The incidence of “anterior knee pain” is high and is located at 22/1,000 persons per year [12, 60]. Women are affected about more than twice as often as men [12, 29, 60]. The causes for anterior knee pain are multifactorial. These include overuse injuries of the extensor apparatus (tendonitis, insertional tendinosis), patellar instability, chondral and osteochondral damage .
The patellofemoral pain syndrome (PFPS) is a common cause for “anterior knee pain” and mainly affects young women without any structural changes such as increased Q-angle or significant pathological changes in articular cartilage [1, 12, 29, 52, 60]. Therefore, PFPS is a diagnosis of exclusion .
Other associated manifestations include crepitus and functional deficit . PFPS symptoms cause many athletes to limit their sportive activities . According to some authors, the PFPS will eventually lead to osteoarthritis [45, 64, 67].
The pathogenesis of PFPS is multifactorial with various functional disorders of the lower extremity to be involved .
Aim of this literature review is to summarize evidence regarding the underlying pathology of PFPS and the best way to treat this condition.
“Patella tracking” in patient with PFPS
The role of the patella maltracking for the emergence of the PFPS has long been a controversial issue.
Recent studies, however, show that maltracking of the patella probably plays a key role. Draper et al.  for example have demonstrated by dynamic MRI that patients with a PFPS squat with increased lateralization and increased lateral tilt of the patella. Witvrouw et al.  showed that a hypermobile patella had a significant correlation with the incidence of patellofemoral pain.
Wilson et al.  used skin marker and an optoelectronic motion capture system to examine gliding of the patella in patients with a PFPS in a standing position and while squatting. In this study, the patella of patients with PFPS had significantly increased lateral translation (maltracking), lateral patellar spin and a tendency towards increased lateral tilt compared to healthy subjects  (Fig. 1).
Role of M. vastus lateralis and M. vastus medialis
Pal et al.  have demonstrated that “patella maltracking” in patients with PFPS correlates with a delayed activation of the M. vastus medialis. An imbalance in the activation of the M. vastus medialis obliquus and M. vastus lateralis was also shown by Cowan et al. . In patients with a PFPS, the M. vastus lateralis was earlier activated than the M. vastus medialis obliquus when patients climbed downstairs and upstairs. In the control group that imbalance did not exist. These findings were supported by several other studies [15, 16, 74]. Patients with patellofemoral problems exhibited atrophy of the vastus medialis obliquus .
Despite these results, however, it is not clear whether the M. vastus lateralis and medialis imbalance are the primary cause for patellar maltracking.
Static or dynamic malalignment?
The role of the Q-angle (static measure) as predictor for PFPS is discussed controversially [39, 41, 45, 51, 59].
Some authors report that an increased Q-angle is associated with PFPS [39, 41]. For example, Rauh et al.  found that cross-country runners with increased Q-angle (>20°) are more prone to knee injury than athletes with normal Q-angle.
In contrast, Park et al.  have shown that the Q-angle is not increased in PFPS patients. Other reports also do not show strong correlations between static measures such as the Q-angle to the onset of PFPS .
That means that the cause for maltracking of the patella and the imbalance of the vastus medialis and lateralis in some patients with a PFPS may not be part of a structural fault (Fig. 2).
Rather a dynamic or functional malalignment is seen in these patients [21, 52].
Myer et al.  studied female middle and high school basketball players. In this study, athletes who developed a new PFPS demonstrated increased knee abduction moments of the symptomatic limb. That means there is a dynamic valgus position of the knee joint, which might be reinforced by an internal rotation of the femur and tibia (Fig. 2).
A dynamic valgus alignment is more frequently observed in female athletes compared to males [27, 28]. These biomechanical and neuromuscular mechanisms may be links to the pathogenesis of PFPS in young female athletes [35, 52, 56]. The functional or dynamic valgus may influence patella tracking leading to lateralization of the patella . Souza et al.  performed kinematic imaging of the patellofemoral joint using an open MRI to measure femur and patella rotation in PFPS patients. In this study, altered patellofemoral joint kinematics in females with PFPS was related to excessive medial rotation of the femur and lateral rotation of the patella .
The functional “malalignment” or dynamic valgus can be visualized clinically with one-legged squats (Fig. 3). Crossley et al.  have demonstrated that a valgus collapse of the knee joint during one-legged squat indicates weakness of the hip abductors.
Hip stability and hip abductor strength
Recent research has shown that functional malalignment does not arise in the knee joint but rather by internal rotation of the femur due to weakness of hip external rotators and abductors (M. gluteus medius and minimus) [2, 13, 14, 46, 57].
Padua et al.  found that decreased M. gluteus medius and M. gluteus maximus strength is related to increased knee valgus after landing a drop jump. Brent et al.  showed that females have decreased relative hip abduction strength in comparison with males. Decreased relative hip abduction strength has also been demonstrated in patients with PFPS [2, 13]. Bolgla et al.  showed that patients with a PFPS have a significant weakness of the external rotators of the hip. Baldon et al.  could also demonstrate that patients with PFPS have lower hip abduction strength.
All these studies are supported by a systematic review which demonstrated strong evidence that females with PFPS have a decreased hip abduction, external rotation and extension strength compared with healthy controls . This evidence does not exist for male PFPS patients.
Petersen et al.  have shown that the stability of the pelvis in PFPS patients can be checked clinically with the patient standing on one leg (Fig. 4). If the patient cannot stabilize the pelvis for 1-min standing on the affected leg, this is a sign of weakness of the hip muscles .
An internal rotation of the tibia can also be caused by rear-foot eversion [42, 52] (Figs. 2, 3).
A systematic review published by Barton et al.  has shown that patients with PFPS may have several disorders of the foot mechanics. These disorders include delayed timing of peak rear-foot eversion, increased rear-foot eversion at heel strike and reduced rear-foot eversion range .
In a recent study, these authors could show  a relationship between earlier rear-foot eversion and the emergence of PFPS. In another study, Barton et al.  could also show that increased peak rear-foot eversion was associated with increased peak internal rotation of the tibia in PFPS patients (Fig. 5).
Mølsgaard et al.  also could demonstrate abnormalities of the navicular bone in high school students with PFPS such as increased navicular drop, navicular drift and dorsiflexion.
Barton et al.  showed that PFPS patients have a more pronated foot type, increased forefoot abduction and increased rear-foot eversion in comparison with a healthy control group.
In conclusion, the literature provides evidence for rear-foot and forefoot abnormalities in PFPS patients.
Dynamic valgus may also have influence on the length of the iliotibial tract. Wu et al.  have shown that the iliotibial tract may also have an influence on patellar tracking. This may be anatomically explained by Kaplans fibres which connect the iliotibial tract with the patella. Other studies about the role of the iliotibial in PFPS patients are lacking.
Hamstring imbalance and tightness
There is some evidence in the literature that there is not only abnormal frontal plane knee motion in patients with PFPS.
Two studies identified a significant association between PFPS and hamstring tightness [47, 71]. These authors found significant hamstring tightness in patients relative to the control group. In another study, Patil et al.  showed by EMG that in patients with PFPS, the lateral hamstrings contracted earlier than the medial hamstrings during maximal arbitrary isometric contractions.
Besier et al.  have shown that patients with PFPS have greater co-contraction of the quadriceps and hamstrings compared to controls without symptoms of PFPS. In this study, females showed 30–50 % higher hamstring and gastrocnemius muscle forces during both walking and running compared to males. These authors concluded that by this mechanism, some PFPS patients might experience increased joint contact force and joint stress in comparison with healthy subjects.
All these changes can lead to high stress on the patella and its supporting structures.
“Knee-spine syndrome” 
Tsuji et al.  examined the correlation between patellofemoral joint pain, lumbar lordosis and sacral inclination, in elderly patients with anterior knee pain. There was a significant difference in sacral inclination between subjects with and without anterior knee pain . Inclination of the sacrum was less (app 5°) in patients with patellofemoral pain . This pathological concept was called the “knee-spine syndrome”.
For younger patients with PFPS, however, this mechanism has not been examined. More research is needed to elucidate the role of this mechanism for the pathogenesis of PFPS.
Psychological factors contributing to PFPS
The importance of psychological factors for the development of PFPS should not be underestimated [36, 37, 54, 55, 65].
Jensen et al.  have shown that pain and knee function can also be associated with psychological factors in some patients with long-lasting PFPS. These authors have shown that patients with PFPS have higher levels of mental distress in comparison with healthy subjects.
Thomee et al.  found that there are similarities regarding the pain experience and pain coping of PFPS patients to other groups of patients with chronic pain. In contrast to other chronic pain patients, higher scores were found on the Pain Catastrophizing Scale .
Piva et al. [36, 37] have identified a psychological predictor for pain and function in PFPS patients. This predictor was fear-avoidance belief about physical activity.
Domenech et al.  support the fear-avoidance model. This study demonstrated a high incidence of psychological distress such as anxiety and depression, pain catastrophizing and kinesophobia in PFPS patients. These factors were strong predictors of pain and disability in PFPS patients.
In some cases, the knee problems can be triggered by secondary disease profit . This may play a role in young competitive athletes, who are no longer capable of the increasing demands. The knee problems then may serve as an explanation for the stagnation or reduced performance .
Trigger for the PFPS
Figure 6 summarizes a possible pathogenesis for the patellofemoral pain syndrome based on findings from the literature.
A possible trigger for the patellofemoral pain syndrome may be overload of the patellofemoral joint (e.g. high-intensity training). The combination of overload with dynamic valgus and functional lateralization of the patella may lead to overuse of the structures of the patellofemoral joint . This overload may cause anterior knee pain.
Anterior knee pain can be a vicious cycle. By anterior knee pain, the muscle activity of the lower extremity may be further inhibited.
Neurophysiological cause of pain in patients with PFPS
The exact cause of pain in patients with PFPS is unclear. Most probably the pain develops in the insertions of the extensor mechanism or within the subchondral bone .
Woitys et al.  observed substance P rich free nerve endings within the retinacula, Hoffa’s fad pad and subchondral bone.
Sanchis-Alfonso and Roselló-Sastre  observed a high expression of several neural markers such as neurofilament protein, S-100 protein, neural growth factor and substance P in the lateral retinacula of patients with patellofemoral maltracking. This study demonstrates that the innervation of the retinacula may play a role for the development of anterior knee pain. Sanchis-Alfonso  hypothesized that Sustance P and NGF expression may be related to mechanical stress within the retinacula. Patellar maltracking might be the cause for this abnormal stress .
In an experimental arthroscopy with local skin anaesthesia, S. Dye experienced strong pain when then probe touched the retinacula, Hoffas fad pad or the peripatella synovium .
However, there is additional evidence that the subchondral bone may also play a role for the origin of pain in PFPS patients. Draper et al.  have demonstrated increased metabolic bone activity in patients with PFPS using F NaF PET/CT.
Rathleff et al.  have shown that not only peripheral but also central mechanisms may cause pain in patients with PFPS. At the knee, adolescents with PFPS had a significantly lower pressure pain thresholds (localized hyperalgesia) compared with controls. On the tibialis anterior, however, adolescents with PFPS had also a lower pressure pain thresholds (distal hyperalgesia) compared with controls. Jensen et al.  could demonstrate an aberrant sensory function in PFPS patients. The mean detection threshold for temperature was significantly increased in PFPS patients compared to healthy controls.