The Steroid Fallout

by Michael E. Farrell, MD

Not long ago, intraarticular steroids were believed to be somewhat of a panacea by patients. They were viewed as a safe, easy, and effective option for joint related aches and pains. Perhaps the optimistic attitudes patients held about steroid joint injections were for good reason. Historically, intraarticular steroid injections have been touted by physicians to be a generally benign procedure with very little risk of systemic side effects. However, more recent literature suggests that systemic effects, such as hypothalamic-pituitary axis (HPA) suppression, may be underestimated.[1] When coupled with reported side effects of chondrotoxicity and subsequent cartilage volume loss, we can appreciate why the routine use of intraarticular steroids has come under recent scrutiny. Within our continuity clinic at MedStar National Rehabilitation Hospital, I’m beginning to notice a pattern of more patients asking questions regarding the safety of steroid injections. This forces us to ask: what are some key points from the literature that physiatrists and physiatrists-in-training should know when attempting to discuss the recent steroid fallout with patients?

The first is that it appears as though systemic absorption, and subsequent HPA suppression, is dependent on the total number of joints injected rather than the total dose of glucocorticoid.[2] Just as orally administered systemic glucocorticoids can impact the HPA, at doses as low as 2.5mg to 7.5mg daily, so can small doses of intraarticular steroid injections. In one study by Armstrong et al., doses of 40mg or greater of methylprednisolone caused near complete cortisol suppression for several days. For patients with pre-existing endocrine disorders, or those concerned about systemic effects, we should be prepared to discuss options for mitigating these risks. This may mean advising against multiple, or bilateral, joint injections at a single office visit and will require a more thoughtful approach to their treatment plan.

Besides systemic effects, another common question is whether or not steroid injections are bad for joints locally through direct harm to cartilage? As physiatrists, we know that functional goals are of the utmost importance when discussing treatment options. In a 2017 JAMA study, receiving as little as four steroid joint injections per year resulted in cartilage volume loss as documented by MRI.[3] Additionally, in a recent systematic review in PM&R Journal by Jayaram et al., the chrondrotoxic effects of commonly used anesthetics were found to be dose-dependent, duration-dependent, and exacerbated with concurrent use of steroids.[4] Concerns raised by these findings have shifted our conversations towards discussing expectations and functional goals. For older patients with severe osteoarthritis whose function is severely limited, the benefits after steroid injections may outweigh the perceived risk of worsening cartilage damage. This is especially the case when total knee replacement is planned as part of the long-term treatment strategy. Still, it seems that more elderly patients have become computer savvy and are using the internet more frequently to obtain their healthcare information. This will ultimately result in voiced concerns about the impact of steroids on joint health. Their questions will provide an excellent opportunity to review clinical anatomy, go over any diagnostic imaging, and revisit their beliefs regarding their long-term treatment plans and goals.

Lastly, an increasing number of patients have become concerned about the total dose of steroid injections they receive over a given period of time. Previous literature has recommended that the maximum doses for epidural injections but never reached consensus on the total dose recommendations for intraarticular injections. In the last month’s issue of PM&R Journal, there was a very helpful article that discussed this very topic. In that article, the recommendations from Stout et al. were as follows: For postmenopausal women and potentially for men over age 50, a maximum cumulative whole body triamcinolone/methylprednisolone dose of 200mg per year and 400mg per 3 years should be considered. In addition, those with osteoporosis and, especially anyone with a fragility fracture, treatment with bisphosphonates could be considered.[1] Considering my own patient population, strict adherence to this recommendation would prove difficult as many have multiple pain-producing joints that impact their function throughout the year. Armed with this info, there has been a surge in patient interest regarding alternative treatment options.

Two potential options with interest from patients are PRP and stem cell injections. PRP, or Platelet Rich Plasma, works on the premise of fractioning out a portion of the blood containing growth and healing factors for injection back into a joint. The other option is the use of stem cell therapy which uses mesenchymal stem cells are harvested from adipose or bone marrow to be injected into the desired area. The largest advantage of either of these procedures is their reported safety within the literature.[5] Many patients seem to be keen on moving away from a pharmacologic approach and like the idea of using their bodies own self-healing mechanisms. In addition, the low side effect profile is highly desirable. The disadvantages are the premium cost incurred by the patient, and the fact that patient selection is key for the procedure to produce results. Either way, it is reasonable to suspect that as more patients begin to question the safety of steroid injections, physiatrists will see a rise in interest in regenerative medicine procedures in outpatient clinics.

Ultimately, as the literature evolves, we must be prepared to provide education to our patients. As physiatrists, our patient’s functional goals and prior response to treatment will most definitely drive these conversations. It is inspiring to see the number of quality research papers being produced by physiatrists within this space. As we get closer to finding more definitive answers on the safety of intraarticular steroid injections, I believe it will be physiatrists who continue to lead the way.

Mike Farrell is a rising PGY-3 in the Department of Physical Medicine and Rehabilitation at MedStar National Rehabilitation. Follow him on Twitter: @mefarrellii

References

1. Stout, A. , Friedly, J. and Standaert, C. J. (2019), Systemic Absorption and Side Effects of Locally Injected Glucocorticoids. PM&R: The Journal of Injury, Function and Rehabilitation, 11: 409–419. doi:10.1002/pmrj.12042
2. Armstrong RD, English J, Gibson T, Chakraborty J, Marks V. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis. 1981;40:571–574.
3. McAlindon TE, LaValley MP, Harvey WF, et al. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA.2017;317(19):1967–1975. doi:10.1001/jama.2017.5283
4. Jayaram, P. , Kennedy, D. J., Yeh, P. and Dragoo, J. (2019), Chondrotoxic Effects of Local Anesthetics on Human Knee Articular Cartilage: A Systematic Review. PM&R: The Journal of Injury, Function and Rehabilitation, 11: 379–400. doi:10.1002/pmrj.12007
5. Jayaram, P. , Ikpeama, U. , Rothenberg, J. B. and Malanga, G. A. (2019), Bone Marrow–Derived and Adipose‐Derived Mesenchymal Stem Cell Therapy in Primary Knee Osteoarthritis: A Narrative Review. Journal of Injury, Function and Rehabilitation, 11: 177–191. doi:10.1016/j.pmrj.2018.06.019