The Korean Journal of Medicine

The Korean Association of Internal Medicine (대한내과학회)
권호 표지
DOI QR코드

DOI QR Code

Recent Update on RANKL Inhibitor

RANKL 억제제의 최신 업데이트

  • Choi, Han Seok (Division of Endocrinology and Metabolism, Department of Internal Medicine, Dongguk University Ilsan Hospital)
  • 최한석 (동국대학교 일산병원 내분비내과)
  • Published : 2018.06.01
⟨ Previous Next ⟩

Abstract

The prevalence of osteoporosis is continuing to increase with growing elderly population. A variety of anti-osteoporotic agents have been used for the prevention and treatment of osteoporosis and osteoporotic fractures. Novel therapeutic agents based on the newly discovered mechanisms in bone biology have been recently introduced. Denosmab, a fully human monoclonal antibody to the receptor activator of nuclear $factor-{\kappa}B$ ligand, is a new therapeutic agent that inhibits osteoclast differentiation, activity, and survival. In the fracture reduction evaluation of denosumab in osteoporosis every 6 months (FREEDOM) trial, denosumab treatment for 36 months significantly increased bone mineral density at all skeletal sites evaluated, thereby resulting in a significant reduction in the risk of vertebral, nonvertebral, and hip fractures. In the FREEDOM Extension study, in which denosumab treatment was continued for up to 10 years, denosumab showed a continued improvement in bone mineral density and a consistently low fracture risk similar to rates observed in the denosumab group during the FREEDOM trial. Denosumab also offered a favorable safety profile with generally low and stable adverse event rates. Denosumab was indicated for treatment of postmenopausal women with osteoporosis at high risk for fracture, treatment to increase bone mass in men with osteoporosis, treatment of bone loss in men receiving androgen deprivation therapy for prostate cancer, and treatment of bone loss in women receiving adjuvant aromatase inhibitor therapy for breast cancer. For these patients, denosumab is an important option for the prevention and treatment of osteoporosis and osteoporotic fractures.

Keywords

References

  1. Choi YJ, Oh HJ, Kim DJ, et al. The prevalence of osteoporosis in Korean adults aged 50 years or older and the higher diagnosis rates in women who were beneficiaries of a national screening program: the Korea National Health and Nutrition Examination Survey 2008-2009. J Bone Miner Res 2012;27:1879-1886. https://doi.org/10.1002/jbmr.1635
  2. Park C, Ha YC, Jang S, Jang S, Yoon HK, Lee YK. The incidence and residual lifetime risk of osteoporosis-related fractures in Korea. J Bone Miner Metab 2011;29:744-751. https://doi.org/10.1007/s00774-011-0279-3
  3. Heaney RP, Abrams S, Dawson-Hughes B, et al. Peak bone mass. Osteoporos Int 2000;11:985-1009.
  4. Raggatt LJ, Partridge NC. Cellular and molecular mechanisms of bone remodeling. J Biol Chem 2010;285:25103-25108. https://doi.org/10.1074/jbc.R109.041087
  5. Baron R, Ferrari S, Russell RG. Denosumab and bisphosphonates: different mechanisms of action and effects. Bone 2011;48:677-692. https://doi.org/10.1016/j.bone.2010.11.020
  6. European Medicines Agency. Prolia 60 mg solution in a prefilled syringe: summary of product characteristics [Internet]. London (UK): European Medicines Agency c2018 [cited 2018 Apr 10]. Available from: http://www.ema.europa.eu/docs/en_GB/document_library/EPAR_-_Product_Information/human/001120/WC500093526.pdf.
  7. Amgen Manufacturing Limited. Prolia (denosumab) injection, for subcutaneous use: Highlights of prescribing information [Internet]. Thousand Oaks (CA): Amgen, c2018 [cited 2018 Apr 10]. Available from: https://pi.amgen.com/-/media/amgen/repositorysites/ pi-amgen-com/prolia/prolia_pi.pdf.
  8. Cummings SR, San Martin J, McClung MR, et al. Denosumab for prevention of fractures in postmenopausal women with osteoporosis. N Engl J Med 2009;361:756-765. https://doi.org/10.1056/NEJMoa0809493
  9. Boonen S, Adachi JD, Man Z, et al. Treatment with denosumab reduces the incidence of new vertebral and hip fractures in postmenopausal women at high risk. J Clin Endocrinol Metab 2011;96:1727-1736. https://doi.org/10.1210/jc.2010-2784
  10. Bone HG, Wagman RB, Brandi ML, et al. 10 years of denosumab treatment in postmenopausal women with osteoporosis: results from the phase 3 randomised FREEDOM trial and open-label extension. Lancet Diabetes Endocrinol 2017;5:513-523. https://doi.org/10.1016/S2213-8587(17)30138-9
  11. Koh JM, Chung DJ, Chung YS, et al. Assessment of denosumab in Korean postmenopausal women with osteoporosis: randomized, double-blind, placebo-controlled trial with open-label extension. Yonsei Med J 2016;57:905-914. https://doi.org/10.3349/ymj.2016.57.4.905
  12. Reid IR, Miller PD, Brown JP, et al. Effects of denosumab on bone histomorphometry: the FREEDOM and STAND studies. J Bone Miner Res 2010;25:2256-2265. https://doi.org/10.1002/jbmr.149
  13. McClung MR, Zanchetta JR, Hoiseth A, et al. Denosumab densitometric changes assessed by quantitative computed tomography at the spine and hip in postmenopausal women with osteoporosis. J Clin Densitom 2013;16:250-256. https://doi.org/10.1016/j.jocd.2012.02.014
  14. Zebaze R, Libanati C, McClung MR, et al. Denosumab reduces cortical porosity of the proximal femoral shaft in postmenopausal women with osteoporosis. J Bone Miner Res 2016;31:1827-1834. https://doi.org/10.1002/jbmr.2855
  15. Keaveny TM, McClung MR, Genant HK, et al. Femoral and vertebral strength improvements in postmenopausal women with osteoporosis treated with denosumab. J Bone Miner Res 2014;29:158-165. https://doi.org/10.1002/jbmr.2024
  16. Orwoll E, Teglbjaerg CS, Langdahl BL, et al. A randomized, placebo-controlled study of the effects of denosumab for the treatment of men with low bone mineral density. J Clin Endocrinol Metab 2012;97:3161-3169. https://doi.org/10.1210/jc.2012-1569
  17. Langdahl BL, Teglbjaerg CS, Ho PR, et al. A 24-month study evaluating the efficacy and safety of denosumab for the treatment of men with low bone mineral density: results from the ADAMO trial. J Clin Endocrinol Metab 2015;100:1335-1342. https://doi.org/10.1210/jc.2014-4079
  18. Gnant M, Pfeiler G, Dubsky PC, et al. Adjuvant denosumab in breast cancer (ABCSG-18): a multicentre, randomised, double- blind, placebo-controlled trial. Lancet 2015;386:433-443. https://doi.org/10.1016/S0140-6736(15)60995-3
  19. Smith MR, Egerdie B, Hernandez Toriz N, et al. Denosumab in men receiving androgen-deprivation therapy for prostate cancer. N Engl J Med 2009;361:745-755. https://doi.org/10.1056/NEJMoa0809003
  20. 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;24:153-161. https://doi.org/10.1359/jbmr.0809010
  21. Zebaze RM, Libanati C, Austin M, et al. Differing effects of denosumab and alendronate on cortical and trabecular bone. Bone 2014;59:173-179. https://doi.org/10.1016/j.bone.2013.11.016
  22. Roux C, Hofbauer LC, Ho PR, et al. Denosumab compared with risedronate in postmenopausal women suboptimally adherent to alendronate therapy: efficacy and safety results from a randomized open-label study. Bone 2014;58:48-54. https://doi.org/10.1016/j.bone.2013.10.006
  23. Recknor C, Czerwinski E, Bone HG, et al. Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. Obstet Gynecol 2013;121:1291-1299. https://doi.org/10.1097/AOG.0b013e318291718c
  24. Miller PD, Pannacciulli N, Brown JP, et al. Denosumab or zoledronic acid in postmenopausal women with osteoporosis previously treated with oral bisphosphonates. J Clin Endocrinol Metab 2016;101:3163-3170. https://doi.org/10.1210/jc.2016-1801
  25. Nakamura T, Matsumoto T, Sugimoto T, et al. Clinical trials express: fracture risk reduction with denosumab in Japanese postmenopausal women and men with osteoporosis: denosumab fracture intervention randomized placebo controlled trial (DIRECT). J Clin Endocrinol Metab 2014;99:2599-2607. https://doi.org/10.1210/jc.2013-4175
  26. Tsai JN, Uihlein AV, Lee H, et al. Teriparatide and denosumab, alone or combined, in women with postmenopausal osteoporosis: the DATA study randomised trial. Lancet 2013;382:50-56. https://doi.org/10.1016/S0140-6736(13)60856-9
  27. Leder BZ, Tsai JN, Uihlein AV, et al. Two years of denosumab and teriparatide administration in postmenopausal women with osteoporosis (The DATA Extension Study): a randomized controlled trial. J Clin Endocrinol Metab 2014;99:1694-1700. https://doi.org/10.1210/jc.2013-4440
  28. Tsai JN, Uihlein AV, Burnett-Bowie SM, et al. Effects of two years of teriparatide, denosumab, or both on bone microarchitecture and strength (DATA-HRpQCT study). J Clin Endocrinol Metab 2016;101:2023-2030. https://doi.org/10.1210/jc.2016-1160
  29. 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;93:2149-2157. https://doi.org/10.1210/jc.2007-2814
  30. McLachlan JM, Marx GM, Bridgman M. Severe symptomatic hypocalcaemia following a single dose of denosumab. Med J Aust 2013;199:242-243. https://doi.org/10.5694/mja13.10038
  31. Okada N, Kawazoe K, Teraoka K, et al. Identification of the risk factors associated with hypocalcemia induced by denosumab. Biol Pharm Bull 2013;36:1622-1626. https://doi.org/10.1248/bpb.b13-00496
  32. Killen JP, Yong K, Luxton G, Endre Z. Life-threatening hypocalcaemia associated with denosumab in advanced chronic kidney disease. Intern Med J 2016;46:746-747. https://doi.org/10.1111/imj.13097
  33. Kendler DL, Roux C, Benhamou CL, et al. Effects of denosumab on bone mineral density and bone turnover in postmenopausal women transitioning from alendronate therapy. J Bone Miner Res 2010;25:72-81. https://doi.org/10.1359/jbmr.090716
  34. Leder BZ, Tsai JN, Uihlein AV, et al. Denosumab and teriparatide transitions in postmenopausal osteoporosis (the DATA-Switch study): extension of a randomised controlled trial. Lancet 2015;386:1147-1155. https://doi.org/10.1016/S0140-6736(15)61120-5
  35. Tsai JN, Nishiyama KK, Lin D, et al. Effects of denosumab and teriparatide transitions on bone microarchitecture and estimated strength: the DATA-Switch HR-pQCT study. J Bone Miner Res 2017;32:2001-2009. https://doi.org/10.1002/jbmr.3198
  36. Bone HG, Bolognese MA, Yuen CK, et al. Effects of denosumab treatment and discontinuation on bone mineral density and bone turnover markers in postmenopausal women with low bone mass. J Clin Endocrinol Metab 2011;96:972-980. https://doi.org/10.1210/jc.2010-1502
  37. Reid IR, Horne AM, Mihov B, Gamble GD. Bone loss after denosumab: only partial protection with zoledronate. Calcif Tissue Int 2017;101:371-374. https://doi.org/10.1007/s00223-017-0288-x
  38. Leder BZ, Tsai JN, Jiang LA, Lee H. Importance of prompt antiresorptive therapy in postmenopausal women discontinuing teriparatide or denosumab: the denosumab and teriparatide follow-up study (DATA-Follow-up). Bone 2017;98:54-58. https://doi.org/10.1016/j.bone.2017.03.006

Cited by

  1. 종설 : 치과위생사가 알아야 할 골다공증과 골 관련 사이토카인 vol.3, pp.2, 2020, https://doi.org/10.22753/jkdhs/2020.3.2.59