Zoledronic Acid-Induced Orbital Inflammatory Disease

Zoledronic Acid-Induced Orbital Inflammatory Disease | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Zoledronic Acid-Induced Orbital Inflammatory Disease amirreza veisi, golbarg piryaiee, mohammadreza tahavvori This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-3951554/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Bisphosphonates are a group of drugs that are used to prevent the loss of bone density and treat osteoporosis and similar bone diseases. Zoledronate (zolenedronic acid) has been increasingly used because of its advantages of intravenous infusion and annual regimens. Here, we present a case of zolendronic acid-related diffuse orbital inflammation. A 67-year-old woman with a history of breast cancer and chemotherapy developed severe unilateral orbital and periorbital swelling approximately 8 hours after receiving her first zoledronate infusion. In this case, the interval between infusion and the beginning of the symptoms was too short compared with most other reported similar cases. Her signs and symptoms relapsed 4 days after discontinuation of the short course of systemic steroid therapy. Orbital inflammation improved after systemic corticosteroid therapy was restarted, but the patient did not relapse following discontinuation of the drug in a tapering manner. Ophthalmology zoledronate orbital inflammation bisphosphonates Figures Figure 1 Figure 2 Introduction Bisphosphonates are a class of drugs that are widely used for the treatment of osteoporosis and cancer-induced bone diseases. 1-4 Among those in this class, zoledronate has been increasingly prescribed in recent years. 2 Despite the advantages of zoledronate, it has many adverse effects, including hypoglycemia, secondary hyperparathyroidism, musculoskeletal pain, active phase response (APR), renal injury, osteoporosis of the jaw, atypical femoral fracture, atrial fibrillation and ocular and orbital inflammation 5,6 . The active phase response (APR) following zoledronate presents with chills, fever, fatigue, myalgia, arthralgia, and influenza-like illness. It usually occurs within 72 hours of administration, mostly after the first infusion, in approximately 40-50% of patients. This acute inflammatory response is usually self-limiting, managed conservatively and decreases with subsequent injections. 3 , 5-10 Although not common, zoledronate can induce inflammation in all ocular layers, including conjunctivitis, episcleritis, scleritis, uveitis, endotheliitis, and orbital inflammation. 11-16 Orbital inflammation may be a severe and potentially vision-threatening adverse effect that has been increasingly reported. 12 , 17-27 Because of the presence of an immunodeficiency state in some patients taking zoledronate, this orbital inflammation may be mistaken for infectious orbital cellulitis. Hence, investigating the characteristics and different aspects of these patients can improve the understanding of the early diagnosis and management of this drug’s adverse effects. 11-16 Case presentation A 67-year-old woman with severe periorbital swelling, proptosis, redness and pain in her right eye was referred to the emergency department following her first infusion of zoledronate (BONSTA, 40 mg) 9 days prior. Her symptoms started approximately 8 hours after the infusion. She suffered from breast cancer and underwent lumpectomy and lymph node dissection followed by chemotherapy (oncotaxel, docetaxel, doxorubicin) and pegfilgrastim 4 months prior. She also mentioned a history of anaphylactic reaction to diclofenac. Orbital inflammation was initially treated with 4 doses of intravenous dexamethasone (8 mg, daily) and a topical steroid just after symptoms developed in the previous medical center. The patient’s APR resolved, and her ocular symptoms improved on day 4; hence, the corticosteroid was discontinued. Her ocular symptoms relapsed 2 days later. She was referred to our clinic 5 days after worsening of orbital and ocular inflammation. She had ocular pain, periorbital swelling, proptosis (hertel exophthalmometry of 19.5 in the right eye and 16.5 on her left side), redness, and severe chemosis on her right side [figure 1.A]. Ocular movements were moderately limited and painful. Her best corrected visual acuity was 20/25 in the right eye and 20/20 in her left eye. Her RAPD and color vision were normal. Anterior and posterior segment examinations were unremarkable. She did not have fever or chills at the time of examination. Because of suspected immunodeficiency, the patient underwent Sino-orbital imaging. Systemic workup by an infectious service and laboratory data were unremarkable except for mild leukocytosis (12 × 10 3 ). The paranasal sinuses were clear, and her nasal endoscopic examination, which was performed by an otorhinolaryngologist, was unremarkable. Radiologic findings via orbital computed tomography (CT) [figure 1.B] and magnetic resonance imaging (MRI) [figure 1.C] revealed right-sided proptosis, periorbital soft tissue swelling, lacrimal gland enlargement, intraorbital fat stranding and thickening of the Tenon capsule, especially surrounding the posterior sclera. No sinus mucosal thickening or signs of sinusitis were noted. According to the patient’s medical history and clinical and paraclinical findings, the probable diagnosis was zoledronate-induced orbital inflammation. After completion of the systemic workup and with the impression of an inflammatory process, oral prednisolone (1 mg/kg) was started. On the next day, her condition significantly improved subjectively and objectively. Chemosis, redness, pain and ocular motility were dramatically improved [figure 2.A]. Figure 2.B shows significant improvement and a reduction in pyroptosis from 19 to 17 mm on day 5 after systemic corticosteroid treatment. The oral corticosteroid was tapered during the course of 35 days. After stopping all the medications, there was no recurrence, and all the ocular examinations were normal [figure 2.C]. Discussion The incidence of cancer and its related bone breakdown have increased in recent years the prescription of bisphosphonates, particularly zoledronate. To date, a few cases of zoledronate-related orbital inflammation have been reported in the literature. 12 , 17 – 27 Orbital inflammation is relatively uncommon and is often accompanied by an APR, which usually presents with fever, chills, fatigue, myalgia, and arthralgia within 72 hours of administration. Our patient experienced very short intervals (approximately 8 hours) between infusion and the presentation of inflammatory symptoms. APR occurs in approximately 40–50% of cases. This acute response is self-limiting and is managed conservatively. It mostly occurs after the first infusion and decreases with subsequent injections. Some physicians have applied rechallenge combined with prophylactic steroids in a few patients to prevent the development of APR, particularly orbital or ocular inflammation. 3 , 5 – 10 , 15 , 28 The exact risk factors for this rare but serious side effect of zoledronic acid are not clear. Some suggest that γδ T cells play a role in triggering the inflammatory cascade by releasing interleukin-1 and interleukin-6. 29 , 30 The role of previous allergic or anaphylactic reactions is not understood. In special cases of cancer-induced osteoporosis, because of the immunodeficiency state, the most important differential diagnosis of orbital inflammation is infectious cellulitis, particularly invasive fungal infection. Hence, orbital and PNS imaging are mandatory for these patients. Interestingly, most cases of zoledronate-induced orbital inflammation are unilateral, and bilateral involvement occurs in 29% of patients. 31 In almost all the reported cases, orbital inflammation was completely resolved with systemic corticosteroids. In our case, incomplete and abrupt discontinuation of systemic corticosteroids led to relapse of orbital inflammation. This may indicate the necessity of an adequate dosage, duration, and tapering manner for corticosteroids. Although APR may have a self-limiting effect, in the presence of severe orbital inflammation, the prescription of systemic corticosteroids is reasonable. In these patients, severe proptosis and orbital congestion may be sight-threatening due to compressive optic neuropathy or exposure keratopathy. 21 Watching and follow-up may be options only for patients with mild inflammation or for patients with contraindications for corticosteroid therapy. In summary, zoledronate-induced orbital inflammation is a side effect that should be addressed after ruling out infectious causes, particularly bacterial and fungal causes. Severe cases require a sufficient dose and duration of systemic corticosteroid treatment in a tapered manner. All physicians, especially those at chemical centers, ophthalmologists, and infectious disease specialists, should be aware of this rare but important side effect of zoledronate administration and pay special attention to the patient’s drug history. Future studies could focus on risk factors and prevent this side effect. Declarations A written consent was obtained from the patient to publish the study and accompanying image. The authors declare no conflicts of interest. References Henry MJ, Pasco JA, Nicholson GC, Kotowicz MA. Prevalence of osteoporosis in Australian men and women: Geelong Osteoporosis Study. Med J Aust. 2011;195(6):321-2. Rodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest. 1996;97(12):2692-6 Olson K, Van Poznak C. Significance and impact of bisphosphonate-induced acute phase responses. J Oncol Pharm Pract. 2007;13(4):223-9. Reid IR, Green JR, Lyles KW, Reid DM, Trechsel U, Hosking DJ, et al. Zoledronate. Bone. 2020;137:115390. Pazianas M, Abrahamsen B. Safety of bisphosphonates. Bone. 2011;49(1):103-10. Papapetrou PD. Bisphosphonate-associated adverse events. Hormones (Athens). 2009;8(2):96-110. Thiebaud D, Sauty A, Burckhardt P, Leuenberger P, Sitzler L, Green JR, et al. An in vitro and in vivo study of cytokines in the acute-phase response associated with bisphosphonates. Calcif Tissue Int. 1997;61(5):386-92. Buckler HM, Mercer SJ, Davison CE, Hollis S, Richardson PC, Anderson DG. Evaluation of adverse experiences related to pamidronate infusion in Paget's disease of bone. Ann Rheum Dis. 1998;57(9):572. Dicuonzo G, Vincenzi B, Santini D, Avvisati G, Rocci L, Battistoni F, et al. Fever after zoledronic acid administration is due to increase in TNF-alpha and IL-6. J Interferon Cytokine Res. 2003;23(11):649-54. Reid IR, Gamble GD, Mesenbrink P, Lakatos P, Black DM. Characterization of and risk factors for the acute-phase response after zoledronic acid. J Clin Endocrinol Metab. 2010;95(9):4380-7. Procianoy F, Procianoy E. Orbital inflammatory disease secondary to a single-dose administration of zoledronic acid for treatment of postmenopausal osteoporosis. Osteoporos Int. 2010;21(6):1057-8. Umunakwe OC, Herren D, Kim SJ, Kohanim S. Diffuse ocular and orbital inflammation after zoledronate infusion-case report and review of the literature. Digit J Ophthalmol. 2017;23(4):18-21. Han LS, Weatherhead RG. Zoledronic acid associated orbital inflammation. Clin Exp Ophthalmol. 2020;48(2):249-50. Fraunfelder FW, Fraunfelder FT. Bisphosphonates and ocular inflammation. N Engl J Med. 2003;348(12):1187-8. Macarol V, Fraunfelder FT. Pamidronate disodium and possible ocular adverse drug reactions. Am J Ophthalmol. 1994;118(2):220-4. Fraunfelder FW, Fraunfelder FT. Adverse ocular drug reactions recently identified by the National Registry of Drug-Induced Ocular Side Effects. Ophthalmology. 2004;111(7):1275-9. Khalid MF, Micieli J. Zoledronic acid-induced orbital inflammation. BMJ Case Rep. 2021;14(8). Phillips PM, Newman SA. Orbital inflammatory disease after intravenous infusion of zoledronate for treatment of metastatic renal cell carcinoma. Arch Ophthalmol. 2008;126(1):137-9. Sharma NS, Ooi JL, Masselos K, Hooper MJ, Francis IC. Zoledronic acid infusion and orbital inflammatory disease. N Engl J Med. 2008;359(13):1410-1. Lefebvre DR, Mandeville JT, Yonekawa Y, Arroyo JG, Torun N, Freitag SK. A Case Series and Review of Bisphosphonate-associated Orbital Inflammation. Ocul Immunol Inflamm. 2016;24(2):134-9. Seth A, Anderson DP, Albiani DA, Barton JJ. Orbital inflammation and optic neuropathy with zoledronic acid for metastatic prostate cancer. Can J Ophthalmol. 2009;44(4):467-8. Missotten G, Verheezen Y. Orbital inflammation after use of zoledronic acid for metastasized prostate carcinoma. Bull Soc Belge Ophtalmol. 2010(315):23-4. Procianoy F, Procianoy E. Orbital inflammatory disease secondary to a single-dose administration of zoledronic acid for treatment of postmenopausal osteoporosis. Osteoporos Int. 2010;21(6):1057-8. Yeo J, Jafer AK. Zolendronate associated inflammatory orbital disease. N Z Med J. 2010;123(1323):50-2. Rahimy E, Law SK. Orbital inflammation after zoledronate infusion: an emerging complication. Can J Ophthalmol. 2013;48(1):e11-2. Tan M, Kalin-Hajdu E, Narayan R, Wong SW, Martin TG. Zoledronic acid-induced orbital inflammation in a patient with multiple myeloma. J Oncol Pharm Pract. 2019;25(5):1253-7. Muruganandam M, Sandhu H. Orbital Inflammation Secondary to Zoledronic Acid, a Rare Presentation. J Clin Rheumatol. 2016;22(7):384. Kennel KA, Drake MT. Adverse effects of bisphosphonates: implications for osteoporosis management. Mayo Clin Proc. 2009;84(7):632-7; quiz 8. Schwab P, Harmon D, Bruno R, Fraunfelder FW, Hyunchung Kim D. A 55-year-old woman with orbital inflammation. Arthritis Care Res (Hoboken). 2012;64(11):1776-82. Rossini M, Adami S, Viapiana O, Tripi G, Zanotti R, Ortolani R, et al. Acute phase response after zoledronic acid is associated with long-term effects on white blood cells. Calcif Tissue Int. 2013;93(3):249-52. Peterson JD, Bedrossian EH, Jr. Bisphosphonate-associated orbital inflammation--a case report and review. Orbit. 2012;31(2):119-23. Additional Declarations The authors declare no competing interests. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-3951554","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":272485202,"identity":"6e61320e-31d8-4e5e-ae3d-acba57b50411","order_by":0,"name":"amirreza veisi","email":"","orcid":"https://orcid.org/0000-0001-8304-3804","institution":"shahid beheshti university of medical sciences","correspondingAuthor":false,"prefix":"","firstName":"amirreza","middleName":"","lastName":"veisi","suffix":""},{"id":272485203,"identity":"1a7e40b8-93ce-4eff-934e-f6a979066e8e","order_by":1,"name":"golbarg 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pain, active phase response (APR), renal injury, osteoporosis of the jaw, atypical femoral fracture, atrial fibrillation and ocular and orbital inflammation \u003csup\u003e5,6\u003c/sup\u003e.\u003c/p\u003e\n\u003cp\u003eThe active phase response (APR) following zoledronate presents with chills, fever, fatigue, myalgia, arthralgia, and influenza-like illness. It usually occurs within 72 hours of administration, mostly after the first infusion, in approximately 40-50% of patients. This acute inflammatory response is usually self-limiting, managed conservatively and decreases with subsequent injections. \u003csup\u003e3\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e5-10\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eAlthough not common, zoledronate can induce inflammation in all ocular layers, including conjunctivitis, episcleritis, scleritis, uveitis, endotheliitis, and orbital inflammation. \u003csup\u003e11-16\u003c/sup\u003e\u003c/p\u003e\n\u003cp\u003eOrbital inflammation may be a severe and potentially vision-threatening adverse effect that has been increasingly reported.\u003csup\u003e12\u003c/sup\u003e\u003csup\u003e,\u003c/sup\u003e\u003csup\u003e17-27\u003c/sup\u003e\u003csup\u003e \u003c/sup\u003eBecause of the presence of an immunodeficiency state in some patients taking zoledronate, this orbital inflammation may be mistaken for infectious orbital cellulitis. Hence, investigating the characteristics and different aspects of these patients can improve the understanding of the early diagnosis and management of this drug\u0026rsquo;s adverse effects. \u003csup\u003e11-16\u003c/sup\u003e\u003c/p\u003e"},{"header":"Case presentation","content":"\u003cp\u003eA 67-year-old woman with severe periorbital swelling, proptosis, redness and pain in her right eye was referred to the emergency department following her first infusion of zoledronate (BONSTA, 40 mg) 9 days prior. Her symptoms started approximately 8 hours after the infusion.\u003c/p\u003e \u003cp\u003eShe suffered from breast cancer and underwent lumpectomy and lymph node dissection followed by chemotherapy (oncotaxel, docetaxel, doxorubicin) and pegfilgrastim 4 months prior. She also mentioned a history of anaphylactic reaction to diclofenac.\u003c/p\u003e \u003cp\u003eOrbital inflammation was initially treated with 4 doses of intravenous dexamethasone (8 mg, daily) and a topical steroid just after symptoms developed in the previous medical center. The patient\u0026rsquo;s APR resolved, and her ocular symptoms improved on day 4; hence, the corticosteroid was discontinued. Her ocular symptoms relapsed 2 days later. She was referred to our clinic 5 days after worsening of orbital and ocular inflammation. She had ocular pain, periorbital swelling, proptosis (hertel exophthalmometry of 19.5 in the right eye and 16.5 on her left side), redness, and severe chemosis on her right side [figure 1.A]. Ocular movements were moderately limited and painful. Her best corrected visual acuity was 20/25 in the right eye and 20/20 in her left eye. Her RAPD and color vision were normal. Anterior and posterior segment examinations were unremarkable. She did not have fever or chills at the time of examination. Because of suspected immunodeficiency, the patient underwent Sino-orbital imaging. Systemic workup by an infectious service and laboratory data were unremarkable except for mild leukocytosis (12 \u0026times; 10\u003csup\u003e3\u003c/sup\u003e). The paranasal sinuses were clear, and her nasal endoscopic examination, which was performed by an otorhinolaryngologist, was unremarkable.\u003c/p\u003e \u003cp\u003eRadiologic findings via orbital computed tomography (CT) [figure 1.B] and magnetic resonance imaging (MRI) [figure 1.C] revealed right-sided proptosis, periorbital soft tissue swelling, lacrimal gland enlargement, intraorbital fat stranding and thickening of the Tenon capsule, especially surrounding the posterior sclera. No sinus mucosal thickening or signs of sinusitis were noted.\u003c/p\u003e \u003cp\u003eAccording to the patient\u0026rsquo;s medical history and clinical and paraclinical findings, the probable diagnosis was zoledronate-induced orbital inflammation.\u003c/p\u003e \u003cp\u003eAfter completion of the systemic workup and with the impression of an inflammatory process, oral prednisolone (1 mg/kg) was started. On the next day, her condition significantly improved subjectively and objectively. Chemosis, redness, pain and ocular motility were dramatically improved [figure 2.A]. Figure\u0026nbsp;2.B shows significant improvement and a reduction in pyroptosis from 19 to 17 mm on day 5 after systemic corticosteroid treatment. The oral corticosteroid was tapered during the course of 35 days. After stopping all the medications, there was no recurrence, and all the ocular examinations were normal [figure 2.C].\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eThe incidence of cancer and its related bone breakdown have increased in recent years the prescription of bisphosphonates, particularly zoledronate. To date, a few cases of zoledronate-related orbital inflammation have been reported in the literature. \u003csup\u003e\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e,\u003cspan additionalcitationids=\"CR18 CR19 CR20 CR21 CR22 CR23 CR24 CR25 CR26\" citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eOrbital inflammation is relatively uncommon and is often accompanied by an APR, which usually presents with fever, chills, fatigue, myalgia, and arthralgia within 72 hours of administration. Our patient experienced very short intervals (approximately 8 hours) between infusion and the presentation of inflammatory symptoms. APR occurs in approximately 40\u0026ndash;50% of cases. This acute response is self-limiting and is managed conservatively. It mostly occurs after the first infusion and decreases with subsequent injections. Some physicians have applied rechallenge combined with prophylactic steroids in a few patients to prevent the development of APR, particularly orbital or ocular inflammation. \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e,\u003cspan additionalcitationids=\"CR6 CR7 CR8 CR9\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e,\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e,\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e The exact risk factors for this rare but serious side effect of zoledronic acid are not clear. Some suggest that γδ T cells play a role in triggering the inflammatory cascade by releasing interleukin-1 and interleukin-6. \u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e,\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e The role of previous allergic or anaphylactic reactions is not understood.\u003c/p\u003e \u003cp\u003eIn special cases of cancer-induced osteoporosis, because of the immunodeficiency state, the most important differential diagnosis of orbital inflammation is infectious cellulitis, particularly invasive fungal infection. Hence, orbital and PNS imaging are mandatory for these patients.\u003c/p\u003e \u003cp\u003eInterestingly, most cases of zoledronate-induced orbital inflammation are unilateral, and bilateral involvement occurs in 29% of patients. \u003csup\u003e\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e\u003c/sup\u003e\u003c/p\u003e \u003cp\u003eIn almost all the reported cases, orbital inflammation was completely resolved with systemic corticosteroids. In our case, incomplete and abrupt discontinuation of systemic corticosteroids led to relapse of orbital inflammation. This may indicate the necessity of an adequate dosage, duration, and tapering manner for corticosteroids.\u003c/p\u003e \u003cp\u003eAlthough APR may have a self-limiting effect, in the presence of severe orbital inflammation, the prescription of systemic corticosteroids is reasonable. In these patients, severe proptosis and orbital congestion may be sight-threatening due to compressive optic neuropathy or exposure keratopathy.\u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u003c/sup\u003e Watching and follow-up may be options only for patients with mild inflammation or for patients with contraindications for corticosteroid therapy.\u003c/p\u003e \u003cp\u003eIn summary, zoledronate-induced orbital inflammation is a side effect that should be addressed after ruling out infectious causes, particularly bacterial and fungal causes. Severe cases require a sufficient dose and duration of systemic corticosteroid treatment in a tapered manner. All physicians, especially those at chemical centers, ophthalmologists, and infectious disease specialists, should be aware of this rare but important side effect of zoledronate administration and pay special attention to the patient\u0026rsquo;s drug history. Future studies could focus on risk factors and prevent this side effect.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003eA written consent was obtained from the patient to publish the study and accompanying image.\u003c/p\u003e\n\u003cp\u003eThe authors declare no conflicts of interest.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n \u003cli\u003eHenry MJ, Pasco JA, Nicholson GC, Kotowicz MA. Prevalence of osteoporosis in Australian men and women: Geelong Osteoporosis Study. Med J Aust. 2011;195(6):321-2.\u003c/li\u003e\n \u003cli\u003eRodan GA, Fleisch HA. Bisphosphonates: mechanisms of action. J Clin Invest. 1996;97(12):2692-6\u003c/li\u003e\n \u003cli\u003eOlson K, Van Poznak C. Significance and impact of bisphosphonate-induced acute phase responses. J Oncol Pharm Pract. 2007;13(4):223-9.\u003c/li\u003e\n \u003cli\u003eReid IR, Green JR, Lyles KW, Reid DM, Trechsel U, Hosking DJ, et al. Zoledronate. 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Arthritis Care Res (Hoboken). 2012;64(11):1776-82.\u003c/li\u003e\n \u003cli\u003eRossini M, Adami S, Viapiana O, Tripi G, Zanotti R, Ortolani R, et al. Acute phase response after zoledronic acid is associated with long-term effects on white blood cells. Calcif Tissue Int. 2013;93(3):249-52.\u003c/li\u003e\n \u003cli\u003ePeterson JD, Bedrossian EH, Jr. Bisphosphonate-associated orbital inflammation--a case report and review. Orbit. 2012;31(2):119-23.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"Shahid Beheshti University of Medical Sciences","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"zoledronate, orbital inflammation, bisphosphonates","lastPublishedDoi":"10.21203/rs.3.rs-3951554/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-3951554/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003eBisphosphonates are a group of drugs that are used to prevent the loss of bone density and treat osteoporosis and similar bone diseases. Zoledronate (zolenedronic acid) has been increasingly used because of its advantages of intravenous infusion and annual regimens. Here, we present a case of zolendronic acid-related diffuse orbital inflammation. A 67-year-old woman with a history of breast cancer and chemotherapy developed severe unilateral orbital and periorbital swelling approximately 8 hours after receiving her first zoledronate infusion. In this case, the interval between infusion and the beginning of the symptoms was too short compared with most other reported similar cases. Her signs and symptoms relapsed 4 days after discontinuation of the short course of systemic steroid therapy. Orbital inflammation improved after systemic corticosteroid therapy was restarted, but the patient did not relapse following discontinuation of the drug in a tapering manner.\u003c/p\u003e","manuscriptTitle":"Zoledronic Acid-Induced Orbital Inflammatory Disease","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-02-16 05:03:34","doi":"10.21203/rs.3.rs-3951554/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"d57e6fe4-238f-452d-bf0a-65c4c63e3418","owner":[],"postedDate":"February 16th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":28721555,"name":"Ophthalmology"}],"tags":[],"updatedAt":"2024-02-16T05:03:34+00:00","versionOfRecord":[],"versionCreatedAt":"2024-02-16 05:03:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-3951554","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-3951554","identity":"rs-3951554","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}