Oral Corticosteroids for Osteoarthritis
Osteoarthritis (OA), a degenerative joint disease, is the most common joint disease in the world. Approximately 40% of men and 47% of women develop OA (Murphy 2008) and in 2017 it affected over 300 million people (James 2018). The knee is the most commonly affected joint, followed by the hand, and then the hip (Oliveria 1995). Treatment options include oral medications, topical medications, joint injections, supplements, physical therapy, bracing and therapy. The purpose of this review is to discuss the role of oral corticosteroids in the treatment of OA.
You are evaluating your treatment options for a healthy 45 year old male with a history of left knee ACL repair in the remote past and mild OA by history and exam today. The patient is inquiring about oral corticosteroids as a treatment option. Which of the following is not a feared adverse effect of glucocorticoids on the musculoskeletal system?
A) Osteopenia and Osteoporosis
B) Avascular Necrosis
D) Muscle Hypertrophy
Inflammation is implicated in the pathogenesis of OA. It is driven by irritation of chondrocytes and can be primary or secondary. The excessive stress leads to increased levels of interleukin 1β (IL-1β) and tumor necrosis factor (TNF)-α expression. Synovitis is considered a key component of OA in all stages of the disease. Persistent synovial inflammation leads to hyperplasia and hypertrophy and eventually osseous changes. This sets the theoretical basis for the use of corticosteroids in the treatment of OA. Note that OA is considered a localized pathological state and not a systemic illness.
Image 1. List of some commonly used oral corticosteroids and their approximate duration of action and potency (courtesy of dvm360.com)
Corticosteroids are a potent immunosuppressant. They work by suppressing PMN leukocytes and suppressing immune system activity and volume in the lymphatic system. At higher doses, they cause adrenal suppression. Common adverse effects include insomnia, nervousness, hyperglycemia and increased appetite. Long term use of corticosteroids can affect multiple organ systems including musculoskeletal, endocrine, gastrointestinal, neuropsychiatric, cardiovascular, dermatologic, ocular and immune (Oray, 2015). Osteonecrosis and osteoporosis are most commonly associated with long term use, but can occur with short term exposure. Glucocorticoid induced myopathy is the most common type of drug induced myopathy characterized by painless muscle weakness, atrophy and fatigue.
Abou-Raya et al (2014) assessed the efficacy of low dose oral prednisone in moderate to severe knee OA over 12 weeks. They included 125 patients who were randomized to either steroids or placebo. The treatment group received 7.5 mg of prednisone daily for 6 weeks. They found a clinically significant reduction in the treatment group for knee pain, physical function, PGA, and 6 minute walk distance at 6 weeks. there was a clinically relevant reduction in the serum levels of IL-1, IL-6, TNF-α, and hsCRP at 6 weeks. These differences remained significant at 12 weeks.
Image 2. Xray demonstrating knee osteoarthritis
Image 3. XR demonstrating severe hand osteoarthritis (courtesy of raleighhand.com)
Kvien et al (2008) conducted an RCT with 83 patients with hand OA assessing the efficacy of dipyridamole combined with low dose prednisolone compared to placebo. They found that the combination was superior to placebo for changes in Australian/Canadian Osteoarthritis Hand Index (AUSCAN) and visual analogue pain scale (VAS). The treatment was well tolerated however more patients in the treatment group experienced headaches.
Wenham et al (2012) assessed the efficacy of low dose oral prednisolone for treating hand OA. This RCT included 70 patients randomly assigned to receive either 5 mg of oral prednisolone or placebo daily for 4 weeks. They found no statistically significant differences in VAS, Australian/Canadian Hand Osteoarthritis Index or joint counts (as seen on MRI).
In a subsequent RCT, Kroon et al (2019) used 10 mg of prednisolone per day in patients with clinical or radiographic evidence of inflammation and a flare up of pain. In this RCT, treatment with prednisolone for 6 weeks was associated with a reduction in pain compared with placebo. These positive effects disappeared upon prednisolone tapering.
Overall, there is very limited research in the use of oral corticosteroids in patients with osteoarthritis. In one small study in knee OA, it was effective for up to 12 weeks. Two of three studies found some benefit for hand OA. It is reasonable to consider oral corticosteroids for these conditions in select patients. Many questions remain. Which patients are appropriate for oral therapy? Which medication, at which dose and for how long? And what about other joints? How does it compare to intra-articular corticosteroids? Ultimately, more research is needed to better clarify the role of oral corticosteroids in patients with osteoarthritis.
Answer is D. Glucocorticoids have potent effects on the MSK System. The risk of these effects increases with more exposure and higher doses. This includes tendinopathies and ruptures, osteopenia and osteoporosis, avascular necrosis and drug induced myopathy. The latter is characterized by painless muscle weakness, atrophy and fatigue. Muscle Hypertrophy is not one of the effects of glucocorticoids.
Oray, Merih, et al. “Long-term side effects of glucocorticoids.” Expert opinion on drug safety 15.4 (2016): 457-465.
- Murphy L, Schwartz TA, Helmick CG, et al. Lifetime risk of symptomatic knee osteoarthritis. Arthritis Rheum 2008;59(9):1207–13
- James, Spencer L., et al. “Global, regional, and national incidence, prevalence, and years lived with disability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017.” The Lancet 392.10159 (2018): 1789-1858.
- Abou-Raya A, Abou-Raya S, Khadrawi T, Helmii M. Effect of low-dose oral prednisolone on symptoms and systemic inflammation in older adults with moderate to severe knee osteoarthritis: a randomized placebo-controlled trial. J Rheumatol. 2014 Jan;41(1):53-9. doi: 10.3899/jrheum.130199. Epub 2013 Dec 1. Retraction in: J Rheumatol. 2018 Dec;45(12):1713.
- Oliveria SA, Felson DT, Reed JI, et al. Incidence of symptomatic hand, hip, and knee osteoarthritis among patients in a health maintenance organization. Arthritis Rheum 1995;38(8):1134–41.
- Claire Y. J. Wenham, Elizabeth M. A. Hensor, Andrew J. Grainger, Richard Hodgson, Sharon Balamoody, Caroline J. Doré, Paul Emery, Philip G. Conaghan, A randomized, double-blind, placebo-controlled trial of low-dose oral prednisolone for treating painful hand osteoarthritis, Rheumatology, Volume 51, Issue 12, December 2012, Pages 2286–2294,
- Kroon, F. P. B. et al. Results of a 6-week treatment with 10 mg prednisolone in patients with hand osteoarthritis (HOPE): a double-blind, randomised, placebo-controlled trial. Lancet 394, 1993–2001 (2019).
- Oray, Merih, et al. “Long-term side effects of glucocorticoids.” Expert opinion on drug safety 15.4 (2016): 457-465.
- Kvien, T. K., et al. “Efficacy and safety of a novel synergistic drug candidate, CRx-102, in hand osteoarthritis.” Annals of the rheumatic diseases 67.7 (2008): 942-948.