Osteoarthritis (OA) of the knee (gonarthrosis) is a degenerative progressing joint disease involving loss of articular cartilage [1].

About 13% of women and 10% of men aged 60 and above suffer from symptomatic knee OA. After 70, the prevalence of this pathology increases to 40%. Disregarding age as a factor, the frequency of symptomatic gonarthrosis is approximately 240 cases per 100,000 people per year [2].

Gonarthrosis is a progressive disease; as a rule, the specifics of its pathogenesis lead to a disability.

The causes of damage to the cartilage associated with osteoarthritis are not fully understood, but may stem from constitutional and genetic factors, trauma, overload disease, etc. Recently, pathological changes in the subchondral bone — ischemia and local necrosis — have been receiving increasing attention as the disease's pathogenetic factors [3]. A history of knee injuries is also considered to be an important aspect [4].

Physical activity restrictions, pain and discomfort associated with movements undermine patients' daily routines and social life, which degrades their quality of life (QOL) [5].

In this connection, investigation of methods of treatment of knee OA is considered to be an important task. With varying efficacy, conservative approaches aim to eliminate clinical manifestations (pain) and partially improve the joint's functional state [6]. However, the respective therapeutic strategies have no effect on the OA pathogenesis and do not help to improve the patients' QOL.

Contemporary orthopedics sees promise in the development and introduction of the new OA treatment techniques that would not only address clinical symptoms but also prevent progression of the pathological process. Injections of platelet-rich plasma (PRP) is one of such techniques [7, 8]. The effects of PRP mainly depend on the platelet secretion products. In addition to organelles, platelet cytoplasm contains many granules carrying over 300 different biologically active substances. There are three types of platelet secretory granules: dense granules (or γ-granules), α-granules and lysosomes. The latter are commonly represented by various enzymes (acid hydrolases). Dense granules contain catecholamines, serotonin, ADP, ATP and calcium, which are involved in the activation of the coagulation cascade. Driven by the growth factors, fibroblasts, endothelial cells and epithelial cells migrate to the injury and multiply there. Subsequently, there forms an extracellular matrix, new vessels grow, and connective tissue matures and remodels. Mediators of α-granules HGF, TNFa, TGFß1, VEGF and EGF deliver the anti-inflammatory effect, and attenuation of inflammation also has an analgesic effect [9–12].

The prupose of this study is to analyze the results of intraarticular and intraosseous administration of platelet-rich plasma (PRP) in knee OA cases.

METHODS

From 2018 through 2022, we examined and treated 187 patients with knee OA, stages 1 through 3 (ages 40 through 70), and subsequently monitored the dynamics of the symptoms and signs of the disease. This part of the study was conducted at the premises of the N. I. Pirogov State Clinical Hospital #1, Moscow, and the Republican Clinical Hospital, Makhachkala (Republic of Dagestan).

The knee OA diagnosis was verified under the applicable regulations [13–15].

The inclusion criteria were: age from 40 to 70 years; knee AO confirmed by radiographic examination; disease stage 1 through 3 under Kellgren classification; walking-associated pain intensity ≥40 mm on the visual analog scale (VAS) over the past 2 weeks; no intake of systemic chondroprotectors and/or cartilage regeneration stimulating drugs within 2 months before the study; no intake of nonsteroidal anti-inflammatory drugs (NSAIDs) for 2 weeks before the study; voluntary consent to participate in the study and adequately cooperate in its context.

The exclusion criteria were: age under 40 and over 70; refusal to participate in the study and/or sign the informed consent form; walking-associated pain intensity <40 mm on VAS; stage 4 damage under Kellgren classification; surgical treatment of gonarthrosis during the previous 6 months; pronounced deformity of the knee joint; exacerbation lasting more than a month; pregnancy and/or lactation; serious or unstable somatic diseases (severe diseases of the liver, cardiovascular system, lungs or kidney, oncological, mental diseases), decompensated diabetes mellitus; intake of tissue regeneration drugs, systemic chondroprotectors withing 2 months before the study; intake of NSAIDs within 2 weeks before the study.

Depending on the technique applied, the patients were divided into three groups. Treatment group (group 1) included 73 patients, 21 male and 52 female, mean age 57.4 ± 2.87 years; they received intraarticular injections of PRP. Comparison group (group 2) included 48 patients, 15 male and 33 female, mean age 56.9 ± 2.85 years; the received intraosseous injections of PRP. Control group (group 3) consisted of 66 people, 21 male and 45 female, means age 57.1 ± 2.86 years; their treatment plan included NSAIDs, a course of chondroprotectors, and a course of glucorticoids administared intraarticularly. In group 1, autologous PRP was injected intraarticularly in a single course, three injections once a week, once a year; in group 2, PRP was injected intraosseously, two injections every two weeks, once a year.

In all groups, the most common stage was 2nd: 37 (50.7%) patients in group 1, 22 patients (45.8%) in group 2, and in 27 (40.9%) patients in the control group. We found no statistically significant intergroup differences in the frequency stage-wise OA diagnosis within the sample.

All patients underwent a comprehensive examination, which included registration of complaints, study of the medical and life history, physical examination and analysis of the objective signs of joint pathology, and assessment of the severity of damage.

Radiography, ultrasonography, and magnetic resonance imaging (MRI) were also parts of the comprehensive primary examination.

The intensity of pain was recorded with the help of the visual analog scale (VAS), and QOL indicators registered with a non-specific SF-36 survey (before treatment, three and six months thereafter).

Statsoft's STATISTICA 10 and Microsoft Excel 2016 (USA) were used for statistical data analysis.

In case of normal distribution of indicators, we applied the Student's test to compare groups, and used the Mann– Whitney test when distribution was nonparametric. Normality of distribution was assessed with the help of the Shapiro-Wilk test. The null hypothesis (α) was considered significant at p = 0.05 (all intergroup comparisons).

RESULTS

Figure fig. 1 shows the initial pain intensity dynamics after over 30 minutes of rest.

These data indicate that before the treatment, all patients (100%) experienced pain after resting for more than 30 minutes.

Three months after treatment, in groups 1 and 2, initial pain after over 30 minutes of rest decreased to 64.4 and 47.90%, respectively, from 100%.

After six and twelve months, the intensity of pain in the treatment group increased to 72.60 and 79.50%, respectively, that in the comparison group — to 62.50 and 68.80%, respectively.

In the control group, the dynamics of the initial pain was not significant; it amounted to 92.40% after three months, 93.90% after six months, and 97.0% after twelve months.

Figure fig. 2 shows the dynamics of indicators of morning joint stiffness in the entire sample.

Compared to the control group, both group 1 and group 2 exhibited a significant decrease in the number of complaints about morning joint stiffness.

Table table presents the knee OA parameters as registered with ultrasonography.

It should be noted that before treatment, the prevalence of synovitis, soft tissue edema, osteophytes, and subchondral sclerosis was comparable between the groups. In the treatment group, the differences in the prevalence of synovitis became significant (compared to baseline) after three months (27.4%); in the treatment and comparison groups — after six months (21.9 and 31.3%, respectively). As for the prevalence of swelling around the joint, the differences in prevalence thereof became significant after 6 months (treatment and comparison groups, 8.2 and 8.3%, respectively). After 12 months, the differences registered between groups have lost significance, but the lowest values were recorded (ultrasonography) in the treatment group.

Figures fig. 3 and fig. 4 show the results of a comparative analysis of physical and mental components of QOL, as registered with the SF-36 survey; time points — before treatment, 3 and 6 months after treatment.

With treatment in the background, groups 1 and 2 exhibited significant positive dynamics: groups 1 after three months (70.40%), group 2 after six months (69.80%).

Six months after treatment, values of the indicators were above baseline in both group 1 and group 2, with group 2 performing better. In control group, the physical component of QOL, according to the SF-36 survey, did not change throughout the study (51.20% — before treatment; 53.50% — after 3 months; 54.0% — after 6 months).

As registered with the SF-36, against the background of treatment, both group 1 and group 2 have shown positive dynamics of the mental component of QOL after 3 months (64.30 and 65.10%, respectively), and after 6 months (65.10% and 66.40%, respectively). In control group, the situation remained largely unchanged (42.20% before treatment, 44.30% after 3 months, and 44.60% after 6 months).

Figure fig. 5 shows pain intensity as recorded with the help of VAS.

Against the background of treatment, groups 1 and 2 exhibited significant (p < 0.05) positive dynamics after 3 and 6 months; after 3 months, the values were better in group 1 (2.80 ± 0.14 and 3.90 ± 0.19, respectively), and after 6 months — in group 2 (3.40 ± 0.17 and 3.0 ± 0.15, respectively). In the control group, therapy failed to relief the pain, and the values remained on the same level throughout the study (before treatment — 6.0 ± 0.3; after 3 months — 5.60 ± 0.28; after 6 months — 5.80 ± 0.29; after 12 months — 5.90 ± 0.30).

DISCUSSION

Knee OA is a pathology that grows more prevalent as the life expectancy of the population increases. This diseases poses a significant social, economic and medical problem, the solution of which should employ non-pharmacological, pharmacological, and surgical methods of treatment at different stages. Surgery, in the form of partial or complete knee replacement, is most often resorted to at late stages of knee OA [16–17]. Regenerative approaches, such as those involving PRP and cell therapy, aim to expand the therapeutic arsenal to prevent or delay surgery. While cell therapy is still in its infancy and has to overcome a number of problems, PRP has been used for more than 15 years, and there is a consolidated position about it in the context of treatment of this disease. An increasing number of randomized clinical trials are being conducted to obtain convincing conclusions about the effectiveness and safety of PRP. Despite the fact that intraarticular injection of PRP as knee OA treatment shows promising results, this method, according to a number of authors, affects only the articular cartilage and the synovial membrane, without affecting the subchondral bone. Intraosseous injections to the subchondral bone can make the protocol more comprehensive [18, 19].

Currently, clinical studies of intraosseous administration of PRP in treatment of knee OA are in the early stages. The rationale for this method largely depends on the growing knowledge about the role of the bone-cartilaginous functional unit in the development of knee OA, as well as on growth of the number of preclinical studies and intraosseous methods of treatment of other bone pathologies [20, 21]. Further research is needed in this area to better understand cellular processes underlying the mechanism of action and to plan further pathways of intraosseous injections.

CONCLUSIONS

Compared to standard therapy, which relies on NSAIDs, chondroprotectors, and intraarticular administration of glucocorticoids, administration of PRP in OA cases yields significantly better results in terms of pain intensity and QOL parameters. Intraosseous injection of PRP allows achieving significantly better results in terms of clinical symptoms and physical component of the patients' QOL.