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Modern Rheumatology Apr 2023To investigate the effect of romosozumab versus denosumab treatment on bone mineral density (BMD), disease activity, and joint damage in patients with rheumatoid... (Randomized Controlled Trial)
Randomized Controlled Trial
Comparison of romosozumab versus denosumab treatment on bone mineral density after 1 year in rheumatoid arthritis patients with severe osteoporosis: A randomized clinical pilot study.
OBJECTIVES
To investigate the effect of romosozumab versus denosumab treatment on bone mineral density (BMD), disease activity, and joint damage in patients with rheumatoid arthritis and severe osteoporosis.
METHODS
Fifty-one postmenopausal women were enrolled and randomized equally into two groups to receive either romosozumab or the denosumab. Changes (Δ) in the BMD (at lumbar spine, total hip, and femoral neck), disease activity score in 28 joints (DAS28)-erythrocyte sedimentation rate (ESR), and van der Heijde-modified Total Sharp Score (TSS) from baseline to 12 months after treatment were evaluated.
RESULTS
The ΔBMD at 12 months in the romosozumab and denosumab groups were 10.2 ± 5.6% and 5.0 ± 3.1% (p = .002) for the lumbar spine, 3.7 ± 4.9% and 3.5 ± 3.0% (p = .902) for the total hip, and 3.6 ± 4.7% and 3.2 ± 4.9% (p = .817) for the femoral neck, respectively. The ΔDAS28-ESR and ΔTSS at 12 months did not differ between these two groups.
CONCLUSIONS
Our results suggest that romosozumab treatment was more effective in increasing the BMD at the lumbar spine than denosumab and may be selected for patients who require a significant increase in the lumbar spine BMD.
Topics: Humans; Female; Bone Density; Denosumab; Pilot Projects; Osteoporosis; Bone Density Conservation Agents; Arthritis, Rheumatoid; Osteoporosis, Postmenopausal
PubMed: 35689558
DOI: 10.1093/mr/roac059 -
Journal of Bone and Mineral Metabolism Nov 2023This pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
This pre-specified exploratory analysis investigated the effect of denosumab on bone mineral density (BMD) and bone microarchitecture in patients with rheumatoid arthritis (RA) treated with conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs).
MATERIALS AND METHODS
In this open-label, parallel-group study, patients were randomly assigned (1:1) to continuous treatment with csDMARDs plus denosumab or continuous treatment with csDMARD therapy alone for 12 months. BMD and bone microarchitecture were measured by dual-energy X-ray absorptiometry (DXA) and high-resolution peripheral quantitative computed tomography (HR-pQCT).
RESULTS
Of 46 patients enrolled in the primary study, 43 were included in the full analysis set. The mean age was 65.3 years, 88.4% were female, and 60.5% had osteoporosis. Areal BMD of the lumbar spine increased from baseline to 6 and 12 months in both groups, but the increase was higher in the csDMARDs plus denosumab group. Areal BMD of the total hip and femoral neck increased from baseline to 6 and 12 months only in the csDMARDs plus denosumab group. Cortical volumetric BMD and cortical thickness of the distal tibia increased in the csDMARDs plus denosumab group at 6 and 12 months but decreased in the csDMARD therapy alone group. Trabecular bone parameters of the distal tibia improved only in the csDMARDs plus denosumab group at 12 months.
CONCLUSION
Denosumab may be recommended for patients with RA treated with csDMARDs to increase BMD and improve bone microarchitecture.
Topics: Humans; Female; Aged; Male; Bone Density; Denosumab; Absorptiometry, Photon; Arthritis, Rheumatoid; Osteoporosis
PubMed: 37480398
DOI: 10.1007/s00774-023-01452-9 -
Supportive Care in Cancer : Official... Jun 2021Bisphosphonates and denosumab are both antiresorptive medications, each with their own mechanism of action; yet both may result in the same adverse effect:...
OBJECTIVE
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). The present systematic review aims to answer the following question: "Are bisphosphonate-related ONJ and denosumab-related ONJ any different, regarding clinical and imaging aspects?"
METHODS
This review followed the Joanna Briggs Review's Manual, and the searches were performed on PubMed, Cochrane, Scopus, Web of Science, and Lilacs databases and on the grey literature (ProQuest, Open Grey, and Google Scholar).
RESULTS
The searches resulted in 7535 articles that were critically assessed. Based on the selection criteria, seven studies were included in the review: five cross-sectional studies and two randomized clinical trials. A total of 7755 patients composed the final population. An increase in bone sequestra, cortical bone lysis, and bone density was observed in bisphosphonate-related ONJ, while larger bone sequestra, more frequent periosteal reactions, and mandibular canal enhancement were noted in denosumab-related ONJ.
CONCLUSION
This systematic review demonstrated that the imaging characteristics of bisphosphonate-related and denosumab-related ONJ are not similar. Although clinically similar conditions, they were found to be radiographically distinct. More studies are necessary to further elucidate these differences.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Cross-Sectional Studies; Denosumab; Diphosphonates; Humans
PubMed: 33140246
DOI: 10.1007/s00520-020-05855-6 -
Nature Medicine Mar 2024Erosive hand osteoarthritis (OA) is a prevalent and disabling disease with limited treatment options. Here we present the results of a monocentric, placebo-controlled,... (Randomized Controlled Trial)
Randomized Controlled Trial
Erosive hand osteoarthritis (OA) is a prevalent and disabling disease with limited treatment options. Here we present the results of a monocentric, placebo-controlled, double-blind, randomized phase 2a clinical trial with denosumab, a receptor activator of nuclear factor-κB ligand inhibitor, evaluating the effects on structure modification in erosive hand OA. Patients were randomized to 48 weeks treatment with denosumab 60 mg every 3 months (n = 51, 41 females) or placebo (n = 49, 37 females). The primary (radiographic) endpoint was the change in the total Ghent University Scoring System (GUSS) at week 24, where positive changes correspond to remodeling and negative changes to erosive progression. Secondary endpoints were the change in the GUSS at week 48 and the number of new erosive joints at week 48 by the anatomical phase scoring system. Baseline mean GUSS (standard deviation) of target joints was 155.9 (69.3) in the denosumab group and 158.7 (46.8) in the placebo group. The primary endpoint was met with an estimated difference between groups of 8.9 (95% confidence interval (CI) 1.0 to 16.9; P = 0.024) at week 24. This effect was confirmed at week 48 (baseline adjusted GUSS (standard error of the mean) denosumab and placebo were 163.5 (2.9) and 149.2 (3.9), respectively; with an estimated difference between groups of 14.3 (95% CI 4.6 to 24.0; P = 0.003)). At patient level, more new erosive joints were developed in the placebo group compared with denosumab at week 48 (odds ratio 0.24 (95% CI 0.08 to 0.72); P = 0.009). More adverse events occurred in the placebo group (125 events in 44 patients (90%)) compared with the denosumab group (97 events in 41 patients (80%)). These results demonstrate that denosumab has structure modifying effects in erosive hand OA by inducing remodeling and preventing new erosive joints. EU Clinical Trials Register identifier 2015-003223-53 .
Topics: Female; Humans; Denosumab; Double-Blind Method; Osteoarthritis; RANK Ligand; Treatment Outcome; Male
PubMed: 38361122
DOI: 10.1038/s41591-024-02822-0 -
Seminars in Oncology Nursing Apr 2022To provide a literature review of the clinical efficacy and safety data of various pharmacological agents used to manage bone health in people affected by cancer. (Review)
Review
OBJECTIVE
To provide a literature review of the clinical efficacy and safety data of various pharmacological agents used to manage bone health in people affected by cancer.
DATA SOURCES
Peer-reviewed articles and research publications identified from PubMed and relevant clinical guidelines were used in this evidence synthesis.
CONCLUSION
Individuals with cancers such as breast and prostate cancers, multiple myeloma, and other malignancies are at a high risk of developing skeletal-related events such as bone fracture, bone metastasis, and osteoporosis. Pharmacologic agents such as bisphosphonates and RANK-L inhibitor (denosumab) are the mainstay therapy options for managing bone health in this population.
IMPLICATIONS FOR NURSING PRACTICE
Nurses and nurse practitioners should be aware of the efficacy data of bisphosphonates and denosumab but also should be well-versed in the appropriate administration of these agents, potential side effect profiles, timely assessment, and interventions to optimize quality of life.
Topics: Bone Density Conservation Agents; Bone Diseases; Denosumab; Diphosphonates; Humans; Neoplasms; Quality of Life
PubMed: 35491330
DOI: 10.1016/j.soncn.2022.151276 -
Journal of Clinical Densitometry : the... 2022Denosumab discontinuation can lead to bone loss despite subsequent bisphosphonate therapy. This bone loss is more severe in patients treated with denosumab for longer...
Denosumab discontinuation can lead to bone loss despite subsequent bisphosphonate therapy. This bone loss is more severe in patients treated with denosumab for longer than 3 years. We aimed to evaluate the bone mass changes after only a single denosumab injection followed by zoledronate administration. We screened all of our patients who received a single denosumab injection and who were included in the osteoporosis register from the Swiss Society of Rheumatology between August 1, 2010, and January 31, 2022. This case series assessed the outcome of patients who were consecutively treated with one denosumab injection followed by a single infusion of zoledronate 6 months later. Bone mineral density (BMD) and bone turnover markers (BTM) changes were analysed before therapy and 18 months later. Percentage BMD changes and T-scores were compared with those of registered patients who received 2.5 years of denosumab treatment and one subsequent infusion of zoledronate. Thirty-two patients (31 female, 1 male) received a single denosumab injection and one zoledronate infusion 6 months later. BTM decreased significantly in this period (p = 0.035). Percentage BMD changes from baseline to 1 year after zoledronate treatment were 7.6% [IQR 3.2, 9.4] at the lumbar spine, 3.5% [1.8, 5.9] at the total hip and 4.6% [1.3, 6.0] at the femoral neck. In contrast, percentage changes from baseline in 110 patients with 2.5 years of denosumab treatment and one zoledronate infusion were 5.6% [3.0, 9.1], 2.3% [0.2, 4.9] and 2.3% [-0.9, 4.7], respectively. Differences between the 2 groups were significant at the lumbar spine (p = 0.014), total hip (p = 0.010) and femoral neck (p = 0.010). A single denosumab injection followed by zoledronate led to a remarkable gain of BMD at the lumbar spine and hip within a short time. This observation could help to identify a new short treatment sequence for patients with osteoporosis.
Topics: Bone Density; Bone Density Conservation Agents; Bone Remodeling; Denosumab; Female; Humans; Male; Osteoporosis; Osteoporosis, Postmenopausal; Zoledronic Acid
PubMed: 35450795
DOI: 10.1016/j.jocd.2022.03.001 -
Nephrology (Carlton, Vic.) Sep 2022
Topics: Bone Density Conservation Agents; Calcium; Denosumab; Humans; Hypocalcemia; Iron
PubMed: 35746864
DOI: 10.1111/nep.14078 -
Annals of Internal Medicine Oct 2020
Topics: Cohort Studies; Denosumab; Female; Humans; Injections; Osteoporosis; Osteoporosis, Postmenopausal; Patients; Population
PubMed: 32716699
DOI: 10.7326/M20-4802 -
Clinical Oral Implants Research Sep 2023To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures. (Review)
Review
OBJECTIVES
To review the current evidence on the relationship between agents that affect bone homeostasis and dental implant failures.
MATERIALS AND METHODS
Electronic searches for bisphosphonates, denosumab, methotrexate, corticosteroids, romosozumab, sunitinib, and bevacizumab were performed using PubMed, MEDLINE (OVID), EMBASE (OVID), Cochrane Central Register of Controlled Trials (Cochrane Library), Cochrane Oral Health Group Trials Register (Cochrane Library) and Web of Science (Thomson Reuters). Manual searches were also conducted to complement the digital searches for recent issues.
RESULTS
Previous publications suggested that bisphosphonates do not compromise the survival of dental implants. However, one study documented an increased risk of implant failure in patients who had received high-dose of intravenous bisphosphonate therapy after implant rehabilitation. There has been an issue of MRONJ around implants in patients who have successfully received implant therapy before and after antiresorptive therapy, leading to late implant failure. Despite evidence on the detrimental effects of denosumab, methotrexate and corticosteroids on bone metabolism, their role in implant survival is not conclusive.
CONCLUSIONS
At present, there is insufficient evidence to establish a potential connection between agents that affects bone homeostasis and implant failure. However, some studies have reported negative results for implant therapy. In addition, implant-related sequestration in patients who received anti-resorptive therapy, despite of successful osseointegration, is also noticeable. Although limited studies are available at present, clinicians should still carefully consider the potential hazards and take appropriate precautions to minimize the risks associated with the medications and implant therapy.
Topics: Humans; Denosumab; Methotrexate; Homeostasis; Diphosphonates
PubMed: 37750523
DOI: 10.1111/clr.14144 -
Endocrine, Metabolic & Immune Disorders... 2022Breast cancer is the most commonly occurring cancer in women worldwide. Early breast cancer is a kind of invasive neoplasm that has not proliferated beyond the breast or... (Review)
Review
BACKGROUND
Breast cancer is the most commonly occurring cancer in women worldwide. Early breast cancer is a kind of invasive neoplasm that has not proliferated beyond the breast or the axillary lymph nodes. Current therapeutic strategies for breast cancer mainly include local therapies such as surgery or radiotherapy and systemic therapies like chemotherapy, endocrine, and targeted therapy. Nowadays, the adjuvant treatment for hormone receptor-positive early breast cancer in postmenopausal women remains the main effective systemic therapy which can improve disease- free survival and overall survival; it involves several endocrine treatment regimens, including Selective Estrogen Receptor Modulators (SERMs), Aromatase Inhibitors (AIs), or a combination of them. AIs have been shown to be more effective in preventing recurrence in postmenopausal women with early breast cancer when compared with tamoxifen, thus representing the standard of care for adjuvant endocrine therapy. Although AIs are usually well-tolerated, they can have some side effects. Apart from the appearance of arthralgias or myalgias and cardiovascular events, AI therapies, reducing already low endogenous postmenopausal estradiol levels, cause increased bone loss and increase fracture risk in postmenopausal women.
OBJECTIVES
The objective of this review is to evaluate the therapeutic options in the management of Aromatase Inhibitor-Associated Bone Loss (AIBL).
METHODS
We reviewed the current literature dealing with different therapeutic options in the treatment of AIBL.
RESULTS
Clinical practice guidelines recommend a careful evaluation of skeletal health in all women with breast cancer before AI therapy initiation. Adequate calcium and vitamin D intake have also been suggested. Pharmacological attempts to minimize AI-related bone loss have focused on the use of antiresorptive agents, such as bisphosphonates and denosumab to protect bone integrity and reduce the risk of fractures. Furthermore, clinical trials have shown that by making the bone microenvironment less susceptible to breast cancer metastasis, these drugs are able to increase disease- free survival.
CONCLUSIONS
AI, that are the pillar of the systemic treatment for patients with hormone receptorpositive breast cancer, are associated with different side effects, and in particular, osteoporosis and fractures. Both bisphosphonates and denosumab are able to prevent this negative effect.
Topics: Aromatase Inhibitors; Bone Density; Bone Density Conservation Agents; Breast Neoplasms; Denosumab; Diphosphonates; Female; Fractures, Bone; Humans; Tumor Microenvironment
PubMed: 34370654
DOI: 10.2174/1871530321666210809153152