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Effect of Exercises on Quality of Life in Patients with Postmenopausal Osteoporosis – Randomized Trial

BACKGROUND: Osteoporosis is a systemic skeletal disease characterised by a low bone density and microarchitectural deterioration of bone tissue leading to decrease of its strength and increased risk of fracture. Drug therapy decreases the risk of fracture, thus influencing on the mechanism of bone remodelling. Non-pharmacological interventions include specific exercises for osteoporosis that improve muscle strength and balance, decrease pain and improve quality of life. AIM: To compare the quality of life in patients with postmenopausal osteoporosis who practice exercises with those who do not practice on the beginning and after a year. MATERIJAL AND METHODS: A randomised Single-blind randomised controlled prospective trial study, which included 92 women with postmenopausal osteoporosis diagnosed and treated at the Institute of Physical Medicine and Rehabilitation in Skopje, Republic of Macedonia. Patients were randomly assigned to three groups: the first group of patients with exercises and physical modalities (gr. I), the second group with exercises (gr. II), and the third control group of patients who did not practice exercises (gr. III). Exercises were practised 3 times a week; each exercise was repeated for 5-8 times. Patients regularly took bisphosphonates, calcium and vitamin D. The follow-up period lasted for one year. Quality of life was determined with a specific questionnaire Qualeffo-41. RESULTS: The results showed, significant statistical difference in terms of pain, physical activity, social life, the perception of own health were shown between the groups (p < 0.0001), only in term of mental function were no significant (p < 0.3). CONCLUSION: Patients who practice exercises for osteoporosis have a significantly better quality of life than patients who do not perform exercises.


Introduction
Osteoporosis is a systemic skeletal disease characterised by a low bone mineral density and microarchitectural deterioration of bone with a consequent decrease of its density and increased risk of fractures [1]. According to the data of the World Health Organization (WHO), osteoporosis is on the fourth place after cardiovascular diseases, cancer and stroke. Approximately 30% of all postmenopausal women in the United States of America and Europe have PO. Ageing of populations worldwide will be responsible for a major increase in the incidence of osteoporosis in postmenopausal women [2]. The first clinical manifestation very often is vertebral fractures, which can happen during normal activities such as stairs climbing, weight bearing etc. Age, deformity as kyphosis, disturbance of balance and non-specific back pain, increases the risk of a fall, for a new fracture, poor quality of life, disability and high mortality [3], [4].
Treatment of these patients has to be comprehensive and include both, pharmacological and non-pharmacological interventions. Drug therapy reduces the risk of fracture by influencing the mechanism of bone remodelling. These drugs decrease the risk of vertebral fracture by 30-70%, hip fractures by 20-40% and non-vertebral fractures by 15-20% [5], [6]. Non-pharmacological interventions include specific physical exercises for osteoporosis to improve muscle strength and balance, decrease pain, and improve quality of life [7]. In general, exercises are simple, do not require large financial costs and specific expensive equipment, and can be done at home. Exercises for osteoporosis are designed so that they enable better spinal stability and posture [8], [9], [10]. In the literature, only a few previous randomised studies have been published about the effect of exercises and physical activity on quality of life in osteoporotic patients. These studies have applied diverse methodologies and have presented controversial results [11], [12]. In our country, no such study has been conducted so far. Also, the questionnaire about the quality of life in postmenopausal osteoporotic patients has been applied for the first time in our country.
Our study aimed to evaluate the effectiveness of exercises for osteoporosis on quality of life in patients with postmenopausal (PO).

Material and Method
This was a randomised blind, one-sided trial, which included 92 patients with postmenopausal osteoporosis (PO) diagnosed and treated at the Institute of Physical Medicine and Rehabilitation in Skopje, R. Macedonia. The inclusion criterion was diagnosed osteoporosis. Diagnostic criterion was taken from total t score -1.5 SD to -2.5 SD, determined with x-ray DXA densitometry. The survey was approved by the Ethics Committee for people research at the Faculty of Medicine, Ss. Cyril and Methodius University, the Republic of Macedonia (Num.03-124/2, approved 22.03.2015year), and each of the patients was previously informed about the research from the researcher and signed informed consent to participate in it. Exclusion criteria were: secondary osteoporosis, fever, lumbar sciatica, pacemaker, cardiorespiratory instability, arrhythmia, malignant disease, neurological diseases.
Patients were randomly assigned to three groups: the first group of patients with exercises and physical modalities (gr. I), the second group with exercises (gr. II), and the third control group of patients who did not practice exercises (gr. III). At the beginning of the study, the first group (gr. I) received physical modalities (interferent currents and magnetic therapy) for 3 weeks, each day with a weekend break. Physical modalities were given for the treatment of pain. Exercise program consisted of: respiratory exercises, active exercises and exercises for strengthening the paravertebral muscles, active exercise for maintaining the range of motion of the joints of upper and lower extremities and spine, exercises for strengthening the muscles of the upper and lower extremities, isometric exercises for strengthening the abdominal muscles and exercises for balance. For weight-bearing exercises, the weight was determined by the functional abilities of the patients, 1 (one) kilogram at the most. Exercises were performed 3 times per week; each exercise was repeated for 5 to 8 times. Patients regularly took bisphosphonates, calcium and vitamin D. The followup period lasted for one year. Quality of life was evaluated with the specifically designed questionnaire for quality of life-Qualeffo-41 at the beginning and the end of the investigation.
Qualeffo-41 is a specially designed questionnaire approved by the International Association for Osteoporosis for measuring the quality of life in patients with postmenopausal osteoporosis [13]. The questionnaire consists of 41 items and includes 5 domains: pain, physical function, social activities, general health perception and mental function. Total score (TS) and domain scores (DS) are calculated by the following formulas: TS = (actual score -lowerest possible score) х 100 score range DS = (average score-lp score*)х100 score range * lowest possible score Total score along with domain scores was standardised to a 100-point scale; score 0 shows that the patient has no problems, that is, the quality of life is excellent, whereas score 100 shows maximum problems, that is, poor quality of life. All patients independently filled in the questionnaire at the beginning and the end of the investigation.
The statistical analysis of the obtained data was made in the statistical program SPSS for Windows 17.0. Qualitative data were presented with absolute and relative numbers; the quantitative data were shown by the measures of descriptive statistics (mean ± SD, median with IQR). Cronbach's alpha was used to determine the degree of internal consistency of the questions in the five areas of the Quality of Life Questionnaire in postmenopausal women (QUALEFFO-41). For comparing the three analysed groups of patients, nonparametric and parametric methods for independent samples were used (Chisquare test, and Kruskal-Wallis test. The values of p < 0.05 were statistically significant.

Results
Patients were with a mean age of 60.64±6.7 years; the youngest patient was 43 years old, and the oldest 73 years. The largest number/percentage of examined patients was at the age of 60 to 69 years-53 (57.61%). According to the level of education, patients with completed high school predominated (48.91%) https://www.id-press.eu/mjms/index (Table 1). Patients of the three groups did not differ significantly in terms of menopausal status (p = 0.3). Patients without physical agents and exercises (gr.I), insignificantly rarely from patients in the other two groups provided anamnestic data for early menopause (36.67%, 46.88%, 56.67% respectively). The presence of risk factors for osteoporosis was 65.63% of patients treated with physical agents and exercises (gr.I), 80% of patients treated with exercise (gr.II), and 73.33% of patients without physical therapy and exercises (gr.III),. Statistical analysis was non-significant, between the three groups, for the frequency of risk factors for PO (p = 0.44). The difference was also non-significant in terms of the number of risk factors present (p = 0.7). The analysis of the three groups compared to the present comorbidity showed that 71.88% of patients treated with physical agents and exercises (gr.I), 56.67% of patients treated with exercise (gr.II), and 76.67% of patients without physical therapy and exercises (gr.III), had accompanying chronic conditions. The tested difference between subjects with and without co-morbidity, and depending on how the disease was treated, was statistically non-significant (p = 0.22) ( Table 2). When comparing the results of QUALEFFO-41 obtained at the beginning and at the end of our study for each group longitudinally, we noticed a significant improvement in all domains in the first and in the second group of patients, whereas in the third group, who did not practice exercises, there were no significant changes in the domains, except in the social life that showed a substantial impairment. We found a statistically significant difference among the three groups of patients in the average score for the domain pain at the end of the investigation (p < 0.000). However, this significant difference was due to the significantly higher average score in the control group compared to the group treated with physical agents and exercises (59.3 ± 21.3 vs 40.87 ± 20.6 p=0.004), and the group treated with exercises alone (59.3 ± 21.3 vs 31.0 ± 23.2 p < 0.0001). This was mainly a result of the regular practising of exercises by patients in the first and the second group. We can conclude that at the end of the follow-up period, patients who did not perform exercises had substantially diminished the quality of life regarding presence and severity of pain in comparison with the other two groups of patients (Table 3).
On the final check-up, a significantly different average score for the domain physical activities among the three groups was observed (p < 0.0001). Post hoc analysis confirmed a significant difference between the control and the first group (41.8 ± 19.3 vs 19.95 ± 13.3; p < 0.0001), and between the control and the second group (41.8 ± 19.3 vs 19.99 ± 15.4; p < 0.0001). After one-year follow-up, patients from the control group, who did not practice exercises for osteoporosis, showed substantially diminished the quality of life regarding physical activities when compared to the other two groups of patients (Table  3). On the final check-up, the difference was statistically significant (p < 0.0001) for the domain social life, which was due to the significantly higher average score for this domain between the control and the first group (67.06 ± 27.9 vs 34.58 ± 19.9, p < 0.0001), and between the control and the second group (67.06 ± 27.9 vs 27.65 ± 21.64, p < 0.0001). The comparison of the quality of life among the three groups from the aspect of social functioning at the end of the investigation, showed that patients from the control group, who did not practice exercises, had a significantly larger number of problems in performing social activities when compared to the other two groups, (Table 3). Significant differences were observed (p < 0.000) in the domain of perception of their general health at the end of the investigation. On the last check-up, the average score for the general health perception in the group treated with interferential currents, magnet and exercises was 45.88 ± 22.1, in the group performing exercises 41.5 ± 21.9, and in the control group, who did not practice exercises, the score was significantly higher (78.2 ± 21.2). At the end of the follow-up period, patients who did not practice exercises rated their general health condition as significantly poorer compared to the patients from the other two groups ( Table 3).
The three groups of patients had nonsignificantly different quality of life regarding their mental functioning, both on admission (p = 0.3) and at the end of the follow-up (p = 0.3), indicating that the method of treatment of primary osteoporosis had no significant impact on their mental functions (Table 3). The comparative analysis of total average scores showed that, on admission, there were no significant differences in quality of life among the three groups of patients (p = 0.1), whereas, at the end of the follow-up, significant differences were registered (p < 0.0001). Post hoc analysis showed a significant difference in total average score between the control and the first group and between the control and the second group (p = 0.00011). The average total score on the last check-up was 28.86 ± 8.4 for the first group, 26.98 ± 11.8 for the second group, and significantly higher for the third group (47.43 ± 11.75) ( Figure 1) (Table 4).

Discussion
There are many general questionnaires for measuring the quality of life to evaluate the general health condition; however, none of them is as specific for PO as is the Qualeffo-4. Over the last decade, its application in assessing the quality of life in patients with OP has been emphasised due to its specificity, coherence and extensiveness. Osteoporosis (OP) can negatively influence the quality of life, thus limiting and restricting the performance of everyday activities. Chronic pain as a result of PO might lead to depression, anxiety, frustration and social isolation. Practising exercises have become an important intervention in increasing the self-confidence in women in performing their activities and tasks. Regular practising of exercises in women with PO has a positive effect on the general health condition, social inclusion, self-respect, better mood and conscience for better body shape and has decreased depression, anxiety and fear from falls. Our study has shown that all patients with PO demonstrated a significant improvement in the quality of life in all domains of the questionnaire for one year. This was supported by the results obtained for the average scores in all domains when we compared them at the beginning and the end of the study. It means that patients with back pain have a poor quality of life. Also, the other domains such as physical functioning, social life, general health perception and mental function showed a substantial improvement at the end of the study. This is also supported by the result in the total Qualeffo-41 score, which at the end of the study was significantly increased. In the last 10 years, a small number of studies has been conducted that examined the influence of exercises on quality of life in patients with OP for one year by applying the Qualeffo-41 questionnaire.
Similar to our study is the investigation of Evstigneeva et al., which demonstrated that after 12 months of performing exercises for PO the questionnaire about the quality of life showed a significant improvement in the quality of life in patients. Total Qualeffo-41 score after 12 months was significantly better in the group of patients who practised exercises (44.2 ± 7.5) compared to the control group (56.6 ± 9.4), p < 0.0001.
In another study, a general questionnaire about the quality of life in patients with PO was applied. Patients were followed for 13 months and were divided into three groups: the first group https://www.id-press.eu/mjms/index practised exercises 3 times per week, the second 2 times per week and the third, control group, did not perform exercises. Their results were similar to our results. The total score about the quality of life in both groups who practiced exercises showed a significant improvement (p < 0.0001); gr. 1 (at the beginning 330.2 ± 22.02 and at the end 369.05 ± 1.5) and gr. 2 (at the beginning 313.3 ± 22.01 and at the end 348.8 ± 22.6), but not in the control group (at the beginning 312.3 ± 35.09 and at the end 311.4 ± 35.7) [14].
The largest number of investigations is with a shorter follow-up period, and usually, the type of the exercises and their influence on the quality of life in patients with PO has been compared. For example, one study compared the effect of the three different types of exercises on the back pain and quality of life in an adult population with low bone density. A total of 98 women participated in the study, divided into three groups. The investigation lasted for 6 months. The results showed no significant difference among the groups in the total score of Qualeffo-41 questionnaire [15].
The study conducted by Schröder et al. comprised 45 patients with PO who were assigned to two groups: the first group had the usual exercise program for PO, and the second group had exercises similar to our program. The total score for the quality of life in both groups showed improvement; in the first group (at the beginning 26.0 ± 11.2 and the end 23.9 ± 10.0; p = 0.766) and in the second group (at the beginning 29.7 ± 9.8 and the end 21.8 ± 8.1; p < 0.001), but the changes in the second group were statistically significant. In three months, there was an improvement in all domains on the Qualeffo-41 questionnaire in both groups, with higher significance in the second group [16].
The study of Schröder et al. covering three months and the study of Liu-Ambrose TY et al., covering six months have shown that even for a shorter period the exercises for PO improved the quality of life in patients with osteoporosis.
Similar results have been demonstrated in the study of Bennell et al., presenting a significant pain decrease and a significant improvement in the domain of physical functioning even though patients practised the exercises only for three months [17], which was not the case in our study.
One of the advantages of exercises is that they do not represent a burden to the home budget and they can be performed at home. They can yield good results as it was presented in the investigation of Papaioannou A et al., where the questionnaire about the quality of life showed a significant improvement after a 12-month follow-up period [18]. It has to be emphasised that practising exercises should be a continuous process in which patients are actively involved.
Exercises should be practised regularly because with advancing age the muscle tissue is decreased as well as the strength of the muscles and physical abilities. Therefore, exercises maintain physical condition, mobility and social life and hence contribute to a better quality of life.
In conclusion, the exercise program for osteoporosis has significantly improved the quality of life in patients after one year of practising in all four domains: pain, physical activities and mobility, social activities and perception about general health condition (p < 0.0001). The role of exercises in the treatment of patients with postmenopausal osteoporosis is undisputable.