Abstract
Mini Abstract
This literature review summarized studies that evaluated the effects of epidural steroid injections (ESIs) on skeletal health. While evidence is limited, studies suggest that ESIs may cause bone loss. Better understanding of these skeletal consequences will help foster strategies to prevent bone loss in the growing population of patients receiving ESIs.
Purpose
Approximately nine million epidural steroid injections (ESIs) are administered annually in the United States to treat radicular back pain. ESIs often provide pain relief and functional improvement. While the overall incidence of adverse events resulting from ESIs is low, their effects on the skeleton are poorly understood. This is an important consideration given the profound skeletal impact of other forms of glucocorticoids.
Methods
Ovid MEDLINE and PubMed search results since 2010, including older, frequently referenced publications were reviewed.
Results
Systemic absorption of glucocorticoids occurs after ESI, which can cause hyperglycemia and endogenous cortisol suppression. The majority of studies investigating the skeletal effects of ESIs are retrospective. Several have found a relationship between low areal bone mineral density (BMD) by dual-energy x-ray absorptiometry and ESI exposure, but this finding is not uniform. Recently a dose-response relationship between ESI exposure and low spine volumetric BMD by computed tomography has been reported. Few studies have investigated the relationship between ESI exposure and fracture risk. Results of these studies are conflicting, and most have not been adequately powered to detect fracture outcomes.
Conclusions
While evidence is limited, studies suggest that ESIs may cause bone loss, particularly those investigating volumetric BMD. Larger doses appear to confer greater risk. Further prospective studies are needed to investigate the relationship between ESI and fracture risk. Better understanding of the skeletal consequences of ESIs will help foster strategies to prevent bone loss in the growing population of patients receiving this treatment.
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References
Hoy D, Bain C, Williams G, March L, Brooks P, Blyth F, Woolf A, Vos T, Buchbinder R (2012) A systematic review of the global prevalence of low back pain. Arthritis Rheum 64(6):2028–2037. https://doi.org/10.1002/art.34347
Millennium WHOSGotBoMCatSotN (2003) The burden of musculoskeletal conditions at the start of the new millennium. World Health Organ Tech Rep Ser 919:i-x, 1-218, back cover
Manchikanti L, Pampati V, Falco FJ, Hirsch JA (2013) Assessment of the growth of epidural injections in the medicare population from 2000 to 2011. Pain Physician 16(4):E349–E364
Hoy D, Brooks P, Blyth F, Buchbinder R (2010) The epidemiology of low back pain. Best Pract Res Clin Rheumatol 24(6):769–781. https://doi.org/10.1016/j.berh.2010.10.002
Murray CJ, Atkinson C, Bhalla K, Birbeck G, Burstein R, Chou D, Dellavalle R, Danaei G, Ezzati M, Fahimi A, Flaxman D, Foreman, Gabriel S, Gakidou E, Kassebaum N, Khatibzadeh S, Lim S, Lipshultz SE, London S, Lopez, MacIntyre MF, Mokdad AH, Moran A, Moran AE, Mozaffarian D, Murphy T, Naghavi M, Pope C, Roberts T, Salomon J, Schwebel DC, Shahraz S, Sleet DA, Murray, Abraham J, Ali MK, Atkinson C, Bartels DH, Bhalla K, Birbeck G, Burstein R, Chen H, Criqui MH, Dahodwala, Jarlais, Ding EL, Dorsey ER, Ebel BE, Ezzati M, Fahami, Flaxman S, Flaxman AD, Gonzalez-Medina D, Grant B, Hagan H, Hoffman H, Kassebaum N, Khatibzadeh S, Leasher JL, Lin J, Lipshultz SE, Lozano R, Lu Y, Mallinger L, McDermott MM, Micha R, Miller TR, Mokdad AA, Mokdad AH, Mozaffarian D, Naghavi M, Narayan KM, Omer SB, Pelizzari PM, Phillips D, Ranganathan D, Rivara FP, Roberts T, Sampson U, Sanman E, Sapkota A, Schwebel DC, Sharaz S, Shivakoti R, Singh GM, Singh D, Tavakkoli M, Towbin JA, Wilkinson JD, Zabetian A, Murray, Abraham J, Ali MK, Alvardo M, Atkinson C, Baddour LM, Benjamin EJ, Bhalla K, Birbeck G, Bolliger I, Burstein R, Carnahan E, Chou D, Chugh SS, Cohen A, Colson KE, Cooper LT, Couser W, Criqui MH, Dabhadkar KC, Dellavalle RP, Jarlais, Dicker D, Dorsey ER, Duber H, Ebel BE, Engell RE, Ezzati M, Felson DT, Finucane MM, Flaxman S, Flaxman AD, Fleming T, Foreman, Forouzanfar MH, Freedman G, Freeman MK, Gakidou E, Gillum RF, Gonzalez-Medina D, Gosselin R, Gutierrez HR, Hagan H, Havmoeller R, Hoffman H, Jacobsen KH, James SL, Jasrasaria R, Jayarman S, Johns N, Kassebaum N, Khatibzadeh S, Lan Q, Leasher JL, Lim S, Lipshultz SE, London S, Lopez LR, Lu Y, Mallinger L, Meltzer M, Mensah GA, Michaud C, Miller TR, Mock C, Moffitt TE, Mokdad AA, Mokdad AH, Moran A, Naghavi M, Narayan KM, Nelson RG, Olives C, Omer SB, Ortblad K, Ostro B, Pelizzari PM, Phillips D, Raju M, Razavi H, Ritz B, Roberts T, Sacco RL, Salomon J, Sampson U, Schwebel DC, Shahraz S, Shibuya K, Silberberg D, Singh JA, Steenland K, Taylor JA, Thurston GD, Vavilala MS, Vos T, Wagner GR, Weinstock MA, Weisskopf MG, Wulf S, Murray, Collaborators USBoD (2013) The state of US health, 1990-2010: burden of diseases, injuries, and risk factors. JAMA 310(6):591–608. https://doi.org/10.1001/jama.2013.13805
Manchikanti L, Pampati V, Hirsch JA (2016) Retrospective cohort study of usage patterns of epidural injections for spinal pain in the US fee-for-service Medicare population from 2000 to 2014. BMJ Open 6(12):e013042. https://doi.org/10.1136/bmjopen-2016-013042
Friedly J, Chan L, Deyo R (2007) Increases in lumbosacral injections in the Medicare population: 1994 to 2001. Spine (Phila Pa 1976) 32(16):1754–1760. https://doi.org/10.1097/BRS.0b013e3180b9f96e
Epstein NE (2017) Neurological complications of lumbar and cervical dural punctures with a focus on epidural injections. Surg Neurol Int 8:60. https://doi.org/10.4103/sni.sni_38_17
Chou R, Hashimoto R, Friedly J, Fu R, Bougatsos C, Dana T, Sullivan SD, Jarvik J (2015) Epidural corticosteroid injections for radiculopathy and spinal stenosis: a systematic review and meta-analysis. Ann Intern Med 163(5):373–381. https://doi.org/10.7326/M15-0934
Schaufele MK, Hatch L, Jones W (2006) Interlaminar versus transforaminal epidural injections for the treatment of symptomatic lumbar intervertebral disc herniations. Pain Physician 9(4):361–366
Bicket MC, Gupta A, Brown CH, Cohen SP (2013) Epidural injections for spinal pain: a systematic review and meta-analysis evaluating the "control" injections in randomized controlled trials. Anesthesiology 119(4):907–931. https://doi.org/10.1097/ALN.0b013e31829c2ddd
Bicket MC, Chakravarthy K, Chang D, Cohen SP (2015) Epidural steroid injections: an updated review on recent trends in safety and complications. Pain Manag 5(2):129–146. https://doi.org/10.2217/pmt.14.53
Cai J, Jiang W, Qiu B, Song Y (2020) Efficacy and safety of epidural steroid injection following discectomy for patients with lumbar disc herniation: a protocol. Medicine (Baltimore) 99(29):e21220. https://doi.org/10.1097/MD.0000000000021220
Lee JW, Lee E, Lee GY, Kang Y, Ahn JM, Kang HS (2018) Epidural steroid injection-related events requiring hospitalisation or emergency room visits among 52,935 procedures performed at a single centre. Eur Radiol 28(1):418–427. https://doi.org/10.1007/s00330-017-4977-7
FDA Drug Safety Communication (2014) FDA requires label changes to warn of rare but serious neurologic problems after epidural corticosteroid injections for pain. https://www.fda.gov/drugs/drug-safety-and-availability/fda-drug-safety-communication-fda-requires-label-changes-warn-rare-serious-neurologic-problems-after
Buehring B, Viswanathan R, Binkley N, Busse W (2013) Glucocorticoid-induced osteoporosis: an update on effects and management. J Allergy Clin Immunol 132(5):1019–1030. https://doi.org/10.1016/j.jaci.2013.08.040
Whittier X, Saag KG (2016) Glucocorticoid-induced osteoporosis. Rheum Dis Clin N Am 42(1):177–189, x. https://doi.org/10.1016/j.rdc.2015.08.005
Van Staa TP, Laan RF, Barton IP, Cohen S, Reid DM, Cooper C (2003) Bone density threshold and other predictors of vertebral fracture in patients receiving oral glucocorticoid therapy. Arthritis Rheum 48(11):3224–3229. https://doi.org/10.1002/art.11283
Weinstein RS, Jilka RL, Parfitt AM, Manolagas SC (1998) Inhibition of osteoblastogenesis and promotion of apoptosis of osteoblasts and osteocytes by glucocorticoids. Potential mechanisms of their deleterious effects on bone. J Clin Invest 102(2):274–282. https://doi.org/10.1172/JCI2799
Hofbauer LC, Zeitz U, Schoppet M, Skalicky M, Schuler C, Stolina M, Kostenuik PJ, Erben RG (2009) Prevention of glucocorticoid-induced bone loss in mice by inhibition of RANKL. Arthritis Rheum 60(5):1427–1437. https://doi.org/10.1002/art.24445
Henneicke H, Gasparini SJ, Brennan-Speranza TC, Zhou H, Seibel MJ (2014) Glucocorticoids and bone: local effects and systemic implications. Trends Endocrinol Metab 25(4):197–211. https://doi.org/10.1016/j.tem.2013.12.006
Mitra R (2011) Adverse effects of corticosteroids on bone metabolism: a review. PM R 3(5):466–471; quiz 471. https://doi.org/10.1016/j.pmrj.2011.02.017
Sutter SA, Stein EM (2016) The skeletal effects of inhaled glucocorticoids. Curr Osteoporos Rep 14(3):106–113. https://doi.org/10.1007/s11914-016-0308-1
Liu J, Guo H, Rai P, Pinto L, Barron R (2018) Medication persistence and risk of fracture among female Medicare beneficiaries diagnosed with osteoporosis. Osteoporos Int 29(11):2409–2417. https://doi.org/10.1007/s00198-018-4630-6
Israel E, Banerjee TR, Fitzmaurice GM, Kotlov TV, LaHive K, LeBoff MS (2001) Effects of inhaled glucocorticoids on bone density in premenopausal women. N Engl J Med 345(13):941–947. https://doi.org/10.1056/NEJMoa002304
Tiso RL, Cutler T, Catania JA, Whalen K (2004) Adverse central nervous system sequelae after selective transforaminal block: the role of corticosteroids. Spine J 4(4):468–474. https://doi.org/10.1016/j.spinee.2003.10.007
Park CH, Lee SH, Kim BI (2010) Comparison of the effectiveness of lumbar transforaminal epidural injection with particulate and nonparticulate corticosteroids in lumbar radiating pain. Pain Med 11(11):1654–1658. https://doi.org/10.1111/j.1526-4637.2010.00941.x
Makkar JK, Singh PM, Jain D, Goudra B (2016) Particulate vs non-particulate steroids for transforaminal epidural steroid injections: systematic review and meta-analysis of the current literature. Pain Physician 19(6):327–340
Bensler S, Sutter R, Pfirrmann CWA, Peterson CK (2018) Particulate versus non-particulate corticosteroids for transforaminal nerve root blocks: comparison of outcomes in 494 patients with lumbar radiculopathy. Eur Radiol 28(3):946–952. https://doi.org/10.1007/s00330-017-5045-z
Stout A, Friedly J, Standaert CJ (2019) Systemic absorption and side effects of locally injected glucocorticoids. PM R 11(4):409–419. https://doi.org/10.1002/pmrj.12042
Kay J, Findling JW, Raff H (1994) Epidural triamcinolone suppresses the pituitary-adrenal axis in human subjects. Anesth Analg 79(3):501–505. https://doi.org/10.1213/00000539-199409000-00017
Friedly JL, Comstock BA, Heagerty PJ, Bauer Z, Rothman MS, Suri P, Hansen R, Avins AL, Nedeljkovic SS, Nerenz DR, Akuthota V, Jarvik JG (2018) Systemic effects of epidural steroid injections for spinal stenosis. Pain 159(5):876–883. https://doi.org/10.1097/j.pain.0000000000001158
Chon JY, Moon HS (2012) Salivary cortisol concentration changes after epidural steroid injection. Pain Physician 15(6):461–466
Abdul AJ, Ghai B, Bansal D, Sachdeva N, Bhansali A, Dhatt SS (2017) Hypothalamic pituitary adrenocortical axis suppression following a single epidural injection of methylprednisolone acetate. Pain Physician 20(7):E991–E1001
Tuel SM, Meythaler JM, Cross LL (1990) Cushing's syndrome from epidural methylprednisolone. Pain 40(1):81–84. https://doi.org/10.1016/0304-3959(90)91054-m
Ramanathan R, Pau AK, Busse KH, Zemskova M, Nieman L, Kwan R, Hammer JH, Mican JM, Maldarelli F (2008) Iatrogenic Cushing syndrome after epidural triamcinolone injections in an HIV type 1-infected patient receiving therapy with ritonavir-lopinavir. Clin Infect Dis 47(12):e97–e99. https://doi.org/10.1086/593314
Horani MH, Silverberg AB (2005) Secondary Cushing's syndrome after a single epidural injection of a corticosteroid. Endocr Pract 11(6):408–410. https://doi.org/10.4158/EP.11.6.408
Lansang MC, Farmer T, Kennedy L (2009) Diagnosing the unrecognized systemic absorption of intra-articular and epidural steroid injections. Endocr Pract 15(3):225–228. https://doi.org/10.4158/EP.15.3.225
Kim WH, Sim WS, Shin BS, Lee CJ, Jin HS, Lee JY, Roe HJ, Kim CS, Lee SM (2013) Effects of two different doses of epidural steroid on blood glucose levels and pain control in patients with diabetes mellitus. Pain Physician 16(6):557–568
Younes M, Neffati F, Touzi M, Hassen-Zrour S, Fendri Y, Bejia I, Ben Amor A, Bergaoui N, Najjar MF (2007) Systemic effects of epidural and intra-articular glucocorticoid injections in diabetic and non-diabetic patients. Joint Bone Spine 74(5):472–476. https://doi.org/10.1016/j.jbspin.2006.10.009
Ward A, Watson J, Wood P, Dunne C, Kerr D (2002) Glucocorticoid epidural for sciatica: metabolic and endocrine sequelae. Rheumatology (Oxford) 41(1):68–71. https://doi.org/10.1093/rheumatology/41.1.68
Gonzalez P, Laker SR, Sullivan W, Harwood JE, Akuthota V (2009) The effects of epidural betamethasone on blood glucose in patients with diabetes mellitus. PM R 1(4):340–345. https://doi.org/10.1016/j.pmrj.2008.12.007
Even JL, Crosby CG, Song Y, McGirt MJ, Devin CJ (2012) Effects of epidural steroid injections on blood glucose levels in patients with diabetes mellitus. Spine (Phila Pa 1976) 37(1):E46–E50. https://doi.org/10.1097/BRS.0b013e31821fd21f
Jain A, Gupta P, Chaurasia R, Singh M, Pandey S (2020) Observational study to evaluate the effect of epidural steroid injection on bone mineral density and bone turnover markers. Pain Physician 23(5):E517–E524
Nah SY, Lee JH, Lee JH (2018) Effects of epidural steroid injections on bone mineral density and bone turnover markers in patients taking anti-osteoporotic medications. Pain Physician 21(4):E435–E447
Al-Shoha A, Rao DS, Schilling J, Peterson E, Mandel S (2012) Effect of epidural steroid injection on bone mineral density and markers of bone turnover in postmenopausal women. Spine (Phila Pa 1976) 37(25):E1567–E1571. https://doi.org/10.1097/BRS.0b013e318270280e
Kim S, Hwang B (2014) Relationship between bone mineral density and the frequent administration of epidural steroid injections in postmenopausal women with low back pain. Pain Res Manag 19(1):30–34. https://doi.org/10.1155/2014/870145
Okano I, Salzmann SN, Jones C, Reisener MJ, Ortiz Miller C, Shirahata T, Shue J, Carrino JA, Sama AA, Cammisa FP, Girardi FP, Hughes AP (2020) The effect of obesity, diabetes, and epidural steroid injection on regional volumetric bone mineral density measured by quantitative computed tomography in the lumbosacral spine. Eur Spine J 30:13–21. https://doi.org/10.1007/s00586-020-06610-5
Kang SS, Hwang BM, Son H, Cheong IY, Lee SJ, Chung TY (2012) Changes in bone mineral density in postmenopausal women treated with epidural steroid injections for lower back pain. Pain Physician 15(3):229–236
Dubois EF, Wagemans MF, Verdouw BC, Zwinderman AH, Van Boxtel CJ, Dekhuijzen PN, Schweitzer DH (2003) Lack of relationships between cumulative methylprednisolone dose and bone mineral density in healthy men and postmenopausal women with chronic low back pain. Clin Rheumatol 22(1):12–17. https://doi.org/10.1007/s10067-002-0648-3
Yi Y, Hwang B, Son H, Cheong I (2012) Low bone mineral density, but not epidural steroid injection, is associated with fracture in postmenopausal women with low back pain. Pain Physician 15(6):441–449
Manchikanti L, Pampati V, Beyer C, Damron K, Cash K, Moss T (2000) The effect of neuraxial steroids on weight and bone mass density: a prospective evaluation. Pain Physician 3(4):357–366
Sutter S, Nishiyama KK, Kepley A, Zhou B, Wang J, McMahon DJ, Guo XE, Stein EM (2014) Abnormalities in cortical bone, trabecular plates, and stiffness in postmenopausal women treated with glucocorticoids. J Clin Endocrinol Metab 99(11):4231–4240. https://doi.org/10.1210/jc.2014-2177
Liu Y, Carrino JA, Dash AS, Chukir T, Do H, Bockman RS, Hughes AP, Press JM, Stein EM (2018) Lower spine volumetric bone density in patients with a history of epidural steroid injections. J Clin Endocrinol Metab 103(9):3405–3410. https://doi.org/10.1210/jc.2018-00558
Kim YU, Karm MH, Cheong Y, Lee J, Kong YG, Kim SH, Suh JH (2016) Effect of epidural steroid injection on bone mineral density in postmenopausal women according to antiosteoporotic medication use. Pain Physician 19(6):389–396
Mandel S, Schilling J, Peterson E, Rao DS, Sanders W (2013) A retrospective analysis of vertebral body fractures following epidural steroid injections. J Bone Joint Surg Am 95(11):961–964. https://doi.org/10.2106/JBJS.L.00844
Kim M, Yang YH, Son HJ, Huh J, Cheong Y, Kang SS, Hwang B (2019) Effect of medications and epidural steroid injections on fractures in postmenopausal women with osteoporosis. Medicine (Baltimore) 98(26):e16080. https://doi.org/10.1097/MD.0000000000016080
Kanis JA, Johansson H, Oden A, McCloskey EV (2011) Guidance for the adjustment of FRAX according to the dose of glucocorticoids. Osteoporos Int 22(3):809–816. https://doi.org/10.1007/s00198-010-1524-7
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Krez, A., Liu, Y., Kanbour, S. et al. The skeletal consequences of epidural steroid injections: a literature review. Osteoporos Int 32, 2155–2162 (2021). https://doi.org/10.1007/s00198-021-05986-4
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DOI: https://doi.org/10.1007/s00198-021-05986-4