September 9, 2018
introduction to corticosteroids cover

Introduction and Comparison of Corticosteroids

Corticosteroids are medications that are commonly injected and many people refer to these injections as “cortisone” injections. The first corticosteroid injection was performed in 1953 and the first clinical trial was performed in 1958 1,8. The medications are synthetically formulated to mimic the steroid hormone cortisone, which is produced by the adrenal gland and released in response to stress. Intra-articular corticosteroids reduce synovial blood flow and alter local collagen synthesis 2. They have also been shown to decrease the local inflammatory modulator response by mechanisms such as interfering with inflammatory cell adhesion, interrupting cytokines like IL-1, and impairing leukotriene and prostaglandin synthesis 3.
There are a few characteristics that are examined when looking at depot corticosteroids.  Solubility seems to be mentioned across the orthopedic specialty often and compounds with lower solubility are thought to remain at the injected site for longer periods of time and, in theory, have less systemic effect.  Triamcinolone acetonide (Kenalog) is the least soluble of the commonly used injectable steroids, followed by triamcinolone hexacetonide (Aristospan) 4.  Crystal structure and duration of action are also typically factored in when choosing corticosteroids.   Microscopic comparison studies have shown methylprednisolone to be the largest particle, triamcinolone to be intermediate and betamethasone to be the smallest 5,6.
comparison of corticosteroids

Image 1. Comparison of corticosteroids (adopted from 4, 5, 6)

The most commonly used corticosteroids include triamcinolone acetonide (Kenalog), betamethasone (Celestone) and methylprednisolone (Depo-medrol).  The doses for triamcinolone and methylprednisolone are typically 20 mg,40 mg and 80 mg per mL. The dosage for betamethasone is usually 6 mg/mL. Triamcinolone and methylprednisolone are branched esters and generally the preferred agents for joints. In a 1994 survey for college of rheumatology members, 35 % preferred methylprednisolone, 31 % preferred triamcinolone hexacetonide and 21 % preferred triamcinolone acetonide for knee osteoarthritis injections .   There were also regional differences with triamcinolone being more used in the West and methylprednisolone being preferred in the East 7.
examples of different corticosteroids used for joint injections

Image 2. Examples of various corticosteroids that are sometimes used in joint injections (adopted from henryschein.com)

There are few direct trials comparing efficacy of the most common corticosteroids used.  One study from 1981 compared triamcinolone 20 mg with 6 mg of betamethasone in forty two patients that underwent a knee injection for osteoarthritis and triamcinolone was found to have decreased pain and tenderness as well an increased range of motion after one week and two weeks 9. Another study in 2004 compared 40 mg of methylprednisolone acetate to 20 mg of triamcinolone hexacetonide in 57 patients with knee OA.  This study showed triamcinolone hexacetonide with less pain and less disability at week 3, but methylprednisolone to be more effective at week 8 10.  Two other studies were performed that showed no difference between methylprednisolone and triamcinolone 11,12.  Two studies have shown that triamcinolone hexacetonide offered longer lasting pain relief for patients with rheumatoid arthritis of the knee 13,14.  One systematic review in 2009 showed a trend that pain control was better with triamcinolone 15.  No difference was found in local site injection when comparing triamcinolone to betamethasone in one trial and hydrocortisone in another 9,16.
Overall, there is limited randomized control trials comparing the efficacy of depot corticosteroids for joint injections 1.  The choice of corticosteroids is typically based on training tradition and clinical experience but other factors are involved such as cost and availability.  Cost and insurance reimbursement can vary by region. The paucity of evidence is the main reason there is so much variability in which agents are used for joint injections.

References

1. Douglas, R. (2012). Corticosteroid injection into the osteoarthritic knee: Drug selection, dose, and injection frequency. International Journal of Clinical Practice,66(7), 699-704.
2. Caldwell JR. Intra-articular corticosteroids. Guide to selection and indications for use. Drugs. 1996;52(4):507–514
3. Lavelle W, Lavelle ED, Lavelle L. Intra-articular injection. Med Clin North Am. 2007;91(2):241–250.
4. Cole, Brian and Harold R. Schumacher. “Injectable corticosteroids in modern practice.” The Journal of the American Academy of Orthopaedic Surgeons 13 1 (2005): 37-46.
5. Derby R, Lee SH, Date ES, Lee JH, Lee CH. Size and aggregation of corticosteroids used for epidural injections. Pain Med. 2008; 9:227-34.
6. Lento P, Ihm J, Kennedy D, Visco C. Peripheral Joint and Soft Tissue Injection Techniques. In Chan L, et al, eds. Braddom’s Physical Medicine & Rehabilitation. 4th Philadelphia, PA: Saunders; 2011:517-540.
7. Centeno LM, Moore ME (1994) Preferred intraarticular corticosteroids and associated practice: a survey of members of the American College of Rheumatology. Arthritis Care Res 7:151–155.
8. Miller JH, White J, Norton TH: The value of intra-articular injections in osteoarthritis of the knee. J Bone Joint Surg Br 1958;40:636-643.
9. Valtonen EJ. Clinical comparison of triamcinolone hexacetonide and betamethasone in the treatment of osteoarthrosis of the knee joint. Scan J Rheumatol Suppl 1981; 41: 1–7.
10. Pyne, D., Ioannou, Y., Mootoo, R., & Bhanji, A. (2004). Intra-articular steroids in knee osteoarthritis: A comparative study of triamcinolone hexacetonide and methylprednisolone acetate. Clinical Rheumatology, 23(2), 116-120.
11. Thorpe P: Intra-articular triamcinolone acetonide and methyprednisolone acetate in arthritis. Curr Ther Res 1985;38:513-518.
12. Bain LS, Balch HW, Wetherly JM, Yeadon A: Intraarticular triamcinolone hexacetonide: Double-blind comparison with methylprednisolone. Br J Clin Pract 1972;26:559-561.
13. Sambrook P, Champion G, Browne C et al. (1989) Corticosteroid injection for osteoarthritis of the knee:peripatellar compared to intra-articular route. Clin Rheumatol 7:609–613.
14. Bird HA, Ring EFJ, Bacon PA (1979) A thermographic and clinical comparison of three intra-articular steroid preparations in rheumatoid arthritis. Ann Rheum Dis 38:36–39.
15. Hepper CT, Halvorson JJ, Duncan STet al. The efficacy and duration of intra‐articular corticosteroid injection for knee osteoarthritis: a systematic review of level 1 studies. J Am Acad Orthop Surg 2009; 17: 638–46.
16. Wright V, Chandler GN, Morison RAH, Hartfall SJ. Intra‐articular therapy in osteo‐arthritis. Comparison of hydrocortisone acetate and hydrocortisone tertiary‐butylacetate. Annals of the Rheumatic Diseases 1960;19:257‐61.

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