Efficacy of a progressive walking program and glucosamine sulphate supplementation on osteoarthritic symptoms of the hip and knee: a feasibility trial

Osteoarthritis (OA) is the most common musculoskeletal disorder and the leading cause of pain and disability in the USA and Australia [1, 2]. In Australia, it affects 7.8% of the population, and projections indicate that the prevalence will increase to 9.8% by 2020 [3].

There is no known cure for OA. The goal of treatment, therefore, is to help reduce patients' pain, prevent reductions in their functional ability and maintain or increase their joint mobility. For individuals with moderate symptoms of OA and no other health problems, international guidelines for initial treatment recommend non-pharmacological treatments, including lifestyle changes [4‐9]. A number of non-pharmacological treatments have been studied for the management of OA, but because there have been few well-conducted studies, the effectiveness of most non-pharmacological treatments is open to question [10].

Exercise, however, as a treatment for OA has been studied in numerous randomised controlled trials, mostly in people with OA of the knee. Most of these have focused on improving the stability of joints, range of movement and aerobic fitness in order to decrease patients' pain and disability [11]. Patients with mild to moderate symptoms of knee or hip OA who have participated in aerobic exercise programs have experienced increases in aerobic capacity [11, 12] and functional ability [13, 14], and decreases in pain, fatigue, depression and anxiety [11‐13, 15]. These results have led to recommendations for the use of aerobic exercise for the treatment of OA [4, 7‐9].

A recent review of randomised controlled trials in patients with knee OA found three types of exercise program (supervised individual, supervised group-based and unsupervised home-based) have been evaluated, with decreases in pain and physical function not differing significantly among participants in the three types [13]. In contrast to pharmacological treatments, which can cause gastrointestinal side effects [16], moderate-intensity aerobic exercises are well tolerated over the long term and have similar effects (effect size [ES] = 0.52) [17] for reducing pain to those seen with paracetamol and nonsteroidal anti-inflammatory drugs (NSAIDs; ES = 0.32) [18]. Compared with supervised programs, home-based programs are more convenient for participants, feasible in community settings and cost-effective for large populations, suggesting their suitability as a public health approach [13].

Walking may be an appropriate activity for home-based programs [19], because it has resulted in greater improvements in pain and greater participation rates than other forms of aerobic exercise, such as running or cycling [20]. In studies assessing the effectiveness of walking for patients with knee OA, moderate improvements in pain (ES = 0.52) and physical functioning (ES = 0.32) have been found [17] without adverse effects on OA symptoms [14]. The Physical Activity Guidelines Advisory Committee recommends that individuals with OA engage in moderate-intensity, low-impact activities such as walking, three to five times per week for 30 to 60 minutes per session [21].

Despite the accumulating international evidence suggesting that aerobic exercise is effective in reducing symptoms of OA of the knee, and to a lesser degree of the hip, an important question remains: What is the appropriate 'dose' of exercise (intensity, frequency, and duration) for significant improvements in symptoms of knee and hip OA? More broadly, the question of an appropriate dose of exercise has yet to be determined for people with arthritis in general [21]. In previous studies, exercise format, duration, intensity, and type of exercise varied widely, making it difficult to specify the required dose for optimal benefits. Even among the studies that used walking, programs have varied in content, duration of sessions and length of the intervention [17]. Only one small study [22] has examined the dose issue, and it focused on intensity of exercise. The researchers found that higher and lower intensity exercises are equally effective in improving symptoms of OA.

One treatment that is used in combination with or without exercise by some people with early hip or knee OA is glucosamine sulphate (GS), a natural occurring substance believed to assist with building and repair of cartilage. It is taken as a complementary medicine that is safe and has few side effects [8]. Two recent randomised trials from Europe have shown that GS slows radiological progression of knee OA [23, 24]. In a meta-analysis of 20 double-blind randomised control trials, glucosamine was reported to improve well-being and to be as safe as placebo [25]. Although results of a review further suggest glucosamine offers moderate improvements in well-being [26], some trials reported little or non-significant effects of glucosamine when compared with placebo [27, 28]. These conflicting results could be due to differences in the type of preparation used (GS or glucosamine hydrochloride), dose or bioavailability of the glucosamine preparation used.

Although some individuals with OA are using both glucosamine and exercise to relieve symptoms, no study has examined the effectiveness of the combined effects of exercise and GS on relieving symptoms of hip and knee OA. The main aim of this feasibility study was to evaluate the combined effects of a progressive walking program and GS intake on symptoms of OA and physical activity participation in people with hip or knee OA. Secondary aims were to compare the effectiveness of two frequencies of walking (three and five days per week) and three step levels (1500, 3000 and 6000 steps per day) of walking, combined with GS intake, and to examine compliance with GS intake and the walking program.

The main aims of this feasibility study were to evaluate the combined effects of a progressive walking program and GS intake on symptoms of OA and on physical activity participation in people with hip and knee OA, and to compare the effectiveness of two frequencies (three and five days per week) and three steps levels (1500, 3000 and 6000 steps) of walking. Thirty-six participants were given GS for 18 weeks of the study. After the first six weeks, they began the 12-week graduated Stepping Out walking program and were randomised to walk three or five days per week.

For the first six weeks, before the introduction of Stepping Out, daily GS supplementation was found to be effective in alleviating symptoms of hip and knee OA. Stiffness and physical function, both measured with WOMAC subscales, improved significantly (median scores improved by 30% and 9%, respectively) although pain, also measured with the WOMAC, did not. Objectively-measured physical function also improved significantly, by 13%. It is possible that these changes were due to increases in physical activity in this period, even though participants were asked to not change their physical activity during this time. The improvements partially support those from previous randomised controlled trials. In these trials [23, 24, 52], improvements were significantly greater for the groups assigned to receive GS than for the groups assigned to receive placebos or alternative therapies. In a three-year trial, Reginster and colleagues [24] found that among patients with knee OA, WOMAC index scores improved 24% with daily GS supplementation and WOMAC physical function scores improved by 22%. Scores on the WOMAC pain scale also improved, by 19%. In a three-year trial by Pavelka and colleagues [23], patients with knee OA who took GS experienced improvements in pain and physical function of 20 to 25%. In a six-month trial [52], patients with knee OA who were assigned to a GS group had improvements in WOMAC index scores of 12% and physical function scores of 13%. In other trials [27, 28, 53], however, no significant improvements with glucosamine supplementation were found. Differences in findings between studies can be explained in part by the participant characteristics of each sample. In the studies that found no improvements, participants tended to have mild symptoms of OA at baseline. In the current study and in other studies that found significant improvements with GS, participants tended to have moderate to moderately-high levels of symptoms (i.e., median scores above the median point in the scale) at baseline. Other differences between studies include the GS preparation used. The bioavailability of GS products can affect the rate that the ingested GS reaches the target tissue to evoke metabolic changes in the articular cartilage [53]. This is the first time that the benefits of GS have been shown in a relatively short six-week period.

The major finding of the current study was that being encouraged to walk five days a week was not more effective than being encouraged to walk three days, in terms of increasing time spent in physical activities, reducing pain and stiffness, increasing physical function, and improving most other measures used in the study. These findings are not surprising given that at each follow up the three-day and five-day walking groups did not differ significantly in the mean number of days actually walked per week, the mean number of daily steps walked on each walking day as measured with a pedometer or their weekly minutes of physical activity as measured by questionnaire. On average, participants in the three-day walking group walked three days per week and participants in the five-day walking group walked slightly less than four days per week, suggesting that it may be difficult to get people with hip or knee OA to walk more than three to four days per week. Another important finding was that increasing the number of steps per walking day from 1500 to 3000 steps per day, in conjunction with GS intake, resulted in a 125% increase in minutes of physical activity, a 17% reduction in pain scores, and improvements in physical function measured subjectively using the WOMAC (a 37% reduction in scores) and objectively using the SPS test (a 12% decrease in time). When the walking step level was increased from 3000 to 6000 steps a day, the primary changes were a 57% increase in physical activity participation and an 8% improvement in objectively-measured physical function. During the six-week follow up, minutes per week of physical activity decreased 46%, but physical function, measured objectively, continued to improve significantly, by 5%. These results suggest that increasing walking by 3000 steps (about 30 minutes) on at least three days per week can significantly reduce pain and increase physical function in people with hip or knee OA and that increasing walking from 3000 steps to 6000 steps on each walking day may offer additional significant improvements in physical function only. In short, more benefit comes from increasing walking by 3000 than from increasing walking by another 3000 steps to 6000 steps.

The improvements in WOMAC pain and physical function are consistent with those reported for randomised controlled trials [14, 15, 44, 54, 55]. Kovar and colleagues [14] examined the effectiveness of an eight-week supervised walking and patient education program for 102 participants with knee OA. Participants who received the program exhibited a significant 27% decrease in arthritis pain and a non-significant 39% improvement in physical function. Similar results were reported by Evcik and Sonel [54] for a three-month randomised controlled trial with 90 participants with knee OA. Participants in a walking group had significant improvements ranging from 51% to 55% on the WOMAC pain subscale and of 57% on the WOMAC physical function subscale, compared with controls. In the most recent study, 34 older adults with knee OA were randomised to receive a pedometer-based walking program with arthritis self-management education or the education only [55]. Participants who received the walking program had an improvement of 10% in pain while the education-only participants reported no improvement in pain. Differences between groups were not statistically significant, possibly due to a lack of power to detect differences because of the small sample size.

Differences in effects among studies are likely to be due to differences in a number of factors, including sample size; eligibility criteria, most notably the criteria for exclusion based on baseline physical activity levels and on measures used to determine OA status; length of the intervention period; the physical activity prescription; the attention from and contact with intervention staff; the mode of intervention delivery; the type of 'rescue medications' allowed during the trial; and the choice of outcome measures. Compared with other studies, the current study was short (18 weeks) and included a small sample. However, it was a feasibility designed to inform a larger study. In previous studies, protocols ranged from supervised exercise in a hospital [14] to unsupervised exercise with weekly phone calls [54]. Some included both supervised and unsupervised exercise [15]. Some studies prescribed a mix of aerobic and strength training exercises [15, 56, 57], and others prescribed just aerobic activity [22, 55]. In the current study, the exercise program was unsupervised walking and contact time with the participants was minimal, in order to test the effectiveness of a program that could be widely disseminated. Another difference was that in the current study, strict eligibility criteria were used to guarantee that only OA sufferers most in need of a physical activity program (i.e., those who were engaging in no or low levels of physical activity) were included. Other studies did not have exclusion criteria based on physical activity [54, 55]. Participants in the current study were allowed rescue analgesia as needed while some previous studies limited these to a maximum dose of 4000 mg per day of paracetamol [27, 53]. The highest dosage of rescue analgesia recorded by participants in our study was 2000 mg per day of paracetamol, which was taken by 63% (n = 12) of those who took rescue medications.

Although the study included a small sample, the findings provide preliminary evidence that OA sufferers can obtain health-related benefits from the combination of GS and walking. Walking 3000 steps per day for exercise, in bouts of at least 1500 steps each, on at least three days per week, provided these benefits. This amount of walking is less than current physical activity recommendations for the general population, but follows the recommendations for people with arthritis [19]. The study also provides support for the acceptability of GS in conjunction with a home-based walking program for people with OA, as participants were willing to comply with taking the glucosamine twice daily, wearing a pedometer, completing log sheets, walking three days per week and progressively increasing their steps per 'walking' day. With positive results, there is a need now to conduct a larger placebo-controlled trial to strengthen the findings and establish definitive data on the efficacy of the Stepping Out program. If the benefits of this program are confirmed, it could be promoted to increase physical activity among people with hip or knee OA.