Effect of Intra-articular Injection of Corticosteroid in the Patients with Osteoarthritis of the Knee - A Hospital-Based Cross-Sectional Study.

BACKGROUND: Osteoarthritis (OA) of the peripheral joints is frequently related with physical disability and decline in health-related quality of life, deciphering into a significant burden on people and humankind. Although IA corticosteroid injections are being in clinical use, their long-term effects on knee OA are least studied and documented. Hence, the study was done with the aim of assessing the effect of intra-articular (IA) injection of corticosteroid in patients with OA of the knee.
METHODS: This prospective observational study was conducted over a period of 6 months between 40 years and 75 years with Grade I and II OA of the knee admitted under the Department of Orthopaedics, Tertiary Care Hospital, Belgaum. Patients' affected knee was injected with 80 mg of triamcinolone after the examination, and follow-ups had done at 2 weeks, 6 weeks, 3 months, and 6 months. The standard pro forma used were Visual Analog Scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), and Knee Injury and Osteoarthritis Outcome Score (KOOS).
RESULTS: The mean age of the participants was 58.96 ± 9.58, ranging from 40 to 75 years, with a slightly higher proportion of females. The proportion of Grade 1 and Grade II OA was 24% and 76%, respectively, and 54.7% had right-sided involvement. The difference between pre Rx: Pre intervention VAS score VAS score and follow-up periods at 2 weeks, 6 weeks, 3 months, and 6 months was statistically significant with respect to VAS scale, KOOS scale, and WOMAC scale (P < 0.001).
CONCLUSION: there was no major adverse effect of corticosteroid injections, and it showed significant improvement in patients. There is a need to conduct large-scale well-controlled clinical trials with an appropriate control group, to be able to document the relative efficacy and safety of IA steroid injection. Copyright:

INTRODUCTION

Osteoarthritis (OA) of the peripheral joints is frequently related with physical disability and decline in health-related quality of life (QOL), deciphering into a significant burden on people and humankind.[12] Although OA affects all joints, the most frequently encountered joints are the hip, knee, and hand. From the past few years to the present, there has been a sharp increase in both the prevalence and incidence of OA. This is mainly accredited to growing prevalence of obesity and to the elderly population.[34] In contrast, there has been an increased incidence of OA among active young adults.[35] In India, the most commonly occurring joint disorder is OA with a prevalence of 22%–39%, making it the second most commonly encountered rheumatological disorder.[6] Among the genders, women are more frequently affected than men; however, the occurrence sharply increases with aging. The symptoms of OA are evident in nearly half of women >65 years of age, while majority of them show radiologic evidence in >65 years of age.[7] Mobility impairment, especially in women, is mainly caused by OA of knee.

The 10th leading cause of nonfatal burden is estimated to be OA. The management of OA mainly aims to control pain, reviving and preserving the mobility and joint function, thus enhancing one's QOL with no scope for retrogressing the OA process. At present, OA is treated with pharmacological and nonpharmacological approaches. These can be offered alone or in combination. The nonpharmacological management consists of patient counseling, with occupational or physical therapy being a prime component of OA treatment. Numerous drugs are available to treat OA, and these include acetaminophen, nonspecific nonsteroidal anti-inflammatory drugs, and COX-2-specific inhibitors.

Although these drugs have shown proven results, few of them possess serious adverse effects.

Other treatment approaches for OA include nonsurgical intervention such as injectable compounds and viscosupplements that imitate synovial fluid or surgical interventions. These treatment options are considered when medical management of OA fails.[8] Over the past few years, intra-articular (IA) corticosteroid injections have been in use to control pain and inflammation in OA.[9] However, from two recent studies, the predictors of response could not be recognized.[10] The American College of Rheumatology practice guidelines suggest the IA corticosteroid injections as part of standard treatment to OA of knee.[11] However, its use is questioned as these in long-term use facilitate joint destruction and atrophy of tissue.[12] However, in vitro and in vivo experimental studies have shown decreased structural changes with IA corticosteroid injections.[1314] Although IA corticosteroid injections are being in clinical use, their long-term effects on knee OA is least studied and documented. Further, there is a lack of literature on the functional impact of IA steroid injections assessed with validated tools such as Western Ontario and McMaster Universities OA Index (WOMAC) and Western Ontario.[15] At present, there is no anatomical or structural assessment of which is presently practicable in OA, as proposed by several researchers. Finally, no structural or anatomical evaluation, which is now feasible in OA, as suggested by many investigators,[16] has not yet been made to rightly address the query of whether steroid injection persuades joint structure damage. Hence, the study was done with the aim of assessing the effect of IA injection of corticosteroid in patients with OA of the knee.

Aim/purpose of the research

The study was done with the aim of assessing the effect of IA injection of corticosteroid in patients with OA of the knee.

METHODS

Study site

This study was conducted in the Department of Orthopaedics at Tertiary Care Hospital, Belgaum.

Study population

Adult patients of age between 40 years and 75 years with Grade I and II OA knee admitted under the Department of Orthopaedics of the study site were considered as the study population.

Study design

The current study was a prospective observational study.

Sample size

The sample size was calculated assuming the expected mean preoperative WOMAC score to be 67.6 and postoperative WOMAC score to be 61.3 with respected standard deviations of 13.4 and 12.5, as per a study by Buyuk et al.[17] The other parameters considered for sample size calculation were 80% power of the study and 5% two-sided alpha error. The sample size was calculated to be able to document the differences between the two-paired means using SPSS version 25.0 statistical package (SPSS Inc., Chicago, Illinois). As per the calculation, the required sample size was 67 individuals. To account for loss to follow-up of 10%, another seven individuals were added to the sample, making the total required minimum sample size to be 74 individuals. The final analysis included 75 individuals.

Sampling method

Convenient sampling was used.

Study duration

The data collection for the study was done from January 2017 to December 2017 for a period of 1 year.

Inclusion criteria

Patients aged between 40 and 75 years

Grade 1 and Grade 2 OA of the knee (according to Kellgren-Lawrence classification).

Exclusion criteria

Bleeding disorders

Septic arthritis or osteomyelitis

Rheumatoid arthritis

Recent febrile illness

Diabetes mellitus

Cellulitis

Corticosteroid or hyaluronic acid injection of the knee within 1 month.

Ethical considerations

Approval from the human ethics committee from the institution was obtained (Ref: MDC/DOME/46, Date: October 17, 2016). All the study participants had given informed consent, and participants willing to sign the informed consent were included in the study.

The study was approved by the institutional human ethics committee, informed written consent was obtained from all the study participants, and only those participants willing to sign the informed consent were included in the study.

Data collection tools

All the relevant parameters were documented in a structured study pro forma along with tools such as the Visual Analog Scale (VAS), Knee Injury and Osteoarthritis Outcome Score (KOOS), and WOMAC score.

Visual Analog Scale

The VAS is generally used for characterizing pain. It is typically presented as a horizontal line on which the patient's pain intensity is represented by a point between the extremes of “no pain at all” and “worst pain imaginable.[18]”

Knee Injury and Osteoarthritis Outcome Score

The KOOS questionnaire is an instrument to assess the patient's opinion about their knee and associated problems. KOOS consists of five subscales: pain, other symptoms, Activities of daily Living (ADL), function in sport and recreation (Sport/Rec), and knee-related QOL. KOOS is patient administered, the format is user-friendly, and takes about 10 min to complete.[19]

Western Ontario and McMaster Universities Osteoarthritis Index

WOMAC is a health status questionnaire designed to assess the pain, stiffness, and physical function in patients with hip and/or knee OA. The WOMAC consists of 24 items divided into three subscales.[20]

Methodology

The individuals were selected based on inclusion and exclusion criteria. The study was conducted over a period of 6 months. History and examination were recorded as per the pro forma. Patients' affected knee was injected with 80 mg of triamcinolone after the examination, and follow-ups had done at 2 weeks, 6 weeks, 3 months, and 6 months. The procedure was done under aseptic precautions with antibiotic cover.

Statistical methods

The VAS score, KOOS, and WOMAC were considered as outcome variables. Descriptive analysis: Descriptive analysis was carried out by mean and standard deviation for quantitative variables and frequency and proportion for categorical variables. Data were also represented using appropriate diagrams such as a bar diagram, pie diagram, and box plots. Time changing quantitative parameters (VAS score, factors associated with KOOS, and factors associated with WOMAC) were compared by using one-way repeated measures ANOVA test. P <0.05 was considered statistically significant. SPSS version 25.0 statistical package (SPSS Inc., Chicago, Illinois).[21]

RESULTS

A total of 75 people were included in the analysis. The mean age of the participants was 58.96 ± 9.58. The minimum age was 40, and the maximum age was 75 (95% CI: 56.76–61.16). Thirty-five (46.70%) participants were male and 40 (53.30%) were female. In the study population, 18 (24%) people had Grade 1 OA and the remaining 57 (76%) people had Grade 2 OA [Table 1].

Table 1

Characteristics of the study participants

Parameter	Frequency, n (%)
Gender
Male	35 (46.70)
Female	40 (53.30)
Side involved
Right OA	41 (54.70)
Left OA	34 (45.30)
Grade of OA
Grade 1	18 (24.00)
Grade 2	57 (76.00)

OA: Osteoarthritis

The mean of VAS score at pre-RX, 2 weeks, 6 weeks, 3 months, and at the end of 6 months was noted down. The difference between pre-RX VAS score and follow-up periods at 2 weeks, 6 weeks, 3 months, and 6 months was statistically significant (P < 0.001) [Table 2]. All the domains of KOOS were assessed for at 2 weeks, 6 weeks, 3 months, and at the end of 6 months [Table 3], and it was statistically significant (P < 0.001) at each time interval. The mean of pre-RX WOMAC scores was 48.43 ± 3.33, it was 92.92 ± 1.8 at 3 weeks, it was 90.79 ± 3.36 at 6 weeks, it was 80.1 ± 2.49 at 3 months, and it was 55.04 ± 2.36 at the end of 6 months. The difference between pre-RX WOMAC-Total and follow-up periods at 2 weeks, 6 weeks, 3 months, and 6 months was statistically significant (P < 0.001) [Table 4].

Table 2

Comparison of mean Visual Analog Scale score at a different time period of the study population (n=75)

Visual Analog Scale score	Mean±SD	P
Pre-RX	5.06±0.4
2 weeks	2.49±0.47	<0.001
6 weeks	3.14±0.33	<0.001
3 months	3.68±0.39	<0.001
6 months	4.57±0.36	<0.001

SD: Standard deviation, RX: PreIntervention

Table 3

Comparison of mean Knee Injury and Osteoarthritis Outcome Score at the different time period of the study population (n=75)

	Mean±SD	P
KOOS pain
Pre-RX	46.66±4.94
2 weeks	91±3.02	<0.001
6 weeks	90.3±3.94	<0.001
3 months	77.63±3.93	<0.001
6 months	48.07±5.46	0.090
KOOS symptoms
Pre-RX	46.29±5.95
2 weeks	90.71±4.59	<0.001
6 weeks	86.33±5.79	<0.001
3 months	70.76±4.76	<0.001
6 months	42.57±5.24	<0.001
KOOS ADL
Pre-RX	47.18±4.41
2 weeks	93.14±2.42	<0.001
6 weeks	90.27±3.67	<0.001
3 months	78.59±2.9	<0.001
6 months	56.8±2.33	<0.001
KOOS sport/recreation (recreation function)
Pre-RX	33.07±8.81
2 weeks	90.8±3.39	<0.001
6 weeks	90.6±4.65	<0.001
3 months	75.47±3.2	<0.001
6 months	70.27±3.38	<0.001
KOOS QOL
Pre-RX	52.33±6.23
2 weeks	74.17±6.53	<0.001
6 weeks	67±8.81	<0.001
3 months	61.67±7.36	<0.001
6 months	48.92±6.77	<0.001

SD: Standard deviation, KOOS: Knee Injury and Osteoarthritis Outcome Score, QOL: Quality of life, ADL: Activities of daily living, RX: PreIntervention

Table 4

Comparison of mean Western Ontario and McMaster Universities Osteoarthritis Index scores at the different time period of the study population (n=75)

WOMAC total	Mean±SD	P
Pre-RX	48.43±3.33
2 weeks	92.92±1.8	<0.001
6 weeks	90.79±3.36	<0.001
3 months	80.1±2.49	<0.001
6 months	55.04±2.36	<0.001

SD: Standard deviation, WOMAC: Western Ontario and McMaster Universities Osteoarthritis Index, RX: PreIntervention

DISCUSSION

Despite a large number of studies, the safety and efficacy of IA steroids administered among persons with knee OA remain inadequate, which further leads to a gap across clinical guiding principles. The study by Raynauld et al.[20] indicated that the beneficial effects did not last long, and McAlindon et al.[22] have stated that their findings did not support the treatment regimen for patients with symptomatic knee OA. The current study was carried out among 75 patients who were diagnosed with Grade 1 and Grade 2 OA and was aimed at assessing the effect of IA injection of corticosteroid among them. The mean age of the participants in our study was found to be 58.96 ± 9.58 years. The mean VAS score prior to diagnosis was found to be 5.06 ± 0.4, and the mean values at 2 weeks, 6 months, 3 months, and the end of 6 months were found to be 2.49 ± 0.47, 3.14 ± 0.33, 3.68 ± 0.39, and 4.57 ± 0.36, respectively, and the difference between the mean scores was found to be statistically significant (P < 0.001); these VAS results were in line with the findings by Askari et al.[23] Similar trends in the VAS during the subsequent follow-ups were reported by Jones and Doherty[10] and Pyne et al.[24] Chansoria et al.[25] also have similar results showing the VAS scores, before intervention (8.9 ± 1.3) and at 1 month (2.8 ± 1.1), 3 months (3.4 ± 1.3), and 6 months (5.1 ± 1.4), respectively. The average KOOS pain score before the intervention was found to be 46.66 ± 4.94 and at 2 weeks, 6 weeks, 3 months, and 6 months were reported to be 91 ± 3.02, 90.3 ± 3.94, 77.63 ± 3.93, and 48.07 ± 5.46, respectively. The difference between the preintervention KOOS and respective follow-up periods was statistically significant (P < 0.001), apart from follow eight up at 6 months (P < 0.09). Similar results showing significant pain relief for the initial 10 weeks and a gradual decrease in the later weeks were reported by Heyworth et al.[26] With respect to the symptom's domain, the difference between the preintervention KOOS and respective follow-up periods was statistically significant (P < 0.001). The same trend of increase in the values at 1 month (50.84 ± 12.95), 2 months (55.56 ± 11.09), 3 months (59.34 ± 10.62), and a sudden fall at the end of 6 months (55.25 ± 8.58) was reported by Nabi et al.[27] Similarly, the difference between preintervention KOOS function in daily living (ADL) at follow-up periods at 2 weeks, 6 weeks, 3 months, and 6 months was statistically significant (P < 0.001). These results were in contrast to that reported by Henriksen et al.[28] where they have reported ADL at baseline and at the end of the trial (14 weeks) to be 61.0 ± 14.7 and 14.9 ± 1.7, respectively. Similarly, the difference between preintervention KOOS QOL and follow-up periods at 2 weeks, 6 weeks, 3 months, 6 months was statistically significant (P < 0.001). Even though the trend of QOL showed an increase in the initial follow up, it has gradually declined in the further follow ups, this was related to the reports by Riis et al.[29] where the QOL was lower in patients with steroidal injections compared to those with placebo. WOMAC, a self-administered instrument, established for measuring pain and physical function in OA, to investigate the impact and associated features of knee pain in the older general population, was used during the assessment.

The mean of total WOMAC scores was 48.43 ± 3.33, and at different follow-ups at 2 weeks, 6 weeks, 3 months, and at the end of 6 months, it was found to be 92.92 ± 1.8, 90.79 ± 3.36, 80.1 ± 2.49, and 55.04 ± 2.36 respectively. The difference between the WOMAC scores before the intervention and at different follow-ups was found to be statistically significant (P < 0.001). The total WOMAC scores reported in this current study were in contrast to those reported by Buyuk et al.[17] where they have reported that the preintervention total WOMAC score to be 67.6 ± 14.4 and at the follow ups at 2 weeks, 3 months, and end of 6 months were reported to be 31.6 ± 17.3, 58.1 ± 18, and 61.3 ± 16.4, respectively – this was according to buyuk et all study. The occurrence of any major adverse events such as infection of the affected joint and joint effusion during the different follow-up periods was absent in the study. Only minor side effects such as nausea, vomiting, sweating, and transient headache were reported. The safety of IA injection of steroids has been established by many other previous studies.

However, the study is not without any limitations. First, in our study, there was no control group, hence the role of various potential confounding factors on the treatment outcomes could not be controlled for. Second, even though validated tools were used to assess the treatment outcomes, the possibility of reporting bias and ascertainment bias could not be ruled out completely. Finally, considering the limited catchment area and conduction of study in a single center, the generalizability of the study findings is very limited.

Hence, in future, there is a need to conduct large-scale well-controlled clinical trials with the appropriate control group, to be able to document the relative efficacy and safety of IA steroid injection. Till such evidence is available and clear guidelines evolve, the IA injections need to be used with caution, after thoroughly explaining the risk and benefits involved to the patients.

CONCLUSION

The current study had included individuals with a mean of age of 58.96 ± 9.58, ranging from 40 to 75 years, with a slightly higher proportion of females. The proportion of Grade 1 and Grade II OA was 24% and 76%, respectively, and 54.7% had right-sided involvement. The mean of pre-RX VAS score was 5.06 ± 0.4 and showed a gross decline to 2.49 ± 0.47 at 2 weeks and gradually increased thereafter to 4.57 ± 0.36 at the end of 6 months. The difference between pre-RX VAS score and follow-up periods at 2 weeks, 6 weeks, 3 months, and 6 months was statistically significant. KOOS also had shown statistically significant improvement from baseline. WOMAC scores also had shown statistically significant improvement from pretreatment levels in the study population.

Limitations

Due to small sample size and limited catchment area the generalizability of the study is limited.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.