Advance in Etiology and Rehabilitation Treatment of Patellofemoral Pain (Review)

Patellofemoral pain (PFP) is the most common chronic musculoskeletal disease seen in sports medicine clinics. The pathogenesis of PFP is not yet clear, but there have been many biomechanical and pathophysiological studies related to PFP. These studies have further improved the understanding of PFP and aided in its treatment. Due to the high prevalence, long course and difficulty in eradicating PFP, most treatment options to date still aim to improve symptoms and have not resulted in an effective treatment approach. Reasonable rehabilitation therapy can relieve pain, improve motor function and help patients regain confidence in life and work. Therefore, further research into the pathogenesis of PFP and the search for a set of standardized and effective rehabilitation methods for PFP are particularly important in the future.


Introduction
Patellofemoral pain (PFP) is a diffuse pain that occurs in the peripatellar or retropatellar region and can be triggered or exacerbated by weight-bearing knee flexion activities (squatting, climbing stairs, running or jumping) (Crossley et al. 2016). In recent years, with the construction of a "Healthy China" and the "National Fitness" boom, running has become increasingly popular, and marathons have become an important way for the general public to actively participate in exercise. While running can improve cardiorespiratory fitness, it can also increase the risk of musculoskeletal injury, with PFP being the most common form of injury. The latest research shows that the prevalence of PFP is as high as 20% in young adults in China (Xu et al. 2018). PFP is one of the more difficult musculoskeletal disorders to treat today, with a lack of effective treatment and medication that provides only short-term relief of pain and eventually progresses to patellofemoral arthritis, which inevitably requires surgery. PFP not only places a significant financial burden on society, but also has a significant impact on patients' quality of life and psychological well-being, as well as the potential for disability, if not treated promptly and effectively. Therefore, it is important to provide long-term rehabilitation exercises to reduce complications. The present review of the etiology of PFP and the latest advances in rehabilitation treatment is intended to provide new ideas and approaches for future research and treatment options.

New Insights into the Etiology of PFP Abnormal Patellofemoral Trajectory
The more positive the trajectory of the patella in the femoral trochlea, the greater the contact area of the patellofemoral joint, the more evenly the stresses are distributed, and the lower the stresses on the patellofemoral joint surface. When the patellar trajectory is abnormal, the contact area between the patellar surface and the femoral trochlea decreases and the stress on the patellofemoral joint surface increases accordingly, resulting in PFP when the stress exceeds the maximum range that the patellofemoral joint can withstand (Liao et al. 2018). Wilson (Wilson et al. 2009) system examined the patellar trajectory of young PFP patients during standing and squatting and found that the patella was significantly more laterally deflected, rotated and had a tendency to increase lateral tilt in PFP patients compared to healthy controls, with poor patellar trajectory most evident when squatting while bearing weight. Similarly, a systematic review that included 40 studies noted that increased lateral patellar displacement on MRI, increased patellar tilt angle, and other indicators of abnormal patellar trajectory were associated with PFP (Macri et al. 2016). In addition, other studies have found that greater patellar tilt is associated with greater pain and that abnormal patellofemoral trajectory leads to progression of patellofemoral arthritis (Hunter et al. 2007). Specifically, lateral displacement is strongly associated with the development of lateral patellofemoral arthritis, whereas medial displacement accelerates the progression of medial patellofemoral arthritis. Of course, most of the current studies are observational and the causal relationship between abnormal patellofemoral trajectory and PFP still needs further investigation.

Muscle Function Abnormalities Muscle Strength Abnormalities
A recent Meta-analysis identified quadriceps weakness as an independent risk factor for PFP (Neal et al. 2019 conducted a year-long prospective study of 629 novice runners and found no clear correlation between hip strength and the development of PFP at running distances below 50km, but stronger hip abduction strength at running distances above 50km reduced the probability of PFP However, stronger hip abduction strength at running distances above 50km reduced the probability of PFP. In view of this, further high-quality studies are needed to explore the specific relationship between hip muscular strength and PFP and the mechanisms involved.

Reduced Muscle Flexibility
Reduced lower limb flexibility can also lead to abnormal patellar trajectories, and White et al (White et al. 2009) compared lower limb muscle tone in patients with PFP and normal controls with passive knee extension and found that lower limb muscle tone was significantly higher in patients with PFP than in normal controls. However, this cross-sectional study did not confirm a causal relationship between muscle flexibility and PFP. Subsequently, Whyte et al (Whyte et al. 2010) investigated the relationship between patellofemoral joint stress and lower limb muscle flexibility during weight-bearing activities and found that muscle tension around the knee joint led to a reduction in patellofemoral joint contact area and an increase in patellofemoral joint stress, which led to the This change was particularly evident in knee flexion at 60°. In an in vitro study, hamstring tension was found to increase patellar flexion, valgus, and valgus by approximately 1°, 0.5°, and 0.2 mm, respectively, and to increase total lateral patellar stress by approximately 5% during knee flexion and extension activities, resulting in abnormal patellar trajectories (Elias et al. 2011

Advances in Rehabilitation Treatment for PFP Exercise Therapy
The 4th edition of the International Association for the Study of PFP Expert Consensus states that exercise therapy can not only reduce pain in patients with PFP in the short term, but can also improve joint function in the medium to long term (Collins et al. 2018). The main targets of exercise therapy include the core muscles, hip muscles and knee muscles, but specific exercise prescriptions remain controversial. Firstly, the optimal frequency of exercise remains unclear. Most current prescriptions instruct patients with PFP to perform functional exercise for 4-6 weeks, 2-4 times per week. chevidikunnan et al (Chevidikunnan et al. 2016) performed core muscle strengthening exercises 3 times per week for 4 weeks in patients with PFP and found significant improvements in symptoms and function in patients with PFP. Meanwhile, Hamstra et al (Hamstra-Wright et al. 2017) instructed 157 patients with PFP in hip and knee strengthening training for 6 weeks, 6 times per week, and found significant improvements in symptoms, function, and core strength before and after rehabilitation, and a relapse rate of only 5% over 2 years. Further research is still needed to determine whether the rehabilitation effect will improve further with increased exercise frequency. Secondly, the choice of exercise modality remains controversial. Although international guidelines clearly suggest that combined hip and knee exercises are superior to knee exercises alone (Collins et al. 2018). However, Hott et al (Hott et al. 2019) instructed 112 young patients with PFP to perform hip exercise, knee exercise and free exercise respectively, with a 3-month follow-up, and found that symptoms and function improved in all 3 groups compared to pre-exercise, and that there were no significant differences between the 3 groups. In addition, a recent Meta-analysis showed that when performing exercise rehabilitation, starting exercises with the proximal muscles resulted in greater pain reduction and improved function (Lack et al. 2015). In light of this, exercise therapy should target core muscles such as the rectus abdominis, muscles of hip abduction and external rotation, quadriceps and hamstrings, but specific exercise prescription choices need to be further validated and individualised differences fully considered.

Gait Retraining
Gait retraining is primarily indicated for patients who have developed PFP as a result of prolonged running. The International Association for the Study of PFP expert consensus states that abnormal gait in the coronal, sagittal and horizontal planes in runners often leads to poor patellar trajectory, increased patellofemoral joint stress and ultimately patellofemoral joint pain (Powers et al. 2017). Therefore, correcting the gait of runners is extremely important to prevent and treat PFP. For example, Roper et al. (Roper et al. 2016) found that instructing runners with PFP to change their running posture from rearfoot to forefoot significantly improved hip and knee mobility and improved knee pain symptoms. Similarly, Bramah et al. (Bramah et al. 2019) instructed patients with PFP to increase their stride frequency by 10% while running and observed significant increases in weekly running volume, maximum pain-free running distance, and significant improvements in pain and function in PFP runners at 4-week and 3-month follow-ups. In addition, Santos et al (Dos Santos et al. 2019) investigated the effects of three gait retraining modalities (forefoot landing, a 10% increase in stride frequency, and trunk tilt) on lower limb biomechanics and clinical symptoms in PFP runners and found that all three modalities had some clinical efficacy and all improved pain and function in PFP runners. However, incorrect running posture can cause considerable damage to the musculoskeletal system and consciously training one's gait can be effective in reducing patellofemoral joint stress and preventing PFP.

Patellar Patches
The Chinese Guidelines for the Treatment of Patellofemoral Arthritis (2020 Edition) state that patellar patches are effective in correcting patellar malposition, reducing patellofemoral joint stress and relieving painful symptoms. mechanical rearrangement in order to reduce pain and improve function in patients with PFP (McConnell et al. 2000). Kenzo then designed the Kinesio patellar patch, based on the classic patellar patch, to apply 10-15% tension towards the patella at the start of the quadriceps and hamstrings, with the aim of correcting poor patellar trajectory and relieving muscle tension (Akbaş et al. 2011). A systematic evaluation including 11 studies found that both patellar patches positively affected pain and quality of life in patients with PFP, however, the Kinesio patellar patch increased muscle flexibility while relieving pain and improving poor patellar trajectory (Chang et al. 2015).
Although, the patellar patch is unanimously recommended by many national and international expert consensus and practice guidelines (Powers et al. 2017; . However, the exact mechanism of action is unclear, while the follow-up period for patella patches is mostly short, and their safety and efficacy for long-term use have not been established. However, the patellar patch can be used in conjunction with other rehabilitation project and does not hinder training or competition during its use, so its use in the rehabilitation project of athlete patients can be attempted.

Foot Orthoses and Special Insoles
Structural abnormalities of the foot can lead to dynamic valgus and ultimately to PFP (Barton et al. 2010;Mølgaard et al. 2011;Luz et al. 2018). Matthews et al (Matthews et al. 2020) randomized 192 patients with PFP into a foot orthosis group and a hip muscle exercise group and found no significant difference in rehabilitation outcomes between the two at 12 weeks of follow-up, confirming that wearing foot orthoses and exercise therapy The results were equally effective. A systematic evaluation that included 11 clinical studies showed that foot orthoses can reduce pain and improve function in the short as well as the long term, but foot orthoses have only a slight effect on lower limb kinematics and muscle activation, and the relationship between the biomechanical effects of orthoses and pain remains unclear (Ahlhelm et al. 2015). In addition, a comparison of the effects of flat shoes and foot orthoses found that although wearing a foot orthosis for 6 weeks improved pain in patients with PFP, there was no significant difference in rehabilitation outcomes between the two at one year follow-up and there were more adverse effects such as chafing and blistering in the foot orthosis group (Hossain et al. 2011). It is worth noting that foot orthoses combined with foot-targeted exercise methods can achieve better results than knee exercise therapy alone (Mølgaard et al. 2018). This suggests that some patients with foot deformities such as valgus and pronator augmentation are more likely to benefit from foot orthoses and special insoles, and that the choice to wear foot orthoses or special insoles should be combined with other rehabilitation therapies.

Electrical stimulation
Theoretically, electrical stimulation can be used as an alternative to exercise therapy to increase muscle contraction and reduce pain. For this reason, electrical stimulation is often used as a complementary therapy to the rehabilitation of patients with PFP. Currently, the two main types of electrical stimulation include neuromuscular electrical stimulation and transcutaneous electrical nerve stimulation, both of which have been shown to be reliable and effective. Studies have shown that 15 min of electrical neuromuscular stimulation improves activation of the gluteus medius during activity and relieves pain symptoms in patients with PFP (Glaviano et al. 2016). Similarly, Son et al (Son et al. 2017) found that transcutaneous electrical stimulation was not only effective in reducing knee pain in subjects, but also in improving pain-induced gait abnormalities. In addition, Talbot et al. (Talbot et al. 2020) found that exercise therapy combined with electrical stimulation significantly increased knee mobility, but there was no significant difference in the effectiveness of the different electrical stimulation treatments. In contrast, most of the current clinical studies on electrical stimulation therapy for PFP are small trials with short follow-up periods and cannot confirm the exact role of electrical stimulation therapy in the rehabilitation of PFP (Martimbianco et al. 2017). Further research is still needed to analyze its therapeutic mechanisms and to standardize optimal treatment protocols.

Conclusion
PFP is one of the most common chronic conditions seen in sports medicine clinics, and is increasingly valued by clinicians and rehabilitation physicians both nationally and internationally, as it is mainly characterized by anterior knee pain during weight-bearing knee flexion activities. Currently, guidelines and expert consensus on PFP are being updated and many rehabilitation therapies are being used with good results in clinical practice. Unfortunately, there have been no breakthroughs in the management of PFP, and thousands of patients are or will be suffering from pain. To change this situation, future research should focus on identifying risk factors, testing effective prevention and treatment measures, developing educational strategies, assessing the impact of psychosocial factors, evaluating the effectiveness of exercise in training, and improving clinicians' assessment skills.