Background Patellofemoral pain (PFP) occurs frequently, and may be related to patellofemoral osteoarthritis (PFOA). Obesity is associated with increased risk of knee OA. This systematic review involves a meta-regression and analysis to determine the relationship between body mass index (BMI) and PFP and PFOA, and to determine the link between BMI and interventional outcomes.
Methods We searched seven electronic databases and reference lists of relevant papers and systematic reviews, for cross-sectional, prospective, human-based observational and interventional studies reporting BMI in individuals with PFP or PFOA compared to healthy controls. Two independent reviewers appraised methodological quality (epidemiological appraisal instrument). Where possible, data from prospective studies were pooled to conduct meta-regression and case–control, and intervention studies to conduct meta-analysis using the following categories: adolescents with PFP, adults with PFP and PFOA.
Results 52 studies were included. We found greater BMI in adults with PFP (standardised mean difference: 0.24, 95% CI 0.12 to 0.36) and PFOA (0.73, 0.46 to 0.99) compared to healthy controls, but not in adolescents with PFP (−0.19, −0.56 to 0.18). We also observed statistical trends (p<0.10) towards higher BMI being a predictor for development of PFP in adults (0.34, −0.04 to 0.71). No significant link between BMI and intervention outcomes in adults with PFP was identified.
Conclusions Higher BMI is present in PFP and PFOA, but not in adolescents with PFP.
Statistics from Altmetric.com
Knee osteoarthritis (OA) is a leading cause of pain and disability worldwide.1 Obesity is known to be related to knee OA,2 ,3 and can be estimated from a person's body mass index (BMI). Higher BMI increases the risk of developing knee OA,4 and these data are clearly synthesised in previous systematic reviews.5 ,6 The patellofemoral (PF) joint is a dominant source of symptoms associated with knee OA.7 This subpopulation of knee OA may require different management approaches to other knee-related OA, and possibly forms part of a continuum with patellofemoral pain (PFP),8 seen frequently in adolescents and adults.9
The PF joint plays a critical role in knee joint function, particularly during daily activities involving large ranges of flexion such as squatting, stair ascent and descent, where it is subjected to loads ∼ 2 to 3×BW.10 Thus, any increase in body mass will heighten the load on the PF joint, potentially increasing joint stress and structural deterioration. The association of BMI with PFP and PFOA has not been systematically evaluated. Owing to the modifiable status of obesity, identifying whether BMI is a risk factor for, or associated with symptoms in PFP and PFOA, and how it affects conservative intervention outcomes could have important clinical implications. This systematic review and meta-analysis and regression aimed to evaluate whether BMI is (1) a risk factor for PFP development; (2) higher in individuals already diagnosed with PFP and PFOA compared to healthy controls; and (3) linked to intervention outcomes in people with PFP and PFOA.
Cross-sectional human observational studies reporting BMI data in people with PFP or PFOA and a healthy control group.
Intervention studies reporting BMI data for responders and non-responders to intervention.
No restrictions were placed on age, sex or method of recruitment. Reviews, case reports and unpublished studies, as well as non-human studies, were excluded.
Assessment of methodological quality and risk of bias
Two independent reviewers (HFH and HR), who remained blind to authors, affiliations and the publishing journal, rated the methodological quality of included studies using the Epidemiological Appraisal Instrument (EAI).11 The full version of the EAI was used for intervention studies and the modified version (excludes items related to intervention/treatment) was used for all other studies. The full version of EAI has 43 items (maximum score possible 86) and the modified version has 29 items (maximum score possible 58). Items were scored as ‘Yes’ (score=2), ‘Partial’ (score=1), ‘No’ (score=0), ‘Unable to determine’ (score=0), or ‘Not Applicable’ (items removed from scoring) and an average score ranging from 0 to 2 was calculated for each study. Studies were then classified as high quality (≥1.4), moderate quality (1.1–1.4) or poor quality (<1.1).11 Final study ratings for each reviewer were collated and examined for discrepancies. Any inter-rater disagreement was discussed in a consensus meeting, and unresolved items were taken to a third reviewer (KMC) for consensus.
Data management and statistical analysis
Data pertaining to BMI, body mass, height, age and sex were independently extracted and entered into an Excel spreadsheet. If sufficient data were not reported in the published article or online supplementary material provided, the corresponding author was contacted to request further data. If unsuccessful in obtaining BMI data, mean body mass and height data were used to estimate BMI (mass (kg)/height2 (m2)), and average SD for the pooled BMI data was used. If multiple studies presented data from one cohort, then the study with a larger sample size was included. Mean age data were used to categorise PFP in adolescents (10–19 years) and adults (>19 years).
Data were divided into three categories:
Where possible, data from prospective studies were pooled to conduct meta-regression (Software R, V.3.0.2). Standardised mean differences (SMD) with 95% CIs were used to estimate differences in BMI between those who did and did not develop PFP. Data from case–control and intervention studies were pooled to conduct meta-analysis (Review Manager 5.3). SMD with 95% CI were calculated for each BMI comparison, and random effects models were used for data pooling during meta-analysis. The magnitude of the pooled SMD was interpreted as follows: SMD ≥1.20 indicated larger effect, moderate effect if 0.60–1.19 and small effect if <0.60.12 Sensitivity analyses were conducted based on methodological quality by excluding studies rated as low quality from meta-analysis and regression. Since BMI data were estimated from average mass and height data if BMI data were not presented, sensitivity analyses were also conducted by excluding the studies for which BMI data were estimated from meta-analysis and regression. Statistical significance was set at p<0.05 and a statistical trend was defined as p<0.1.13
A level of evidence was assigned based on the methodological quality ratings and homogeneity (p>0.05)/heterogeneity (p<0.05) of the pooled data. Definitions for ‘levels of evidence’ were guided by and adapted from recommendations made by van Tulder et al:14
Strong evidence provided by pooled results derived from three or more studies, including a minimum of two high-quality studies, which were statistically homogeneous (p>0.05); may be associated with a statistically significant or non-significant pooled result
Moderate evidence provided by statistically significant pooled results derived from multiple studies that were statistically heterogeneous (p<0.05), including at least one high-quality study; or from multiple moderate-quality or low-quality studies, which were statistically homogeneous (p>0.05)
Limited evidence provided by results from one high-quality study or multiple moderate-quality or low-quality studies that are statistically heterogeneous (p<0.05)
Very limited evidence provided by results from one moderate or low-quality study
Conflicting evidence provided by pooled results that are insignificant and derived from multiple statistically heterogeneous studies (p<0.05) (regardless of quality).
Search strategy, methodological quality and risk of bias
The comprehensive search strategy identified 9843 titles, with the last search conducted on 10 November 2015 (figure 1). Following removal of duplicate publications and conference proceedings, titles of 7894 publications were evaluated. The full texts of 377 articles were retrieved, with 52 articles meeting the selection criteria. Fifty-two studies (39 case–control, 10 prospective, 3 intervention) were included in this systematic review (tables 1⇓–3). The average methodological quality scores ranged from 0.76 to 1.67 and the median score was 1.13 (tables 4 and 5).
Is BMI a risk factor for PFP?
In adolescents, a single high-quality prospective study revealed that BMI did not significantly increase the risk of developing PFP in adolescents (−0.17, −0.51 to 0.17, p=0.32 (equivalent to mean difference, 95% CI −0.66, −1.98 to 0.66))15 (figure 2). Nine prospective studies in adults with PFP were included in meta-regression. BMI data were estimates from mean body mass and height for five studies. Pooled data from nine studies (5 high-quality and 4 moderate-quality) showed that higher BMI did not increase the risk of developing PFP in adults (0.12, −0.01 to 0.26; I2=0%, p=0.08 (equivalent to mean difference, 95% CI 0.34, −0.04 to 0.71))16–24 (figure 2). Sensitivity analyses revealed that exclusion of low quality studies from meta-regression did not change the results (0.12, −0.04 to 0.28; I2=0%, p=0.13). Excluding studies for which BMI data were estimated from meta-regression did not change the results (0.16, −0.05 to 0.37; I2=0%, p=0.13).
Is BMI higher in people with PFP and PFOA?
There was no significant difference in BMI between adolescents with PFP and healthy controls from two studies in adolescents (1 moderate-quality and 1 high-quality) (−0.19, −0.56 to 0.18; I2=0%, p=0.38 (equivalent to mean difference, 95% CI −0.54, −1.59 to 0.51))25 ,26 (figure 3). A total of 33 studies in adults with PFP were included in meta-analysis. BMI data were estimated from mean body mass and height for 25 studies. Pooled data from 33 (methodological quality: low=19, moderate=12, high=2) studies provided moderate evidence of higher BMI in adults with PFP compared to healthy controls (0.24, 0.12 to 0.36; I2=23%, p=0.0001 (equivalent to mean difference, 95% CI 0.84, 0.43 to 1.26))27–59 (figure 4). Sensitivity analyses revealed that exclusion of low-quality studies from meta-analysis did not change the results (0.25, 0.09 to 0.41, I2=12%, p=0.002). By excluding studies for which BMI data were estimated from meta-analysis, there was no significant difference between groups (0.22, −0.05 to 0.49, I2=43%, p=0.12). Four moderate-quality studies provided limited evidence of higher BMI in people with PFOA compared to healthy controls (0.73, 0.46 to 0.99; I2=0%, p<0.00001 (equivalent to mean difference, 95% CI 3.22, 2.22 to 4.23))60–63 (figure 5). Sensitivity analysis revealed that exclusion of studies for which BMI data were estimated from meta-analysis did not change the results (0.59, 0.24 to 0.93, I2=0%, p=0.0008).
Is BMI linked to intervention outcomes?
In adults with PFP, pooled data from three studies (3 moderate quality) showed no statistically significant link between BMI and intervention outcomes (−0.19, −0.49 to 0.11; I2=0%, p=0.22 (equivalent to mean difference, 95% CI −0.55, −1.74 to 0.65))64–66 (figure 6). There were no intervention studies available in adolescents with PFP and adults with PFOA who met the eligibility criteria.
Summary of findings
This systematic review with meta-regression and analysis synthesised BMI in populations with PFP and PFOA, and included 52 (39 case–control, 10 prospective, 3 intervention) studies. Meta-regression revealed trends of higher BMI predicting PFP development in adults. Meta-analyses indicated that BMI is higher in adults with PFP (small effect) and PFOA (moderate effect), but not in adolescents with PFP compared to healthy controls.
BMI in adolescents and adults with PFP and adults with PFOA
This systematic review was the first to explore the association of BMI with PFP and PFOA. Our meta-analysis indicates that adolescents with PFP do not have higher BMI compared to pain-free controls. However, adults with PFP have greater BMI than those without. Also, people with PFOA have an even greater BMI than controls. This apparent progressive increase in BMI difference with age may be explained by considering physical activity levels in people with PFP. Research highlights that adolescents and adults with PFP reduce their levels of physical activity due to the persistent pain associated with the condition.67 ,68 Reduced physical activity can hasten higher BMI,69 which would increase patellofemoral joint loads and stress, potentially perpetuating and exacerbating the condition.70–72 It is plausible that increased PF stress, resulting from higher BMI,27–59 could be a contributing factor to cartilage degeneration. However, longitudinal prospective studies are needed to test this hypothesis.
BMI and risk for PFP
A trend that did not reach significance indicated that higher BMI may predict the development of PFP in adults. Obesity is a well-recognised risk factor for incidence and progression of knee OA.73 Mechanical and systemic mechanisms have been proposed to explain how increased body mass may contribute to the development of knee OA.74 In weight-bearing joints, obesity increases load on the joint, which in turn promotes cartilage degeneration.75 ,76
Obesity is associated with OA in non-weight-bearing joints.77 ,78 Therefore, mechanical stress alone cannot explain this relationship. It has been suggested that adipokines produced by adipose tissue may alter the articular cartilage metabolism.79 Serum leptin levels have been identified in many joint tissues including chondrocytes, osteophytes, synovium and infrapatellar fat pad,80–83 and higher leptin levels were associated with the prevalence and incidence of radiographic knee OA.84 Obese individuals with knee OA had elevated release of Interleukin-6, known to be involved in inflammation, within their infrapatellar fat pad tissue.85 It is possible that increased production of Interleukin-6 may amplify the inflammation profile, thus contributing to cartilage degradation. Given that PFP is thought to be a precursor for PFOA,8 controlling BMI in adults with PFP may limit the mechanical and non-mechanical consequences and therefore slow or delay development and/or progression of PFOA. There are no known prospective studies investigating the impact of body mass (overweight/obesity) on progression of PFP and development and progression of PFOA. Longitudinal data will assist in determining if BMI predicts development and progression of PFP and PFOA.
BMI and intervention outcomes
Pooled data revealed that BMI was not associated with intervention outcomes in adults with PFP. This finding is consistent with previous research investigating prognostic factors for PFP.86 Based on the WHO guidelines, obesity is defined as BMI ≥30 kg/m2 and overweight as BMI ≥25 kg/m2.87 In this systematic review, the mean BMI of responders (24.0 kg/m2) and non-responders (24.6 kg/m2) to intervention was within normal range. It is plausible that BMI above the normal range (>25 kg/m2) may influence intervention outcomes. Furthermore, our finding that BMI does not predict intervention outcomes is based on pooled data from three studies in adults with PFP; therefore, it should be interpreted with caution. Better data reporting for responders and non-responders to interventions in future studies will aid in determining whether BMI (normal BMI, overweight, obese) predicts intervention outcomes.
Limitations and future directions
We acknowledge several limitations. First, all relevant studies were included in this systematic review, regardless of methodological quality. Therefore, it is possible that this systematic review is subject to bias through the inclusion of low-quality studies. However, the levels of evidence applied to the pooled data take into account quality, quantity and homogeneity of studies. Further to this, sensitivity analyses based on methodological quality revealed no differences in findings when data from low-quality studies were excluded. Second, we restricted the search to studies published in English. Inclusion of data from non-English language studies may alter the outcomes. Third, a small number of studies contributed to each meta-analysis (except for studies in adults with PFP) and meta-regression, and thus results of this systematic review should be interpreted with caution. Fourth, owing to only a limited number of relevant studies reporting BMI data, studies presenting average mass and height data were included in this systematic review and estimated mean BMI data were used in the analyses. Therefore, inclusion of these data may have influenced the overall results. Exclusion of these data from sensitivity analyses revealed no differences in findings of prospective studies in adults with PFP, and case–control studies in adults with PFOA. The difference in case–control studies in adults with PFP was not significant; however, this may represent a reduction in sample size from n=1101 (PFP=934; control=671) to n=555 (PFP=370; control=185).
A final consideration is that there is a limitation associated with using BMI as a surrogate measure of body fat. BMI is a measure of excess body mass rather than excess body fat; thus, a higher muscle mass can influence the relationship between BMI and body fat. Future studies may consider using measures of body fat percentage such as dual energy X-ray absorptiometry (DEXA) to further discern the impact of increased body fat and muscle mass on PFP. Furthermore, considering that BMI differences are absent in adolescents with PFP, small in adults with PFP and moderate in adults with PFOA, we propose that greater BMI or body fat may be related to pain persistence. However, further research is needed to explore this and understand the influence of body fat on disease progression, and how to address it.
PFOA is an important source of symptoms in knee OA, and is strongly associated with disability. Our systematic review revealed an association of higher BMI with PFP and PFOA conditions in adults.88 This has important clinical implications, as chronicity of these conditions can substantially add to disability. Further to this, obesity is also associated with a broad range of other health issues including diseases such as hypertension, Type II diabetes, knee OA, depression as well as physical and psychosocial impairments.89 Affliction of one or more of these chronic health conditions will significantly add to disease burden in individuals with PF conditions. Therefore, comprehensive management programmes targeting body weight in individuals with PF conditions (eg, physical interventions, exercise, education and nutrition) may aid in reducing physical disability90 and thus warrant intensive investigation.
Adults with PFP and PFOA have higher BMI compared with healthy controls, but no such association was observed in adolescents with PFP. To better understand the role of BMI in disease development and progression in populations with PFP and PFOA, longitudinal data are required.
What are the findings?
Adults with patellofemoral pain have a higher body mass index than healthy controls.
Adults with patellofemoral osteoarthritis have a higher body mass index than healthy controls.
Body mass index does not appear to be linked to intervention outcomes in adults with patellofemoral pain.