Comparison Side Effects of Denosumab and Zoledronic Acid in Osteoporosis Patients Over 65 Years Old

Year 2021, , 135 - 139, 30.06.2021

Rabia Bağ Soytaş Suna Avcı , Hakan Yavuzer , Serdar Özkök Alper Döventaş , Deniz Suna Erdinçler

https://doi.org/10.15321/GenelTipDer.2021.300

Abstract

Objective: We aimed to compare the rates of denosumab and zoledronic acid in patients receiving osteoporosis treatment and the side effects of these drugs.

Material and Method: In our study, the files of the applicants were searched between January 2016-December 2017; those with denosumab and zoledronic acid. Clinical and demographic data, laboratory values of beginning of treatment, 6 months and 1 year and side effects were recorded.

Results: 171 patients were included. Denosumab group was older, their urea and creatinine levels were higher and GFRs were lower. Hypocalcemia was observed only in denosumab group (1 (1.23%) patient). Acut renal failure occured in 4 (% 5,19) patients with denosumab and 2 (%2,12) patients with the other group during 1 month follow up. Flu-like symptomps were observed only in zoledronic asit group (2 (%2,12) patients). Bilateral spontaneous fracture of the ischium pubis was observed in 1 (1.29%) of the former, spontaneous 6 teeth loss in 1 (1.06%) of the latter group.

Conclusion: There were no significant differences between two groups in terms of side effects. Side effects were lower than those reported in the literature; in addition to comorbidity, multiple drug use and rare side effects should be kept in mind.

Keywords

Geriatric, Zoledronic acid, Denosumab, Side effect

65 Yaş Üstü Osteoporoz Hastalarında Denosumab ve Zoledronik Asit’in Yan Etkilerinin Karşılaştırılması

Abstract

Amaç: Osteoporoz tedavisi alan hastalarda, zoledronik asit ve denosumab kullanım oranları ile bu iki ilacın yan etkilerini karşılaştırmayı amaçladık.

Gereç ve Yöntem: Çalışmamızda Ocak 2016-Aralık 2017 tarihleri arasında başvuran hastaların dosyaları taranarak, osteoporoz tanısıyla zoledronik asit ve denosumab almış olanlar belirlendi. Klinik ve demografik verileri, tedavi başlangıcı, 6. ay ve 1. yıl laboratuvar değerleri ile ilaç yan etkileri kaydedildi.

Bulgular: Çalışmaya 171 hasta dâhil edildi. Denosumab alanlar daha yaşlı, üre ve kreatinin değerleri daha yüksek, kreatinin klirensleriyse daha düşüktü. Yan etki açısından değerlendirildiğinde hipokalsemi, denosumab verilenlerin 1’inde (%1,29) görülürken; zoledronik asit verilenlerde rastlanmadı. Denosumab alanların 4’ünde (% 5,19), zoledronik asit alanların ise 2’sinde (% 2,12) 1 aylık takipte akut böbrek yetmezliği gelişti. Zoledronik asit alanların 2’sinde (% 2,12) grip benzeri semptomlar görülürken; denosumab alanlarda gözlenmedi. Ayrıca zoledronik asit alanların 1’inde (% 1,06) tedavi sonrası çene osteonekrozu olmaksızın, 6 dişinde kendiliğinden dökülme; denosumab alanların 1’inde (% 1,29) ise iskium pubiste bilateral spontan kırık tespit edildi.

Sonuç: İki ajan karşılaştırıldığında, yan etki açısından iki grup arasında anlamlı fark olmadığı; gelişen yan etkilerin ise literatürde belirtilenden daha az olduğu; kullanılacak ajanın seçiminde komorbidite yanı sıra, çoklu ilaç kullanımı ve nadir yan etkilerin akılda tutulması gerektiği kanısına varıldı.

Keywords

Geriatri, Zoledronik asit, Denosumab, Yan Etki

References

• Compston JE, McClung MR, Leslie WD. Osteoporosis. Lancet. 2019;393(10169):364-376.
• Rachner TD, Khosla S, Hofbauer LC. Osteoporosis: now and the future. Lancet 2011; 377: 1276-87.
• Johnston CB, Dagar M. Osteoporosis in Older Adults. Med Clin North Am. 2020;104(5):873-884.
• Lentle B, Cheung AM, Hanley DA, et al. Osteoporosis Canada 2010 guidelines for the assessment of fracture risk. Can Assoc Radiol J 2011; 62: 243-50.
• Kanis JA, McCloskey EV, Johansson H, et al. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporos Int 2013; 24: 23-57.
• Cauley JA, El-Hajj Fuleihan G, Arabi A, et al. Official Positions for FRAX® clinical regarding international differences from Joint Official Positions Development Conference of the International Society for Clinical Densitometry and International Osteoporosis Foundation on FRAX®. J Clin Densitom 2011; 14: 240-62.
• Kanis JA, Johansson H, Harvey NC, McCloskey EV. A brief history of FRAX. Arch Osteoporos. 2018;13(1):118. Published 2018 Oct 31.
• Hernlund E, Svedbom A, Ivergård M, et al. Osteoporosis in the European Union: medical management, epidemiology and economic burden. A report prepared in collaboration with the International Osteoporosis Foundation (IOF) and the European Federation of Pharmaceutical Industry Associations (EFPIA). Arch Osteoporos 2013; 8: 136.
• Cosman F, Beur SJ, LeBoff MS, et al. Clinician’s Guide to Prevention and Treatment of Osteoporosis. Osteoporos Int 2014; 25: 2359-2381.
• McClung M, Harris ST, Miller PD, et al. Bisphosphonate therapy for osteoporosis: benefits, risks, and drug holiday. Am J Med 2013; 126: 13-20.
• Lippuner K. The future of osteoporosis treatment - a research update. Swiss Med Wkly 2012; 142: 13624.
• Diab DL, Watts NB. Denosumab in osteoporosis. Expert Opin Drug Saf 2014; Feb;13(2):247-53
• Diker-Cohen T, Rosenberg D, Avni T, Shepshelovich D, Tsvetov G, Gafter-Gvili A. Risk for Infections During Treatment With Denosumab for Osteoporosis: A Systematic Review and Meta-analysis. J Clin Endocrinol Metab. 2020;105(5):dgz322.
• Gambacciani M, Levancini M. Management of postmenopausal osteoporosis and the prevention of fractures. Panminerva Med. 2014;56(2):115-131.
• Xu XL, Gou WL, Wang AY, et al. Basic research and clinical applications of bisphosphonates in bone disease: what have we learned over the last 40 years? J Transl Med 2013; 11: 303.
• Rizzoli R, Reginster JY. Adverse drug reactions to osteoporosis treatments. Expert Rev Clin Pharmacol 2011; 4: 593-604.
• Lewiecki EM. Treatment of osteoporosis with denosumab. Maturitas. 2010 Jun; 66(2): 182-6.
• Deeks ED. Denosumab: A Review in Postmenopausal Osteoporosis [published correction appears in Drugs Aging. 2018 Mar 9;:]. Drugs Aging. 2018;35(2):163-173.
• Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women. J Clin Endocrinol Metab 2008; 93: 2149.
• Miller PD, Bolognese MA, Lewiecki EM, et al. Effect of denosumab on bone density and turnover in postmenopausal women with low bone mass after long-term continued, discontinued, and restarting of therapy: a randomized blinded phase 2 clinical trial. Bone 2008; 43: 222.
• McClung MR, Lewiecki EM, Cohen SB, et al. Denosumab in postmenopausal women with low bone mineral density. N Engl J Med 2006; 354: 821.
• Anastasilakis AD, Toulis KA, Goulis DG, et al. Efficacy and safety of denosumab in postmenopausal women with osteopenia or osteoporosis: a systematic review and a meta-analysis. Horm Metab Res 2009; 41: 721.
• Brown JP, Prince RL, Deal C, et al. Comparison of the effect of denosumab and alendronate on BMD and biochemical markers of bone turnover in postmenopausal women with low bone mass: a randomized, blinded, phase 3 trial. J Bone Miner Res 2009; 24: 153.
• Black DM, Delmas PD, Eastell R, et al. Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis. N Engl J Med 2007; 356: 1809.
• Etminan M, Forooghian F, Maberley D. Inflammatory ocular adverse events with the use of oral bisphosphonates: a retrospective cohort study. CMAJ 2012; 184: E431.
• Fraunfelder FW, Fraunfelder FT. Bisphosphonates and ocular inflammation. N Engl J Med 2003; 348: 1187.
• Chatterjee S, Agrawal D. Bilateral Acute Anterior Uveitis and Conjunctivitis following Intravenous Zoledronic Acid. J Assoc Physicians India. 2017;65(7):110-111.
• Sharma NS, Ooi JL, Masselos K, et al. Zoledronic acid infusion and orbital inflammatory disease. N Engl J Med 2008; 359: 1410.
• Pazianas M, Clark EM, Eiken PA, et al. Inflammatory eye reactions in patients treated with bisphosphonates and other osteoporosis medications: cohort analysis using a national prescription database. J Bone Miner Res 2013; 28: 455.
• Patel DV, Bolland M, Nisa Z, et al. Incidence of ocular side effects with intravenous zoledronate: secondary analysis of a randomized controlled trial. Osteoporos Int 2015; 26: 499.
• Black DM, Reid IR, Boonen S, et al. The effect of 3 versus 6 years of zoledronic acid treatment of osteoporosis: a randomized extension to the HORIZON-Pivotal Fracture Trial (PFT). J Bone Miner Res 2012; 27: 243.
• Pazianas M, Compston J, Huang CL. Atrial fibrillation and bisphosphonate therapy. J Bone Miner Res 2010; 25: 2.
• Eguia A, Bagán-Debón L, Cardona F. Review and update on drugs related to the development of osteonecrosis of the jaw. Med Oral Patol Oral Cir Bucal. 2020;25(1):e71-e83.
• Fizazi K, Carducci M, Smith M, et al. Denosumab versus zoledronic acid for treatment of bone metastases in men with castration-resistant prostate cancer: a randomised, double-blind study. Lancet. 2011; 377(9768): 813–22.
• Fizazi K, Lipton A, Mariette X, et al. Randomized phase II trial of denosumab in patients with bone metastases from prostate cancer, breast cancer, or other neoplasms after intravenous bisphosphonates. J Clin Oncol 2009; 27(10): 1564–71.
• Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases. J Clin Oncol 2007; 25(28): 4431–7.
• Smith MR, Egerdie B, Hernandez Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009; 361(8): 745–55.
• Avguštin N, Kovač D, Kojc N, Mlinšek G, Lindič J. Acute granulomatous interstitial nephritis and acute rejection in a kidney transplant recipient after zoledronic acid therapy - a case report and review of the literature. Clin Nephrol. 2017;88(13):97-100.
• Chang JT, Gren L, Beitz J. Renal failure with the use of zoledronic acid. N Engl J Med. 2003; 349: 1676-1678.
• Cipriani C, Pepe J, Clementelli C, et al. Effect of a single intravenous zoledronic acid administration on biomarkers of acute kidney injury (AKI) in patients with osteoporosis: a pilot study. Br J Clin Pharmacol. 2017;83(10):2266-2273.
• Cheng L, Ge M, Lan Z, et al. Zoledronate dysregulates fatty acid metabolism in renal tubular epithelial cells to induce nephrotoxicity. Arch Toxicol. 2018;92(1):469-485.
• Bergner R, Diel IJ, Henrich D, et al. Differences in nephrotoxicity of intravenous bisphosphonates for the treatment of malignancy-related bone disease. Onkologie. 2006; 29: 534-540.
• Balla J. The issue of renal safety of zoledronic acid from a nephrologist’s point of view. Oncologist. 2005; 10:306-308.
• Hillner BE, Ingle JN, Chlebowski RT, et al. American society of clinical oncology 2003 update on the role of bisphosphonates and bone health issues in women with breast cancer. J Clin Oncol. 2003; 21: 4042-4057.
• Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009; 361:756.
• Huang SY, Yoon SS, Shimizu K, et al. Denosumab Versus Zoledronic Acid in Bone Disease Treatment of Newly Diagnosed Multiple Myeloma: An International, Double-Blind, Randomized Controlled Phase 3 Study-Asian Subgroup Analysis. Adv Ther. 2020;37(7):3404-3416.
• Schussheim DH, Jacobs TP, Silverberg SJ. Hypocalcemia associated with alendronate. Ann Intern Med. 1999; 130: 329.
• Malouf NM, Heller HJ, Odvina CV, et al. Bisphosphonate-induced hypocalcemia: report of 3 cases and review of literature. Endocr pract. 2006; 12: 48-53.
• Macisaac RJ, Seeman E, Herums G. Seizures after alendronate. J Royal Soc Med. 2002; 95: 615-616.
• Tsvetov G, Amitai O, Shochat T, Shimon I, Akirov A, Diker-Cohen T. Denosumab-induced hypocalcemia in patients with osteoporosis: can you know who will get low?. Osteoporos Int. 2020;31(4):655-665.