Assessment of the Effectiveness of Knee Joints Treatment With the Use of ⁹⁰Y

Prospective Ultrasound and Clinical Analysis

Abstract

Purpose 

The purpose of this prospective study was to assess the effectiveness of knee joints treatment by radiosynoviorthesis with the use of ⁹⁰Y based on ultrasound and clinical analysis.

Materials and Methods 

Ninety-seven patients were qualified for treatment from October 2016 to June 2017, and observation period lasted until December 2017. Bioethics Committee of the Medical University of Silesia approved this study. The effectiveness of knee joints treatment with the use of ⁹⁰Y was based on 927 ultrasound measurements of fluid and 927 synovial thickness in 3 sites of the suprapatellar recess, 309 assessments of patient’s disability documented in Lequesne questionnaire, 309 assessments of pain on visual analog scale, as well as 103 overall self-assessment. Statistical methods were used to process the results.

Results 

A reduction in fluid was found in 62.14% of the knees; synovial thickness reduction was observed in 97.09% of all knees. The greatest benefit from the therapy was experienced by patients complaining of morning stiffness lasting more than 15 minutes (in 85.71% of joints). There was reduction in pain at rest in 94.52% of knee joints and in 80.39% of joints with pain while walking. At the second follow-up visit after treatment, the percentage of improvement in self-assessment was 74.76%.

Conclusions 

Statistically significant decreases in the amount of fluid and thickness of the synovial membrane as well as the level of disability and the intensity of pain after radiosynoviorthesis ⁹⁰Y treatment were demonstrated.

Intra-articular administration of an isotope called radiosynoviorthesis (RSV) is a safe, minimally invasive method of treating drug-resistant arthropathy accompanied by exudate and/or joint pain. The ⁹⁰Y isotope is used in the treatment of knee joints, and for some patients, RSV allows to avoid surgery. Patients were referred for treatment from specialist clinics or GP clinics. Patients were qualified in accordance with the currently applicable list of model radiological procedures in the field of nuclear medicine—Official Journal of the Minister of Health, item 82, announcement of the Minister of Health of December 22, 2014. The Bioethics Committee of the Medical University of Silesia accepted the examination at the committee meeting (May 16, 2015). Each participant signed a statement that he/she consents to 2 follow-up visits from the date of treatment, together with an ultrasound examination of the treated joint and filling in a questionnaire.

PATIENTS AND METHODS

A total of 97 patients were observed, including 6 patients who had both knee joints treated. One hundred three knee joints were included in the analysis. The analysis covered 97 patients, including 57 women (58.76%) and 40 men (41.24%). The mean age of the patients was 61 ± 11 years (range, 25–83 years). Older patients predominated in the analyzed group; the most numerous subgroup of patients was those aged older than 60 years; it was 57 patients who stands for 58.76%. There were 35 (36.08%) middle-aged patients between the ages of 40 and 60 years, and only 5 (5.16%) patients were younger than 40 years. The mean body mass index was 30.29, the minimum was 21.23, and the maximum was 50.00. In the analyzed group of 97 patients, only 13 (13.40%) had a normal body mass index value, below 25. There were 35 overweight patients (36.08%) and 49 (50.52%) with obesity. In 61 cases, the treatment concerned the right knee joint (59.22%), and in 42 cases, the left knee joint (40.78%). Patients with degeneration of the knee joints with thickening and synovitis were most often treated (64 joints, 62.14%). The second most frequent subgroup was rheumatoid diseases (16 joints, 15.53%). The diagnoses in this subgroup included rheumatoid arthritis (RA) (n = 14), ankylosing spondylitis (AS) (n = 1), and unspecified polyarthritis (n = 1). The last subgroups were diagnoses other than those mentioned so far. In this subgroup of 23 (22.33%) knee joints, diagnoses of recurrent exudative knee arthritis with no specific etiology were predominant (n = 17); less numerous subgroups were synovial pigment nodular synovitis (n = 2), Lyme disease (n = 1), and joint diseases with recurrent exudative inflammation after arthroplasty (n = 3).

Methods

The qualification and intra-articular administration of the ⁹⁰Y isotope were performed at the Department of Nuclear Medicine, Clinica Medica, Tychy, Poland. Patients were qualified for treatment from October 2016 to June 2017; the observation period lasted until December 2017. After 2017, no longer observation (ultrasound measurements self-assessment of treatment) was conducted as it was out of patient’s consent and scope of this research. The qualifying visit included the following: an interview and physical examination, ultrasound with measurement of the amount of fluid in the suprapatellar recess, thickness of the synovium, and assessment of the popliteal fossa for the presence of a popliteal cyst. The patients were administered intra-articular ⁹⁰Y colloidal citrate suspension manufactured by CIS Bio International, France. One of the 2 activities of the ⁹⁰Y isotope was used: 185 MBq (n = 79) or 148 MBq (n = 24 only for joints with Baker cyst). Control visits were scheduled after 3 and 6 months from the day of ⁹⁰Y administration. The amount of fluid in the suprapatellar recess and the maximum thickness of the synovial membrane were measured in millimeters during ultrasound examination. Each time, the ultrasound measurement was performed twice, and the average of these measurements was recorded in the measurement database. To maintain the reproducibility of the measurements, the suprapatellar recess was examined in the supine position of the patient on his back, with an approximately 30-degree flexion of the knee joint, in the longitudinal position of the head relative to the patella, in accordance with the “Musculoskeletal Ultrasound Technical Guidelines V. Knee,” developed by the European Society of Musculoskeletal Radiology.¹ The suprapatellar recess was assessed in 3 projections: directly in front of the patella, laterally, and medially. The fluid was identified as a hypoechogenic area reacting to pressure with the transducer at the measurement site. The synovial membrane was identified as the area in the scan field, most often hypoechogenic, not moving under pressure with the transducer. The amount of fluid and the thickness of the synovium were measured in millimeters perpendicular to the femur.

To assess disability, Lequesne questionnaire² (in the version intended for the assessment of patients with knee joint diseases) was carried out before the procedure and at 2 follow-up visits. The following parameters were assessed in the Lequesne questionnaire: night pain (0 to 2 points), morning stiffness (0 to 2 points), pain intensification after 30 minutes of standing (0 to 1 points), pain while walking (0 to 2 points), pain when getting up from a sitting position without the help of hands (from 0 to 1 point), the maximum distance that the patient can walk (from 0 to 6 points), the need to use crutches (from 0 to 2 points), climbing stairs (0 to 2 points), going down stairs (0 to 2 points), squatting or kneeling (0 to 2 points), and walking on an uneven surface (0 to 2 points). The questionnaire allowed the patient to obtain a maximum of 24 points. The level of disability, as the sum of all points obtained by the patient, was assessed according to a scale: none (0 points), slight (1–4 points), moderate (5–7 points), severe (8–10 points), very severe (11–13 points), and extremely severe (≥14 points).

The questionnaire assessed also the scale of pain experienced by the patient. The visual analog scale (VAS) scale was printed in the form of a ruler with a range from 0 to 10. The patient indicated with a finger the pain intensity from 0, no pain at all, to 10, the strongest pain imaginable, separately for pain at rest and for pain while walking. A long-term pain scale was not performed.

During the follow-up visits, the patient was asked to self-assess the effectiveness of treatment in the opinion of the patient, expressed in the words: no improvement or improvement.

The statistical analysis was performed in the Statistica v.10 StatSoft Polska program and in the test version of the PQStat software, Statistical Calculation Software. The level of statistical significance was assumed in all calculations (α = 0.05). This meant that the value of P ≤ 0.05 obtained in the tests was indicative of statistically significant differences, and P > 0.05 indicated no such differences. All the calculated P values are given to 4 decimal places. In the work, for quantitative data, basic statistics were calculated, that is, mean, standard deviation, median, interquartile range, and minimum and maximum value.

The normality of data distribution was verified with the Shapiro-Wilk test. The Mann-Whitney test was used to compare two independent groups with non-normal distributions. One-way analysis of variance (ANOVA) was used to compare three dependent groups, where each group was normally distributed and the assumption of homogeneity of variance was met. The test verifying which groups differed from each other was the Scheffe test. In the case when three dependent groups with non-normal distribution were compared the Friedman’s test was used. In a situation where the obtained P value allowed to question the validity of the null hypothesis assuming equality of medians, post-hoc tests were additionally performed for Friedman’s test, using Dunn’s test with Bonferroni correction, due to multiple testing. In this way, it was precisely clarified between which groups there were statistically significant differences. To verified existence of dependence between categorical data were analyzed using the following tests: Chi-square, Chi-square with Yate’s correction or Fischer’s exact test, depending on the observed values and calculated expected values.

RESULTS

Ultrasound Analysis

Nine hundred twenty-seven measurements of the amount of fluid in the suprapatellar recess were performed. Basic statistics were determined for the individual measurements of the amount of fluid at 3 time points (before treatment, at the first control visit, and at the second control visit), in 3 places of the suprapatellar recess (in front of the patella, laterally from the patella, and medially from the patella). In addition, the sum of the 3 measurement sites at the adopted time points was determined, which was the total amount of fluid in the suprapatellar recess (Table 1). In the case of measurements directly in front of the patella, statistically significant differences (P = 0.0092) were observed between the measurement of fluid before treatment and 3 months after injection. The amount of fluid between the 2 measurements decreased. In the case of measurements lateral from the patella, statistically significant differences were observed between the measurement of fluid before treatment and 3 months after injection (P = 0.0219), and before treatment and 6 months after injection (P = 0.0032). The amount of fluid between the 2 measurements decreased significantly in both cases. Only the case of measurements taken medially from the patella statistically significant differences between the measurements of the amount of fluid was not found. In the overall approach, that is, considering the sums of measurements, statistically significant differences were found between the sum of fluid measurements before treatment and the sum of fluid measurements 6 months after injection (P = 0.0008). The amount of fluid measured before treatment and at the second follow-up visit was statistically significantly different.

TABLE 1 - Basic Statistics Determined for the Measurement of the Amount of Fluid—Group of n = 103 Knee Joints

Parameter	n	Mean, mm	Median, mm	SD, mm	IQR, mm	Min, mm	Max, mm
F0F	103	7.09	6.60	4.32	4.30–9.60	0.00	30.30
F3F	103	6.01	5.50	3.69	4.00–8.70	0.00	17.50
F6F	103	6.06	6.00	3.61	3.40–8.80	0.00	14.70
F0L	103	5.61	5.30	4.80	0.00–8.60	0.00	23.50
F3L	103	4.08	3.40	3.79	0.00–6.70	0.00	14.00
F6L	103	3.80	3.20	3.81	0.00–6.50	0.00	16.40
F0M	103	4.00	2.40	4.91	0.00–6.70	0.00	22.40
F3M	103	3.23	2.40	3.69	0.00–6.30	0.00	14.90
F6M	103	2.78	1.70	3.39	0.00–4.50	0.00	15.00
SUM F0	103	16.70	14.60	11.60	8.80–22.20	0.00	76.20
SUM F3	103	13.32	12.70	8.57	6.10–18.60	0.00	34.20
SUM F6	103	12.65	11.20	8.58	6.00–19.30	0.00	41.10

Amount of fluid before treatment (t = 0), at the first control visit (t = 3), and at the second control visit (t = 6), in front of the patella, laterally from the patella, and medially from the patella. The sum of the 3 measurement sites at the adopted time points was determined, which was the total amount of fluid in the suprapatellar recess (SUM F0, SUM F3, SUM F6).

Nine hundred twenty-seven measurements of the thickness of the synovial membrane in the suprapatellar recess were made and included in the analysis. Basic statistics were determined for individual measurements of the thickness of the synovial membrane at 3 time points (before the treatment, at the first control visit, and at the second control visit), in 3 sites of suprapatellar recess (in front of the patella, lateral to the patella, and medially to the patella). In addition, the sum of the 3 measurement sites in the adopted time points was determined, which was the total thickness of the synovial membrane in the suprapatellar recess (Table 2).

TABLE 2 - Basic Statistics Determined for the Measurement of the Synovial Membrane Thickness—Group of n = 103 Knee Joints

Parameter	n	Mean, mm	Median, mm	SD, mm	IQR, mm	Min, mm	Max, mm
M0F	103	5.50	4.70	3.34	3.70–6.50	0.00	29.30
M3F	103	4.29	3.70	2.26	2.90–5.20	0.00	14.70
M6F	103	3.73	3.30	2.02	2.30–4.60	0.00	10.80
M0L	103	5.96	5.60	3.88	4.50–7.40	0.00	24.00
M3L	103	4.39	4.10	3.14	2.70–5.70	0.00	19.90
M6L	103	3.63	3.50	3.01	2.10–4.90	0.00	17.20
M0M	103	3.01	2.70	3.71	0.00–4.50	0.00	18.20
M3M	103	2.22	0.00	3.77	0.00–3.40	0.00	31.60
M6M	103	1.75	0.00	2.50	0.00–2.90	0.00	14.70
SUM M0	103	14.47	12.50	9.01	10.00–16.70	2.70	71.50
SUM M3	103	10.90	9.30	7.51	7.00–12.10	2.80	66.20
SUM M6	103	9.11	8.40	5.87	5.10–11.40	1.20	34.80

Thickness of the synovial membrane before the treatment (t = 0), at the first control visit (t = 3), and at the second control visit (t = 6), in front of the patella, lateral to the patella, and medially to the patella. The sum of the 3 measurement sites in the adopted time points was determined, which was the total thickness of the synovial membrane in the suprapatellar recess (SUM M0, SUM M3, SUM M6).

Statistically significant differences were found between all the measurements of the thickness of the synovium in the group of 103 knee joints. In the case of measurements taken directly in front of the patella, statistically significant differences in the thickness of the synovial membrane were observed between all the comparisons made: measurement of the thickness of the synovial membrane before treatment and measurement of the thickness of the synovial membrane 3 months after injection (P < 0.0001); pretreatment synovial thickness measurement and synovial thickness measurement 6 months after injection (P < 0.0001); measurement of synovial thickness 3 months after injection and measurement of synovial thickness 6 months after injection (P = 0.0001). The median decreased with successive measurements. The same results were obtained for measurements taken laterally from the patella. Statistically significant differences in synovial thickness were observed between all the comparisons made: measurement of synovial thickness before treatment and measurement of synovial thickness after 3 months (P < 0.0001); pretreatment synovial thickness measurement and synovial thickness measurement after 6 months (P < 0.0001); synovial thickness measurement after 3 months and synovial thickness measurement after 6 months (P = 0.0028). For measurements taken medially from the patella, statistically significant differences in the thickness of the synovial membrane were observed between the measurement of the thickness of the synovial membrane before treatment and the measurement of the thickness of the synovial membrane after 3 months (P < 0.0001), and the measurement of the thickness of the synovial membrane before treatment and measurement of synovial thickness after 6 months (P < 0.0001). Overall, the differences were between all comparisons: the sum of synovial thickness measurements before treatment and the sum of synovial thickness measurements after 3 months (P < 0.0001), the sum of measurements before treatment and the sum of measurements of synovial thickness after 6 months (P < 0.0001), and the sum of measurements of synovial membrane thickness after 3 months and the sum of measurements of synovial thickness after 6 months (P = 0.0001).

Clinical Analysis

The analysis of disability included 309 sums of points obtained from the Lequesne questionnaire, which patients completed 3 times, and showed a statistically significant decrease in the level of disability. Statistically significant differences were observed between the sum of points obtained in the Lequesne questionnaire before treatment and the sum of points obtained at the first control visit (P < 0.0001), and the sum of points obtained in the Lequesne questionnaire before treatment and the sum of points obtained at the second visit in the controls (P < 0.0001). There was no statistically significant decrease in the level of disability (P = 0.2090) between the sum of points obtained in the Lequesne questionnaire at the first and second control visits (Table 3).

TABLE 3 - Basic Statistics for the Sum of Points From the Lequesne Questionnaire in Terms of Disability Level—Group of n = 103 Knee Joints

Parameter	n	Mean, Points	Median, Points	SD, Points	IQR, Points	Min, Points	Max, Points
Disability level before treatment	103	11.98	11.50	3.70	9.50–14.50	2.50	21.00
Disability level after treatment, first visit	103	9.08	9.00	3.92	6.00–12.00	0.00	18.50
Disability level after treatment, second visit	103	8.12	8.50	4.04	5.00–11.00	0.00	17.50

The further analysis included 309 values of rest pain indicated before treatment and at follow-up visits (Table 4). The analysis of patients’ VAS scores for rest pain showed a statistically significant decrease in the perceived rest pain value between the pretreatment visit and the follow-up visits (P < 0.0001 for both measurements). There was no statistically significant decrease in the intensity of rest pain (P = 0.5228) between the measurements at the first and second control visit.

TABLE 4 - Basic Statistics for Pain Intensity at Rest—Group of n = 103 Knee Joints

Parameter	n	Mean, Points	Median, Points	SD, Points	IQR, Points	Min, Points	Max, Points
Pain intensity at rest before treatment	103	3.16	3.00	2.55	0.00–5.00	0.00	9.00
Pain intensity at rest after treatment, first visit	103	0.86	0.00	1.57	0.00–2.00	0.00	7.00
Pain intensity at rest after treatment, second visit	103	0.46	0.00	1.05	0.00–0.00	0.00	5.00

The analysis of the results of perceived pain marked by patients on the VAS scale for pain while walking (Table 5) showed a statistically significant decrease in the value of perceived pain between the visit before the treatment and the follow-up visits (P < 0.0001 for both measurements). There was also statistically significant (P = 0, 0010) decrease in pain intensity during walking between the measurement at the first and second follow-up visits.

TABLE 5 - Basic Statistics for Pain Intensity While Walking—Group of n = 103 Knee Joints

Parameter	n	Mean, Points	Median, Points	SD, Points	IQR, Points		Min, Points	Max, Points
Pain intensity when walking, before treatment	103	5.70	6.00	2.08	5.00	7.00	0.00	10.00
Pain intensity during walking after treatment, first visit	103	3.80	4.00	2.14	2.00	5.00	0.00	9.00
Pain intensity during walking after treatment, second visit	103	2.82	3.00	2.25	1.00	4.00	0.00	9.00

DISCUSSION

There are only single studies that take into account the ultrasound evaluation of the knee joints before and after ⁹⁰Y treatment. According to the literature review in the field of response to treatment with RSV, estimates of a positive response to treatment range from 40% to 90%. This wide range is caused by different kinds of isotopes, joints, diseases, and methods. It caused the limitation in comparison with the results of this study with other described in articles.

In the group of 103 joints analyzed in this study, statistically significant decrease in the amount of fluid after the applied treatment was demonstrated. In publications using ultrasound measurements, Zalewska et al³ presented a statistically significant reduction in the amount of fluid in all the studied groups of patients: RA, spondyloarthritis (SpA), and osteoarthritis (OA), without specifying the number of patients and/or the percentage of people who had a reduction in the amount of fluid.³ Matryba et al,⁴ in the group of 56 different types of joints subjected to RSV, including 39 knee joints, classified the exudate on a 4-point scale based on ultrasound evaluation. Before the treatment, the inflammatory exudate was found in 47 cases, including 24 patients of moderate, 15 mild and 8 high degrees. In the posttreatment ultrasound examination (56 ± 21 days), the presence of exudate was found in 43 cases, including 21 patients to a moderate degree, 19 to a slight degree, and 3 to a high degree. These data concern the entire study group, without distinguishing the group of knee joints. It is therefore not possible to draw conclusions on the ultrasound assessment of fluid volume before and after ⁹⁰Y treatment of the knee joints.⁴ The work of Chatzopoulos et al,⁵ in which 97 knee joints were examined in patients diagnosed with osteoarthritis of the knee, is characterized by a fairly detailed description of the technique of ultrasound measurement of the amount of fluid in the suprapatellar recess. For evaluation after 6 months, 90 joints were included after the administration of ⁹⁰Y, of which a significant exudate before treatment, assessed by the authors of the study as fluid “thickness” exceeding 5 mm, was present in 21 joints (23.3%), and after 6 months from treatment, 16 (76%) joints experienced regression of exudate. It should be borne in mind that these were the joints that were treated for the first time. Moreover, Chatzopoulos et al⁵ distinguished in their work a group of 62 knee joints, which were checked twice: after 6 and 12 months. In this group, significant exudate was found in 13 cases, and exudate regression after 6 months in 9 (69.2%) of them.⁵ These results are similar to the efficacy of ⁹⁰Y treatment in terms of fluid reduction obtained in the described study. Some studies assess the response to treatment without isolating the issue of fluid reduction but treating it as a component of the assessed response to treatment together with, for example, pain reduction, which makes it impossible to draw unambiguous conclusions as to this aspect of treatment.⁴ There are also studies in which the issue of exudate reduction was omitted, so they do not constitute a source of knowledge on this subject.⁶ Ultrasound assessment of fluid in the knee joints also requires a detailed description of the methods of measuring parameters in scientific works (in the material and method), because, as Mandl et al⁷ points out, the measurements differ depending on the position of the lower limb during the examination. Mandl et al,⁷ analyzing 148 examined knee joints positioned in 6 different degrees of flexion, from 0 degrees to 90 degrees, concluded that a 30-degree flexion causes the most sensitive fluid detection.⁷

Synovial hypertrophy is currently a very popular topic among scientists trying to discover the pathomechanisms of joint diseases. These works cover a wide range of topics, including the detection of synovial hypertrophy in imaging studies (ultrasonography, magnetic resonance imaging), the relationship between synovial hypertrophy and pain, the effect of administered drugs on the thickness, and/or volume of the synovial membrane. However, there are only few publications on the ultrasound assessment of the synovium before and after treatment with ⁹⁰Y. In our study, synovial thickness reduction was observed in 100 knee joints, which is 97.09% of all knees included in the study. Zalewska et al³ indicated a statistically significant reduction in the thickness of the synovial membrane in all analyzed groups already 1 month after the intra-articular administration of ⁹⁰Y, but similarly to fluids, without the number of patients.³

There are divergent opinions in the literature regarding the advisability of accurate measurements of the synovium. Chatzopoulos et al⁵ considered such a measurement impractical due to the asymmetric thickness of the synovial membrane in the inflamed knee joint.⁵ In the article by Sarmanova et al,⁸ measurements of the amount of fluid and thickness of the synovial membrane on 3 sides of the suprapatellar recess were made, showing the relationship between pain experienced by the patient and the thickness of the synovial membrane.⁸ Similarly, Abbasi et al⁹ indicated a correlation between the ultrasound features of synovitis and pain assessment. These 2 publications are not directly connected with ⁹⁰Y treatment, but they support the advisability of precise measurements of the thickness of the synovial membrane in the context of searching for the cause of pain. This also applies to the explanation of the causes of failure of RSV therapy related to the initial significant thickness of the synovium and the relatively short range of radioisotope radiation.

Ultrasound examination is a valuable source of information on the location and degree of synovial thickening, but the limitations of this imaging method should be considered.

New possibilities of ultrasound assessment of the hypertrophy and the features of synovitis may be provided by the use of contrast agents, which are currently not widely used due to their very high cost.

The results of presented study demonstrated a statistically significant reduction in the level of knee joint disability after treatment with the ⁹⁰Y isotope. The difference was significant, especially after 3 months from injection. There was no statistically significant decrease in the level of disability (P = 0.2090) between the sum of points obtained in the Lequesne questionnaire at the first and second control visits. In the study by Dos Santos et al,¹⁰ the effectiveness of radiation synovectomy with ⁹⁰Y, the Lequesne disability assessment was used before treatment and at 1, 4, 12, 32, 48 weeks after treatment. Twenty-eight knee joints with a diagnosis of RA were examined. The average score before treatment was 17; after 4 weeks, the sum decreased to 11.7, and after 12 weeks, it was 12. It was noted that the degree of disability was reduced shortly after treatment. Later observations did not show such a significant improvement. Reducing disability is possible in knee joints in which the dominant role in pathogenesis can be attributed to chronic inflammation. The limitations most likely associated with mechanical damage to the joint can be eliminated only to a small extent.

Examination of a sample of 103 knee joints showed a statistically significant reduction in the intensity of rest pain in patients between the pretreatment visit and the follow-up visits. There was no statistically significant decrease in the intensity of rest pain (P = 0.5228) between the measurements at the first and second control visit. The analysis of the results of perceived pain marked by patients on the VAS scale for pain while walking showed a statistically significant decrease in the value of perceived pain (P < 0.0001 for both measurements) between the visit before the treatment and the follow-up visits. It was also statistically significant (P = 0.0010) decrease in pain intensity during walking between the measurement at the first and second follow-up visits. Bridgman et al¹¹ conducted a study by administering the isotope ⁹⁰Y to 22 knee joints and saline solution to 20 joints, which was the control group. In the 6-month follow-up, he did not show a statistically significant reduction in pain after the treatment with the ⁹⁰Y isotope. As emphasized by the author of this publication, the failure could have been caused by the too low dose of the administered isotope, amounting to 3 mCi.¹¹ In another study from the 1990s, Grant et al¹² pointed to the superiority of the analgesic effect of intra-articular corticosteroid during a 6-month observation compared with ⁹⁰Y during a 6-month observation. The observation period of patients was extended to 6 years, and the author, pointing to a large number of knees, which at that time required surgery to remove the hypertrophied synovium or arthroplasty, nevertheless included radioisotope treatment of the knee joints.¹² Liepe et al,¹³ analyzing the change in pain intensity in 68 knee joints treated with ⁹⁰Y, showed a statistically significant reduction of pain symptoms. After 6 months of observation, he demonstrated the superiority of isotope treatment, consisting in a longer-lasting analgesic effect, compared with the administration of corticosteroid.¹³ Miszczyk et al¹⁴ presented the results of a 6-month observation, according to which complete pain relief was observed in 37.5% of treated knees and partial pain relief also in 37.5%, which in total gives a pain reduction in 75% of treated knee joints. In a 6-month follow-up, Chatzopoulos et al⁵ showed a reduction in night pain in as many as 95% of joints in patients treated with ⁹⁰Y.⁵ Zalewska et al³ showed a statistically significant reduction of pain a month after the administration of ⁹⁰Y.³ Kim et al¹⁵ indicated a very good response in the reduction of pain in 67% of knee joints treated with ⁹⁰Y for RA. The results presented in the article on pain reduction are similar to the current publications.