Author(s): Mihir Joshi, MD, Mahmood Gharib, MD
Originally published: April 13, 2016 Last updated: August 29, 2024
Jump to:

Overview and Description

Steroid injections play a prominent role in musculoskeletal care and pain management in PM&R; this article will review steroid pharmacology, various types of steroids, indications, basic techniques, adverse effects and complications.

Naturally occurring corticosteroids can be classified as mineralocorticoids, glucocorticoids, and adrenal androgens.  The primary glucocorticoid found in humans is cortisol and is produced by the adrenal cortex under the regulation of the hypothalamic-pituitary-adrenal axis.1 Normal production is approximately 5-10 mg/m2 per day, which is roughly equivalent to 20-30 mg/day of hydrocortisone or 5-7 mg/day of oral prednisone.2,3 Synthetically produced cortisol analogues are commonly used for injections.

Glucocorticoids are lipophilic and diffuse through the cell membrane to bind glucocorticoid receptors in the cytoplasm. High-dose glucocorticoids alter sodium and calcium cycling at the cell membrane level. This results in a rapid decrease in inflammation by targeting a wide variety of cells, including T-lymphocytes, macrophages, fibroblasts, neutrophils, eosinophils, and basophils.4

Steroids act as powerful anti-inflammatories primarily by reducing the transcription of genes involved in inflammation but also through the increased synthesis of phospholipase A2 inhibitors, decreasing bradykinin, histamine, prostaglandins and leukotrienes and directly stabilizing neural membranes and inhibiting C-fiber transmission.5,6,7

The most commonly used synthetic corticosteroids are derivatives of prednisolone; methylation of prednisolone produces methylprednisolone, while fluorination of prednisolone produces triamcinolone, betamethasone and dexamethasone. Fluorination may also lead to increased absorption and potency.7,8

Relevance To Clinical Practice

Potency, solubility, size, and duration

Commercial preparation of corticosteroids involves esterification to enhance stability and water solubility. Certain steroid esters such as methylprednisolone acetate (Depo-Medrol®) and triamcinolone acetonide (Kenalog®) remain partially insoluble in suspension and particulate out of solution, while other steroid esters, such as dexamethasone sodium phosphate, stay in suspension and are classified as non-particulate. Particulate steroids have a depot property which leads to slower absorption and is postulated to allow for longer duration of benefit after injection.

Particulate preparations, while commonly used for peripheral injections, may have serious adverse events when used for axial spine injections, including blood vessel injury or spasm, or even embolization through arterial vessels leading to spinal cord infarction and paralysis. Methylprednisolone has a significantly higher percentage of large particles compared to other injectable corticosteroids and may lead to increased incidence of vessel occlusion. Light microscopy studies have demonstrated that the particles in these steroid preparations are either larger than red blood cells or form aggregates larger than red blood cells9. Triamcinolone preparations have an intermediate particle size while betamethasone has the smallest particulate size.9,10

Table 1: Potency, Solubility and Preparations*

Steroids and Corticosteroids – Table 1

Indications

Steroids are frequently used to control inflammation when more conservative measures (i.e., NSAIDs, rest, ice, compression, elevation, physical therapy) have been exhausted.6 Typically, steroids can provide short-term pain relief (from weeks to months); few injections are associated with long-term relief of symptoms.

Studies support the use of corticosteroid injections for carpal tunnel syndrome, trigger finger, de Quervain’s tenosynovitis, and bursitis and tenosynovitis associated with rheumatic diseases. The role of corticosteroid injectables for rotator cuff disease remains unclear.12 The use of injectable corticosteroids has shown short-term pain relief for subacromial impingement syndrome, adhesive capsulitis, medial and lateral epicondylitis, and hip or knee osteoarthritis.13

Although spinal steroid injections are commonly used for treatment of axial and radicular neck or low back pain due to traumatic or degenerative conditions, the US Food and Drug Administration (FDA) has not approved any drug for spinal injection to treat neck and back pain. The FDA requires the addition of Warning labels for injectable corticosteroids to describe the risks of rare but serious adverse events, including loss of vision, stroke, paralysis, and death.14

Contraindications

Steroid injections are contraindicated in the setting of overlying soft tissue infections, sepsis, bacteremia, anatomic inaccessibility, articular instability, septic arthritis, avascular necrosis, periarticular fracture and Charcot joints. A joint with a surgical implant would be a relative contraindication,6 posing the risk of periprosthetic infection. 

Precautions should be taken in patients with diabetes mellitus (DM), as part of the considerations of their overall comorbidities. The American Academy of Orthopedic Surgeons,15 American College of Sports Medicine,16 American Diabetes Association,17 and American Medical Society for Sports Medicine18 do not have established recommendations with regards to steroid injections in patients with diabetes mellitus. However, precautions should be taken after an injection is performed. Transient increases in post-injection blood glucose levels (BGL) were noted in ten studies. Mean blood sugar elevations have ranged from 125 to 320 mg/dL with peak post-injection BGL occurring within 1 to 5 days. BGL returned to baseline within 10 days and usually in less than 24 hours. Patients with Type 1 DM or insulin-dependent diabetes mellitus (IDDM) had higher post-injection BGL than those with Type 2 DM not requiring insulin in two studies. Patients with HgA1c >7.0% had BGLs that were higher and lasted longer than those with lower HgA1c levels. Although none of the studies specifically evaluated complications from elevated BGL, no adverse events were reported in any of the studies.19

There is no established causal link between injected corticosteroids and effects on anticoagulation therapy, in either direction. However, within the scope of this article it is worth noting that precautions and risk-benefit determination should always occur when considering steroid injections for patients on systemic anticoagulation medications. These risks are due to the invasive nature of a percutaneous procedure, regardless of injectate. There have been studies which have established the safety of continuing anticoagulation with warfarin before peripheral aspirations/injections with only a small increased risk of bleeding.20 Nevertheless, practitioners should check the patient’s INR the day of the procedure and reference the established guidelines from spine specialty societies (ASRA, NASS, ASIPP) for the selected procedure. In addition ensure that the patient is not experiencing any episodes of unexplained bruising or bleeding.21 Studies also confirm that there is no need to hold and it is safe to continue anti-platelet drugs and direct oral anticoagulants, such as Xarelto and Eliquis before most peripheral steroid injections.21,22 The possibility of bleeding, bruising, or hemarthrosis should always be discussed with the patient and documented.

One notable exception to the general acceptability of continuing blood thinners is any epidural steroid injection delivered via interlaminar approach. The posterior epidural venous plexus traverses just posterior to the posterior epidural space, which is accessed with any interlaminar epidural steroid injection. Due to the gauge of needle (typically 18-20 gauge) utilized in these injections, and the limited space for a hematoma to form, there is a higher risk of clinically significant epidural hematoma with possible cord compression. For this reason, society guidance recommends cessation of anti-coagulation therapy prior to interlaminar procedures. The decision to hold or continue anti-coagulation agents should be done in conjunction with the patient and their treatment team.

Precautions should be taken with patients being treated for a psychotic illness. Systemic steroids can trigger or aggravate a psychotic episode. Consider discussing with a patient’s psychiatrist before providing an injection.21

Dilution

Due to the low volume and high concentration of most steroid preparations ranging from 10-80mg/ml, saline, contrast media, or local anesthetic agents are frequently used as diluents. Increasing the total volume of the injectate can facilitate spread to a larger area or a higher spinal level than can safely be accessed. For example, interlaminar cervical epidural steroid injections are not recommended to be performed any higher than the C6-C7 level due to the reduced epidural space and the increased risk of dural puncture at higher levels. In such instances, the typical 1ml of steroid solution is diluted in 1-3ml of chosen diluent to allow upward spread. The same can be done for caudal epidural steroid injections at the sacral hiatus, as total volumes of up to 10-20ml are routinely used to facilitate upward spread to the target level of the lumbar spine. The total volume of injection should be tailored to the patient, particularly in cases of severe canal stenosis at or near the level of injection. In addition, dilution may decrease the risk of atrophy when placed in smaller or superficial structures such as the hand. Dilution does increase the risk of infection, especially when using multidose vials.

When local anesthetics are used in conjunction with the steroid agent, the immediate analgesic response may help confirm placement and provide useful diagnostic information. However, the parabens in local anesthetics such as lidocaine may lead to flocculation, or precipitation of the steroid mixture in the syringe.23 When possible, the use of preservative-free preparations is recommended.

The most commonly used anesthetic adjuvants are lidocaine hydrochloride, bupivacaine hydrochloride, or ropivacaine hydrochloride. The strength of the agent is provided as a percentage, which refers to the mass in grams of solute per 100ml of solution. Thus, 1% lidocaine is 1000mg per 100ml, or 10mg/ml. There are reference tables available through the American Society of Anesthesiology indicating the maximum safe dose in mg/kg for the various local anesthetic agents, though for a single injection in an adult the total amount tends to be well under the safe limit. Lidocaine acts rapidly within seconds and with an estimated duration of 30 minutes. Bupivacaine has a slower onset of action, taking 30 minutes to achieve its full effect, with an estimated duration of 8 hours or more.21 Ropivacaine has a comparable pharmacokinetic profile to bupivacaine and may be preferred as it is both less cardiotoxic and chondrotoxic than bupivacaine. It should be noted that ropivacaine uniquely causes the non-particulate steroid dexamethasone to crystallize when the two are combined, therefore, care should be used in anesthetic choice when a non-particulate steroid solution is desired.

Steroids and Corticosteroids – Table 2

Preservatives can be added to anesthetics to prevent the growth of microorganisms introduced during the manufacturing process.24 Such preservatives are commonly added to anesthetics dispensed in multi-dose containers and less commonly added to drugs intended for single use.25 Anesthetic solutions containing anti-microbial preservatives (e.g. benzyl alcohol or parabens-containing compounds) should not be used for epidural or spinal anesthesia because the safety of these agents has not been established with regard to these types of procedures.26 Due to the unclear risks, preservative-free anesthetic solutions are recommended for neuraxial epidural or intrathecal procedures.

Steroids and Corticosteroids – Table 3

Common injection procedures

Peripheral Joints

  • Thoroughly cleanse skin with alcohol, betadine or chlorhexidine.
  • Use a 21-30 gauge needle (larger diameter and 2 length for larger joints, smaller diameter and shorter length for superficial injections).
  • The use of image guidance (ultrasound or fluoroscopy) is recommended for all injections due to increased accuracy and safety.
  • If utilizing fluoroscopy, perform an arthrogram using 1-5ml of contrast media to confirm intra-articular placement and avoidance of vasculature.
  • Aspirate prior to injection.
    • Negative aspiration cannot rule out intravascular injection.
    • Synovial fluid aspiration is ideal as it confirms needle placement, fluid should be straw-colored. Any deviations from the norm should prompt further investigation including fluid analysis, culture and sensitivities. Steroid should not be injected if there is concern for infection.
  • The injectate should flow relatively easily into the intraarticular or bursal space; if resistance is encountered, repositioning should be attempted.6
Steroids and Corticosteroids – Table 4

Spinal Interventions

Steroids have been increasingly utilized in spinal interventions and steroid selection (particulate versus non-particulate) can help reduce risk of injury to the patient.

Central nervous system injuries have been attributed to blood vessel injury, spasm or embolization of particulate steroid through vessels. Blood vessel injury can be attributed to direct needle trauma or effects of dye. Embolization, however, can cause segmental infarct directly related to effects of particulate size in various steroid formulations. Methylprednisolone has a higher percentage of large particles, followed by triamcinolone, and betamethasone having the smallest particulate size.10

Dexamethasone is a non-particulate steroid with little to no large particles. For transforaminal procedures throughout the spine, dexamethasone is preferred as an inadvertent intravascular injection with a particulate steroid could have life threatening consequences. The safety of preservative agents, such as benzyl alcohol or methylparaben, found in diluents has not been established with regard to intrathecal injection.26 There have been case studies documenting adverse events associated with preservatives that include – lower extremity weakness with sensory deficits,27 epidural tissue damage,28 and chronic adhesive arachnoiditis.29 For safety purposes, preservative-free anesthetic solutions should be used as diluents for all steroid injections to the spine.  

Steroids and Corticosteroids – Table 5

Side effects

Side effects can be broken down into local effects and systemic effects

  • Local side effects
    • infection (rare as evidenced by one study that found an infection incidence of 0.005% in more than 400,000 consecutive injections32)
    • post-injection flare (2-6% of patients, crystal induced synovitis causing inflammation, typically lasts up to 12-48 hours and is treated with NSAIDs and ice6)
    • skin changes/hypopigmentation
    • tissue/fat atrophy
    • tendon rupture
    • avascular necrosis
    • bleeding/bruising (e.g., hematoma) – attributable primarily to the injection itself, usually self-limited
  • Systemic Side Effects
    • steroid presence in bloodstream (intraarticular methylprednisolone acetate of either 40 or 80mg led to detectable levels in the serum with peak levels at 2 and 12 hours post-injection)
    • suppressed endogenous serum cortisol level for 1 week post-injection33
    • acute hyperglycemia, persisting for up to 3 days with a peak glucose level of 300 mg/dL34
    • facial flushing (up to 15% of patients, most frequently associated with triamcinolone10,34)

Particulate steroids have been linked to worsened local and systemic side effects because of their longer duration in tissue. Triamcinolone aggregation within serum suggested that the embolization of particulate corticosteroids in transforaminal injections could be the cause of rare complications that include spinal cord and brain infarction.35

Safety

The safe maximum number and frequency of steroid injections is uncertain. Most studies have evaluated safety in the context of rheumatoid arthritis and osteoarthritis.

In rheumatoid arthritis, studies have shown no change in joint arthroplasty rates between patients who received four or more injections annually versus those receiving less frequent injections.10,23

In osteoarthritis, intraarticular knee steroid injections versus saline injections every 3 months for 2 years produced no significant difference with regards to cartilage thickness, suggesting that steroids in osteoarthritis patients were neither chondro-destructive nor chondro-protective.36 Osteoarthritis patients tend to have a shorter duration of action with most of the benefit lasting a maximum of 6 weeks.

For intra-articular injections, corticosteroid use has shown to be beneficial at lower doses and shorter duration of exposure. Higher doses and longer duration were shown to cause gross cartilage damage and chondrotoxicity.37 This is reflected in new CMS guidance not to exceed total body doses of 10mg dexamethasone, 15mg betamethasone, or 40mg methylprednisolone per treatment session.

Local anesthetic agents all have chondrotoxic potential, and of the available agents ropivacaine at concentrations of 0.5% or less was found to be the least chondrotoxic.48

More recent studies suggest that chronic joint injections may accelerate cartilage degeneration and osteoarthritis progression and should be avoided in patients with subchondral insufficiency fractures and osteonecrosis.38,39

Specific to the hip, there is emerging data that suggests steroid injections are associated with a rare but significant risk of rapidly progressive osteoarthritis of the hip (RPOH).49,50 The mechanism of RPOH development is not well-understood, nor is the causative link to steroid injections.

Due to the potential of corticosteroid side effects, general recommendations are that steroid injections be performed no more than 3-4 times annually,9 although rheumatoid patients may be able to tolerate more frequent injections.23

In practice, it is difficult for patients and practitioners to keep track of patient total steroid dosage annually. A single patient may be receiving injections in multiple joints and the spine from multiple practitioners on a recurring basis. Practitioners who perform steroid injections are encouraged to discuss the risks of cumulative steroid dosing with patients, and coordinate injections such that there is a 2-4 week gap between any two injections to allow for renormalization of the HPA axis.

In light of the COVID-19 pandemic and the development of vaccine agents, new attention has been given to the immunomodulatory effect of steroid injections, and their impact on vaccine response. Though the evidence is limited, current recommendations are to wait 1-2 weeks between any steroid injection and vaccine, whether the vaccination is to be done before or after the steroid injection.51,52 This is based on a conservative estimate of 4-week derangement of the HPA axis after steroid injection, and peak efficacy of the vaccine being approximately 2 weeks post-vaccination.

It is important to be aware of where the medications that are being utilized come from. In 2012, an outbreak of fungal meningitis was associated with contaminated methylprednisolone from a specific compounding pharmacy.  As compounding pharmacies are not registered with the FDA, consider using a pharmacy that participates in voluntary accreditation with the Pharmacy Compounding Accreditation Board.7

Intramuscular glucocorticoids are generally avoided due to risk of muscle atrophy.4

Non-systemic administration is preferred to systemic if at all possible due to the many adverse effects that come with oral or intravenous glucocorticoids.4

Gaps in Knowledge/Evidence Base

Previously, there was uncertainty over the use of particulate versus non-particulate steroids for epidural steroid injections. Certain data suggested superiority of particulate steroids for the short-term treatment of lumbar radicular pain but newer studies have failed to demonstrate any difference over longer follow up periods.40 In addition, consensus guidelines have recommended caution with particulate steroids in epidural steroid injections due to previously discussed risks of arterial thromboembolism.

Controversy exists regarding whether injections with steroids produce superior clinical effects compared with local anesthetics or saline. Although in some studies steroids were found to be superior than control agents at 1 month, 3 months, and 6 months post injection, with diminishing pain control from 3 months to 1 year,41 epidural corticosteroid injections for radiculopathy or spinal stenosis with sodium chloride solution or bupivacaine were shown to be ineffective by others, or suggesting that lidocaine alone or lidocaine in conjunction with steroids were significantly effective.42

Overall, further studies are needed to help clarify optimal steroid selection, dosing and frequency and the efficacy of landmark guided versus ultrasound guided peripheral joint injections.40,43

Cutting Edge/Unique Concepts/Emerging Issues

Ultrasound guidance is becoming increasingly popular in both peripheral and axial injections as a means of improving accuracy without the radiation exposure of fluoroscopy. 

Some physicians have started using intrathecal betamethasone in cancer patients, especially those with vertebral bone metastases, when conservative options have been exhausted.  Intrathecal steroid injections were found to provide long lasting analgesia without any apparent complications in pelvic and perineal cancer patients.44

It has also been speculated that complications from intrathecal steroid injection stem from chemical additives such as antioxidants and preservatives.31

Low dose of a single intra-articular dexamethasone injection has shown promise in prevention of post traumatic osteoarthritis.45 Intra-articular administration of extended-release triamcinolone acetonide (TA-ER) presents as a newer steroid formulation that in some studies provided significant reduction in knee pain compared with saline-placebo at week 12.46 TA-ER consistently exceeded the pain relief of saline-placebo at 5-6 months, suggesting that it may be an effective non-opioid treatment option.47

References

  1. Orth DN, Kovacs WJ. The adrenal cortex. In: Wilson, J, ed. Williams Textbook of Endocrinology. 9th Philadelphia, PA: Saunders; 1998:517-665.
  2. Williams GH, Dluhy RG. Disorders of the adrenal cortex. In: Harrison T, Braunwald E, eds. Harrison’s Principles of Internal Medicine. 15th New York, NY: McGraw-Hill; 2001:2084-2105.
  3. Coursin DB, Wood KE. Corticosteroid supplementation for adrenal insufficiency. JAMA. 2002;287:236-240.
  4. Yasir M, Goyal A, Bansal P, et al. Corticosteroid Adverse Effects. [Updated 2020 Jul 4]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan-.  Available from:https://www.ncbi.nlm.nih.gov/books/NBK531462/
  5. Qin C, Greenwood B, Myers DA. Corticosterone acts directly at the amygdala to alter spinal neuronal activity in response to colorectal distension. J Neurophysiol. 2003;89(3):1343-1352.
  6. Walsh N, Eckmann M. Pharmacology for the Interventional Pain Physician. In: Gans B, Walsh N, Robinson L, eds. Delisa’s Physical Medicine & Rehabilitation: Principles and Practice. 5th Philadelphia, PA: Lippincott Williams & Wilkins; 2010:1852-1854.
  7. Anitescu M, Benzon H. Pharmacology for the Interventional Pain Physician. In: Benzon H, et al, eds. Practical management of pain. 5th Philadelphia, PA: Saunders; 2014:596-614.
  8. Cole BJ, Schumacher HR. Injectable corticosteroids in modern practice. J Am Acad Othop Surg. 2005;13:37-46.
  9. 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.
  10. 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.
  11. Provenzano D, Chandwani K. Joint Injections. In: Benzon H, et al, eds. Practical management of pain. 5th Philadelphia, PA: Saunders; 2014:966-980.
  12. Freire, V., Bureau. Injectable Corticosteroids: Take Precautions and Use Caution. Semin Musculoskelet Radiol 2016; 20(05): 401-408
  13. Foster, Z., Voss T.,  Hatch J., Frimodig A., Am Fam Physician. 2015 Oct 15;92(8):694-699.
  14. https://www.fda.gov/media/88483/download
  15. American Academy of Orthopedic Surgeons. Clinical practice guidelines. http://www.aaos.org/guidelines/. Accessed December 20, 2020.
  16. American College of Sports Medicine. Position stands. http://acsm.org/public-information/position-stands. Accessed December 20, 2020.
  17. American Diabetes Association. Standards of care. http://professional.diabetes.org/content/clinical-practice-recommendations/. Accessed December 20, 2020.
  18. American Medical Society for Sports Medicine. AMSSM publications and position statements. http://www.amssm.org/Publications.html. Accessed December 20, 2020.
  19. Waterbrook AL, Balcik BJ, Goshinska AJ. Blood Glucose Levels After Local Musculoskeletal Steroid Injections in Patients With Diabetes Mellitus: A Clinical Review. Sports Health. 2017;9(4):372-374. doi:10.1177/1941738117702585
  20. Clearfield DA, Ruane JJ, Diehl J. Examining the Safety of Joint injections in Patients on Warfarin. Practical Pain Management Journal. Volume 12, Issue #7. Epub 2012 Aug . Accessed on December 24, 2020.
  21. Saunders, S., & Longworth, S. (2018). Injection techniques in Musculoskeletal medicine: A practical manual for Clinicians in primary and secondary care (5th ed.). London: Elsevier Health Sciences.
  22. Yui JC, Preskill C, Greenlund LS. Arthrocentesis and Joint Injection in Patients Receiving Direct Oral Anticoagulants. Mayo Clin Proc. 2017 Aug;92(8):1223-1226. doi: 10.1016/j.mayocp.2017.04.007. PMID: 28778256.
  23. Roberts, WN. Intraarticular and soft tissue injections: What agent(s) to inject and how frequently? In: UpToDate, Furst DE (ed), UpToDate, Waltham, MA. (Accessed on September 25, 2015).
  24. MacPherson, RD. Pharmaceutics for the anaesthetist. Anaesthesia. 2001;56: 965– 979.
  25. Hodgson PS, Neal JM, Pollock JE, Liu SS. The neurotoxicity of drugs given intrathecally (spinal). Anesth Analg. 1999;88:797-809.
  26. DailyMed – LIDOCAINE HYDROCHLORIDE- Lidocaine Hydrochloride Anhydrous Injection, Solution. U.S. National Library of Medicine, National Institutes of Health, 29 Oct. 2020, dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=afd7c91b-3283-49e7-b79f-1c8d0c1a53bd.
  27. Craig DB, Habib GG. Flaccid paraparesis following obstetrical epidural anesthesia: possible role of benzyl alcohol. Anesth Analg. 1977;56:219-221.
  28. Du Pen SL, Ramsey D, Chin S. Chronic epidural morphine and preservative- induced injury. Anesthesiology. 1987;67:987-988.
  29. Sghirlanzoni A, Marazzi R, Pareyson D, Olivieri A, Bracchi M. Epidural anaesthesia and spinal arachnoiditis. Anaesthesia 1989; 44: 317–21.
  30. Kang S, Hwang B, Son H, et al. The Dosages of Corticosteroid in Transforaminal Epidural Steroid Injections for Lumbar Radicular Pain Due to a Herniated Disc. Pain Physician. 2011;14:361-370.
  31. Rathmell J. Atlas of Image Guided Intervention in Regional Anesthesia and Pain Medicine. 2nd Philadelphia, PA: Lippincott Williams & Wilkins; 2012.
  32. Hollander JL, Jessar RA. Intra-synovial corticosteroid therapy: a decade of use. Bull Rheum Dis. 1961;11:239.
  33. Armstrong, RD, English J. Serum methylprednisolone levels following intra-articular injection of methylprednisolone acetate. Ann Rheum Dis. 1981;40:571-74.
  34. Gray RG, Tenebaum J. Local corticosteroid injection treatment in rheumatic disorders. Semin Arthritis Rheum. 1981;10:231.
  35. Wahezi, Sayed E et al. Aggregation properties of triamcinolone acetonide injection in human serum: considerations when performing epidural steroid injections. Journal of pain research vol. 12 1033-1039. 20 Mar. 2019, doi:10.2147/JPR.S181038
  36. Raynauld JP, Buckland-Wright C. Safety and efficacy of long-term intraarticular steroid injections in osteoarthritis of the knee: a randomized, double-blind, placebo-controlled trial. Arthritis Rheum. 2003;48:370.
  37. Wernecke C, Braun HJ, Dragoo JL. The Effect of Intra-articular Corticosteroids on Articular Cartilage: A Systematic Review. Orthopaedic Journal of Sports Medicine. May 2015. doi:10.1177/2325967115581163
  38. McAlindon TE, LaValley MP, Harvey WF, Price LL, Driban JB, Zhang M, Ward RJ. Effect of Intra-articular Triamcinolone vs Saline on Knee Cartilage Volume and Pain in Patients With Knee Osteoarthritis: A Randomized Clinical Trial. JAMA. 2017 May 16;317(19):1967-1975. doi: 10.1001/jama.2017.5283. PMID: 28510679; PMCID: PMC5815012.
  39. Andrew J. Kompel, Frank W. Roemer, Akira M. Murakami, Luis E. Diaz, Michel D. Crema, and Ali Guermazi. Intra-articular Corticosteroid Injections in the Hip and Knee: Perhaps Not as Safe as We Thought?. Radiology 2019 293:3, 656-663
  40. MacVicar J et al. The effectiveness of lumbar transforaminal injection of steroids: a comprehensive review with systematic analysis of the published data. Pain Med. 2013; 14:14-28.
  41. Lee JH, Kim DH, Shin KH, et al. Comparison of Clinical Efficacy of Epidural Injection With or Without Steroid in Lumbosacral Disc Herniation: A Systematic Review and Meta-analysis. Pain Physician. 2018 Sep;21(5):449-468. PMID: 30282390.
  42. Manchikanti L, Knezevic NN, Boswell MV, Kaye AD, Hirsch JA. Epidural Injections for Lumbar Radiculopathy and Spinal Stenosis: A Comparative Systematic Review and Meta-Analysis. Pain Physician. 2016 Mar;19(3):E365-410. PMID: 27008296.
  43. Particulates vs. Non-Particulates: Steroid Choice for Lumbar Tranforaminal Injections Factfinder. Spine Intervention Society website. http://www.spinalinjection.org/?page=PVNPLFF Accessed February 28, 2016.
  44. Raj P. Neural Blockade with Local Anesthetics and Steroids in the Management of Cancer Pain. In Waldman S, ed. Pain Management. 2nd Philadelphia, PA: Saunders; 2011:319-323.
  45. Grodzinsky AJ, Wang Y, Kakar S, Vrahas MS, Evans CH. Intra-articular dexamethasone to inhibit the development of post-traumatic osteoarthritis. J Orthop Res. 2017 Mar;35(3):406-411. doi: 10.1002/jor.23295. Epub 2017 Mar 2. PMID: 27176565.
  46. Conaghan PG, Hunter DJ, Cohen SB, et al. Effects of a Single Intra-Articular Injection of a Microsphere Formulation of Triamcinolone Acetonide on Knee Osteoarthritis Pain: A Double-Blinded, Randomized, Placebo-Controlled, Multinational Study. J Bone Joint Surg Am. 2018 Apr 18;100(8):666-677. doi: 10.2106/JBJS.17.00154. PMID: 29664853.
  47. Langworthy MJ, Conaghan PG, Ruane JJ, et al. Efficacy of Triamcinolone Acetonide Extended-Release in Participants with Unilateral Knee Osteoarthritis: A Post Hoc Analysis. Adv Ther. 2019 Jun;36(6):1398-1411. doi: 10.1007/s12325-019-00944-3. Epub 2019 Apr 9. PMID: 30968336;
  48. https://pubmed.ncbi.nlm.nih.gov/30676699/
  49. https://www.sciencedirect.com/science/article/pii/S2352344123001474
  50. https://pubmed.ncbi.nlm.nih.gov/35596119/
  51. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8728555/
  52. https://www.ipsismed.org/news/news.asp?id=548668

Original Version of the Topic

David Haustein, MD, Daren Subnaik, DO. Steroids and Corticosteroids. 4/13/2016

Previous Revision(s) of the Topic

Laurentiu Dinescu, MD, Maksim Shmargun, MD, Abhishek Reddy, MD, Vivek Mukherjee, MD. Steroids and Corticosteroids. 3/11/2021

Author Disclosures

Mihir Joshi, MD
Nothing to Disclose

Mahmood Gharib, MD
Nothing to Disclose