Treatment of patellofemoral chondropathy with BIOART

The patella is a sesamoid bone, roughly triangular in shape, placed inside the quadriceps muscle tendon. This bone, articulating with the trochlear groove of the femur, mechanically constitutes the fulcrum of extensor mechanisms of the lower limb. Both the articular surfaces of the patella itself and those of the trochlear sulcus are covered by an articular cartilage that is on average 4 to 6 mm thick [1,2]. The normal sliding mechanisms of the patellofemoral joint are controlled by static factors, i.e. non-contractile and dynamic, i.e. contractile. Static factors are represented by the patella size, femoral condyles and their size, the shape/angle of the trochlear sulcus and the alignment of the lower limb [3-6].


Introduction
The patella is a sesamoid bone, roughly triangular in shape, placed inside the quadriceps muscle tendon. This bone, articulating with the trochlear groove of the femur, mechanically constitutes the fulcrum of extensor mechanisms of the lower limb. Both the articular surfaces of the patella itself and those of the trochlear sulcus are covered by an articular cartilage that is on average 4 to 6 mm thick [1,2].
The normal sliding mechanisms of the patellofemoral joint are controlled by static factors, i.e. non-contractile and dynamic, i.e. contractile. Static factors are represented by the patella size, femoral condyles and their size, the shape/angle of the trochlear sulcus and the alignment of the lower limb [3][4][5][6].
The patellofemoral syndrome is characterized by a set of morpho-functional alterations that determine the onset of an anterior knee. These functional alterations of the anatomical structures above and below, such as axial or rotational changes of the lower limb, or the morpho-functional alterations of the foot, can negatively infl uence the mechanics of the patellofemoral joint [6][7][8][9][10][11][12]. From an etiopathological point of view, the basis of the patellofemoral syndrome are alterations essentially attributable to a malalignment, or to a dysplasia of the patella and/or femoral trochlea [6][7][8][9][10][11][12][13][14][15][16]. In the fi eld of patellofemoral syndrome, joint biomechanics plays a fundamental role. In fact, an abnormality of shape and/or position of the patella itself, has a direct relapse on its functionality, determining an altered sliding in the trochlear groove. A bad patellar sliding can lead to a cartilaginous alteration commonly referred to as "chondrosis" or "arthrosis", whose etiology is due to the action of compressive forces not adequately distributed over the entire surface of the patellofemoral joint itself. In particular, an increase in the amplitude of the fl exion movements of the knee, which is found in many recreational-sports activities, increases the extent of compression forces at the patellofemoral level, and can cause an alteration of the articular surface, which can be found also in young individuals [15][16][17][18][19]. In 1964, Outerbridge had classifi ed the articular cartilage lesions according to four different degrees: I degree characterized by softening and swelling less than 1⁄2 inch (1.27 cm), II degree with fragmentation and fi ssuring minor than 1⁄2inch, III degree with fragmentation and fi ssure greater than 1⁄2 inch 1.5 cm, IV, the most serious, III degree with erosion of the cartilage in the direction of the subchondral bone.
From a clinical point of view, the patellofemoral syndrome is characterized by constant pain in the anterior part of the knee joint. Sometimes an antalgic pseudo-articular block may occur, but the amplitude of movement is however in most reduced. An important hypotonotrophy of the quadriceps muscle is often associated to this syndrome. In the process of chronicity, soft joint structures (such as the patellar tendon, the suprapatellar, prepatellar and anserine bag, the medial and lateral retinacula, the medial, lateral and superior folds, the saphenous nerve at the tubercle) can be involved of the adductors or tendon of the goose leg. At a clinical examination, pain is evoked requiring an isometric contraction, against resistance, in a range between 0 and 20 ° of fl exion. Conventional radiography, carried out in different angles of knee fl exion and especially MRI, confi rm the clinical diagnosis [6][7][8][9][10][11][12][13][14][15][16][17][18].
The treatment of patellofemoral condropathy is mostly conservative. In addition to careful functional re-education, the use of chondroprotectors may be useful. Under this term medicines and supplements are grouped as substances able to counteract the degenerative processes, favoring the normalization of the articular cartilage and the synovial fl uid in which it is immersed and from which it draws nourishment and protection. More specifi cally, chondroprotectors are compounds capable of expressing one or more of the following characteristics: stimulating chondrocytes in the production of new cartilaginous matrix, stimulating synoviocytes in the synthesis of hyaluronic acid, inhibiting cartilage degradation by chondrolytic enzymes and preventing fi brin formation in the subchondral and synovial vasculature [19]. Among the most studied and used chondroprotectors are listed hyaluronic acid, glucosamine, chondroitin sulfate (galactosaminglucuronoglycan sulfate), hydrolyzed collagen, methylsulfonylmethane (MSM). In particular, the infi ltrations of hyaluronic acid are used in the conservative treatment of patellofemoral chondropathies. This technique, tested for the fi rst time in the early 1970s, involves intra-articular injection of sodium hyaluronate. Since then, international studies and extensive case studies have confi rmed the effectiveness of infi ltration of hyaluronic acid, especially in the treatment of condrophaty. Intra-articular injection of hyaluronic acid is also known as viscos-supplementation, referring to the viscoselastic properties of this substance. Not all the studies agree on the effi cacy of hyaluronic acid infi ltration in conservative treatment: some meta-analyses have even shown effi cacy only slightly higher than with placebo. Other studies have established that the infi ltration of hyaluronic acid produces a pain reduction comparable to that of intra-articular injections of cortisone [20].
These fi nding s highlight the need of further investigations to treat the patellofemoral chondropathies.
The aim of the study is to evaluate the effi cacy and tolerability of the medical device "Bioart" in patients with gonarthrosis.   (Table 1) and the Lequesne Index for functional limitations were used.

Study population
WOMAC is probably the most commonly used test utilised to assess the results of treatment for knee conditions. Each WOMAC item has 5 potential responses (from "none" to "very great"). The Lequesne Index assigns a score to each answer up to a total that is recorded and represents the reference value for the subsequent assessment. These evaluations are performed before the start of treatment and at 12 weeks. Lawrence). No proprioception tests investigating the articular function were performed on patients before or after the treatment.

Patients treatment
The patients enrolled in the study did not report any previous knee surgery or previous or current documented rheumatic or autoimmune diseases.
Before the start of treatment, all patients underwent an orthopedic examination. Post-treatment joint status (3 months) was assessed by ultrasound and magnetic resonance imaging. Moreover, during the treatment, patients did not undergo any rehabilitation protocols.
Having arranged the patient in a supine position, with the knee involved slightly fl exed using a popliteal pillow and after thorough disinfection of the skin (alcohol or iodinebased antiseptic), 200 mg of Bioart mixed with physiological solution were injected into the affected joint. In patients with I degree chondropathy, the intraarticular injection of Bioart was repeated twice a week. In patients with II and III degree chondropathy, the intra-articular injection was repeated three times a week apart.

Statistical analysis
The sample size was calculated on the basis of the 95% Confi dence Interval (CI) precision of the primary outcome. More specifi cally, 20 patients were required to obtain an estimate precision of 0.11 of the estimated standard deviation, considering the absence of information on the outcome. The results are expressed as mean ± Standard Deviation (SD). Data were tested for normality using the Kolmogorov-Smirnov test. Differences between before and after treatment for the whole population were evaluated using the paired t-test. When the assumptions for parametric test were not met, Wilcoxon signed-rank test was used. Differences are considered signifi cant at a p value of <0.05.

Results
Twenty-three patients out of 25 completed the planned treatment period. None of the subjects had an adverse reaction to Bioart. All of them showed excellent tolerance of the treatment.
As mentioned above, the WOMAC pain rating scale at baseline revealed a higher score in patients with grade II (44.4±9.7) and grade III (52.3±9.1) chondropathy, compared to those with grade I chondropathy (29.4±5.7, p<0.001). At the end of the cycle of infi ltrations, all patients showed a signifi cant reduction in WOMAC score (Figure 1), regardless of their age, gender and initial chondropathy grade. The average pretreatment score was 44.4±9.8 (min 22, max 60) and the average post-treatment score was 25.7±9.0 (min 12, max 47) ( Figure   2). The difference between before and after the infi ltration All patients underwent a physical examination to establish whether they met the criteria for patellofemoral chondropathy, according to the Kellgren-Lawrence Scale. At inclusion, each patient presented recent radiographic images of the affected joint/s.This material was graded using the Kellgren and Lawrence system. As regards the Lequesne pain and dysfunction index, no signifi cant difference was observed between the different grades of chondropathy at baseline (grade I 17.4±2.0, grade II 18.5±1.1, grade III 19.2±.0.8, p=ns). After treatment, all patients showed a score improvement, regardless of their gender, age or chondropathy grade. On average patients went from 18.0±1.1 to 10±1.2 points (p<0.001) (Figure 4). Already at follow-up after 12 weeks, 7 patients (30%) showed a partial regression of chondropathy on MRI. A representative image of MRI before and after treatment is shown in Figure 5.

Discussion
The conservative treatment of patellofemoral condropathy has a well-documented background in the scientifi c literature of the last fi fty years. The use of NSAIDs, cortisone drugs and chondroprotectors is common in conventional medicine.
The mechanism of action of corticosteroids is well established: inhibition of prostaglandin synthesis, reduction   Recent studies have instead seen the use of platelet-rich plasma [24], which occurred effectively in the treatment of the syndrome.
The aim of our study was to verify the effi cacy of Bioart, a device based on native equine collagen.