Outcomes of osteoarthritis treatment – results of an 8-year follow-up study

INTRODUCTION

Osteoarthritis (OA) is the most common chronic joint disease and is characterized by chronic pain and joint deformity, resulting in a gradual loss of joint function. The disease typically occurs in patients in their 40s and 50s and predominantly affects women. The main risk factors for the development of OA are age, genetic predisposition, female gender, previous injury or continuous load on the joint, other joint or metabolic diseases (rheumatoid arthritis, gout, diabetes), and obesity (1–6). The American College of Rheumatology (ACR) has established classification criteria for identifying patients with symptomatic OA that include clinical, physical, and radiographic findings (1, 6–9). The knees and hips are commonly affected, as these are weight-bearing joints (7, 9–12). The hand joints are also affected, especially the distal and proximal interphalangeal joints, in which larger bony growths, called Heberden’s and Bouchard’s nodes, can develop (8, 11, 12).

The treatment of OA is a complex process that includes non-pharmacological, pharmacological and surgical approaches, and often a combination of several forms of treatment is required for optimal results to be achieved (11). Surgical treatment is indicated for a relatively small number of patients with advanced OA. The greatest problems for patients with OA are pain and limitation of daily activities (11–13). Treatment goals for patients with OA are to reduce pain, improve mobility, and ultimately restore (or improve) functional ability (14). In general, it is recommended that initial treatment be directed towards self-care and treatment that can be carried out by the patients themselves, while avoiding passive methods carried out by health professionals (e.g. physiotherapists) (15–19). Physical therapy exercises in patients with hip and knee OA are the main non-pharmacological measure to improve function and reduce pain (20–22). The positive effect of hydrokinesitherapy on quality of life may depend on body mass index (BMI) (4, 23). Orthoses, that is, medical support devices, can significantly relieve pressure on the joints and reduce pain in patients with hip and knee OA (24, 25). The main effect of drugs used in the treatment of OA is analgesia, and the main disadvantage of systemic drug administration is non-specificity with respect to the localization of OA (11, 12). Paracetamol can be effective as an initial oral analgesic, while non-steroidal anti-rheumatic drugs (NSAIDs) have proven to be effective and are used in practice as the first line of treatment for patients with OA. NSAIDs should be used at the lowest effective dose, for the shortest possible time. (11, 12, 26–28). Opioids are indicated in patients with OA who experience moderate to severe pain and who are refractory to other analgesic therapy or in whom other medications are contraindicated (11, 12, 29). In these patients, surgical treatment should be considered. Topical NSAIDs and capsaicin may be effective as an alternative to oral analgesics/NSAIDs in patients with knee OA and may be used as the first-line pharmacological treatment option in patients with mild to moderate disease (30–32). Intra-articular glucocorticoid injections have been proved to be beneficial in the treatment of patients with hip and knee OA (33, 34). Patients with symptomatic hip and knee OA whose disease significantly impairs their quality of life and limits their daily activities, and in whom adequate pain relief and function improvement have not been achieved with a combination of non-pharmacological and pharmacological measures, are candidates for artificial joint implants (35). Alloarthroplasty is an effective method that results in significant symptom relief and recovery of functional limitations (36). Total hip arthroplasty (THA) has been shown to have a better effect on the quality of life of patients than total knee arthroplasty (TKA) (12). Older age, higher preoperative pain, musculoskeletal comorbidities, and contralateral hip OA are predictors of poorer outcomes after hip arthroplasty (37), and higher pain, functional limitations, poor mental health, and medical comorbidities are predictors of poor outcomes after knee arthroplasty (38). Partial (unicompartmental) knee arthroplasty is used if the joint is only partially involved, while osteotomy is reserved for younger patients with hip OA, especially in cases of dysplasia (39, 40). Studies have shown that arthroscopic debridement is ineffective in unselected patients with knee OA (41). In patients with knee OA, arthrodesis is considered as a salvage procedure in cases where arthroplasty is not an option or has failed to yield successful results (42).

The aim of this paper is to evaluate the success of treatment in patients with OA treated with different treatment methods during an eight-year follow-up study.

PARTICIPANTS AND METHODS

The study was conducted as a prospective clinical observational cohort study conducted over a period of 8 years on 77 participants with OA from Eastern Croatia who were treated at the University Hospital Centre Osijek. All participants underwent screening, the first inclusion round (1st February 2008 – 31st January 2009), and at the final round (1st February 2016 – 31st January 2017) participants who were monitored in the study until the final round were examined.

The inclusion criteria for this study included:

1. osteoarthritis diagnosis made by a rheumatologist according to the current classification criteria for osteoarthritis of the American College of Rheumatology (ACR),

2. signed informed consent to participate in the study, which the patient must confirm by signing the informed consent form,

3. registered permanent residence / permanent residence in one of the five counties of Eastern Croatia which must be continuous during the study duration,

The exclusion criteria for this study included:

1. patients with a confirmed diagnosis of cardiovascular diseases (previous myocardial infarction, confirmed coronary artery disease through diagnostic tests, angina pectoris, ischemic cardiomyopathy, previous ischemic stroke, transient ischemic attack, confirmed aortic dissection or aneurysm, confirmed peripheral artery disease), diagnosed primary cardiomyopathy, uncorrected severe valve disease or decompensated heart failure before the first round,

2. patient’s refusal to participate in further study analysis after the first round,

3. permanent cessation of residence in one of the five counties of Eastern Croatia during the study duration, with migration within the region not being an exclusion criterion,

4. patient’s unavailability after the first study round.

During the follow-up, participants were instructed to inform the investigators of any changes in their health status, diagnosis of new diseases, changes in medication therapy, or surgical procedures by in-person visit, telephone/fax, e-mail, or through contact initiated by the investigator at least once a year. The participants also attended their regular check-ups at the rheumatology clinic, where all changes in their health status were recorded, and at the final round, a thorough check of the participants’ medical documentation was performed. In the study, we used data collected during the eight-year follow-up, medical histories, outpatient forms from the archives and computer database of the Division of Rheumatology, Clinical Immunology and Allergology, and the Department of Physical Medicine and Rehabilitation, and data obtained from family physicians.

Clinical and laboratory methods include a detailed analysis of the medical history, completion of a pre-prepared form for the first initial round, final round and annual follow-up forms, physical examination with anthropometric measurements; assessment of general health status, assessment of pain intensity, completion of the AUSCAN index form for hand osteoarthritis (43), completion of the Lequesne index form for hip osteoarthritis (44), completion of the Lequesne index form for knee osteoarthritis (44) and completion of the Croatian translation of the Health Assessment Questionnaire (HAQ) (45).

Ethical standards

This research was conducted in accordance with the Declaration of Helsinki and approved by the ethics committees of the University Hospital Centre Osijek and the School of Medicine in Osijek (no.: 602-04/21-08/07).

Written informed consent for participation was obtained from all participants.

Statistical methods

Descriptive statistics were used to describe and summarize the study data. Inferential statistics were used to test hypotheses. Independent samples t-test was used to test the significance of mean differences. Depending on the results of Levene’s test, a t-test assuming equal or unequal variances was used to determine statistical significance between groups. Chi-square test of independence was used to analyse the relationship between qualitative variables. Fisher’s exact test was used in cases in which the assumptions for the chi-square test were not met. The significance level was set at p < 0.05, while 0.05 < p < 0.10 was considered a trend (marginally significant). The IBM SPSS Statistics version 26, New York, USA, was used for the analysis.

RESULTS

Demographic data

Out of the 77 participants who were included in the study after screening, a total of 55 OA patients completed the study. Participants who died and those who refused further participation during the course of the study (22 participants in total; 17 died and 5 refused further participation) were excluded from the analysis. The average age of the deceased patients was 76.94, and the leading causes of death were cardiovascular diseases. There were 25.45% of former smokers, and 10.9% of active smokers. The average duration of follow-up was 8 years and 4 months. The subjective assessment of the state of the disease (OA) in relation to the beginning of the study was: extremely worsened 10.9%, significantly worsened 36.36%, slightly worsened 25.45%, equal 10.9%, slightly improved 7.27%, significantly improved 9.09%. Table 1 shows the demographic data and parameters monitored during the course of the study at the initial and final round.

The frequency of pain medication use at the beginning of the study was 90.9% and at the end of the study it was 89.1%. Table 2 shows the types of medications used for the treatment and control of OA symptoms during the course of the study.

All participants underwent physical therapy measures prescribed by a physiatrist under the supervision of a physiotherapist at least two times during the course of the study.

Comparison of participants who underwent surgery and those who did not

Out of a total of 55 participants included in the outcome analysis, 23 (41.81%) participants underwent orthopaedic surgery (9 participants underwent total knee arthroplasty (TKA) and 15 participants underwent total hip arthroplasty (THA).

The subjective assessment of the state of the disease in relation to the beginning of the study in participants who did not undergo surgery was: extremely worsened 9.36%, significantly worsened 40.63%, slightly worsened 21.86%, equal 11.5%, slightly improved 3.13%, significantly improved 12.5%.

The subjective assessment of the state of the disease in relation to the beginning of the study in patients who underwent surgery was: extremely worsened 13.4%, significantly worsened 30.43%, slightly worsened 30.43%, equal 8.7%, slightly improved 13.04%, significantly improved 4.35%. Table 3 shows the compared parameters for participants who underwent surgery and those who did not at the beginning and the end of the study.

Knees

The knee area affected by osteoarthritis was present in 44 out of 55 participants (80%), and 9 participants (41.67%) underwent orthopaedic surgery for total knee arthroplasty (TKA). The average duration of OA in the group of patients who did not undergo surgery was 5.41 years, while in the group of patients who underwent surgery it was 7.51 years, which is not a statistically significant difference (t=1.045, p=0.30). The average severity of OA measured by the Lequesne index was 13.83 (4–22) in the group of patients who did not undergo surgery and 11.78 (4–19) in the group of patients who underwent surgery, which is not a statistically significant difference (t=-0.82, p=0.42).

Hips

The hip area affected by osteoarthritis was present in 36 out of 55 participants (65.45%), and 15 participants (20.45%) underwent orthopaedic surgery for total hip arthroplasty (THA) (1 participant underwent bilateral and 14 participants unilateral total hip arthroplasty). The average duration of OA in patients who did not undergo surgery was 6.56 years and in patients who underwent surgery it was 4.26 years, which does not represent a statistically significant difference (t=-1.08, p=0.29). The average severity of OA measured by the Lequesne index in was 11.9 (5–19) in patients who did not undergo surgery and 12.93 (2–20) in patients who underwent surgery, which does not represent a statistically significant difference (t=0.62, p=0.54).

DISCUSSION

In this study, two or more joint areas were affected in the majority of participants, which is consistent with the results of previous studies (1, 11, 46). During the eight-year follow-up period, over two-thirds of participants described their subjective assessment of OA status as worsening compared to the state of the disease at beginning of the study. The overall disability assessment measured by the HAQ score did not show a significant difference at the beginning and the end of the study, nor did it show a difference in the assessment of significant disability (HAQ > 1). The assessment of chronic pain on VAS was moderately high throughout the course of the study, while the overall health assessment was unsatisfactory. These parameters indicate a generally unsatisfactory success in the treatment and control of OA symptoms during the course of the study.

During the course of the study, the participants occasionally underwent inpatient physical therapy, which is an important step in the treatment of OA (1, 2). Passive physical therapy methods are most valuable in the form of preparing the joints for therapeutic exercises and during the exacerbation phase of the disease (47). Physical therapy with controlled exercise in OA of the hip and knee significantly reduces pain and improves joint function and the quality of life, especially in younger patients with moderate OA. However, the effect of physical therapy may decrease as the disease progresses (48). Thermal modalities of physical therapy and transcutaneous electrical nerve stimulation (TENS) also help in short-term pain control in patients with hip and knee OA, and the effect can last from 2 to 4 weeks (11, 12). The participants were on average obese, which contributes to the severity of the disease and reduced adherence to physical therapy exercises. A smaller number of participants were smokers, while the number of former smokers was significantly higher, which is an indicator of the relative success of (secondary) prevention and education in this area. According to a recent meta-analysis conducted by V. Silverwood et al., smoking has a neutral effect on the risk of developing OA and successful treatment of this disease (49).

The use of medication therapy was very high. Topical or systemic NSAIDs and paracetamol/opioid combinations were most commonly used medications. In numerous studies, NSAIDs have proven to be effective and in practice they represent the first line of treatment for patients, which is in line with the results of our study (27, 28, 30, 32). Gastrointestinal side effects of NSAIDs are most often more pronounced in the elderly or in combination with certain medications, e.g. glucocorticoids, and therefore they should be used in the lowest effective dose, for the shortest possible amount of time (11, 12). Weak opioids are used in patients with hip and knee OA (for moderate to severe pain) in whom other therapy methods have proven to be ineffective or contraindicated, with relatively common side effects (nausea, constipation, dizziness) (29). According to the results of a meta-analysis of 18 placebo-controlled randomized studies, the effect of opioids on pain in OA can be assessed as moderate to severe, and in terms of their effect on physical function, it can be assessed as mild to moderate (29, 50). Nowadays, a fixed-dose combination of weak opioids and pure analgesics is widely used, which is in accordance with the data stated in our study (29, 50). Tramadol is often used in a fixed-dose combination with paracetamol, with the aim of achieving a synergistic effect and a lower risk of side effects. In order to reduce the risk of side effects, in the case of weak and strong opioid use, the treatment is started with a lower dose of the medication, and then the dose is increased if necessary (51).

Through a comparison of subjective and objective indicators in this study, no difference was found in the success of symptom control and preservation of joint function with the use of surgical treatment methods. A meta-regression analysis of disability in patients with knee OA with a body weight reduction of more than 5% showed a significant improvement (52). A study conducted by Skou et al. described a significant reduction in pain intensity, improvement in function, and overall quality of life in patients who underwent total knee arthroplasty (TKA) and 12 weeks of nonsurgical treatment, compared to a group that underwent 12 weeks of nonsurgical treatment alone, but surgical treatment had a significantly higher rate of complications (deep vein thrombosis, infections) (53). There are no criteria according to which the use of surgical methods is the best choice for a patient. Total hip or knee arthroplasty was proved to be the best choice (54–56). Recent studies show good results in pain control and improvement of functional status with the use of minimally invasive surgical procedures in the treatment of OA, especially of the hip and knee, but such procedures were not performed or available to the participants of this study (57). Lower body mass index (BMI) is associated with better dynamic balance, which indicates the importance of optimizing body mass index, especially in combination with therapeutic exercises (56, 57, 58). Reducing the body mass index is also important at the molecular level due to the reduction of pro-inflammatory cytokines (e.g. resistin, adiponectin, leptin) and their role in the pathogenesis of OA (59). The results of our study do not show a significant difference in the improvement of quality of life and control of OA symptoms between participants who underwent total hip (THA) or knee arthroplasty (TKA) and those who did not undergo surgery, which is different from the results of treatment outcomes in some recent studies (56, 60). Considering the generally poor outcomes of OA treatment in this study, possible explanations are poor adherence to home exercises, i.e. sedentary lifestyle, tendency to obesity due to dietary patterns specific to this area, presence of comorbidities, reliance on widespread use of analgesics and antirheumatic drugs for symptom control, late decision-making for orthopaedic procedures, application of new surgical techniques that were not available at the time of this study, and generally unhealthy lifestyle choices and lack of motivation to change them.

The conducted study is limited by a relatively small sample size considering the overall prevalence of osteoarthritis. Therefore, it is possible that the patients included in the conducted study were suffering from a more severe form of this disease and were more motivated for a regular follow-up. Nevertheless, we believe that the findings obtained from the conducted study can serve as a possible guide for conducting larger studies of osteoarthritis in our country.

CONCLUSION

The effect of OA treatment in this study was unsatisfactory, regardless of the use of conservative or surgical treatment methods. It is necessary to educate the patients in a better way, especially in the persistence of applying physical therapy (self-help) at home, changing a sedentary lifestyle, and implementing methods for a better control and reduction of body weight, as shown by numerous studies. The use of medications should be rationalized and complementary to physical therapy, while surgical treatment methods should be reserved as a method of last but timely treatment choice. The approach to osteoarthritis as the main representative of non-inflammatory rheumatic diseases remains very complex and demanding, primarily due to its high prevalence, and the inability of current therapeutic measures to achieve control of the course of the disease, which has been achieved in recent decades in the example of inflammatory rheumatic diseases.

Author Contributions: Dražen Bedeković: research design, research implementation, data analysis, article writing; Ivica Bošnjak: research implementation, data analysis; Damir Kirner: research implementation; Višnja Prus: research design, research implementation, data analysis; Srđan Novak: data analysis, article writing, supervision.

Acknowledgments: The authors report no acknowledgments.

Funding: The authors declare self-funded research.

Conflict of interest statement: The authors declare that they have no conflict of interest relevant to this manuscript.

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Table 1. Demographic data and parameters monitored during the course of the study

Tablica 1. Demografski podatci i parametri praćeni tijekom istraživanja

Legend / Tumač: OA – osteoarthritis / osteoartritis, BMI – body mass index / indeks tjelesne mase, HAQ – Health Assessment Questionnaire, VAS – visual analogue scale/mm / vizualno-analogna skala/mm, TEP – total endoprosthesis (arthroplasty) / totalna endoproteza

* Proportion of patients / Proporcija bolesnika

** Data in parentheses represent the interval between the measured minimum and maximum values. / Podatci u zagradama su interval između izmjerene minimalne i maksimalne vrijednosti.

Table 2. Medications used to treat OA during the course of the study

Tablica 2. Lijekovi primijenjeni za liječenja OA tijekom istraživanja

Table 3. Comparison of parameters for participants that underwent surgery and participants that did not undergo surgery during the course of the study

Tablica 3. Uspoređeni parametri za operirane i neoperirane ispitanike tijekom istraživanja

* Data in parentheses represent the interval between the measured minimum and maximum values. / Podatci u zagradama su interval između izmjerene minimalne i maksimalne vrijednosti.