You don’t need to be part of the Ehlers-Danlos Dazzle for very long before you hear about the big bad collagen destroying wolf lurking in our common treatments known as steroids. It’s true; the medication used to reduce inflammation to help heal joint injuries and many other things can actually weaken healthy collagen. Of course, not all steroids are the same, and they don’t have the same effect on everyone. In this post we’ll discuss these differences, some possible alternatives to taking steroids when appropriate, and how to better protect your health and aid healing when taking steroids appears to be your only treatment option.
Steroids – Why, When and How
Corticosteroids have both analgesic and anti-inflammatory properties, making them attractive for use in some of our most common health problems including asthma, allergic response, pain and inflammation caused by an injury or illness. They can also suppress the immune system and are often used to control flares in autoimmune disease.
There are many ways a doctor can dispense steroids. If you’re asthmatic, you probably take a steroid fairly regularly, either orally or through an inhaler. If you have a systemic infection or a flare-up of a chronic condition you can’t get out of, a doctor might prescribe an oral round of prednisone or administer a shot. If you tear your meniscus tendon in your right knee, the doctor could administer a localized injection in her office. You may also be administered corticosteroids in the event of an allergic reaction, which can be administered orally, by injection, through a corticosteroid inhaler or intramural spray or topically (1).
Collagen and Steroids: Frenemies Forever?
If you’ve read recent news about the FDA’s new label warnings on epidural steroid injections, you know they’ve discovered a high incidence of injury occurring during/after these injections. In part, this is due to the location of the injections, which are placed directly into the spine’s soft tissues (4). A poorly placed injection could result in spinal injury including stroke, death or paralysis. But the locations of these injections is not the only thing that’s problematic about steroid use.
When a tendon is injured, steroids seem to do their job well and appear to be safe. It’s when they’re used on an uninjured tendon that they become problematic, actually causing a weakening of the tendon that makes it vulnerable to stress. In a 2011 study by Anthony S. Wei, MD, John J. Callaci, PhD, Dainius Juknelis, MD, et al a group of rats with healthy tendons were injected with corticosteroids. The healthy rats “showed an increase of >4.5-fold (p = 0.001) in the type-III to type-I collagen expression ratio, without structural injury to the tendon. This ratio returned to baseline levels by three weeks (1).” In other words, the rats’ tendons became weak and fragile.
In a second set of rats, Wei et al., created injuries in the tendons of another group of rats being studied prior to being administered localized injections of corticosteroids. The results? The corticosteroids worked as they should, bringing the inflammation down in the joint without altering the acute phase response. Wei’s summary of the experiment captures the overall results well: “A single dose of corticosteroid does not alter the acute phase response of an injured rotator cuff tendon in the rat. However, the same steroid dose in uninjured tendons initiates a short-term response equivalent to that of structural injury (1) .”
In confirmation of these findings, a study going back to 1986 also showed that mice on anabolic steroids were more inclined to tendon rupture when dosed, particularly when exercised (2). I find this terribly ironic when considering it’s been used as a sports enhancement drug for decades. Not many athletes are very good with injured tendons. I can’t imagine what people are thinking when they take any form of steroid for “health improvement.”
In 1998, the effects of inhaled corticosteroids (IC) on skin collagen synthesis and thickness in asthmatic patients was studied by K. Haapasaari, O. Rossi, J. Risteli, and A. Oikarinen. This study found that inhaled corticosteroids (IC) only decreased the collagen synthesis of skin and bone when combined with a round of oral steroids. In this study, patients were followed for two years. The patients taking only low to moderate dose IC showed no change in skin collagen synthesis or bone density over the two year period (3).
This is possibly due to the fact that the degradation and turnover of collagen slow down, so that the net amount of collagen remains relatively constant. This assumption is supported by numerous cell culture studies, which have shown that corticosteroids decrease the activities of matrix metalloproteinases, i.e. enzymes that degrade collagens. This could also explain partially why even a marked decrease in the de novo synthesis of collagen in soft tissues, including skin, did not result in a significant change in the amount of collagen (3).
The study goes on to recommend monitoring of the skin for patients taking both an IC and oral or injected doses combined while it notes this generally isn’t necessary for inhaler use alone, reinforcing the notion that the destructive nature of steroids on collagen is dose dependent.
Mushtaq and Ahmed agree in their assessment that dose and duration matter most to collagen disruption. In their discussion of glucocorticoid (GC) steroid use in children with chronic inflammatory conditions, they note that aggressive steroid use can lead to adverse growth and bone health. “Impairment of childhood growth with an approximate cortisone dose of 1.5 mg/kg/day was first described over 40 years ago; osteopenia in children receiving a prednisolone dose of less than 0.16 mg/kg/day has also been reported (5).
Loss of bone and deterioration in short term growth are dependent on the type and dose of GC and occur most prominently over the first six months of treatment. Although it is generally believed that GC affect trabecular bone more than cortical bone, a recent study of fractures in children following steroid exposure as part of acute lymphoblastic leukaemia (ALL) treatment showed a high incidence of cortical bone involvement, suggesting that the disease process may interact with GC usage in influencing site of bone loss (5).
There are many complex chemical changes that influence this slowing in growth. What’s most important here is that even in children, while it can slow growth for an initial period, it does not appear to last or affect growth or bone health long term.:
Although earlier studies did not show a relation between inhaled steroids and growth, there is now good evidence in children with relatively mild asthma that inhaled steroids can temporarily slow growth and alter bone and collagen turnover. The magnitude of this effect may be influenced by the dose delivery system as well as the systemic bioavailability of the inhaled steroid used. This effect may be most pronounced over the first few weeks of treatment. Long term studies are difficult due to a number of confounding factors including the plethora of drugs, delivery systems, compliance, and disease severity, but there is no clear evidence that final height is compromised following inhaled GC therapy in children with asthma. Studies of bone mineral density in children with asthma have not shown any significant abnormality but have only concentrated on those children who are on relatively low doses of inhaled steroids (5).
All of these studies say the same thing; the higher the dose, the more likely it is for steroids to cause changes in collagen formation, leaving soft tissues at risk of injury, but only in the short term. What I didn’t find was any study that said there were long-term deleterious effects in adults. In 2005, Cole and Schummacher reviewed injectable corticosteroids. Their findings:
Intra-articular corticosteroids are commonly used to treat osteoarthritis and inflammatory arthritis: meta-analyses confirm their benefit in reducing pain and symptoms. Intra-articular corticosteroid injections have been shown to be safe and effective for repeated use (every 3 months) for up to 2 years, with no joint space narrowing detected. Fewer clinical trials are available for extra-articular uses for injectable corticosteroids, although there is evidence of efficacy in a variety of soft-tissue conditions. The accuracy of injections affects outcomes. Postinjection flare, facial flushing, and skin and fat atrophy are the most common side effects. Systemic complications of injectable corticosteroids are rare (6).”
Despite all of this evidence, Mayo Clinic warns on their general article about steroids and their side effects that oral corticosteroids are most likely to cause significant side effects due to their affects on the entire body, but still warn that effects are largely dose dependent, but caution that long term use can cause osteoporosis and fractures and can thin the skin, cause bruising and impede wound healing (7).
Steroids and Collagen Disorders
Collagen is a beautiful thing, when it works right. It is the glue that holds our bodies together. Not only is our skin, hair, muscle and connective tissue all comprised primarily of collagen, so too are our bones and organs. It’s perfectly logical to ask whether or not certain patients might be at greater risk for short and long term effects. Unfortunately, nobody’s bothered to try to find an answer.
In collagen disorders like Ehlers-Danlos Syndrome, Loeys-Dietz, Marfan Syndrome, Hypermobile Spectrum Disorders, and Joint Hypermobile Syndrome, the body manufactures collagen incorrectly in some way. Collagen synthesis can also be affected by mast cell degranulation. In some people with mast cell conditions (MCAD, MCAS, mastocytosis, etc.), the structural soft tissues of the body seem to function almost normally. In many, however, collagen is greatly affected by mast cell degranulation. For those who have both, like myself, the health of our collagen can fluctuate wildly based on how well our conditions are being treated, exposure to triggers, and so forth.
It makes sense we might be at greater risk when using steroids. We also have a greater need for them. So what’s the answer? Is it any more dangerous for bendy type zebras than the general population? I would love to know as much as you, but it’s never been studied! At least not that I could find. It’s disappointing, I know. Few things snap me out of a bad MCAS flare like a quick steroid injection, but I haven’t had one since I’ve been diagnosed with EDS.
I honestly thought this would be a very different post. There are many in the community who adamantly decry the use of steroids in our populations and probably for good reason. I’d imagine many of us get hurt inside of that three week window. But are we giving up on something that might be really useful and without long term side effects?
To Steroid or Not to Steroid, That is the Question
We won’t have definitive answers until someone decides it’s important enough to study. Of course we want to be safe, but we also need to be practical. First, there are times when corticosteroid use is life saving and pretty much the only answer. In this case, of course you should always just say yes to drugs. An injured zebra is much better than a dead one.
In the case of topical steroids (hydrocortisone), they thin the skin and while I couldn’t find anything that states it, my understanding is that corticosteriods are often used in dermatology to break down scar tissue because it works so well. Obviously, you want to use these creams sparingly and give your skin plenty of time to heal before using them again. I use this cream myself from time to time because with reactions like this, benadryl just doesn’t cut it:
If you have to use an inhaler for asthma and/or allergic reaction, every study I read pointed to these being quite safe so long as the dose is low and you don’t overuse them. I myself use an inhaler and feel a bit better about using it now that I’ve done this research.
It’s hard to know what’s right for sure as a zebra, but I came up with this list of 9 ways in which you can protect yourself when facing the option to use steroids, including some alternative natural anti-inflammatory substances that one might consider before opting for steroids:
Then I gathered this list from those white coat fellows over at Mayo Clinic. The article this was taken from was written by clinic staff and provides a good overview of ALL of the possible side effects when taking steroids, not just those involving collagen structures (7).
It would be nice if I could have wrapped this article up with a firm answer about the effects of steroid use in our community. It’s impossible to tell how steroids might affect us over healthy populations or even against people with different forms of chronic illness because of the lack of collagen involvement in those conditions. Given the usefulness of these drugs, My personal choice is to continue to use them sparingly and with a great deal of respect for their power. Be sure if you do need to take steroids, you do everything you possibly can to protect yourself!
- The Effect of Corticosteroid on Collagen Expression in Injured Rotator Cuff Tendon
- Organisation of collagen fibrils in tendon: changes induced by an anabolic steroid. I. Functional and ultrastructural studies.
- Effects of long-term inhaled corticosteroids on skin collagen synthesis and thickness in asthmatic patients
- FDA’s new label warnings on epidural steroid injections
- The Impact of Corticosteroids on Growth and Bone Health
- Injectible Corticosteroids in Modern Practice
- Prednisone and other corticosteroids