Effectiveness of Short-Term Use Denosumab and Risedronate Using β-Crosslaps and Histopathology as a Parameter in Osteoporotic Rat Model

Afrisya Bimo Siwendro, Ahmad Ramdan, Yoyos Dias Ismiarto, Anglita Yantisetiasti, Dliyauddin fachri

Abstract


Osteoporosis is a condition of decreased bone mass density. Pharmacological management uses drugs that decrease bone resorption or increase bone formation. The most commonly used drugs are bisphosphonates. Risedronate is one of these bisphosphonates. It inhibits osteoclasts, resulting in osteoclast apoptosis. Denosumab is a human monoclonal antibody that inhibits receptor activator kappa-B ligand, inhibiting osteoclast activation. Both drugs are widely used. Research on the efficacy of these two mechanisms has yet to obtain conclusive results. β-cross-laps is a parameter that can be used to evaluate the effectiveness of therapy through monitoring the bone resorption process. This experimental study used female rats >9 weeks old and was conducted at the Pharmacology and Therapeutic Laboratory, Universitas Padjadjaran Bandung, Indonesia, from  June to September 2021. This study utilized a simple random sampling to allocate 24 experimental animals into three groups: control, risedronate, and denosumab. β-Crosslaps expression values before ovariectomy, post ovariectomy before receiving medication, and post ovariectomy and receiving medication was recorded and statistically analyzed using the SPSS version 24.0. The analysis of 24 samples revealed a statistically significant decrease in the median value of β-Crosslaps after ovariectomy in the denosumab group (p=0.036) when compared to the control group, whereas the decrease in the risedronate group was not significant (p=0.687). Administration of denosumab in rat models is more effective in reducing bone resorption compared to risedronate.

Keywords


β-cross-laps, denosumab, risedronate, osteoporosis

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References


  1. Aslan M, Çogendez E, Education ZK, Eken M, Education ZK, Arioglu P, et al. Serum beta crosslaps as a predictor for osteoporosis in postmenopausal women. İstanbul Tıp Fakültesi Dergisi. 2015;78:36–40.
  2. Suzuki T, Nakamura Y, Kato H. Calcium and vitamin D supplementation with 3-year denosumab treatment is beneficial to enhance bone mineral density in postmenopausal patients with osteoporosis and rheumatoid arthritis. Therapeutics and clinical risk management. 2019;15:15.
  3. Golob AL, Laya MB. Osteoporosis: screening, prevention, and management. Medical Clinics. 2015;99(3):587–606.
  4. Dima L. Diab, Nelson B. Watts, Paul D. Miller, Bisphosphonates pharmacology and use in the treatment of osteoporosis. In: David W. Dempster, Jane A. Cauley, Mary L. Bouxsein, Felicia Cosman, Marcus and Feldman’s, Editors. Osteoporosis. 5th ed. Cambridge: Academic Press; 2021; p. 1721–36.
  5. Augoulea A, Tsakonas E, Triantafyllopoulos I, Rizos D, Armeni E, Tsoltos N, et al. Comparative effects of denosumab or bisphosphonate treatment on bone mineral density and calcium metabolism in postmenopausal women. J Musculoskelet Neuronal Interact. 2017;17(1):444–9.
  6. Langdahl B, Ferrari S, Dempster DW. Bone modeling and remodeling: potential as therapeutic targets for the treatment of osteoporosis. Ther Adv Musculoskelet Dis. 2016;8(6):225–35. doi:10.1177/1759720X16670154
  7. Saag KG, Pannacciulli N, Geusens P, Adachi JD, Messina OD, Morales-Torres J, et al. Denosumab versus risedronate in glucocorticoid-induced osteoporosis: final results of a twenty-four-month randomized, double-blind, double-dummy trial. Arthritis Rheumatol. 2019;71(7):1174–84.
  8. Hu M, Zhang Y, Guo J, Guo C, Yang X, Ma X, Xu H and Xiang S. Meta-analysis of the effects of denosumab and romosozumab on bone mineral density and turnover markers in patients with osteoporosis. Front Endocrinol (Lausanne). 2023;14:1188969. doi:10.3389/fendo.2023.1188969
  9. Dempster DW, Brown JP, Fahrleitner-Pammer A, Kendler D, Rizzo S, Valter I, et al. Effects of long-term denosumab on bone histomorphometry and mineralization in women with postmenopausal osteoporosis. J Clin Endocrinol Metab. 2018;103(7):2498–509.
  10. Tourolle DC, Dempster DW, Ledoux C, Boaretti D, Aguilera M, Saleem N, et al. Ten-year simulation of the effects of denosumab on bone remodeling in human biopsies. JBMR Plus. 2021;5(6):e10494. doi:10.1002/jbm4.10494
  11. McClung MR, Lippuner K, Brandi ML, Zanchetta JR, Bone HG, et al. Effect of denosumab on trabecular bone score in postmenopausal women with osteoporosis. Osteoporos Int. 2017;28(10):2967–73. doi: 10.1007/s00198-017-4140-y




DOI: https://doi.org/10.15395/mkb.v56.3016

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