d i c a p s a s s o c i a t e d w i t h R A c a n b e devastating, leading to pain, activity restriction, and diminished quality of life, while placing a strain on the health care system and society.(5) Besides pharmacological and surgical interventions, conventional therapies such as physical therapy, occupational therapy, and c o m p r e h e n s i v e r e h a b i l i t a t i o n a n d s e l f m a n a g e m e n t p r o g r a m s a r e c o m m o n l y a n d f r e q u e n t l y u s e d i n t e r v e n t i o n s . D e s p i t e d i f f e r e n t p a t h o p h y s i o l o g i c a l p r o c e s s e s , patients suffering from RA experience pain and a gradual decline in muscle strength, eventually resulting in loss of function and quality of life. Increasing evidence shows that p h y s i c a l e x e r c i s e i m p r o v e s f u n c t i o n a n d prevents loss of function in RA.(6) Owing to a fear of enh ancing joint inf lammation and accelerating cartilage destruction, it has been advocated that exercise in active RA should be restricted to gentle assisted range of motion (ROM) exercises. On the contrary, exercise w a s f o u n d t o h a v e b e n e f i c i a l e f f e c t s o n f u n c t i o n , p a i n a n d m u s c l e s t r e n g t h . A n intensive exercise program consisting of ROM strengthening and aerobic exercises is more effective than a conservative exercise program, a n d d o e s n o t h a v e d e l e t e r i o u s e ff e c t s o n disease activity.(7) In RA patients with active disease, an inpatient program with frequent exercise therapy was found to be superior to usual care regarding disease activity as well as muscle strength. Long term high impact exercise has been proven to be beneficial regarding function and muscle strength in p a t i e n t s w i t h l o w d i s e a s e a c t i v i t y i n a n outpatient setting. In this study, exercise also did not increase disease activity.(8) Hand function is recognized as being important to those diagnosed with RA, because reduction in muscle power and grip can lead t o i n c r e a s i n g d i f f i c u l t i e s i n p e r f o r m i n g activities of daily living. O’Brien et al gave hand strengthening and stretching exercises as a home program for 6 months and showed significant results compared with stretching and joint protection.(9) Theoretically, the effect of strengthening exercises can be expected after 2-3 weeks because of neural adaptation, but muscle adaptation itself can be seen after minimally 4 weeks of training.(10) The aim of this study was to examine the e f f e c t o f R O M i s o m e t r i c s t r e n g t h e n i n g exercises, combined with therapeutic heating using paraffin baths on grip strength and hand function in RA patients. METHODS Research design This study was a single-blind, randomized controlled trial and conducted between January and May 2006. Subjects Subjects were RA patients in the subacute phase who had already been treated, aged 20- 70 years, male or female, meeting the criteria of the American College of Rheumatology.(11) Additional inclusion criteria were : (i) having joint involvement in the hand, which may be recognized from intrinsic muscle atrophy and/ 159 Univ Med Vol.27 - No.4 or a Hand Function Index (HFI) score of 5- 35.(12) (ii) never done structured ROM and hand strengthening exercise before; and (iii) willing to be involved in the study. Exclusion criteria were: (i) presence of peripheral nerve problems or muscle disease accompanied with atrophy; (ii) hand muscle weakness; (iii) sensory problems in the hand; (iv) finger amputation, open wound, fracture and contracture; (v) memory and cognitive problems. Additional exclusion criteria were: (i) severe hypertension with systolic blood pressure of more than 150 mmHg and diastolic blood pressure of more than 100 mmHg; (iii) h a n d d e f o r m i t y r e l a t e d t o R A , i n c l u d i n g radioulnar or metacarpophalangeal (MCP) subluxation, boutonniere and swan neck; and (iii) doing strenuous grip activities in their activity of daily living, such as washing clothes. The study protocol was approved by the Committee of Medical Research Ethics of the Faculty of Medicine, University of Indonesia. Interventions All subjects meeting the inclusion and exclusion criteria, after having been given an explanation about the study program and the mechanisms of joint protection, were randomly assigned to the intervention group or the control group, using optimal allocation with a simple randomization. Subjects in the intervention group were given heat therapy using paraffin baths 3 times a week at Cipto Mangunkusumo Hospital, followed by isometric strengthening exercises. Strengthening exercises were done b y o p p o s i n g t h e r e s i s t a n c e g i v e n b y t h e r e s e a r c h e r ’s h a n d o r b y p u t t y, w i t h o u t performing any movement of the joints. Muscle contraction was sustained for 6 seconds and repeated up to 6 times for each joint, alternately for the right and left hands. Every subject in this group also did ROM exercises once a day at home. These were performed over the 6-week study period. Subjects in the control group only had therapeutic heating using paraffin baths 3 times a week at the hospital and did not do any home exercises. All outcome assessments were undertaken at baseline and 6 weeks following randomization. Outcome measures Hand function was assessed using the HFI by giving a score according to the ability of the subject to do some finger activity then totally summed up. The minimum score is 4 and the maximum 42. The lower the score, the better the hand function. ROM was measured using a goniometer, and grip strength (GS) of the right and left hands was measured using a modified sphygmomanometer. The sphygmomanometer was modified by rolling up the cuff and securing it within a bag made of nonstretch material so that when inflated to a specific point, the cuff attains a constant circumference of 6 inches. For each hand, GS was measured 3 times alternately. The best values were taken for each GS. GS measurements were done using a standardized protocol in which the subject had to sit with the shoulder in neutral rotation, the e l b o w f l e x e d 9 0 0, t h e f o r e a r m i n n e u t r a l position, the wrist extended 300, and the ulnar d e v i a t e d 1 5 0. T h e p r e s s u r e o f t h e sphygmomanometer should be adjusted to 20 mmHg before taking any measurements. Statistical analysis Descriptive statistics was done to know the distribution of the variables age, gender, education level, job and medication. Changes i n o u t c o m e m e a s u r e s w e r e e x a m i n e d b y calculating 95% confidence intervals of the d i f f e r e n c e b e t w e e n b a s e l i n e a n d e n d l i n e scores. Between-group differences in score changes were determined by Student’s t test for unpaired samples. The significance level was set at 0.05. 160 Bastian, Tulaar, Hartono, et al Grip strength and hand function RESULTS Subjects Seventeen subjects were involved in this study, with eight subjects in the intervention group and nine in the control group. All subjects successfully followed the study to completion. Subjects’ compliance in getting treatment in the hospital in the intervention group was 93%, while that in the control group was 79%. In the interventional group, subjects’ compliance to do ROM exercises at home was 96.4%. All subjects were right handed. The age of the subjects ranged from 20 to 70 years (Table 1). The majority of the subjects, totalling 14 p a t i e n t s ( 8 2 . 3 % ) w e r e f e m a l e a n d o n l y 3 patients were male. From the educational perspective, 8 subjects had an educational level of high school (47%) and 7 subjects had a master degree (41.2%). Hand Function H a n d f u n c t i o n b e f o r e a n d a f t e r intervention can be seen in Table 2. HFI before and after intervention between the two groups showed non-significant results, in which the p value was more than 0.05. Grip Strength Grip strength before and after intervention can be seen in Table 2. GS before and after intervention between interventional and control group showed non-significant results in which the p value for right and left GS was more than 0.05. Figure 1. Flowchart of the number of subjects who completed the study RA patients attending rheumatology outpatient departmen (n=54) Declined (n=33) : - died (n=1) - fail to be contacted (n=3) - not interested (n=14) - mobility difficulty (n=12) - moved to another city (n=3) Assessed for eligibility (n=21) Participants randomized (n=17) Not randomized (n=4) not meet inclusion criteria Intervention group (n=8) Control group (n=9) Intervention group analysed after 6 weeks (n=8) Control group analysed after 6 weeks (n=9) 161 Univ Med Vol.27 - No.4 Range of motion R a n g e o f m o t i o n b e f o r e a n d a f t e r intervention can be seen in Table 3. ROM before and after intervention between the intervention and control group showed non- significant results for all joints. Using the paired t-test, it was found that there was a significant improvement in ROM for 12 areas of joints in the intervention group and 2 areas of joints in the control group. DISCUSSION The greatest prevalence of RA is in the 50- 59 year subgroup and 82.3% are female. This reconfirms the literature stating that RA is frequently found in the fourth and fifth decades and the incidence of RA is higher in females.(2) HFI was used in this study to measure hand function before and after intervention, because it has been proved to be a simple and fast tool for evaluating function and disease activity in RA.(12) Between the two groups, there was no s i g n i f i c a n t d i f f e r e n c e b e f o r e a n d a f t e r intervention. In the interventional group, there was a significant difference in hand function before and after intervention (Table 2), but there was none in the control group. This indicated that there were significant differences of hand function after intervention in both groups, but the difference was higher in the interventional g r o u p . H F I s h o w e d b e t t e r i m p r o v e m e n t Characteristic Intervention (%) n=8 Control (%) n=9 Age (year) 20-29 1 (12.5) 1 (11.1) 30-39 2 (25) 2 (22.2) 40-49 - 2 (22.2) 50-59 4 (50) 1 (11.1) 60-70 1 (12.5) 3 (33.3) Sex Female 7 (87.5) 7 (77.8) Male 1 (12.5) 2 (22.2) Education Junior High School 1 (12.5) 1 (11.1) High School 4 (50) 4 (44.4) Master Degree 3 (37.5) 4 (44.4) Occupation House wife 2 (25) 2 (22.2) Retired 2 (25) 2 (22.2) Civil servant - 1 (11.1) Teacher 3 (37.5) 2 (22.2) Student - 1 (11.1) Unemployed 1 (12.5) 1 (11.1) Medication Methothrexate 8 (100) 6 (66.7) Steroids 5 (62.5) 3 (33.3) NSAIDs* 5 (62.5) 5 (55.6) Others** 2 (25) 4 (44.4) Table 1. Demographic and clinical data of 17 patients participating in the study at baseline *NSAIDs = Non steroid anti inflammation drugs; **Others (Sulcolon and Chloroquine) 162 Bastian, Tulaar, Hartono, et al Grip strength and hand function H FI = H an d Fu nc tio n In de x; R G S= ri gh t g ri p st re ng th ; L G S= le ft g ri p st re ng th ; n s= n ot s ig ni fi ca nt (p >0 .0 5) In te rv en ti on G ro up C on tr ol G ro up P ar am et er B as e lin e E nd li ne M ea n di ff er en ce w it hi n gr ou p p B as e lin e E nd li ne M ea n di ff er en ce w it hi n gr ou p p M ea n di ff er en ce be tw ee n gr ou p p H FI 16 .8 8 ± 9. 46 14 .6 3 ± 10 .1 6 2. 25 ± 0 .7 0. 00 3 17 .1 1 ± 5. 75 15 .4 4 ± 4. 82 1. 67 ± 0 .9 3 0. 15 3 0. 58 ± 0 .2 3 ns R G S 89 .5 0 ± 18 .4 5 98 .0 0 ± 18 .7 3 8. 5 ± 0. 28 0. 00 0 89 .1 1 ± 15 .3 3 87 .5 6 ± 12 .7 2 1. 55 ± 2 .6 1 0. 72 5 6. 95 ± 2 .3 3 ns LG S 82 .7 5 ± 30 .6 3 91 .2 5 ± 29 .9 5 8. 5 ± 0. 68 0. 00 1 85 .3 3 ± 18 .1 9 88 .0 0 ± 13 .2 7 2. 67 ± 4 .9 2 0. 31 6 5. 83 ± 4 .2 4 ns Ta bl e 2. H an d fu nc ti on a nd g ri p st re ng th b ef or e an d af te r in te rv en ti on Ta bl e 3. J oi nt r an ge o f m ot io n be fo re a nd a ft er i nt er ve nt io n W =w ri st ; R =r ig ht ; L =l ef t; F= Fl ex io n; E =E xt en si on ; M C P= m et ac ar po ph al an ge al ; P IP = pr ox im al in te rp ha la ng ea l; ns = no t s ig ni fi ca nt ( p > 0. 05 ) In te rv en ti on al G ro up C on tr ol G ro up P ar am et er B as e lin e E nd li ne M ea n di ff er en ce w it hi n gr ou p p B as e lin e E nd lin e M ea n di ff er en ce w it hi n gr ou p p M ea n di ff er en ce be tw ee n gr ou p p R W E 53 .7 5 ± 13 .8 2 60 .6 3 ± 15 .6 8 6. 88 ± 1 .8 6 0. 00 1 55 .0 0 ± 13 .9 2 52 .5 0 ± 10 .0 0 2. 5 ± 3. 92 0. 34 7 4. 38 ± 2 .0 6 ns R M C P1 F 61 .5 0 ± 14 .9 2 67 .5 0 ± 14 .5 3 6. 00 ± 0 .3 9 0. 01 3 58 .6 7 ± 15 .1 3 60 .3 3 ± 13 .9 6 1. 66 ± 1 .1 7 0. 60 5 4. 34 ± 0 .7 8 ns LM C P2 F 85 .0 0 ± 8. 42 90 .2 5 ± 5. 39 5. 25 ± 3 .0 3 0. 02 7 86 .0 0 ± 5. 57 88 .1 1 ± 4. 14 2. 11 ± 1 .4 3 0. 10 0 3. 14 ± 1 .6 ns LM C P2 E 20 .0 0 ± 9. 26 24 .2 5 ± 6. 45 4. 25 ± 2 .8 1 0. 08 5 20 .6 7 ± 8. 89 25 .3 3 ± 10 .0 5 4. 66 ± 1 .1 6 0. 01 9 0. 41 ± 1 .6 5 ns LM C P3 E 20 .0 0 ± 9. 26 24 .2 5 ± 6. 45 4. 25 ± 2 .8 1 0. 08 5 20 .8 9 ± 9. 06 24 .6 7 ± 9. 90 3. 78 ± 0 .8 4 0. 03 3 0. 47 ± 1 .9 7 ns LM C P4 F 84 .5 0 ± 8. 80 88 .2 5 ± 5. 90 3. 75 ± 2 .9 0. 03 5 83 .7 8 ± 9. 46 87 .2 2 ± 7. 14 3. 44 ± 2 .3 2 0. 06 0 0. 31 ± 0 .5 8 ns LM C P5 F 82 .5 0 ± 10 .9 9 88 .2 5 ± 4. 95 5. 75 ± 6 .0 4 0. 04 0 86 .4 4 ± 7. 67 86 .6 7 ± 8. 00 0. 23 ± 0 .3 3 0. 89 2 5. 52 ± 5 .7 1 ns R M C P4 E 84 .5 0 ± 8. 99 84 .7 5 ± 9. 07 0. 25 ± 0 .0 8 0. 04 4 20 .0 0 ± 8. 66 21 .7 8 ± 9. 08 1. 78 ± 0 .4 2 0. 08 6 1. 53 ± 0 .3 4 ns LM C P4 E 18 .7 5 ± 9. 91 24 .2 5 ± 6. 45 5. 5 ± 3. 46 0. 03 6 22 .0 0 ± 9. 54 24 .7 8 ± 10 .0 2 2. 78 ± 0 .4 8 0. 08 5 2. 72 ± 2 .9 8 ns R PI P3 F 99 .2 5 ± 10 .7 9 10 4. 00 ± 9 .7 2 4. 75 ± 1 .0 7 0. 03 2 10 2. 67 ± 8 .3 1 10 4. 56 ± 6 .9 1 1. 89 ± 1 .4 0. 17 6 2. 86 ± 0 .3 3 ns R PI P4 F 10 1. 00 ± 1 1. 95 10 6. 63 ± 1 1. 55 5. 63 ± 0 .4 0. 02 1 10 2. 67 ± 1 0. 10 10 7. 33 ± 5 .4 1 4. 66 ± 4 .6 9 0. 07 1 0. 97 ± 4 .2 9 ns R PI P5 F 99 .0 0 ± 8. 35 10 5. 00 ± 9 .4 4 6. 00 ± 1 .0 9 0. 01 2 10 2. 33 ± 1 0. 37 10 2. 44 ± 7 .4 5 0. 11 ± 2 .9 2 0. 96 9 5. 89 ± 1 .8 3 ns LP IP 3F 10 0. 25 ± 1 5. 51 10 4. 88 ± 1 4. 52 4. 63 ± 0 .9 9 0. 02 6 10 5. 67 ± 7 .2 8 10 8. 33 ± 4 .7 4 2. 66 ± 2 .5 4 0. 05 5 1. 97 ± 1 .5 5 ns LP IP 4F 10 0. 75 ± 1 3. 39 10 6. 75 ± 1 0. 31 6. 75 ± 3 .0 8 0. 00 2 10 5. 33 ± 7 .3 5 10 7. 44 ± 5 .5 0 2. 11 ± 1 .8 5 0. 13 0 4. 64 ± 1 .2 3 ns 163 Univ Med Vol.27 - No.4 especially by a combination of therapeutic exercises and heating. It is important to note that HFI measures the ability of the wrist and f i n g e r s t o m o v e i n t h e i r R O M , t h u s improvement in ROM is indicated by a higher HFI. There was no significant improvement in right and left grip strengths between the two groups. There was a significant difference in right and left grip strengths in the interventional group (Table 2), but not in the control group. It is known from the literature that strengthening exercises can have effect after a minimum of 4 weeks.(10) This was proved in the isometric strengthening of quadriceps muscle in patients with osteoarthritis of the knee.(13) Other studies showed that exercise in RA patients needed a longer time to take effect, such as in the study by Hakkinen for 2 years.(14,15) Myositis in RA patients can result in muscle weakness, and can be confirmed by muscle biopsy, in which there is type II muscle atrophy, acute myositis and focal necrosis. Medications such as steroid agents also can result in myopathy.(16) Table 1 indicates that 62.5% of subjects in the interventional group and 33.3% of subjects in the control group took steroid agents. In the control group, right GS decreased after intervention, while left GS increased. This may be due to the great variability in clinical manifestations, joint involvement, disease course a n d r e s p o n s e t o t r e a t m e n t . T h e r e w a s n o significant difference between the two groups. ROM before and after intervention in the i n t e r v e n t i o n a l g r o u p s h o w e d s i g n i f i c a n t differences in 12 joints (Table 3), while in the control group there were differences in only 2 joints.This may be due to the variability in baseline characteristics between the two groups. In the interventional group, ROM improvement may have been the result of the heating and ROM exercises that were done at home. In the control group, ROM improvement could have been the result of therapeutic heating. As has been commonly recognized, the effect of heating is to improve tissue extensibility, decrease joint stiffness and pain, and help reduce infiltrate resolution in the inflammation.(17) There were no significant differences between the 2 groups in HFI, GS and ROM, possibly as a result of the limited number of subjects in this study. The duration of this study which was only 6 weeks may have been one of t h e f a c t o r s r e s u l t i n g i n a n o n - s i g n i f i c a n t difference in GS and ROM between the two groups. Moreover, ROM exercises in this study were done only once a day. In this study, joint pain was not assessed. It is well-known that pain can stimulate reflex inhibition of muscular contraction, but the investigators attempted to reduce pain by giving the patient education about joint protection and b y m e a s u r i n g t h e G S u s i n g a m o d i f i e d sphygmomanometer.(18,19) CONCLUSION R O M a n d i s o m e t r i c s t r e n g t h e n i n g exercises combined with therapeutic heating using paraffin baths for 6 weeks in RA patients can increase hand function. GS and ROM better than therapeutic heating using paraffin baths alone. REFERENCES 1. Goronzy JJ, Weyand CM. Arthritis rheumatoid: epidemiology, pathology, and pathogenesis. In: Klippel JH, editor. Primer on the rheumatic diseases. 12th ed. Atlanta: Arthritis Foundation; 2001. p. 632-3. 2. Stenstrom CH, Minor MA. Evidence for the benefit of aerobic and strengthening exercise in rheumatoid arthritis. Arthritis Rheum 2003; 49: 428–34. 3. American College of Rheumatology Subcommittee on Rheumatoid Arthritis. Guidelines for the 164 Bastian, Tulaar, Hartono, et al Grip strength and hand function management of rheumatoid arthritis: 2002 update. Arthritis Rheum 2002; 46: 328–46. 4. Astin JA, Beckner W, Soeken K. Psychological interventions for rheumatoid arthritis: a meta- analysis of randomized controlled trials. Arthritis Rheum.2002; 47: 291–302. 5. Kobelt G, Eberhardt K, Johansson B. Economic consequences of the progression of rheumatoid arthritis in Sweden. Arthritis Rheum 1999; 42: 347– 56. 6. de Jong Z, Vliet Vlieland TPM. Safety of exercise in patients with rheumatoid arthritis. Curr Opin Rheumatol 2005; 17: 177–82. 7. van den Ende CHM, Breedveld FC, le Cessie S, Dijkmans BAC, de Mug AW, Hazes JMW. Effect of intensive exercise on patients with active rheumatoid arthritis: a randomised clinical trial. Ann Rheum Dis 2000; 59: 615–21. 8. Bulthuis Y, Drossaers-Bakker KW, Taal E, Raskan J, Oostveen J, van’t Pad BP, et al. Arthritis patients show long term benefits from 3 weeks intensive training directly following hospital discharge. Rheumatology 2007; 46: 1712-7. 9. O’Brien, AV, Jones P, Mullis R, Mulherin D, Dziedzic K. Conservative hand therapy treatments in rheumatoid arthritis – a randomized controlled trial. Rheumatology 2006; 45: 577-83. 10. Kisner C, Colby LA. Resistance exercise. In: Therapeutic exercise foundations and techniques. 4th ed. Philadelphia; F.A. Davis; 2002. p. 68-9. 11. Arnett FC, Edworthy SM, Bloch DA, McShane DJ, Fries JF. The American Rheumatism Association 1987 revised criteria for the classification of rheumatoid arthritis. Arthritis Rheum 1988; 31: 315–24. 12. Kalla AA, Smith PR, Brown GMM, Meyers OL, Chalton D. Responsiveness of Keitel functional index compared with laboratory measures of diseases activity in eheumatoid arthritis. Br J Rheumatol 1995; 34: 141-9 13. Widjanantie SC. Pengukuran fungsi lutut dengan time up and go test dan stair climbing test pada latihan isometrik otot kuadrisep pasien osteoartritis lutut (thesis). Jakarta: Program Studi Ilmu Rehabilitasi Medik, Fakultas Kedokteran Universitas Indonesia; 2006. 14. Hakkinen A, Sokka T, Hannonen P. A home-based two year strength training period in early rheumatoid arthritis led to good long-term compliance: a five- year follow up. Arthritis Rheum 2004; 51: 56-62. 15. Hakkinen A, Sokka T, Kautiainen H, Kotaniemi A, Hannonen P. Sustained maintenance of exercise induced muscle strength gains and normal bone mineral density in patients with early rheumatoid arthritis: a five year follow up. Ann Rheum Dis 2004; 63: 910-6. 16. Hicks JE, Joe GO, Gerber LH. Rehabilitation of the patient with inflammatory arthritis and connective tissue disease. In: DeLisa JA, Gans BM, Walsh NE, Bockenek WL, Frontera WR, et al, editors. 4th ed. Philadelphia: Lippincot Williams & Wilkins; 2005. p. 737. 17. Basford JR. Therapeutic physical agents. In: DeLisa JA, Gans BM, Walsh NE, Bockenek WL, Frontera WR, et al, editors. 4th ed. Philadelphia: Lippincot Williams & Wilkins; 2005. p. 255. 18. Harris ED. Clinical features of rheumatoid arthritis. In: Ruddy S, Harris ED, Sledge CB, editors. Kelley’s textbook of rheumatology. 6th ed. Philadelphia: W.B. Saunders; 2001. p. 969, 984. 19. Harris ED. Treatment of rheumatoid arthritis. In: Ruddy S, Harris ED, Sledge CB, editors. Kelley’s textbook of rheumatology. 6th ed. Philadelphia: W.B. Saunders; 2001. p. 1004-18.