Females less likely to heal from ACL injuries than males in animal model | Hacker News Reader

Females less likely to heal from ACL injuries than males in animal model

medicalxpress.com

51 pointsPaulHoule57 comments

This is for those that enjoy playing regular soccer, skiing or basketball:

I hope you never have a knee injury. It sucks. But what sucks even more is reinjury. Control your urge to play again. Professionals get back on the field in 4-6 months and thats their full time job.

Trying to get back on the horse in that timeframe without a professional support structure will result in reinjury. Running on a treadmill and some PT does not mean you are ready for a contact sport. Your reflexes and natural balance take a while to reset to baseline.

I hope this message saves someone from reinjury

My (bilateral...) PCL injury took about 18 months to resolve. It was way longer than anyone was willing to tell me at the time.

The good news is that it's now like it never happened, but I suspect that's because my only exercise during those 18 months was walking and light calisthenics.

Edit: I'm a male, FYI.

I would add onto this. If your injury was non-contact, and many are, make sure you are strengthening the muscles around the joint. After a partial ACL tear, I have become obsessed with single leg stability exercises, as well as improving overall strength at the hips and ankles, to take stress off of my knee.

The doctor said it wouldn't heal on its own, but it did with no surgical intervention.

I think that few people make a real concerted effort to rehab like you did. Thanks for the inspiration. Will look into it.

I don't think the mice model for ACL injuries is a very good one here. The main difference between the knee anatomy of women vs men comes from the difference in pelvis, which in turns comes from the fact that human babies have huge heads. All other animals have small heads relatively speaking. The average litter size for mice is 6 to 8 pups, so the difference in pelvis size between female mice and male mice is probably very small compared to the difference for humans. Moreover, humans are bipedal, so pelvis differences result in knee differences. For the quadrupedal mice, if there are any pelvis differences they would probably not result in knee differences.

Hormones play an important role too:

https://scholar.google.com/scholar?cites=1738817161826894917...

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC164356/

It's always fascinating to see how they attempt to study things like this. Press releases put these broad sweeping titles on articles that make it sound to the lay observer like some sort of interventional trial was done in humans tracking some outcome we care about like time to full function return or level of permanent impairment, after incurring otherwise similar levels of tissue damage.

Then you read it and it's dead rabbit tissue put into a machine that simulates repetitive stress and the outcome measured isn't actually healing (because dead tissue can't heal), but the expression of anabolic genes known to be associated with healing in live animals.

I'm sure it's interesting work and far more feasible to do than a proper RCT, which is almost certainly illegal because you can't randomly select humans and injure them. The best way to simulate an RCT is to select people who are already injured, but then to ensure there is some comparability in the level of injury, you'd likely need to look at athletes, in sports played by both men and women, and only look at non-contact injuries. The controls to get reliable data start to become onerous quickly. So it's far easier to cut dead meat off an animal and put it in a simulator.

Readers just need to be aware of the limitations of mechanistic studies in non-human subjects, especially when it involves artificial stimulus of excised tissue and not even injuring real rabbits. The results don't support a title like this. The researchers realize this. Other scientists reading their results realize this. But consumers of science and health content in the news reading press releases do not realize this and end up forming this broad web of reinforced "facts" they believe in that they think have scientific backing behind them, when in reality they very much do not.

In case you read the comments first and are wondering: ACL = anterior cruciate ligament

For those still wondering: ACL is one of the ligaments responsible for limiting the range of motion of the knee. It primarily provides rotational stability, and is the most frequently injured knee ligament.

it does provide rotational stability (along with the PCL, between the femur and tibia; the condyles help here too) but it’s primarily job is lateral stability in the front-to-back direction, because without that, you cannot negotiate uneven terrain at all. this is vividly illustrated in a dissection by manipulating the knee with and without cutting the ACL. with no ACL, the knee is a wobbly mess, especially in the front to back (ventral-dorsal) direction.

ACL injuries have long been known to be worse in women because of anatomical differences in weight distribution relative to hip to femur to tibia angles, both statically but especially in motion.

I remember years ago reading on nytimes that girls played soccer more likely to torn ACL, and in the piece several said theirs popped more than once

It is more likely to happen when they are menstruating so they can get some protection by tracking their periods so that they avoid hard training on dangerous days.

Despite the downvotes, I believe this is true: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC164356/

It's completely true and part of best practices in women's sports.

Huh, I wonder what the mechanism is there. I wouldn't expect periodic hormonal changes to weaken a ligament.

Why not? There are androgen and estrogen receptors in many tissues throughout the body.

Correlation/causation. Could be as simple as being more tired than usual. Being tired is more dangerous for lots of sports, and is true for men as well (just not on a predictable schedule).

I remember our wrestling coach constantly comparing the sport to womens' sports with higher injury rates.

"No need to be careful - this isn't [cheerleading|womens' soccer|volleyball] where you could actually get hurt"

That's a fun anecdote. I referee high school and youth wrestling and there are several coaches who are paraplegic or quadriplegic because of neck or spinal injuries they got wrestling. I assume there are other injured people who didn't want to have anything to do with the sport after their injury.

It is an epidemic in professional women's soccer. At any given time a third of the top players in the world are sidelined with an ACL.

So what is the problem, they are pushing things to hard and too far?

Growing popularity of the women's game has meant more games and fewer breaks in competition.

That, and women's basketball, and women's ice hockey, etc. See

https://www.theguardian.com/sport/2023/oct/19/las-vegas-aces...

My sports photography habit has gotten me out to all kinds of games and I've discovered I really like women's field hockey which is almost exclusively a female sport in North America. I was surprised to find out that men's field hockey is super big internationally, because unlike soccer, people in the US never got the message the field hockey was a huge international game.

Overall women and girls are playing more than, say, 10 years ago. But they still play considerably less than men and boys, at all levels, at least in soccer, and there are many, many more joint injuries.

My non-medical person understanding is that the physiology and mechanics in the knee are very different but beyond that it is a "no one knows" situation which seems shameful.

Again, have zero medical background and am not a woman but my mental model from my wife and daughters' experience and from paying a lot of attention to professional women's soccer is that it is simultaneously true that there are a huge number of physical/biological things when it comes to athletics that completely different in women and yet also that they are entirely unstudied. Like it is just a crazy giant blind spot.

The male body is optimized for running.

The female body design is a compromise between that and surviving childbirth.

They're also more likely to get concussions from things like headers. The female body is just not as adept at physical activity as the male one. It's almost like its main focus is on creating babies.

I remember that article from the NY Times Magazine, it was from 2008. Here's a link for anyone that's interested: https://nyti.ms/3ScsVm5

It's long but a good read, particularly if you've got daughters in sports.

This takes me back to my time as a student, when on a winter sports trip a girl in the group tore both ACL's in what I heard was a relatively low speed fall on skies. From what I heard it took a long time to recover and I'm not sure if there was ever a full recovery.

I am a ski race coach, every expert female skier that I know has had at least one ACL replacement, have lost count of the number of them that I have had to help off the hill.

My theory is that women's knees are a fair bit narrower than those of a man of the same height so that they generate more torque on the ligaments.

At what age do you notice this typically happens at?

i'ev heard it was the wider hips, too, which put the ligaments at an angle, and with less muscle mass, compared to males with more leg muscle mass and straight pull ligaments

I tore my acl and meniscus by jumping from what I thought was a reasonable height. Evidently all my weight landing on one leg was too much. Did indeed hear a "pop". I remember talking with doctor and they mentioned to me that football players often tear their acl/meniscus and "don't immediately realize" because of the all the surrounding muscle that compensates. In my case, I immediately realized.

Nearly two decades later, this cadaver* replacement feels much stronger than the stock.

*I also learned you could opt for your own tissue or from a cadaver. With your own tissue, recovery was longer. With cadaver, they cautioned there was a "non-zero" (read:infinitesimal) chance of contracting HIV. I thought that was an unusual disclaimer.

1 in 1.8 million for HIV and 1 in 750k for Hep C according to Google. When I had my surgery 10 years ago I remember them quoting worse numbers, I think 1 in 300k for the latter. I went with the self-graft, though moreso bc they said cadaver had slightly higher reinjury chance.

I'm glad they've added that disclaimer. My mother contracted HIV from donated blood she received during surgery.

I'm sure that testing is much better in the decades since then, and I'm sure that non-zero should be read as infinitesimal in this modern era, but the chances of contracting something may not be non-zero, and if another AIDS-like virus were to come along and it were to take a few years before it became known and detectable, those might be more susceptible to being transmitted through implantation.

Androgen hormones are widely known to aid in recovery. This is nothing new.

I personally dislike these kinds of comments. The idea that androgens aid in recovery may be known in theory, but this study provides empirical evidence to support that claim. So yes, there is scientific value in it.

Perhaps. But I don't feel they're saying "in theory". They're saying we've already seen that XX and XY recover differently, and this is simply another example of something we already know.

Sure a link or two might have helped. But there is value in pointing out "no new news here" if that provides context.

Your usage of XX and XY has my interest piqued.

Does that shorthand save typing over man and woman or male and female?

Or is the goal separating phenotype from genotype and being scientifically and politically clear what the discussion is about?

It's intended to speak to the biological and not "gender".

there is no "in theory", steroids and recovery time are pretty well known, both in research, and via athletes who are, like, totally not doping

example from 1999: https://pubmed.ncbi.nlm.nih.gov/9934411/

> Anabolic steroids may aid in the healing of muscle contusion injury to speed the recovery of force-generating capacity. Although anabolic steroids are considered renegade drugs, they may have an ethical clinical application to aid healing in severe muscle contusion injury, and their use in the treatment of muscle injuries warrants further research.

Well if that's the cause that's very good news, since we already know how to give people hormone therapy.

While the side-effects might at first seem dramatic, we accept far worse side-effects from, say, surgery.

I feel something must be missing from this model. At face value, the abstract level summary implies that tissue remodeling and repair just... doesn't occur for females. That seems incredibly not plausible (in humans).

I'd be interested to see similar studies with different tissue donors (obviously human would be ideal... though getting a reasonable supply of healthy young-ish human ACLs is a sad thought). I can't help but wonder if choice donor (bunnys) are having an outsized influence on the results. Bunnys are famously r-selection. Maybe mommy bunnys just... get an especially raw deal in terms of tissue remodelling potential.

Also, the strain they measured in their ACLs seem high?? From what I understand human ACLs have a strain at breaking of 25-30%, so their observed strains (5-10% at 2MPa, 10-20% at 4MPA and 20-40% at 8MPa) seem... off.

The most common repair process right now is to be your own tissue donor, a bit of hamstring tendon is used to replace the ACL.

I'm having that done tomorrow morning followed by 4 months of video games.

The summary does not say that healing doesn't occur for females, but rather that the variance of healing is not effected in similar ways as for males.

Males adjust their healing (or to be specific, the increased expression of anabolic genes) based on the injury. Low to medium injuries resulted in increase healing, while larger force decreased healing. This adaptation to injury allows for greater healing in average, while female rabbits maintain the same relative lower rate of healing regardless of injury.

Since we are talking about rabbits it is important to look at sex difference in that species. Males fight each other with only a few being able to successfully reproduce. Female rabbits do not. Males that successfully reproduce will need to repeatably heal themselves from minor to medium injuries. Thus we could explain the variance as being a natural results of that process.

Yes that's true (I plead the coffee still kicking in). Even in a baseline (steady) state, where anabolic and catabolic forces are in balance, a degree of continuous tissue remodelling is taking place, that will gradually tend to heal injuries (to a first approximation).

At least in the human body, I understand it is the lack of blood flow that typically makes the ACL a difficult ligament to repair, in both sexes

"In rabbits".

In dead rabbits.

I don't understand the headline.

IMO you might as well avoid all high impact activities if you can, male or female. The risk of a life changing injury is just too high. Stick to low impact activities like walking, cycling, resistance training etc.

I downvoted because high-impact activities are known to build bone density. I honestly don't know what causes one person to get injured and not another, but I don't think it's the "impact" of running, which is what our bodies were made to do. High- (or medium?-)impact activity may very well be part of the mix of what keeps you strong into your golden years.

Resistance training is known to build bone density too.

Our bodies weren't "made to" run on concrete. Our (male) ancestors hunted by chasing animals on soft ground for a long time, sure. That's a lot lower impact than a lot of sports that injure people.

> resistance training

> low impact or low risk

strongly depends on what you're doing

Anecdata: I've sustained many more injuries from lifting than from any other activities, combined, in my life.

It's still absolutely worth it, but I'm not sure walking and lifting can be classed in the same category of "low impact".

Some advice from an old man: the risk-to-reward ratio of heavy deadlifts is too high, regardless of how perfect your form is. If you absolutely must do them, use the hex bar.

I hit my heaviest deadlift years ago. 2.5x my bodyweight. I basically quit after that realising this would only stop once I got injured.

You don't have to keep going heavier and heavier, though. You can stick to bodybuilding and higher reps.

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