1 Introduction

The infrapatellar fat pad (IFP) is located within the knee joint capsule but remains outside the synovial membrane. It plays a critical biomechanical role by absorbing the forces generated within the knee joint.^1–3 Anatomically, it is bordered by the patellar tendon and the joint capsule anteriorly, patella superiorly, proximal tibia and deep infrapatellar bursa inferiorly, and the knee joint synovium posteriorly.⁴ It is directly attached to the anterior horns of the menisci and proximal tibia and is tethered superiorly to the intercondylar notch by the infrapatellar plica, also called the ligamentum mucosum.³ Functionally, the IFP acts as a cushion within the knee joint, absorbing compressive forces, aiding in the even distribution of synovial fluid, and supporting the vascularization of the surrounding ligamentous structures.^5–8

At the microscopic level, the IFP functions as a reservoir of mesenchymal stem cells, which have the potential to differentiate into cartilaginous and fatty tissue cell types while also producing factors that inhibit apoptosis and fibrosis.⁹ However, when the IFP is damaged and inflamed, it becomes a site for immune cell infiltration and a source of harmful proinflammatory molecules.⁹

There are biomechanical implications of disruption of the IFP as well. An IFP with compromised structural integrity due to chronic inflammation and trauma may not have preserved the ability to redistribute biomechanical loads and relieve shock. Fibrotic changes lead the IFP to become less flexible and more rigid, altering its ability to accommodate the degrees of knee extension and flexion^10,11 The compromised function of the IFP in the setting of damage and subsequent fibrosis leads to a reduction in these structural regulatory elements, culminating in the disintegration of the knee joint's functional and structural integrity.^11–13

To our knowledge, this study represents the first retrospective assessment of the relationship between IFP integrity in the setting of ACL injury and the development of patellofemoral chondrosis (PFC) by utilizing a combination of pre and post-operative MRI scans, clinical data, and operative reports. It is our aim that this article will add to the expanding knowledge of the relationship between IFP edema and the development of future PFC. Given the biomechanical and inflammatory roles of the IFP, we hypothesized that injury to the IFP in the setting of ACL injury will result in the progression of significant PFC upon review of future MRI.

2 Methods

2.1

2.1 Cohort

This retrospective study received approval from the Institutional Review Board (IRB) of the University of Miami. The study population was derived from MRI reports queried from the University of Miami's database using the keywords "ACL" and "anterior cruciate ligament" in the impression section. The inclusion period spanned from January 2009 to October 2022. The study included adults aged 18–45 who had sustained a complete ACL tear and subsequently underwent reconstructive surgery at our institution. Included patients in the study were required to have an MRI within 4 weeks post-injury and a follow-up MRI within two years post-surgery. For each patient included in the study, this was their first ACL tear and associated reconstruction. Patients with a history of prior knee trauma/injury, knee instability, osteoarthritis, inflammatory arthropathy, joint infection, crystalline arthropathy, prior knee surgeries, trochlear dysplasia, patella alta, patella baja, and history of prior lateral patellar dislocations were excluded from the study. Patients demonstrating significant postoperative disruption or destruction of the infrapatellar fat pad were excluded to minimize confounding factors related to secondary tissue alterations. All participants had intact extensor mechanisms (i.e. normal quadriceps and patellar tendons, normal medial patellofemoral ligaments, normal medial and lateral patellar retinaculum, and normal patellar alignment) on their initial x-ray scans. Fig. 1 details the anatomical structures relevant to this study in a sagittal T1 MRI. Patients who did not follow up in clinic or were missing clinical documentation were also excluded from the study. Fig. 2 details the process for selecting patients for inclusion in our study.

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Fig. 1 A &B Sagittal T1w (A) and proton density with fat saturation (B) MR images demonstrate the infrapatellar plicae (green arrow), infrahoffitic recess (red arrow), and deep infrapatellar bursa (blue arrow).

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Fig. 2 Flow chart showing patient selection criteria for Hoffa's Fat Pad injury.

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2.3

2.3 Image analysis

Initial and follow-up imaging of patellofemoral (PF) chondrosis was assessed using the modified Outerbridge criteria (Fig. 3). Infrapatellar fat pad (IFP) injury was qualitatively graded by two trained musculoskeletal radiologists using a four-grade scale. The grading criteria were as follows: Grade 0 = none, Grade 1 ≤ 10 % of the area (demonstrated in Fig. 4A and B), Grade 2 = 10–20 % of the area (demonstrated in Fig. 5A and B), and Grade 3 ≥ 20 % of the area (demonstrated in Fig. 6A and B). The inter-rater reliability was assessed using the Intraclass Correlation Coefficient (ICC) to ensure evaluation consistency.

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Fig. 3 Modified Outerbridge Criteria.¹⁵.

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Fig. 4 A&B Proton density fat-suppressed MR sagittal images of IFP without edema (grade 0) (A) and with mild edema comprising less than 10 % (grade 1) (B).

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Fig. 5 A&B Proton density fat-suppressed sagittal MR images (A and B) depicting moderate amount of edema, between 10 and 20 % (grade 2) around the infrapatellar plicae (blue arrows), fluid in the supra-Hoffitic recess (white arrow) and infra-Hoffitic recess (red arrow).

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Fig. 6 A&B Proton density fat-suppressed sagittal MR images (A and B) demonstrating a large amount of edema and laceration greater than or equal to 20 % of the area (grade 3) of the IFP (blue arrows), fluid in the supra-Hoffitic recess (white arrow) and infra-Hoffitic recess (red arrow).

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3 Results

A total of 69 patients were included in the study (mean age of 28.14 ± 7.38 years, range 18–45 years old). 21 females and 48 males were selected with an average of 459 ± 213 days between initial and follow-up MRI scans. Overall, 95 % of participants had an IFP on the initial presentation. Fifty-four percent (n = 37) of participants had PF chondrosis (grade 1 and above) at the time of presentation. On the follow-up scan, seventy-five percent (n = 52) of patients had PF chondrosis. At the time of injury, 4 patients had 0 % IFP edema, 37 patients had edema consisting of ≤10 % of the area, 18 patients had edema 10–20 % of the area, and 10 patients had edema ≥20 % of the area. Further details regarding the demographic data of our study are detailed in Table 2.

No significant correlation was found between the severity of initial IFP injury and initial PF chondrosis (r = −0.04, P = 0.61). However, a positive correlation was observed between the severity of initial IFP injury and the development of PF chondrosis, with an average interval of 459 days between the initial and final scans (r = 0.36, P < 0.0001). Additionally, a positive correlation was identified between the patient's age and follow-up level of PF chondrosis (r = 0.392, P < 0.001). A significant difference was detected in the development of PF chondrosis when comparing grade 1 and grade 2 IFP injuries (P < 0.001). No significant differences were observed when comparing grade 0 and grade 1 IFP edema (P = 0.78) or grade 2 and grade 3 IFP injuries (P = 0.72) (Table 3) (Figs. 7 and 8).

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Fig. 7 Bar Chart of PF Chondrosis Frequency Pre- and Post-ACLR. The chart displays the number of patients exhibiting each grade of chondrosis according to the Modified Outerbridge Criteria before and after undergoing Anterior Cruciate Ligament Reconstruction (ACLR).

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Fig. 8 Relationship Between Initial Infrapatellar (IFP) Fat Pad Edema Grade and Average Change in Patellofemoral (PF) Chondrosis Grade. This line chart illustrates the average change in PF chondrosis grade following MRI evaluation across different initial IFP edema grades (0–3). Each point on the line represents the mean increase in PF chondrosis grade for the corresponding initial IFP edema grade.

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4 Discussion

We aimed to assess the relationship between initial IFP injury and subsequent PFC chondrosis in young (18–45) adults who sustained an ACL tear and underwent reconstruction. The results of our study support the finding that the IFP potentially contributes to the maintenance of knee cartilage homeostasis, acting as a deterrent against cartilage degradation over time. We found that participants who had IFP edema with architectural distortion and/or laceration (grade 2 and grade 3) on initial MRI imaging had increased progression of PF articular cartilage loss on follow-up MRI. These findings are likely multifactorial, involving disrupted IFP paracrine signaling, heightened proinflammatory activity, and a diminished capacity for mechanical support and synovial fluid distribution following injury.^8,14–18

Adipose tissue has been shown to secrete inflammatory mediators such as nitric oxide, TNF-α, MCP1, prostaglandin E2, and various inflammatory interleukins, as well as growth factors including fibroblast growth factor (FGF), transforming growth factor-β (TGF-β), and vascular endothelial growth factor (VEGF), which have all been demonstrated to be involved in the degradation of cartilage.^6,18 Like other adipose tissue, the IFP is responsible for the secretion of proinflammatory and proangiogenic factors that may contribute to the onset of knee OA.^12,14,17 Specifically, Ushiyama et al. found that the IFP produces bFGF, VEGF, TNF-α, and IL-6, cytokines that are responsible for modulating chondrocyte metabolism.¹⁷ The IFP secretes adipokines, via adipocytes, such as leptin, adiponectin, resistin, chemerin, and FABP4, which may also contribute to OA development.^5–7 Abnormal secretion or disruption of these factors is believed to effect the development of OA, driven by the complex interactions between these chemical signals and the chondrocytes comprising the knee's articular cartilage and synovium.

In line with our findings, the severity of the initial IFP injury might be correlated with the extent of future joint degeneration. In a study conducted by Heilmeier et al., twenty-six young healthy males who had torn their ACL with IFP involvement had levels of inflammatory markers measured from synovial fluid prior to reconstructive ACL surgery. It was noted that the degree of IFP involvement correlated with synovial fluid levels of cytokines IL-6, IL-8, and TNFα, as well as cartilage degradation markers MMP-1 and MMP-3.¹⁹ The study by Heilmeier et al. provides evidence that suggests a causal link between the extent of IFP injury and the subsequent breakdown of cartilage, offering a potential mechanism for how initial IFP trauma may predict the progression of joint degeneration.^7,11,12 It should also be noted that modern, minimally invasive arthroscopic ACL reconstructive methods.

In addition to the effects of cytokines and chemokines from the damaged IFP, tissue disruption and altered mechanical properties are also believed to contribute to OA developmentl.^11–13 The IFP serves to both distribute synovial fluid and absorb forces within the knee joint.¹⁶ Infrapatellar fat pads from OA knee joints have been found to possess increased tissue stiffness, which may affect the ability to redistribute loads compared to healthy controls.^8,12 In addition to increased tissue stiffness, injured IFPs demonstrate a random distribution of fibers in the interlobular septa between adipocytes, altering its shear stiffness and strength.⁸ A healthy IFP has a linear arrangement of fibers in the interlobular septa, which may help to resist torsional stresses.^8,16

It should be noted that with modern minimally invasive ACL reconstructive surgery, some surgeons remove portions of the IFP to gain better arthroscopic visualization of the knee joint. The current literature has contrasting opinions on whether the IFP should be preserved. A study by Wen et al., in 2023 advocated for the preservation of the fat pad during ACL reconstructive surgery as they found improvements in knee pain and knee function when compared to those with resected IFPs.²⁰ A study by Asai et al., in 2020 compared the clinical outcomes of ACL reconstructive surgery with and without partial resection of the IFP. Of all clinical parameters assessed, there was no difference in clinical outcomes between these two groups, most notably regarding anterior knee pain.²¹ In our study, we selected for studies that demonstrated the least amount of surgical disruption as possible to avoid these potential confounding factors.

It is important to mention that the average time between imaging in this study was 459 days. A fifty-seven percent incidence of knee OA has been reported 14 years following ACL reconstruction, compared to just eighteen percent in the contralateral knee that did not suffer from an ACL tear.²² Anyone who has undergone ACL reconstruction may be at risk for the development of OA.^23,24 With a longer follow-up period, there is a higher chance for trauma and other knee pathologies to develop, contributing further to the degradation of the joint with factors beyond those directly related to IFP disruption.^25,26

One limitation of this study is the single-center design, which inherently limits the generalizability of our findings beyond our specific patient population and healthcare setting. Another limitation is the selective nature of follow-up MRIs, which were obtained only in response to patient-reported symptoms such as pain or re-injury. Additionally, the study did not differentiate between different ACL reconstruction techniques, such as variations in surgical approaches, graft choices, and fixation methods. These differences could potentially impact the development of IFP edema or its relationship with knee OA.^23,27 Finally, the retrospective design limits our findings to association rather than causation which would necessitate a prospective study.

Despite these limitations, our study builds on previous findings by Liu, Z et al. which classified the IFP edema by signal intensity, by incorporating a more multidimensional approach that includes pre and post-operative MRI scans in the setting of ACL tears that necessitated reconstructive surgery. Previous research has explored the multifactorial causes that the IFP may play in the development of knee OA,^{7,8,11,12,14,16,17,28} and this study builds upon these findings in a manner that highlights a possible correlation between the severity of IFP edema and subsequent cartilage degeneration, which may provide a foundation for future studies concerned with understanding the underpinnings of this relationship.

Consent statement

Due to the retrospective nature of the study, obtaining informed consent from patients or their guardians was not feasible. The IRB of The University of Miami Miller School of Medicine granted a waiver of informed consent as the research involved no more than minimal risk to the subjects, and the waiver did not adversely affect the rights and welfare of the subjects. However, we confirm that all necessary permissions and approvals were obtained for accessing and using patient data.

No additional interventions or procedures were performed on patients as part of this study. The data used were collected as part of routine clinical care and were stored securely in accordance with institutional data protection policies.

Author contributions

Griffin Harris BS – original draft, analysis, writing and review, Nikhil Patel BS- writing and review, Richard Wang MD-data acquisition, writing and review, Anmol Patel BS- writing and review, Selina Deiparine MD-data acquisition, writing and review, Thomas M Best MD,PhD-writing and review, Jean Jose DO- idea conception, writing and review, The order of authorship has been agreed upon by all authors, who have each reviewed and approved the final version of this manuscript.

Ethical statement

The study protocol was reviewed and approved by the Institutional Review Board (IRB) of The University of Miami Miller School of Medicine (IRB approval number: 20220801).

Patient confidentiality and privacy were strictly maintained throughout the study. All patient data were anonymized and de-identified prior to analysis to ensure that no personal identifiers were accessible. Informed consent was waived by the IRB due to the retrospective nature of the study, as the research involved no more than minimal risk to the subjects, and the waiver did not adversely affect the rights and welfare of the subjects.

No additional interventions or procedures were performed on patients as part of this study. The data used were collected as part of routine clinical care and were stored securely in accordance with institutional data protection policies.

Funding statement

The authors would like to acknowledge that no external funding was received for the completion of this study. The research, data collection, analysis, and manuscript preparation were carried out solely through the authors' own resources and institutional support. No financial support or grants were provided by any funding agencies, commercial entities, or non-profit organizations for this work.