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Current Osteoporosis Reports Feb 2023To review the pathophysiology, the clinical consequences as well as way of mitigating the effects of denosumab discontinuation. (Review)
Review
PURPOSE OF REVIEW
To review the pathophysiology, the clinical consequences as well as way of mitigating the effects of denosumab discontinuation.
RECENT FINDINGS
Treatment with denosumab (DMAB) is reversible and upon discontinuation there is a rapid increase in bone turnover and a subsequent bone loss. During this phase of high bone turnover, an increased risk of fractures has been reported. Therefore, treatment with DMAB could be considered life-long. However, side-effects may prompt the need for discontinuation and moreover, treatment with DMAB may have increased BMD to levels where continuing treatment does not provide further fracture risk reduction. Patients stopping DMAB should be offered subsequent antiresorptive treatment with an intense monitoring regimen during the initial year as most of the bone loss occurs within these initial 12 months. In this review, we evaluated the literature published over the past 1 to 3 years investigating DMAB withdrawal with focus on bone turnover markers, bone mineral density, and fracture risk and the transition to other anti-osteoporosis therapies. Furthermore, we summarized the current recommendations of international guidelines. In this review, we evaluated the literature published over the past 1 to 3 years investigating denosumab (DMAB) discontinuation and the transition to other anti-osteoporosis therapies. Additionally, we summarized the current recommendations of international guidelines.
Topics: Humans; Female; Denosumab; Bone Density Conservation Agents; Osteoporosis; Bone Density; Fractures, Bone; Osteoporosis, Postmenopausal
PubMed: 36564572
DOI: 10.1007/s11914-022-00771-6 -
Scientific Reports Jun 2021Denosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no... (Comparative Study)
Comparative Study
Denosumab and romosozumab, a recently approved new drug, are effective and widely known molecular-targeted drugs for postmenopausal osteoporosis treatment. However, no studies have directly compared their therapeutic effects or safety in postmenopausal osteoporosis. This retrospective observational registry study compared the efficacy of 12-month denosumab or romosozumab treatment in postmenopausal osteoporosis patients. The primary outcome was the change in bone mineral density (BMD) at the lumbar spine. Secondary outcomes included BMD changes at the total hip and femoral neck, changes in bone turnover markers, and adverse events. Propensity score matching was employed to assemble patient groups with similar baseline characteristics. Sixty-nine patients each received either denosumab or romosozumab for 12 months. The mean 12-month percentage change from baseline in lumbar spine BMD was 7.2% in the denosumab group and 12.5% in the romosozumab group, indicating a significant difference between the groups. The percentage changes in BMD at both the total hip and femoral neck were also significantly higher at 12 months in the romosozumab group than in the denosumab group. In denosumab patients, bone formation and bone resorption markers were significantly decreased at 6 and 12 months from baseline. In the romosozumab group, the bone formation marker was significantly increased at 6 months and then returned to baseline, while the bone resorption marker was significantly decreased at both time points. Adverse events were few and predominantly minor in both groups, with no remarkable difference in the incidence of new vertebral fractures. Romosozumab showed a higher potential for improving BMD than denosumab in this clinical study of postmenopausal osteoporosis patient treatment.
Topics: Aged; Aged, 80 and over; Antibodies, Monoclonal; Biomarkers; Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Middle Aged; Molecular Targeted Therapy; Osteoporosis, Postmenopausal; Propensity Score; Treatment Outcome
PubMed: 34083636
DOI: 10.1038/s41598-021-91248-6 -
Current Osteoporosis Reports Feb 2019Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is... (Review)
Review
PURPOSE OF REVIEW
Denosumab discontinuation is associated with a rebound effect manifesting by an increased risk of multiple spontaneous vertebral fractures. The purpose of this review is to (1) better characterize this risk and (2) find solutions to avoid it.
RECENT FINDINGS
In the absence of a potent bisphosphonate prescription at denosumab discontinuation, the frequency of multiple vertebral fractures is common or frequent (≥ 1/100 and < 1/10). In five recent case series, the median number of vertebral fractures was 5 within 7 to 20 months (median 11) after the last denosumab injection. Prescribing bisphosphonate before starting denosumab and/or after stopping denosumab may reduce this risk. However, only small case series have evaluated these strategies. After the second denosumab dose, there is a rebound effect with an increased risk of multiple vertebral fractures. A potent bisphosphonate prescribed at denosumab discontinuation could reduce this risk. As denosumab discontinuation is characterized by many uncertainties, denosumab is a second-line treatment for osteoporosis. Studies are urgently needed to define the management of denosumab discontinuation.
Topics: Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Osteoporosis, Postmenopausal; Risk Factors; Spinal Fractures; Withholding Treatment
PubMed: 30659428
DOI: 10.1007/s11914-019-00502-4 -
La Clinica Terapeutica 2023Denosumab, an antiresorptive agent, has shown results in improving bone mineral density and reducing fractures in postmenopausal women. While bisphosphonates are... (Review)
Review
OBJECTIVE
Denosumab, an antiresorptive agent, has shown results in improving bone mineral density and reducing fractures in postmenopausal women. While bisphosphonates are commonly used as initial therapy for osteoporosis, some studies suggest that denosumab could be an alternative initial treatment for high-risk patients, particularly the elderly population. This narrative literature review aimed to assess the use of denosumab in elderly individuals with osteoporosis, excluding its oncology applications.
METHOD
Multiple online databases including Scopus, PubMed, EMBASE, Cochrane Central Register of Controlled Trials (CENTRAL), and PEDro were searched for relevant English-language trials.
RESULTS
Between about hundred identified, the review selected 21 articles full-meeting the inclusion criteria. These papers all reporting that Denosumab demonstrated significant efficacy in reducing vertebral and nonvertebral fractures in postmenopausal and senile osteoporosis.
CONCLUSION
Even if limited evidence exists regarding its long-term effectiveness in elderly patients, nevertheless denosumab may be considered a first-line treatment for high-risk elderly patients with senile osteoporosis, particularly for those unable to take bisphosphonates. It has shown superior outcomes in improving bone density and reducing fracture risk, even in frail elderly individuals. Long-term use of denosumab has been reported as safe and effective, enhancing treatment compliance and outcomes.
Topics: Humans; Aged; Female; Denosumab; Osteoporosis; Bone Density; Diphosphonates; Frail Elderly
PubMed: 38048119
DOI: 10.7417/CT.2023.5023 -
The Journal of Clinical Endocrinology... Mar 2022We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and...
CONTEXT
We have previously reported that teriparatide is associated with substantial increases in bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) and small declines at the distal radius in 41 premenopausal women with idiopathic osteoporosis (IOP), all severely affected with low trauma fractures and/or very low BMD. Effects of teriparatide dissipate if not followed by antiresorptives.
OBJECTIVE
To assess the effects of 12 and 24 months of denosumab in premenopausal women with IOP completing 24 months of teriparatide.
METHODS
This was a preplanned phase 2B extension study. Premenopausal women with IOP who had completed a course of teriparatide received denosumab 60 mg every 6 months over 24 months. The main outcome measure was within-group change in BMD at the LS at 12 months. Secondary outcomes include change in 12-month BMD at other sites, 24-month BMD at all sites, trabecular bone score (TBS), and bone turnover markers (BTMs).
RESULTS
After completing teriparatide, 32 participants took denosumab for 12 months and 29 for 24 months, with statistically significant increases in BMD at the LS (5.2 ± 2.6% and 6.9 ± 2.6%), TH (2.9 ± 2.4% and 4.6 ± 2.8%), and FN (3.0 ± 3.8% and 4.7 ± 4.9%). Over the entire 24-month teriparatide and 24-month denosumab treatment period, BMD increased by 21.9 ± 7.8% at the LS, 9.8 ± 4.6% at the TH, and 9.5 ± 4.7% at the FN (all P < .0001). TBS increased by 5.8 ± 5.6% (P < .001). Serum BTM decreased by 75% to 85% by 3 months and remained suppressed through 12 months of denosumab. Denosumab was generally well tolerated.
CONCLUSION
These data support the use of sequential teriparatide and denosumab to increase BMD in premenopausal women with severe osteoporosis.
Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Female; Humans; Lumbar Vertebrae; Osteoporosis; Osteoporosis, Postmenopausal; Teriparatide
PubMed: 34849989
DOI: 10.1210/clinem/dgab850 -
Expert Opinion on Drug Safety Feb 2014Denosumab is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand. It is an antiresorptive agent that reduces... (Review)
Review
INTRODUCTION
Denosumab is a fully human monoclonal antibody against the receptor activator of nuclear factor kappa-B ligand. It is an antiresorptive agent that reduces osteoclastogenesis.
AREAS COVERED
This drug evaluation reviews denosumab for use in osteoporosis. Denosumab has been shown to improve bone mineral density (BMD) and to reduce the incidence of new vertebral, hip and nonvertebral fractures in postmenopausal women. It prevents bone loss and reduces vertebral fracture risk in men with nonmetastatic prostate cancer who are receiving androgen deprivation therapy. It has also been shown to improve BMD in men with osteoporosis unrelated to androgen deprivation therapy. Safety concerns include infections, cancer, skin reactions, cardiovascular disease, hypocalcemia, osteonecrosis of the jaw and atypical femur fractures.
EXPERT OPINION
Although bisphosphonates are typically preferred as initial therapy for osteoporosis, denosumab could be used as initial therapy in select patients at high risk for fracture, including older patients who have difficulty with the dosing requirements of oral bisphosphonates, patients who are intolerant of or unresponsive to other therapies, and in those with impaired renal function. Additional data is needed to address issues regarding treatment duration and discontinuation, as well as to provide more information regarding denosumab's efficacy and safety.
Topics: Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Denosumab; Fractures, Bone; Humans; Osteoporosis
PubMed: 24289327
DOI: 10.1517/14740338.2014.860133 -
Journal of Bone and Mineral Research :... Jul 2018Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with... (Randomized Controlled Trial)
Randomized Controlled Trial
Romosozumab is a bone-forming agent with a dual effect of increasing bone formation and decreasing bone resorption. In FRActure study in postmenopausal woMen with ostEoporosis (FRAME), postmenopausal women with osteoporosis received romosozumab 210 mg s.c. or placebo once monthly for 12 months, followed by denosumab 60 mg s.c. once every 6 months in both groups for 12 months. One year of romosozumab increased spine and hip BMD by 13% and 7%, respectively, and reduced vertebral and clinical fractures with persistent fracture risk reduction upon transition to denosumab over 24 months. Here, we further characterize the BMD gains with romosozumab by quantifying the percentages of patients who responded at varying magnitudes; report the mean T-score changes from baseline over the 2-year study and contrast these results with the long-term BMD gains seen with denosumab during Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) and its Extension studies; and assess fracture incidence rates in year 2, when all patients received denosumab. Among 7180 patients (n = 3591 placebo, n = 3589 romosozumab), most romosozumab-treated patients experienced ≥3% gains in BMD from baseline at month 12 (spine, 96%; hip, 78%) compared with placebo (spine, 22%; hip, 16%). For romosozumab patients, mean absolute T-score increases at the spine and hip were 0.88 and 0.32, respectively, at 12 months (placebo: 0.03 and 0.01) and 1.11 and 0.45 at 24 months (placebo-to-denosumab: 0.38 and 0.17), with the 2-year gains approximating the effect of 7 years of continuous denosumab administration. Patients receiving romosozumab versus placebo in year 1 had significantly fewer vertebral fractures in year 2 (81% relative reduction; p < 0.001), with fewer fractures consistently observed across other fracture categories. The data support the clinical benefit of rebuilding the skeletal foundation with romosozumab before transitioning to antiresorptive therapy. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals, Inc.
Topics: Aged; Antibodies, Monoclonal; Bone Density; Denosumab; Fractures, Bone; Humans; Osteogenesis; Risk Factors
PubMed: 29573473
DOI: 10.1002/jbmr.3427 -
The New England Journal of Medicine Feb 2023
Topics: Humans; Bone Density Conservation Agents; Denosumab; Fibrous Dysplasia of Bone; Treatment Outcome
PubMed: 36812441
DOI: 10.1056/NEJMc2214862 -
Rheumatology International Nov 2018Glucocorticoid therapy is the number one cause of secondary osteoporosis particularly effecting young individuals. Possessing an increased risk for fractures,... (Review)
Review
Glucocorticoid therapy is the number one cause of secondary osteoporosis particularly effecting young individuals. Possessing an increased risk for fractures, glucocorticoid-induced osteoporosis might interfere with patients' well-being and quality of life. Therefore, proper treatment of bone loss and prevention from fractures are of great importance. There are a limited number of therapeutic and preventative options for glucocorticoid-induced osteoporosis. Denosumab, with its high anti-resorptive potential, has been studied several times among patients on glucocorticoid therapy. However, a comprehensive look analysing the current data is lacking. Thus, the objective of the current article is to evaluate the current evidence on the efficacy, as well as the safety profile of denosumab in glucocorticoid-induced osteoporosis. Pubmed/MEDLINE, Scopus and Web of Science databases were searched for the terms denosumab, glucocorticoid-induced osteoporosis, steroid-induced osteoporosis, glucocorticoids and osteoporosis. Relevant data regarding the efficacy and safety of denosumab among patients with glucocorticoid-induced osteoporosis was analysed. Denosumab contributes to increased bone mineral density and decreased bone-turnover marker levels among glucocorticoid users. It is an effective therapeutic option with a favourable safety profile in glucocorticoid-induced osteoporosis.
Topics: Bone Density; Bone Density Conservation Agents; Bone Remodeling; Bone and Bones; Denosumab; Glucocorticoids; Humans; Osteoporosis; Risk Factors; Treatment Outcome
PubMed: 30019224
DOI: 10.1007/s00296-018-4106-1 -
Endocrinology and Metabolism (Seoul,... Apr 2022Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of... (Review)
Review
Denosumab, which has been approved for the treatment of osteoporosis since 2010, is a fully humanised monoclonal antibody against a cytokine, receptor activator of nuclear factor kappa B ligand (RANKL), involved in bone resorption. Continued use of denosumab results in a potent and sustained decrease in bone turnover, an increase in bone mineral density (BMD), and a reduction in vertebral and hip fractures. The anti-resorptive effects of denosumab are reversible upon cessation, and this reversal is accompanied by a transient marked increase in bone turnover that is associated with bone loss, and of concern, an increased risk of multiple vertebral fractures. In this review, we outline the effects of denosumab withdrawal on bone turnover markers, BMD, histomorphometry, and fracture risk. We provide an update on recent clinical trials that sought to answer how clinicians can transition away from denosumab safely with follow-on therapy to mitigate bone loss and summarise the recommendations of various international guidelines.
Topics: Bone Density; Bone Remodeling; Denosumab; Female; Humans; Osteoporosis; Osteoporosis, Postmenopausal
PubMed: 35417954
DOI: 10.3803/EnM.2021.1369