In 2011, Zbojniewicz and Laor described a focal area of bone marrow edema around the closing physis and termed the pathology a focal periphyseal edema (FOPE) zone1. Since then radiologic studies and case reports have confirmed the presence of this pathology and described it as a possible source of joint pain2-7. Plain radiographic images are usually negative. Magnetic resonance imaging (MRI) findings show an area of T1 hypointense and T2 hyperintense marrow edema in the center of the physis, extending into the adjacent metaphysis and epiphysis2,7. The etiology is believed to be due to microtrauma around the physiologic physeal fusion likely secondary to the relative change in elasticity as the physis closes1,7. Nearly all reported cases have occurred in the distal femur or proximal tibia and present with knee pain2-4,6,7.
The patients were informed that data concerning the case would be submitted for publication, and their parents provided consent.
Case 1. The first patient is a 14-year-old female presenting with right knee pain after gymnastics. The pain persisted over the medial side of knee despite conservative measures. The pain was worse with squatting and stairs. Radiographs of the knee were negative. An MRI was obtained which showed a FOPE zone of the distal femur (Fig. 1). After reassurance, she was able to return to all activities.
She returned to the clinic 1 year later, with recurrent medial joint line pain attributed to her recent increase in activity with the marching band. Clinical examination revealed medial patellar facet tenderness with medial femoral condyle pain. She endorsed increased pain during activities along with vague mechanical symptoms. A repeat MRI was ordered to assess her medial meniscus. MRI revealed persistent, albeit markedly improved, edema in the same FOPE zone (Fig. 2). No meniscal injury was found. At final follow-up, the patient had persistent activity-related pain.
Case 2. The second patient is also a 14-year-old female who presented for left knee pain 1 month after a knee injury during soccer. She reported pain and swelling with activity. On clinical examination, there was medial joint line tenderness as well as pain with palpation over the femoral insertion of the medial collateral ligament (MCL). She was stable to varus/valgus stress examination as well as to anterior and posterior drawer testings. She had pain with squatting. Radiographs of the knee were negative. An MRI was ordered to assess her menisci and collateral ligaments. A distal femur FOPE zone was noted on MRI (Fig. 3). No meniscal or ligamentous injury was found. After a period of reconditioning, she was able to return to all activities, including soccer.
Three years later, she again presented with continued intermittent pain with activities. The pain was nonresponsive to indocin, but decreased with activity modification. Any activity caused a rise in pain, with inability to perform strenuous activities. She was tender along the medial joint line with difficulty in the deep knee flexion position. Repeat MRI was performed which showed improved but persistent bone edema in the distal femur (Fig. 4). At the last office visit, several months after the second presentation, the patient's symptoms were unchanged with intermittent, activity-related pain.
Case 3. The third patient was a 13-year-old female softball player who presented after 1 month of persistent knee pain. The pain was intermittent and located over the medial joint line, medial femoral condyle, and along MCL. Knee radiographs were concerning for lateral femoral nonossifying fibroma versus neoplasm. MRI was ordered for further evaluation and showed a FOPE zone of the distal femur. No meniscal, ligamentous, or cartilaginous injury was seen on MRI (Fig. 5). The patient was treated conservatively with nonsteroidal anti-inflammatory drugs (NSAIDs) and rest as needed. The patient was able to return to sports, but had persistent intermittent knee pain with activity. The patient has yet to return for re-evaluation.
This case series adds to the growing body of evidence that FOPE zones, are a possible cause of joint pain in adolescents around the time of physeal closure. Although not all FOPE zones are painful, the majority of the described cases were associated with nonspecific knee pain2. FOPE zones are distinct from traumatic physeal injuries sustained in trauma. Injuries to the physis can be diagnosed on plain radiographs with physeal widening as well as MRI showing edema around the physis8. Bai et al. compared MRI of 28 patients with knee pain; 12 patients without a history of trauma concerning for FOPE and 16 with a history of trauma. It was determined that there is statistically more physeal edema in traumatic physeal injuries, and that FOPE zones can be correctly differentiated from traumatic physeal injuries7. Additionally, it is important to differentiate an FOPE zone from other causes of bone edema including bone tumors and osteomyelitis. Bone tumors and osteomyelitis usually present with asymmetric bone edema which rarely cross the physis. In contrast, FOPE zones are typically symmetric focal changes on both sides of the central physis6.
Current published recommendations are for conservative management after diagnosis of an FOPE zone1,2,6. Giles et al. recently published a case series of 4 patients. Of the 4 patients, 2 patients had continued symptoms after an average of 20 months follow-up. All 4 adolescents were found to have lower patient reported Pediatric International Knee Documentation Committee scores compared to their peers greater than 1 year after diagnosis, leading them to conclude that FOPE-associated knee pain may not be clinically benign4. Our series of 3 patients would support the concern that FOPE zones may lead to continued knee pain even after 1 year of conservative treatment as all of our patients had persistent pain. One patient even had residual pain 3 years after diagnosis. Repeat MRI of 2 patients showed persistent but improved bone edema, correlating clinically with continued pain.
The prevalence of FOPE zones is unknown. It is possible that some adolescents are never diagnosed as the patient may be asymptomatic or the knee pain is never evaluated by MRI. Additionally, a diagnosis of bone edema on MRI does not always correlate clinically with symptoms. Two separate studies have published results of knee MRIs performed on asymptomatic soccer players and found the prevalence of bone edema in 41.3% to 64.3% of asymptomatic knees9,10.
Analysis of all published cases of FOPE demonstrates a slight female predominance, with 21 of the 39 (55%) FOPE zone diagnoses being in adolescent females1-7. Additionally, Ueyama et al. followed their patients for 2 years and showed no limb length discrepancies or deformity secondary to the FOPE lesion6. FOPE zones are usually around the knee, involving the distal femoral and proximal tibial physes. Sakamoto and Matsuda did publish a case report of an 11-year-old male who was found to have an FOPE zone of the greater trochanteric apophysis, which had clinical and MRI findings similar to those previously described in the distal femur and proximal tibia physes5.
This case series is limited by the small sample size. After evaluation of our 3 patients and review of all published cases of FOPE zones, we recommend that adolescents diagnosed with FOPE be initially treated conservatively, with activity modifications and NSAIDs as needed. Follow-up radiographs and repeat MRI are unnecessary, especially when symptoms are improving. Improved understanding of FOPE zones will help decrease unnecessary testing and promote more efficient and cost-effective care4. However, repeat MRI in our experience may demonstrate persistent but diminished periphyseal edema. Our series as well as the cases published by Giles et al. do reveal that not all patients diagnosed with FOPE have a benign course, with some having persistent pain over 2 years after the original diagnosis. More aggressive successful treatment for this small subset of patients has yet to be described but investigation beyond conservative treatment may be warranted in those with chronic bone edema and persistent pain.
1. Zbojniewicz AM, Laor T. Focal Periphyseal Edema (FOPE) zone on MRI of the adolescent knee: a potentially painful manifestation of physiologic physeal fusion? AJR Am J Roentgenol. 2011;197(4):998-1004.
2. Beckmann N, Spence S. Unusual presentations of focal periphyseal edema zones: a report of bilateral symmetric presentation and partial physeal closure. Case Rep Radiol. 2015;2015:465018.
3. Bochmann T, Forrester R, Smith J. Case report: imaging the clinical course of FOPE: a cause of adolescent knee pain. J Surg Case Rep. 2016;2016(11).
4. Giles E, Nicholson A, Sharkey MS, Carter CW. Focal periphyseal edema: are we overtreating physiologic adolescent knee pain? J Am Acad Orthop Surg Glob Res Rev. 2018;2(4):e047.
5. Sakamoto A, Matsuda S. Focal periphyseal edema zone on magnetic resonance imaging in the greater trochanter apophysis: a case report. J Orthop Case Rep. 2017;7(4):29-31.
6. Ueyama H, Kitano T, Nakagawa K, Aono M. Clinical experiences of focal periphyseal edema zones in adolescent knees: case reports. J Pediatr Orthop B. 2018;27(1):26-30.
7. Bai RJ, Zhan HL, Liu Y, Qian ZH, Ye W, Li YX, Zhang HB. Focal periphyseal edema zone on MRI and clinical significance of the adolescent knee [in Chinese]. Zhonghua Yi Xue Za Zhi. 2016;96(25):1965-70.
8. Jawetz ST, Shah PH, Potter HG. Imaging of physeal injury: overuse. Sports Health. 2015;7(2):142-53.
9. Soder RB, Simoes JD, Soder JB, Baldisserotto M. MRI of the knee joint in asymptomatic adolescent soccer players: a controlled study. AJR Am J Roentgenol. 2011;196(1):W61-65.
10. Matiotti SB, Soder RB, Becker RG, Santos FS, Baldisserotto M. MRI of the knees in asymptomatic adolescent soccer players: a case-control study. J Magn Reson Imaging. 2017;45(1):59-65.