Page:Fabella prevalence rate increases over 150 years, and rates of other sesamoid bones remain constant - a systematic review.pdf/8

8 Fabella: more common than it once was, M. A. Berthaume et al. the natives of Taiwan. As such, we have classified this sample as being from Taiwan, even though no such political entity existed at the time. According to Hessen (1946), Hanamuro (1927) included individuals from Formosa as well, but classified them as 'Formosa-Chinesen', indicating they were immigrants from mainland China into Taiwan. As such, we classified their sample as being from China. A summary of prevalence rates reported in the literature can be found in Table 2.

We identified one outlier in our dataset (Fig. 3), as the number of fabellae (n = 2) was exceptionally low for that number of knees (n = 62). This is not to say the data are incorrect, only that it is an outher from the other 56 studies, and thus was excluded from further analyses.

There were five studies for which the method remained 'unknown', either because the method was not mentioned in the study or we were not able to obtain the original study and identify the method. We assumed Parsons & Keith (1897) used anatomical dissections, as the X-ray was invented in 1895, making it unlikely they used X-rays to collect their data. For the four other studies, all imputed datasets yielded consistent results for Sugiyama (1914), Ooi/Oi (1930), and Mikami (1932), classifying the first two as anatomical dissections and the third as X-ray. According to the imputed data, Pichler (1918) was categorized as X-ray 15/20 times, MRI 3/20 times, and CT 2/20 times. As MRI and CT scanners were not invented in 1918, we assume Pichler used X-rays to collect their data.

The logistic regression revealed a strong increase in prevalence rates through time (Pslope < 0.01, Pintercept < 0.01; Fig. 4). The r code and raw data used to conduct the analysis are available in the Data S1 and Table S1. Assuming median random and fixed effects, the results show that:

logit(Prevalence) = -33.3390 + (1.6314 * 10-2) * Year

Interestingly, recent studies show a higher variance in prevalence rates compared with older studies. This is because there is an increase in maximum prevalence rates, with no real increase in minimum prevalence rates, causing a larger spread of the data. Although different populations were examined before and after 1960, and a genetic component may be involved in population-related fabella prevalence rates (Sarin et al. 1999), the authors are confident that the observed increase in fabella prevalence rates is not affected by these factors, as described below.

Prevalence rates were reported in four countries both before and after 1960: China, Japan, Korea, and USA. For China and Korea, there was one study before and one study after 1960; in both countries, the more recent study had a higher prevalence rate (Fig. 5). For USA and Japan, there were several studies both before and after 1960, and Pearson's linear regressions revealed positive relationships between prevalence rate and time in both countries. As there were relatively few studies in each country, we chose simpler Pearson's linear regressions in lieu of binomial mixed effect models to provide a visualization of the average change in prevalence rate over time. As random effects were ignored, little faith should be put in the regression equations and their P-values (Fig. 5). Although it is not possible to hold genetics constant between the older and newer studies, particularly in countries that have large levels of genetic diversity, such as USA, this evidence supports the idea that the increase in prevalence rates is not a by-product of different populations being used in studies before and after 1960.

Why would there be an increase in fabella prevalence rate over time? Skeletal phenotypes result from a combination of genetic and environmental factors. Although fabella formation appears to have a genetic component, it is improbable a genetic mutation is responsible for the worldwide increase in prevalence rates; the probability of a mutation occurring in Homo sapiens and spreading throughout the entire species in the past 100 years is an unprecedented and unlikely scenario.

Environmentally, it is possible that the increase in prevalence rates could be due to a hormonal or epigenetic shift.

Fig. 3 Plot of the natural log of sample size (number of knees) and number of fabellas for the 57 studies considered for this analysis. A Pearson's correlation revealed a statistically significant relationship between the two variables (y = 0.82350 * x -0.60879; t-value = 11.149, P = 2.96e-16), with an intercept that is not statistically different from zero (t-value = 1.541, P = 0.129). The data for Brazil (Silva et al., 2010) represent an outlier for this dataset. © 2019 Anatomical Society