Mystery arthritis-linked knee bone 3x more common than 100 years ago

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The fabella, a small bone in the knee once lost to human evolution, has made a surprising resurgence over the last century. The new findings could help clinicians treating patients with knee issues and provide insight into human evolution over the past 100 years.

The bone, linked to knee problems and pain, is buried in a tendon behind the knee, and was once rare in humans. Now a study by Imperial College London researchers has found that fabellae are becoming more common in humans. The results, which spanned over 21,000 knee studies over 150 years, showed that between 1918 and 2018, the rate of fabellae occurrence in humans increased more than threefold.

Through the analysis, they reviewed 21,676 individual knees over 27 countries. The earliest records they looked at, which were from 1875, showed that fabellae were found in 17.9% of the population. From this, the researchers created a statistical model which predicted prevalence rate while controlling for country of study and method of data collection – such as X-rays, anatomical dissection, and MRI scanning.

Their analysis showed that in 1918, fabellae were present in 11.2% of the world population, and by 2018, they were present in 39% – a 3.5-fold increase.

Lead author Dr Michael Berthaume, from Imperial’s department of bioengineering, said: “We don’t know what the fabella’s function is – nobody has ever looked into it!”

The fabella is a sesamoid bone, meaning it grows in the tendon of a muscle: the kneecap, for instance, is the largest sesamoid bone in the human body.

Berthaume added: “The fabella may behave like other sesamoid bones to help reduce friction within tendons, redirecting muscle forces, or, as in the case of the kneecap, increasing the mechanical force of that muscle. Or it could be doing nothing at all.”

Having a fabella has its drawbacks. People with osteoarthritis of the knee are twice as likely to have a fabella than people without osteoarthritis – however, it is unknown if the fabella causes osteoarthritis in the knee, and if so, how. It can also cause pain and discomfort on its own, and can get in the way of knee replacement surgery.

The study authors say their findings could have implications for how we treat patients with knee pain, or those who need knee replacements or treatment for osteoarthritis. Berthaume said: “We are taught the human skeleton contains 206 bones, but our study challenges this. The fabella is a bone that has no apparent function and causes pain and discomfort to some and might require removal if it causes problems.

“Perhaps the fabella will soon be known as the appendix of the skeleton.”

In old world monkeys, the fabella can act as a kneecap, increasing the mechanical advantage of the muscle. But when the ancestors of great apes and humans evolved, it seemed to disappear.

Berthaume said: “As we evolved into great apes and humans, we appear to have lost the need for the fabella. Now, it just causes us problems – but the interesting question is why it’s making such a comeback.”

The answer, says Berthaume, could lie in nutrition. “We found evidence of fabella resurgence across the world, and one of the few environmental changes that have affected most countries in the world is better nutrition.”

Researchers found the fabella seems to be the only sesamoid bone in the human body to be increasing in prevalence. Sesamoid bones are known to grow in response to mechanical forces.

Berthaume added: “The average human, today, is better nourished, meaning we are taller and heavier. This came with longer shinbones and larger calf muscles – changes which both put the knee under increasing pressure. This could explain why fabellae are more common now than they once were.”

Not all people have fabellae, however, and there is likely a genetic component controlling the ability to form one – but for those who can form a fabella, this increased mechanical forces might drive their formation.

The researchers say they are now looking at how prevalence differs across genders, ages, and regions and the proportion of people who have fabella in one or both knees. They also hope to delve into the genetics of the bone and how its inclusion in the human skeleton has changed over time.

This work was funded by the National Institute for Health Research.

Abstract
The fabella is a sesamoid bone located behind the lateral femoral condyle. It is common in non‐human mammals, but the prevalence rates in humans vary from 3 to 87%. Here, we calculate the prevalence of the fabella in a Korean population and investigate possible temporal shifts in prevalence rate. A total of 52.83% of our individuals and 44.34% of our knees had fabellae detectable by computed tomography scanning. Men and women were equally likely to have a fabella, and bilateral cases (67.86%) were more common than unilateral ones (32.14%). Fabella presence was not correlated with height or age, although our sample did not include skeletally immature individuals. Our systematic review yielded 58 studies on fabella prevalence rate from 1875–2018 which met our inclusion criteria, one of which was an outlier. Intriguingly, a Bayesian mixed effects generalized linear model revealed a temporal shift in prevalence rates, with the median prevalence rate in 2000 (31.00%) being ~ 3.5 times higher than that in 1900 (7.64%). In all four countries with studies before and after 1960, higher rates were always found after 1960. Using data from two other systematic reviews, we found no increase in prevalence rates of 10 other sesamoid bones in the human body, indicating that the increase in fabella prevalence rate is unique. Fabella presence/absence is due to a combination of genetic and environmental factors: as the prevalence rates of other sesamoid bones have not changed in the last 100 years, we postulate the increase in fabella prevalence rate is due to an environmental factor. Namely, the global increase in human height and weight (due to improved nutrition) may have increased human tibial length and muscle mass. Increases in tibial length could lead to a larger moment arm acting on the knee and on the tendons crossing it. Coupled with the increased force from a larger gastrocnemius, this could produce the mechanical stimuli necessary to initiate fabella formation and/or ossification.

Authors
Michael A Berthaume, Erica Di Federico, Anthony MJ Bull

Imperial College London material
Journal of Anatomy abstract


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