Influence of infrapatellar fat pad size on the development and severity of chondromalacia patella

Abstract

The inflammatory role of the infrapatellar fat pad (IPFP) in cartilage damage has been well-documented, yet its potential protective function as a shock absorber remains underexplored. This retrospective cohort study aimed to evaluate the relationship between the IPFP size and chondromalacia patella (CP), while also examining the effects of age, sex, and body mass index (BMI). Magnetic resonance imaging scans from 311 patients aged 40 to 65 years were retrospectively analyzed. Axial sequences classified CP severity, and sagittal sequences measured IPFP areas. CP was graded according to the International Cartilage Repair Society system, and patients were grouped into control (no CP), mild CP (grades 1–2), and severe CP (grades 3–4) categories. Demographic data, including age, sex, and BMI, were collected, and statistical analysis explored the relationships between IPFP area, CP severity, and these factors. Of the patients, 145 (46.6%) had no CP, while 166 (53.4%) had varying CP severity. Patients with CP had significantly smaller IPFP areas (6.16 ± 0.67 cm²) compared to controls (6.96 ± 0.87 cm², P < .001). The mean IPFP area decreased progressively with increasing CP severity. After adjusting for confounders, a smaller IPFP area was significantly associated with the presence and severity of CP (P < .001). These findings provide evidence that a larger IPFP area plays a protective role in maintaining patellar cartilage integrity and mitigating CP progression, as demonstrated by a significant inverse correlation between IPFP area and CP severity, independent of age, sex, and BMI. A comprehensive, multidisciplinary approach integrating biomechanical, metabolic, and inflammatory factors is warranted to fully elucidate the role of IPFP in CP.

1. Introduction

The precise function of the infrapatellar fat pad (IPFP), located within the knee joint, remains a topic of ongoing debate. Traditionally, the IPFP has been recognized for its fundamental roles, including filling dead space, functioning as part of an anatomo-functional unit within the knee joint, contributing to the joint environment, distributing load, and absorbing shock.^[1] A recent study has demonstrated that the IPFP plays a significant biomechanical role by modulating joint stress and enhancing mechanical stability.^[2] Fontanella et al demonstrated that in patients with osteoarthritis (OA), the IPFP undergoes mechanical changes that may influence joint loading and patellofemoral joint (PFJ) pressure distribution, further reinforcing its biomechanical role in joint stability.^[2] Beyond its biomechanical functions, the IPFP’s rich vascular supply and sensory innervation suggest a more complex and specialized role.^[1,3,4] Studies have also highlighted the involvement of the IPFP in inflammatory processes associated with knee OA, where increased lymphocytic infiltration, vascularization, and thickening of the interlobular septa have been observed in osteoarthritic patients.^[5,6] Furthermore, the IPFP may function as an endocrine organ by secreting adipokines such as leptin and adiponectin, further reinforcing its role in OA progression.^[4,7,8]

Studies investigating the volume of the IPFP in osteoarthritis (OA) have yielded conflicting results. Some studies report an increase in IPFP volume, which has been associated with more severe symptoms such as knee pain.^[9–12] Conversely, other studies have reported a decrease in IPFP volume in advanced OA stages due to fibrosis and structural remodeling.^[13,14] These discrepancies suggest that changes in IPFP volume are influenced by disease stage and methodological differences across studies, underscoring the necessity for further investigations to elucidate these variations.

Chondromalacia patella (CP), characterized by the softening and degeneration of patellar cartilage, is a common cause of chronic anterior knee pain.^[15] As an early stage of PFJ OA, CP has the potential to progress and lead to further joint damage.^[15,16] Magnetic resonance imaging (MRI) is a valuable tool for diagnosing CP, demonstrating high sensitivity and specificity in detecting early cartilage changes.^[17] Given the anatomical and biomechanical interrelationships between the IPFP, the PFJ, and the patella, it has been suggested that IPFP dimensions may influence CP development, either by contributing to cartilage degeneration or by providing a protective effect.^[10,11]

The objective of this study was to investigate the relationship between IPFP size and the development and severity of CP. MRI was utilized to compare IPFP areas between individuals with and without CP, aiming to elucidate the impact of IPFP size variations on CP progression. Additionally, the influence of demographic variables, including sex, age, and body mass index (BMI), was examined. It was hypothesized that smaller IPFP areas would be associated with increased CP severity, whereas larger IPFP areas might serve a protective role against cartilage degeneration.

2. Methods

2.1. Study population

This retrospective cross-sectional study was approved by the institutional review board (approval number 2023/847). It included patients aged 40 years and older who presented with knee pain between January 1, 2022, and December 31, 2022. The inclusion and exclusion criteria are outlined below.

2.2. Inclusion criteria

• Age ≥ 40 years.

• Presence of clinical symptoms of anterior knee pain.

• Availability of knee MRI scans.

• No prior history of knee surgery.

2.3. Exclusion criteria

• History of knee surgery.

• Recent trauma.

• Significant joint effusion.

• Inflammatory joint diseases (e.g., rheumatoid arthritis).

• Other structural knee pathologies that could interfere with the assessment of the IPFP and patellar cartilage.

A formal control group was established, consisting of patients without CP who had normal cartilage (grade 0) based on MRI findings. These patients were retrospectively identified and served as a reference group for comparisons with CP patients. While this control group was not randomly assigned, it provides a structured comparison to evaluate differences in imaging parameters between patients with and without CP. Demographic data, including sex, age, and BMI, were recorded for all participants.

For statistical comparisons, patients were classified into 2 groups: the CP group (grades 1–4) and the control group (grade 0, without CP). This classification was based on MRI findings according to the modified International Cartilage Repair Society (ICRS) grading system. The control group consisted of patients with normal cartilage (grade 0), while the CP group included patients with varying degrees of patellar cartilage damage (grades 1–4). This binary classification was chosen to facilitate statistical analysis and to compare CP patients with individuals without cartilage damage.

2.4. MRI protocol

MRI was performed using a 1.5-T Philips Medical Systems unit with a transmit-receive extremity coil. Patients were scanned in the supine position with knees flexed at 15°, and no intravenous contrast was administered. The following sequences were used:

1. Sagittal T1-weighted fast spin-echo (T1W FSE).

2. Sagittal fat-suppressed proton density-weighted fast spin-echo (FS PDW FSE).

3. Coronal T1-weighted fast spin-echo (T1W FSE).

4. Coronal fat-suppressed proton density-weighted fast spin-echo (FS PDW FSE).

5. Axial fat-suppressed proton density-weighted fast spin-echo (FS PDW FSE).

2.5. Assessment of MRI

The maximal IPFP area (cm²) was manually measured from sagittal T1-weighted MRI images using the OsiriX software (Fig. 1). The largest cross-sectional area of the IPFP was recorded for each patient. To ensure consistency, all measurements were performed by a single observer with excellent intra-rater reliability (ICC > 0.9).

Figure 1.

Sagittal TSE fat-suppressed MRI showing the area measurement of the IPFP and signal hyperintensity in the subcortical bone, consistent with grade 4 CP. CP = chondromalacia patella, MRI = magnetic resonance imaging.

2.6. Patellar cartilage assessment

Patellar cartilage defects were evaluated using axial fat-suppressed PDW sequences and graded using the modified ICRS grading system (Fig. 2). CP was classified into grade 0 (normal), mild (grades 1–2), or severe (grades 3–4). The relationship between CP severity, IPFP size, and demographic factors was then analyzed.

Figure 2.

Axial knee TSE fat-suppressed MRI: (A) shows normal patellar cartilage signal and thickness, while (B) demonstrates grade 4 CP, characterized by cartilage thinning and areas of high signal within the subchondral bone. CP = chondromalacia patella, MRI = magnetic resonance imaging.

2.7. Statistical analysis

All statistical analyses were conducted using IBM SPSS Statistics for Windows, Version 20.0 (IBM Corp., Released 2011, Armonk). Descriptive statistics were presented as means, standard deviations, and percentages. The intraobserver reliability was evaluated using the intraclass correlation coefficient, with a score of 0.8 or above indicating excellent reliability. The normality of the data was confirmed using the Shapiro–Wilk test. Pearson correlation was employed to assess the relationship between IPFP area, age and BMI. Comparisons between groups were conducted using Pearson chi-squared test for categorical variables and independent t-tests for continuous variables. The differences among CP severity groups were assessed using 1-way analysis of variance. Additionally, binary logistic regression analysis was used to identify significant predictors of CP presence, while multinomial logistic regression analysis was performed to determine the association between CP severity and potential confounders, including age, BMI, and IPFP area. The threshold for statistical significance was set at P < .05.

3. Results

A total of 354 patients were initially assessed for eligibility. After 43 patients were excluded due to specific reasons (15 with a history of knee surgery, 10 with trauma history, 8 with significant effusion, 5 with inflammatory diseases, and 5 with other knee pathologies), 311 patients were included in the final analysis. Table 1 presents the baseline characteristics of the study population, including age, sex, side, BMI, and IPFP area.

Table 1.

Baseline characteristics of the study population (n = 311).

Characteristic	Value
Mean age (yr)	49.4 ± 6.81 (range: 40–65)
Sex
Female (%)	164 (52.7%)
Male (%)	147 (47.3%)
Side
Right (%)	161 (51.8%)
Left (%)	150 (48.2%)
Mean BMI (kg/m2)	25.29 ± 1.6 (range: 21.8–29.7)
IPFP area (cm2)	6.53 ± 0.86 (range: 5.28–9.72)

Abbreviations: BMI = body mass index, IPFP = infrapatellar fat pad.

Table 2 summarizes the distribution of patients according to the modified ICRS grading system based on MRI findings. Among the 311 patients, 46.6% (n = 145) had normal cartilage (grade 0) and were classified as the control group, while 53.4% (n = 166) were diagnosed with CP (grades 1–4). Among the 166 patients with CP, 25.4% had mild CP (grades 1 and 2), while 28% had severe CP (grades 3 and 4).

Table 2.

Distribution of patients by the modified international cartilage repair society grading system.

Cartilage Grade	Description	Number of patients (%)
Normal
Grade 0	Normal cartilage with gray-scale stratification	145 (46.6%)
Mild CP
Grade 1	Normal contour with increased signal in articular cartilage	36 (11.6%)
Grade 2	Linear to ovoid foci of increased signal involving < 50% thickness	43 (13.8%)
Severe CP
Grade 3	Linear to ovoid foci of increased signal involving > 50% of cartilage thickness but not extending down to bone	48 (15.4%)
Grade 4	Complete loss of articular cartilage or surface flap	39 (12.5%)

Abbreviation: CP = chondromalacia patella.

For further analysis, patients were classified into the CP group (grades 1–4) and the control group (grade 0, without CP), as described in the Methods section. Table 3 presents a detailed comparison of baseline characteristics, including age, sex, BMI, and IPFP area, between these 2 groups. Specifically, CP patients were, on average, older (52.46 ± 7.1 years) compared to the control group (45.9 ± 4.36 years), and they had a significantly higher BMI (26.09 ± 1.51 kg/m² vs 24.38 ± 1.14 kg/m²; P < .001). Furthermore, the IPFP area was significantly smaller in CP patients (6.16 ± 0.67 cm²) compared to controls (6.96 ± 0.87 cm²; P < .001), indicating a possible association with CP development or progression. Additionally, CP was more prevalent in females (61.4%) than in males (38.6%). Conversely, the control group had a higher percentage of males (57.2%) than females (42.8%) (P < .001). No significant difference was observed between CP and control groups regarding the affected knee side (right vs left) (P = .909, Table 3).

Table 3.

Comparison of baseline characteristics between patients with and without chondromalacia patella.

Characteristic	Control (n = 145, 46.6%)	Chondromalacia patella (n = 166, 53.4%)	P-value
Mean age (yr)	45.9 ± 4.36 (40–56)	52.46 ± 7.1 (40–65)	<.001*
Sex
Female (%)	62 (42.8%)	102 (61.4%)	<.001**
Male (%)	83 (57.2%)	64 (38.6%)
Side
Right (%)	76 (52.4%)	85 (51.2%)	.909**
Left (%)	69 (47.6%)	81 (48.8%)
Mean BMI (kg/m2)	24.38 ± 1.14 (21.8–28.1)	26.09 ± 1.51 (22.3–29.7)	<.001*
IPFP area (cm2)	6.96 ± 0.87 (5.38–9.72)	6.16 ± 0.67 (5.28–8.56)	<.001*

Abbreviations: BMI = body mass index, IPFP = infrapatellar fat pad.

^*Independent sample t test.

^**Pearson chi-square test.

Sex-related differences in IPFP area were observed in both groups. In the CP group, females had a significantly smaller IPFP area (5.94 ± 0.54 cm²) compared to males (6.52 ± 0.69 cm²), with a mean difference of −0.59 cm² (P < .001, 95% confidence interval [CI] = −0.79 to −0.38). Similarly, in the control group, females had a significantly smaller IPFP area (6.47 ± 0.75 cm²) than males (7.33 ± 0.76 cm²), with a mean difference of −0.86 cm² (P < .001, 95% CI = −1.11 to −0.61).

A significant negative correlation was identified between IPFP area and both age (r = −0.312, P < .001) and BMI (r = −0.392, P < .001) when data from all patients were included in the analysis. The IPFP area was significantly smaller in patients with CP (6.16 ± 0.67 cm²) compared to the control group (6.96 ± 0.87 cm²) (P < .001, Table 3). Furthermore, a significant negative correlation was found between the severity of CP and IPFP area (r = −0.545, P < .001). Patients with severe CP exhibited a reduction in IPFP area, with a mean of 5.83 ± 0.38 cm², in comparison to those with mild CP (6.53 ± 0.72 cm²) or the control group (6.96 ± 0.87 cm²). This difference was statistically significant (P < .001; Tables 4 and 5). Furthermore, patients with mild CP exhibited diminished IPFP areas in comparison to the control group (P < .001).

Table 4.

Comparison of baseline characteristics by chondromalacia patella severity.

Characteristic	Control (n = 145, 46.6%)	Mild CP (n = 79, 25.4%)	Severe CP (n = 87, 28%)	P-value
Mean age (yr)	45.9 ± 4.36 (40–56)	50.48 ± 6.9 (40–65)	54.25 ± 6.84 (41–65)	<.001*
Sex
Female (%)	62 (42.8%)	38 (48.1%)	64 (73.6%)	<.001**
Male (%)	83 (57.2%)	41 (51.9%)	23 (26.4%)
Side
Right (%)	76 (52.4%)	37 (46.8%)	48 (55.2%)	.549**
Left (%)	69 (47.6%)	42 (53.2%)	39 (44.8%)
Mean BMI (kg/m2)	24.38 ± 1.14 (21.8–28.1)	25.37 ± 1.21 (22.3–29.2)	26.74 ± 1.47 (22.4–29.7)	<.001*
IPFP area (cm2)	6.96 ± 0.87 (5.38–9.72)	6.53 ± 0.72 (5.33–8.56)	5.83 ± 0.38 (5.28–7.34)	<.001*

Abbreviations: ANOVA = analysis of variance, BMI = body mass index, CP = chondromalacia patella, IPFP = infrapatellar fat pad.

^*One-way ANOVA test with Tukey HSD and Bonferroni post hoc analysis (P < .001).

^**Pearson Chi-square test.

Table 5.

Statistical relationships between chondromalacia patella groups and variables.

	Age	Sex	BMI	IPFP
Normal and Mild CP	<0.001*	0.71	<0.001*	<0.001*
Normal and Severe CP	<0.001*	<0.001*	<0.001*	<0.001*
Mild and Severe CP	<0.001*	0.002*	<0.001*	<0.001*

Abbreviation: ANOVA = analysis of variance, CP = chondromalacia patella.

^*One-way ANOVA.

When the severity of CP was considered, statistically significant differences were observed in BMI, IPFP area, and sex distribution (Table 4). BMI values increased significantly with CP severity (P < .001), and post hoc analyses (Tukey HSD and Bonferroni) confirmed significant differences between all groups (P < .001). Similarly, the IPFP area significantly decreased with CP severity (P < .001). The mean IPFP area was 6.96 ± 0.87 cm² in the control group, 6.53 ± 0.72 cm² in the mild CP group, and 5.83 ± 0.38 cm² in the severe CP group, with post hoc comparisons confirming significant differences across all groups (P < .001). Additionally, sex distribution varied significantly across CP severity levels (P < .001). The proportion of females increased from 42.8% in the control group to 48.1% in the mild CP group and 73.6% in the severe CP group. However, CP severity was not significantly associated with the affected knee side (right vs left, P = .549).

The statistical relationships between age, sex, BMI, and IPFP area across the different groups of CP are summarized in Table 5.

Binary logistic regression identified increasing age, higher BMI, and smaller IPFP area as significant predictors of CP (P < .001 for each), while sex was not a significant predictor (P = .425; Table 6).

Table 6.

Binary logistic regression analysis for predicting chondromalacia patella.

Variables	β	Odds ratio	95% CI	P-value
Age	0.129	1.137	1.076 to 1.202	.001
Sex	−0.272	0.762	0.673 to 2.557	.425
BMI	0.721	2.057	1.593 to 2.657	.001
IPFP area	−0.973	0.378	0.242 to 0.59	.001

Note: R² = 0.409 (Cox & Snell), R² = 0.547 (Nagelkerke).

Abbreviations: BMI = body mass index, CP = chondromalacia patella, IPFP = infrapatellar fat pad.

In multinomial logistic regression analysis, after adjusting for age and BMI, a smaller IPFP area was significantly associated with CP severity (P < .001; Table 7).

Table 7.

Multinomial logistic regression analysis to detect the severity of chondromalacia patella.

Severity of CP	Variables	β	Odds ratio	95% CI	P-value
Mild CP	Age	0.114	1.12	1.06 to 1.185	<.001
	BMI	0.56	1.75	1.339 to 2.281	<.001
	IPFP area	−0.158	0.596	0.397 to 0.893	.012
Severe CP	Age	0.149	1.161	1.084 to 1.256	<.001
	BMI	1.262	3.534	2.438 to 5.123	<.001
	IPFP area	−3.668	0.026	0.011 to 0.093	<.001

Note: The reference category is: control.

Abbreviations: BMI = body mass index, CP = chondromalacia patella, IPFP = infrapatellar fat pad.

4. Discussion

This study provides valuable insights into the potential role of the IPFP in protecting patellar cartilage integrity. Our findings indicate that patients with CP have significantly smaller IPFP areas than controls, with a strong inverse correlation between IPFP size and CP severity. This suggests that a larger IPFP may help reduce stress on the patellar cartilage, potentially slowing disease progression. Notably, this association remained significant even after adjusting for age and BMI, reinforcing the hypothesis that IPFP size plays a key role in joint homeostasis and cartilage health, particularly in CP.

Our findings align with previous studies emphasizing the protective role of the IPFP in knee health.^[18–21] Ragab and Serag^[18] reported a negative correlation between IPFP size and osteoarthritic changes, reinforcing our observation that CP patients exhibit significantly smaller IPFP areas than controls. Similarly, Duran et al^[21] found that female patients had smaller IPFP volumes, consistent with our finding that CP is more prevalent among female patients. These findings suggest that a larger IPFP may serve a protective role against cartilage damage by mitigating mechanical stress and modulating inflammatory responses. These results further support the hypothesis that progressive reduction in IPFP size may be linked to worsening CP severity, highlighting the need for further investigation into its role in CP progression and cartilage preservation.

While the mechanical function of the IPFP has been well established, recent studies suggest that it may also undergo pathological changes that contribute to knee osteoarthritis.^[9,10,22] MRI hypointense signals have been associated with chronic inflammation, fibrosis, and synovial thickening, all of which may accelerate disease progression.^[22] These signal alterations have also been linked to cartilage defects, bone marrow lesions, and knee pain, as well as symptomatic and radiographic OA progression, particularly in advanced disease stages.^[9,10] However, our study primarily focused on the morphological assessment of the IPFP and did not include MRI-based inflammatory markers. Therefore, the potential role of IPFP signal alterations in CP progression remains uncertain and beyond the scope of our study. Future research incorporating advanced MRI techniques to quantify IPFP signal changes could provide a better understanding of its inflammatory role and its potential impact on CP severity. Additionally, such investigations may help identify imaging biomarkers for early CP detection and monitoring.

Aside from pathological changes, demographic factors, particularly age, may influence the morphology of the IPFP. Previous studies suggest that the morphology of the IPFP changes with age.^[18,21,22] Our study found a weak but significant negative correlation between IPFP area and age, indicating a slight reduction in IPFP size over time. Ragab and Serag^[18] also reported a decrease in IPFP area with age, while Duran et al^[21] found that individuals with patellar cartilage defects, especially females, had significantly smaller IPFP volumes, suggesting that age-related reductions in IPFP size contribute to knee joint structural changes. Additionally, Han et al^[22] found that hypointense signals in the IPFP were associated with knee cartilage defects and bone marrow lesions, with structural changes increasing with age. However, contrasting findings by Chuckpaiwong et al^[20] observed that IPFP volume may increase with age in OA patients, possibly due to localized inflammation and structural remodeling. Conversely, other studies have reported a decrease in IPFP volume in advanced OA stages, likely due to fibrosis, adipose tissue degeneration, and structural remodeling.^[13,14] These discrepancies highlight the complexity of IPFP’s role in knee joint health and suggest that its function may vary depending on OA stage and disease severity. Our findings indicate that smaller IPFP areas are more prevalent in individuals with CP, supporting the hypothesis that IPFP undergoes dynamic structural changes throughout OA progression. Despite these insights, the mechanisms underlying this association remain unclear. Age-related alterations in adipose tissue composition, vascularization, and inflammatory responses could play a role in this process, providing insights into the potential involvement of IPFP in CP pathogenesis and knee joint health.

Similarly, our study demonstrated that sex is significantly associated with CP prevalence, with CP being more common in female patients. Additionally, as CP severity increased, the proportion of female patients increased. The finding that females had significantly smaller IPFP areas than males in both the CP and control groups suggests that IPFP morphology may exhibit sex-related differences. This result aligns with previous studies.^[21–24] Duran et al^[21] reported that females had significantly smaller IPFP volumes than males, which was more pronounced in individuals with patellar cartilage defects. Consistently, Han et al^[22] found that females had smaller IPFP areas, which were associated with knee joint health. Furthermore, Teichtahl et al^[23] reported that males had larger IPFP areas, which were linked to reduced lateral tibial cartilage loss. In contrast, Pan et al^[24] suggested that a larger IPFP in females may help reduce cartilage loss and lower the risk of pain progression. While these findings indicate that sex-related differences in IPFP morphology may have implications for knee joint health, the precise mechanisms underlying this relationship remain uncertain. Existing studies suggest that IPFP morphology exhibits sex-related differences and may play a role in knee joint health.^[21–24] However, further research is needed to comprehensively evaluate the structural and functional effects of IPFP in relation to sex differences.

In addition to demographic factors such as age and sex, metabolic parameters like BMI may also influence IPFP morphology and its protective role in knee health. Given the potential interplay between obesity, mechanical stress, and inflammatory processes, exploring the association between BMI and IPFP size is crucial. In consideration of the data presented in published literature, particularly the findings of Teichtahl et al^[23] and Masaki et al,^[25] it seems reasonable to posit that BMI will have an effect on the IPFP area. In this study, a weak but statistically significant negative correlation was observed between BMI and IPFP area, indicating that as BMI increases, IPFP area decreases. This finding is noteworthy, as Masaki et al^[25] did not identify a significant relationship between BMI and IPFP volume in their study. However, they reported a positive correlation between IPFP volume and cartilage damage in OA patients, suggesting that IPFP should not always be considered a protective structure. Similarly, Teichtahl et al^[23] found that IPFP size is more strongly associated with lean body mass rather than systemic obesity, which aligns with our observed weak negative correlation between BMI and IPFP area. This supports the hypothesis that higher BMI is associated with a reduction in IPFP area, potentially diminishing its protective effect on cartilage. It is similarly conceivable that IPFP’s function in knee health is more intricate and is shaped by biomechanical or inflammatory factors that vary between populations.^[5,7,11,26] Furthermore, Hussain et al^[27] reported that increased BMI is particularly associated with patellar cartilage defects in females. Similarly, Kok et al^[28] found a positive correlation between increased subcutaneous knee fat and cartilage defects, with this effect being more pronounced in females. These findings further support the inverse relationship between BMI and IPFP area observed in our study.

Beyond the influence of BMI, previous studies have also investigated the role of IPFP size in knee joint structural changes and OA progression. Ragab and Serag^[18] and Duran et al^[21] reported that a reduction in IPFP area or volume is associated with structural changes in the knee joint and OA progression, suggesting that IPFP shrinkage may contribute to cartilage degeneration. On the other hand, Chuckpaiwong et al^[20] highlighted the complexity of IPFP’s role in OA development by reporting that IPFP volume may increase in OA patients due to inflammation and structural remodeling. However, He et al^[29] found that although there was no significant change in IPFP volume or area, an increase in IPFP signal intensity was more strongly associated with cartilage degeneration and OA progression. This finding suggests that the metabolic functions of IPFP may play a more significant role in OA pathology than its structural properties.^[29]

The effects of age, sex, and BMI on IPFP morphology suggest that multiple factors contribute to its structural variations. Beyond these demographic and metabolic influences, the IPFP itself may play a crucial role in maintaining patellar cartilage integrity.

Previous studies have linked a larger IPFP size to the preservation of cartilage integrity and attenuation of structural changes in the knee joint.^[23,24,30] Cai et al^[30] reported that a greater IPFP volume was associated with increased tibial and patellar cartilage volume, along with fewer structural abnormalities in the knee joint. Moreover, individuals with smaller IPFPs exhibited a higher prevalence of cartilage defects, osteophytes, and bone marrow lesions, supporting the hypothesis that IPFP may mitigate cartilage loss and joint damage.^[30] Additionally, Teichtahl et al^[23] demonstrated that a larger IPFP volume correlates with reduced knee pain and slower lateral tibial cartilage volume loss, reinforcing its role as a local shock absorber that alleviates mechanical loads on the knee joint. The absence of a significant association between IPFP volume and BMI or fat mass further suggests that IPFP is not merely a marker of systemic obesity but an independent factor influencing joint health.^[23] Furthermore, Pan et al^[24] found that a larger IPFP area was associated with reduced knee pain, preserved tibial cartilage volume, and a lower incidence of cartilage defects in women. These findings suggest that the IPFP is not solely a mechanical buffer but also an active biological structure that may contribute to joint health by modulating cartilage degeneration.^[24]

However, in contrast to studies suggesting that the IPFP plays a protective role, a study by Cowan et al^[31] reported potential negative effects of increased IPFP volume. They found a significant association between larger IPFP volume and PFJ OA as well as knee pain. Their study demonstrated that IPFP volume in individuals with PFJ OA was significantly larger compared to asymptomatic controls, and this difference remained significant even after adjusting for age, sex, and BMI. Additionally, they observed a significant correlation between greater IPFP volume and increased knee pain. These findings suggest that the IPFP is not solely a mechanical cushion but may also be involved in biological processes related to pain mechanisms. However, due to the cross-sectional design of the study, it remains unclear whether an increase in IPFP volume is a cause or a consequence of knee pain.^[31]

On the other hand, Steidle-Kloc et al^[32] questioned this role of the IPFP, reporting no significant association between IPFP volume and knee pain. Their study did not find strong evidence supporting either a pain-exacerbating or pain-relieving effect of IPFP volume, suggesting that IPFP is not a sole determinant of knee pain.^[32] This finding implies that the IPFP’s influence on knee health is shaped not only by its volume but also by its tissue properties and inflammatory processes.

Our study did not evaluate clinical parameters such as pain; rather, it focused solely on the relationship between IPFP area and CP. Our findings suggest that a larger IPFP area may reduce the likelihood of CP development and play a protective role against patellar cartilage degeneration. In contrast, Cowan et al^[31] reported that IPFP volume was larger in patients with PFJ OA and may be associated with knee pain. These differing results suggest that the structural and functional role of the IPFP may vary depending on the stage of the disease. Since CP is considered an early stage of PFJ OA, the protective effect of the IPFP may still be present at this stage. While a smaller IPFP area in the early stage may be linked to inadequate absorption of biomechanical loads, an increase in IPFP volume in later stages may be associated with inflammatory changes and fibrotic remodeling. However, some studies indicate that in advanced OA stages, IPFP volume may actually decrease due to fibrosis and structural remodeling, suggesting that its role is highly stage-dependent.^[13,14] Therefore, longitudinal studies are needed to better understand stage-dependent changes in the IPFP.

In the literature, the IPFP is described not only as a mechanical structure but also as an active participant in inflammatory processes during OA progression.^[33,34] Reviews by Clockaerts et al^[33] and Zhou et al^[34] emphasize that the IPFP is a biologically active tissue that may contribute to joint degeneration. Studies suggest that the IPFP may be associated with synovial inflammation, osteophyte formation, and cartilage degeneration, indicating that it could influence joint health by modulating inflammatory processes. Furthermore, the IPFP interacts with the synovium, cartilage, subchondral bone, and peripheral nerve network, potentially playing a role in OA pathogenesis. These interactions may affect both cartilage degradation and pain mechanisms, further highlighting the complex involvement of the IPFP in joint homeostasis.^[33,34]

While our study provides valuable insights, certain limitations should be acknowledged. Due to technical constraints, our analysis was based on 2-dimensional sagittal MRI slices, preventing volumetric calculations; however, area-based assessments ensured standardized and reproducible measurements in CP patients. Additionally, the cross-sectional design precludes establishing a causal relationship between IPFP size reduction and CP progression, highlighting the need for longitudinal studies. Furthermore, our study focused solely on morphological characteristics and did not evaluate potential inflammatory markers, such as synovial inflammation or hypointense MRI signals, which could provide further insights into CP pathogenesis. Future research should employ advanced imaging techniques to assess volumetric variations and investigate the inflammatory role of IPFP in knee pathology.

5. Conclusion

In conclusion, our study provides evidence that a larger IPFP area plays a protective role in maintaining patellar cartilage integrity and mitigating CP progression, as demonstrated by a significant inverse correlation between IPFP area and CP severity, independent of age, sex, and BMI. These findings suggest that IPFP is not merely a passive anatomical structure but an active determinant of knee joint health, with potential implications for CP pathogenesis. Given its structural and functional complexity, future studies should employ longitudinal designs to establish causality and investigate its interactions with inflammatory pathways. A comprehensive, multidisciplinary approach integrating biomechanical, metabolic, and inflammatory factors is essential to fully elucidate IPFP’s role in knee pathology.

Author contributions

Conceptualization: Sercan Capkin, Zeynep Ayvat Ocal, Mehmet Akdemir.

Data curation: Sercan Capkin, Ali Ihsan Kilic, Zeynep Ayvat Ocal.

Formal analysis: Sercan Capkin, Ali Ihsan Kilic, Zeynep Ayvat Ocal.

Investigation: Sercan Capkin, Zeynep Ayvat Ocal.

Methodology: Sercan Capkin, Ali Ihsan Kilic, Zeynep Ayvat Ocal, Mehmet Akdemir, Mahmud Aydin.

Supervision: Sercan Capkin, Mert Kahraman Marasli.

Writing – original draft: Sercan Capkin, Mehmet Akdemir, Mahmud Aydin, Mert Kahraman Marasli.

Writing – review & editing: Sercan Capkin, Mahmud Aydin, Mert Kahraman Marasli.