Since 2014, five more pivotal head-to-head trials have been published. Houchen Lyu, Bakr Jundi, [], and Daniel H Solomon. Methods: received a scholarship from Chinese PLA General Hospital and received support from Young Scientists Fund of the National Natural Science Foundation of China (Grant 81702176). Only one study reported denosumab to have lower osteoporotic fracture incidence than that of alendronate at 24 months. (16) showed that denosumab resulted in greater BMD improvement in lumbar spine and total hip from 12 months to 36 months when compared with alendronate and zoledronic acid. D.H.S. 2004 Aug;20(8):1291-300 Disclaimer, National Library of Medicine Results of this study suggest that, in patients treated with a prior bisphosphonate, switching to denosumab would result in greater BMD increase than would switching to another bisphosphonate. Trim-and-fill results suggested only zero to three missing studies were needed to achieve a symmetrical funnel plot. This active drug is also available as a biosimilar medication.. Biologic drugs, such as Prolia, are made Medicalnewstoday.com Clipboard, Search History, and several other advanced features are temporarily unavailable. McClung MR, Geusens P, Miller PD, et al. Characterised by reduced bone mineral density (BMD) and weakened bone structure (2,3,68), osteoporosis decreases bone resistance to low-energy trauma and increases bone fragility and fracture risk (6,8,9). In patients previously treated with a bisphosphonate, the difference was 1.75% at spine, 1.22% at total hip, and 1.20% at femoral neck. Arch Osteoporos. Lacey DL, Boyle WJ, Simonet WS, Kostenuik PJ, Dougall WC, Sullivan JK, San Martin J, Dansey R. Bench to bedside: elucidation of the OPG-RANK-RANKL pathway and the development of denosumab, Denosumab and bisphosphonates: different mechanisms of action and effects. At 24 months, the respective increase differences were 1.74% (95% CI, 1.05% to 2.43%; P < 0.001), 1.22% (95% CI, 0.66% to 1.77%; P < 0.001), and 1.19% (95% CI, 0.65% to 1.72%; P < 0.001). [19]ETTINGER B, BLACK D M, MITLAK B H, et al. If data were presented in figures, the GetData software (http://getdata-graph-digitizer.com/index.php) was used to extract data from the figures. 2022 Sep 1;19(17):10898. doi: 10.3390/ijerph191710898. 2015 Nov;94(44):e1674. Subjects were randomised to denosumab 30 mg Q3M or placebo twice yearly or, on an open-label basis, to alendronate once weekly. We conducted a patient-level pooled analysis of four studies to estimate the efficacy and safety of transitioning to denosumab vs. continuing bisphosphonate treatment in postmenopausal women who previously received oral bisphosphonates. The point estimates of spine BMDimprovement difference for denosumab was only 0.4% greater than for zoledronic acid and 0.8% greater than for alendronate at 12 months. Iolascon G, Paoletta M, Liguori S, Gimigliano F, Moretti A. Ther Adv Musculoskelet Dis. Antiresorptive drugs (e.g. Anastasilakis AD, Polyzos SA, Gkiomisi A, Saridakis ZG, Digkas D, Bisbinas I, Sakellariou GT, Papatheodorou A, Kokkoris P, Makras P. Denosumab versus zoledronic acid in patients previously treated with zoledronic acid.
Bisphosphonates vs Denosumab: Preventing SREs in Breast Cancer With Alendronate, risedronate, and zoledronic acid decrease the risk of spine, hips, and other nonvertebral fractures. Kendler DL, McClung MR, Freemantle N, Lillestol M, Moffett AH, Borenstein J, Satram-Hoang S, Yang YC, Kaur P, Macarios D, Siddhanti S; DAPS Investigators . In contrast, bisphosphonates bind bone mineral, where they are absorbed by mature osteoclasts, inducing osteoclast apoptosis and suppressing resorption. Osteoporosis is a systemic skeletal disease that increases with age and is common among postmenopausal women (15). Black DM, Delmas PD, Eastell R, et al. Osteocytes are derived from osteoblasts (bone-forming cells) that were buried as new bone tissue formed, and they direct bone remodelling in response to mechanical strain and other stimuli. As shown in Figure 1, these two cell types work together with resident bone osteocytes in the basic multicellular units (BMUs) that carry out bone remodelling (1,9,24). 2010 Jun;66(2):182-6. doi: 10.1016/j.maturitas.2010.02.008. Effect of denosumab treatment discontinuation and reinitiation on bone mineral density in the lumbar spine (A) and total hip (B). MECHANISM OF ACTION: Denosumab is a human monoclonal antibody that binds to the human RANK ligand (RANKL) on the surface of osteoclasts and their precursors . 2022 Oct;9(30):e2203031. A bibliometric research based on hotspots and frontier trends of denosumab. Longitudinal studies with longer follow-up and large sample size are needed to confirm the efficacy difference. The site is secure. Before At the end of 2010, the mean difference in BMD improvement was 1.05% (95% CI, 0.66% to 1.44%) at lumbar spine, 0.92% (95% CI, 0.70% to 1.15%) at total hip, and 0.68% (95% CI, 0.34% to 1.01%) at femoral neck. 2019 Nov 1;104(11):5611-5620. doi: 10.1210/jc.2019-00924. Delmas PD.
Bristol Myers Squibb to Participate in the Wolfe Research Healthcare Zoledronic acid comes as a solution (liquid) to inject into a vein over at least 15 minutes. Denosumab compared with ibandronate in postmenopausal women previously treated with bisphosphonate therapy: a randomized open-label trial. This article aims to review the mechanisms of action of pharmacological therapies for osteoporosis and to clarify the differences between the bisphosphonates and denosumab, a newly approved antiresorptive agent with a novel mechanism of action (7,11). An official website of the United States government.
(PDF) Bisphosphonate guidelines for treatment and prevention of myeloma Some bisphosphonates available for treatment in India are listed in Denosumab is a human monoclonal antibody that binds with and inhibits cytokine RANKL.
Pharmacological Aspects of Antiresorptive Drugs: Bisphosphonates and Alendronate subjects discontinued treatment at Month 24 and were observed until Month 48.
Denosumab - Wikipedia It inhibits osteoclast formation, decreases bone resorption, increases bone mineral density (BMD), and reduces the risk of fracture. Bisphosphonates and denosumab are both antiresorptive medications, each with their own mechanism of action; yet both may result in the same adverse effect: medication-related osteonecrosis of the jaw (ONJ). McClung MR, Lewiecki EM, Cohen SB, Bolognese MA, Woodson GC, Moffett AH, Peacock M, Miller PD, Lederman SN, Chesnut CH, Lain D, Kivitz AJ, Holloway DL, Zhang C, Peterson MC, Bekker PJ; AMG 162 Bone Loss Study Group . Second, the efficacy comparison of BMD increase and fracture risk reduction were not well reported at 24 months. Denosumab: mechanism of action and clinical outcomes, Re-use of this article is permitted in accordance with the Terms and Conditions set out at. Atypical femoral fracture in a bisphosphonate-nave patient on denosumab for osteoporosis. Second, only one study reported the efficacy difference on fracture end point between denosumab and bisphosphonates at 2 years; more studies are needed to clarify the fracture risk reduction benefit of denosumab compared with bisphosphonate. MECHANISM OF ACTION 7. Learn More Searching for the Answers Within Once-monthly ibandronate for postmenopausal osteoporosis: review of a new dosing regimen. Clinical studies, as well as in vitro and in vivo experiments have demonstrated that byproducts from joint replacements induce an inflammatory reaction that can result in periprosthetic osteolysis (PPOL) and aseptic loosening (AL). Methods: When zoledronic acid injection is used to treat high blood levels of calcium caused by cancer it is usually given as a single dose. This may explain differences in the degree and rapidity of reduction of bone resorption, their potential differential effects on trabecular and cortical bone, and the reversibility of their actions. Effect of alendronate on risk of fracture in women with low bone density but without vertebral fractures: results from the Fracture Intervention Trial. (45); reviewed in Ref. Other risk factors for ONJ include cancer, radiotherapy, poor oral hygiene, pre-existing dental disease or infection, anemia, and coagulopathy. Would you like email updates of new search results? Prolia is a brand-name drug that contains the active drug denosumab. You may switch to Article in classic view. doi: 10.1002/14651858.CD001347.pub2. Brown JP, Josse RG. Primary hyperparathyroidism features continuous excessive parathyroid hormone secretion and is associated with hypercalcaemia and bone fragility (28). 6). BMD increases with denosumab are greater than with bisphosphonates. Only one study demonstrated greater osteoporotic fracture reduction with denosumab treatment. Postmenopausal women can safely transition from a bisphosphonate to denosumab, which is more effective at improving BMD than continuing with a bisphosphonate. Denosumab increased BMD more than bisphosphonate at 12 months (mean difference, 1.42%; 95% CI, 0.95% to 1.89%; Denosumab improved BMD significantly more than bisphosphonate treatment at the lumbar spine, total hip, and femoral neck at 12 and 24 months. You may notice problems with Black DM, Cummings SR, Karpf DB, Cauley JA, Thompson DE, Nevitt MC, Bauer DC, Genant HK, Haskell WL, Marcus R, Ott SM, Torner JC, Quandt SA, Reiss TF, Ensrud KE; Fracture Intervention Trial Research Group . This topic review will discuss the use of denosumab as a . Risk ratio of (a) any, MeSH H.L. The ePub format is best viewed in the iBooks reader. Disclaimer, National Library of Medicine Structural insights into the binding of zoledronic acid with RANKL. See this image and copyright information in PMC. Thus, de-escalation of denosumab, ZA and pamidronate treatment from 4- to 12-weekly is a reasonable treatment option in these patients . Bone density and markers of bone turnover in predicting fracture risk and how changes in these measures predict fracture risk reduction, Therapy of endocrine disease: denosumab vs bisphosphonates for the treatment of postmenopausal osteoporosis. Bessette L, Ste-Marie LG, Jean S, et al. Denosumab acts by binding to and inhibiting RANKL, leading to the loss of osteoclasts from bone surfaces. Because bisphosphonates inhibit bone resorption, they are used in the treatment of hypercalcemia, osteoporosis, metastatic bone disease, and Paget . The available information and outcomes of all the eligible studies were independently extracted by two researchers (H.L., B.J.). These treatments reduce the risk of osteoporotic fractures and stabilise or increase bone mass and strength (10). Bone. Previous phase 3 clinical trials found both drugs increased BMD and reduced the risk of fracture compared with placebo (812). Denosumab is a fully human monoclonal antibody that binds RANKL, preventing RANKL from activating RANK, its receptor on the osteoclast surface (11). When internalized from the bone surface, bisphosphonates inactivate or promote apoptosis of osteoclasts (5). The better performance of denosumab relative to that of bisphosphonates in increasing BMD was found in treatment-nave patients and patients who previously had received bisphosphonate treatment. 8600 Rockville Pike For the continuous variable (i.e., percentage changes in BMD), weighted mean difference and 95% CIs were calculated. BP, bisphosphonate; DMAb, denosumab; MD, mean difference. Longitudinal studies with longer follow-up and large sample size are needed to confirm the efficacy difference. Denosumab compared to bisphosphonates to treat postmenopausal osteoporosis: a meta-analysis. 2022 Jun;8(2):68-74. doi: 10.1016/j.afos.2022.05.002. The care gap in diagnosis and treatment of women with a fragility fracture. Search terms and MeSH headings used included mechanism of action combined with the word osteoporosis and each of the following: denosumab, antiresorptive, bisphosphonate, parathyroid hormone and RANK ligand.
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