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Hemodialysis International.... Oct 2023The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
The effects of denosumab on bone mineral density (BMD) and metabolism in patients with end-stage renal disease (ESRD) remain controversial. Hence, we performed a systematic review and meta-analysis of observational studies.
METHODS
The MEDLINE, EMBASE, and Cochrane Library databases were searched in June 2022 to identify studies that evaluated the risk of denosumab-associated hypocalcemia and changes in bone metabolism, changes in BMD from baseline to post-treatment in patients with ESRD.
FINDINGS
Twelve studies with 348 participants were included. The pooled incidence of hypocalcemia during denosumab treatment was 35.0% (95% confidence interval [CI], 25%-46%; I = 63.6%). There were no significant changes in either the serum calcium or phosphate levels from the baseline to post-treatment period; the mean differences were 0.04 mg/dL (95% CI, -0.12 to 0.20 mg/dL) and -0.39 mg/dL (95% CI, -0.89 to 0.12 mg/dL). We found significant changes in the alkaline phosphatase and parathyroid hormone levels; the standardized mean differences were -2.98 (95% CI, -5.36 to -0.59) and -3.12 (95% CI: -4.94 to -1.29), respectively. Denosumab may increase BMD, with mean differences of 9.10% (95% CI: 4.07%-14.13%) and 9.00% (95% CI: 5.93%-12.07%) for the femoral neck and lumbar spine, respectively.
DISCUSSION
Denosumab increased the BMDs of the lumbar spine and femoral neck in patients with ESRD. The onset of hypocalcemia must be carefully monitored during denosumab administration.
Topics: Humans; Bone Density; Denosumab; Hypocalcemia; Bone Density Conservation Agents; Renal Dialysis; Kidney Failure, Chronic
PubMed: 37264758
DOI: 10.1111/hdi.13098 -
The Annals of Pharmacotherapy Oct 2018To assess the cost-effectiveness as well as adherence and patient preference for denosumab compared with oral bisphosphonates for the treatment of osteoporosis. (Review)
Review
OBJECTIVE
To assess the cost-effectiveness as well as adherence and patient preference for denosumab compared with oral bisphosphonates for the treatment of osteoporosis.
DATA SOURCES
Two comprehensive PubMed literature searches (from data inception to December 2017) were performed. The first search included the terms osteoporosis, denosumab, bisphosphonate, and adherence or persistence or compliance or preference. The search terms osteoporosis, denosumab, cost, and effectiveness were used in the second literature search. Additional references were included from reviewing literature citations.
STUDY SELECTION AND DATA EXTRACTION
All English-language clinical trials on adherence (as compliance and persistence) or patient preference for denosumab compared with oral bisphosphonates were evaluated. In addition, articles analyzing the cost-effectiveness of denosumab compared with generic alendronate were evaluated.
DATA SYNTHESIS
Four studies that assessed patient preference showed positive outcomes for preference and satisfaction for subcutaneous use of denosumab every 6 months versus oral alendronate weekly, oral ibandronate monthly, or oral risedronate monthly. Three studies evaluated persistence and compliance and/or adherence and showed improved persistence and compliance rates with denosumab compared with bisphosphonate therapy. Twelve articles and 3 abstracts assessed cost-effectiveness of denosumab compared with generic alendronate. The majority of articles showed that denosumab was cost-effective, and even cost-saving in patients older than 75 years of age and those who have a history of previous fractures, lower bone mineral density T-scores, and more risk factors.
CONCLUSIONS
Denosumab compared with oral bisphosphonates may improve patient preference and adherence as well as provide a cost-effective treatment strategy, especially among higher-risk and older adults with osteoporosis.
Topics: Administration, Oral; Aged; Aged, 80 and over; Bone Density Conservation Agents; Cost-Benefit Analysis; Denosumab; Diphosphonates; Fractures, Bone; Health Care Costs; Humans; Medication Adherence; Middle Aged; Osteoporosis; Patient Preference; Treatment Outcome
PubMed: 29616561
DOI: 10.1177/1060028018768808 -
The Consultant Pharmacist : the Journal... Mar 2018To review and summarize studies on the effects of denosumab on bone mineral density following the discontinuation of therapy. (Review)
Review
OBJECTIVE
To review and summarize studies on the effects of denosumab on bone mineral density following the discontinuation of therapy.
DATA SOURCES
A search of PubMed (1966-July 2017) and International Pharmaceutical Abstracts (1970-July 2017) was conducted using the Medical Subject Headings (MeSH) terms denosumab, osteoporosis, and withholding treatment in combination with free term searches including the words drug holiday, discontinue, discontin*, and drug discontinuation.
STUDY SELECTION AND DATA EXTRACTION
An initial review yielded 10 articles. Four articles that addressed the effects of denosumab discontinuation on markers of overall bone health, fracture risk, or bone histology were included in the final review.
DATA SYNTHESIS
Denosumab is a monoclonal antibody indicated for the treatment of osteoporosis in men and postmenopausal women. Denosumab has proven beneficial effects on bone remodeling and bone mineral density, and these effects have been noted to be reversed upon treatment discontinuation because of the agent's lack of incorporation into bone matrix. After 12 to 24 months off denosumab therapy, BMD, BTMs levels, as well as histologic and histomorphometric analyses, were reflective of baseline values. The number of studies evaluating the residual skeletal effects of denosumab is limited, and the sample sizes in the articles reviewed were relatively small.
CONCLUSION
An evaluation of studies showed that the discontinuation of denosumab results in loss of bone mineral density and a decline to near baseline values within 12 months of discontinuing therapy. Larger extension studies in a more diverse population need to be conducted to extrapolate the data to other patient groups.
Topics: Biomarkers; Bone Density; Bone Density Conservation Agents; Bone Remodeling; Denosumab; Female; Humans; Male; Osteoporosis; Osteoporotic Fractures; Time Factors
PubMed: 29720299
DOI: 10.4140/TCP.n.2018.142 -
Revista Espanola de Anestesiologia Y... 2023
Topics: Denosumab; Antibodies, Monoclonal, Humanized
PubMed: 37276963
DOI: 10.1016/j.redare.2022.11.001 -
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 -
Calcified Tissue International Jan 2023There is limited evidence on the use of romosozumab (ROMO) in the treatment of osteoporosis in patients on hemodialysis (HD); thus, we aimed to investigate this topic.... (Observational Study)
Observational Study
There is limited evidence on the use of romosozumab (ROMO) in the treatment of osteoporosis in patients on hemodialysis (HD); thus, we aimed to investigate this topic. This prospective, observational, single-center cohort study included 13 prior osteoporosis treatment-naïve patients on HD with osteoporosis. They first received ROMO once monthly for 12 months (210 mg; subcutaneously once every month). Thereafter, they received denosumab (DENO) for an additional 12 months (60 mg; subcutaneously once every 6 months). We examined the incidence of new fractures; treatment safety; and temporal changes in the bone mineral density (BMD), bone metabolism markers, and vascular calcification. No new cases of fractures were noted. The median one-year percentage changes (from the baseline) in the BMDs at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were + 9.0%, + 2.5%, and + 4.7%, respectively. These changes were maintained for 24 months. The corresponding relative changes from the baseline to 24 months thereafter were + 14.9%, + 5.4%, and + 6.5%, respectively. The percentage changes in TH BMD and FN BMD were negatively correlated with baseline BMD. Coronary artery and thoracic aorta calcification scores increased slightly from baseline to 12 months thereafter. However, fatal events (cardiovascular disease-associated and all-cause deaths) did not occur during ROMO treatment. Effectiveness of ROMO was better in patients who had severe osteoporosis with low TH BMD, low FN BMD, and high tartrate-resistant acid phosphatase 5b level at ROMO initiation.
Topics: Humans; Female; Denosumab; Bone Density Conservation Agents; Prospective Studies; Cohort Studies; Osteoporosis; Bone Density; Fractures, Bone; Bone Diseases, Metabolic; Renal Dialysis; Osteoporosis, Postmenopausal
PubMed: 36287217
DOI: 10.1007/s00223-022-01031-6 -
Current Osteoporosis Reports Dec 2022Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where... (Review)
Review
PURPOSE OF REVIEW
Inhibition of receptor activator of nuclear factor kappa-B ligand (RANKL) with denosumab is an effective treatment in a number of conditions including osteoporosis where suppression of bone resorption is desired. However, denosumab discontinuation is associated with rebound increase in bone resorption and subsequent loss in bone mass and a rapid return to baseline fracture risk. We review recent data on the rebound increase in bone resorption following denosumab discontinuation and the potential mechanisms behind this phenomenon.
RECENT FINDINGS
Osteoclasts have been considered to be highly specialised cells that undergo apoptosis after fulfilling their function of bone resorption. However, recent studies suggest that osteoclasts are longer lived cells which migrate through vasculature and are capable of undergoing fission into a novel cell type (the osteomorph) and re-fusion in a process termed osteoclast recycling. The life cycle of the osteoclast is more complex than previously appreciated. Osteoclast recycling provides a novel mechanistic framework to examine changes in osteoclast biology in response to treatment of bone diseases and provides an exciting new avenue towards personalised medicine.
Topics: Humans; Osteoclasts; Denosumab; RANK Ligand; Bone Resorption; Osteoporosis
PubMed: 36201122
DOI: 10.1007/s11914-022-00756-5 -
General Dentistry 2019Bisphosphonates have been implicated in the induction of medication-related osteonecrosis of the jaw (MRONJ) since 2004. Since then, the spectrum of drugs implicated in... (Review)
Review
Bisphosphonates have been implicated in the induction of medication-related osteonecrosis of the jaw (MRONJ) since 2004. Since then, the spectrum of drugs implicated in the onset of MRONJ has broadened to include other antiresorptive and antiangiogenic drugs. Denosumab is an antiresorptive drug that has been on the market since 2010. Denosumab inhibits osteoclast formation, function, and survival and increases bone mineral density. As a result, denosumab is indicated for the treatment of osteoporosis and bone metastases. This article reports 2 cases of MRONJ associated with denosumab use. The characteristics and progression of MRONJ in patients who take denosumab are reviewed, and therapeutic measures are discussed.
Topics: Bisphosphonate-Associated Osteonecrosis of the Jaw; Bone Density Conservation Agents; Denosumab; Diphosphonates; Humans; Osteoporosis
PubMed: 30644830
DOI: No ID Found -
Calcified Tissue International Jul 2018
Review
Topics: Bone Density; Bone Density Conservation Agents; Denosumab; Humans; Osteoporosis
PubMed: 29926143
DOI: 10.1007/s00223-018-0436-y -
Bone Sep 2023Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Increased RANKL expression is observed in the bone tissue of fibrous dysplasia of bone/McCune-Albright syndrome (FD/MAS). In one animal model of FD/MAS, the inhibition of RANKL reduced tumor volume. A beneficial effect of denosumab on pain in patients refractory to bisphosphonates has been reported, but without systematic quantification of pain improvement. This work describes the clinical experience of our group on the efficacy on pain of denosumab treatment, along with safety, in FD/MAS patients refractory to bisphosphonates.
MATERIALS AND METHODS
We have conducted a retrospective multicenter study in 6 academic rheumatology centers in France. We have collected patients and FD/MAS characteristics, duration of prior exposure to bisphosphonates, denosumab treatment modalities (dosage - administration regimen - number of courses); evolution of pain evaluated by Visual Analogic Scale (VAS).
RESULTS
13 patients were included (10 women and 3 men) 45 years on average, 5 MAS, 4 monostotic and 4 polyostotic forms. The average duration post-diagnosis of FD/MAS was 25 years and the mean duration of prior exposure to bisphosphonates was 4.7 years. Pain could be analyzed in 7 patients, showing a significant improvement from a mean VAS of 7.8 to 2.9 (-4.9 points, p = 0.003). In one patient with fronto-orbital FD/MAS, a 30 % decrease in lesional volume, assessed by MRI, was observed within 6 months of treatment, that was sustained over the following 12 months. Treatment regimens were heterogeneous. No hypercalcemia was observed after treatment cessation and the clinical tolerance was good.
DISCUSSION
This study suggests that denosumab reduces pain in patients with DF/MAS refractory to bisphosphonates, and quantifies this improvement for the first time in a multicenter study. In our cohort, no patients who discontinued denosumab developed hypercalcemia and clinical tolerance was overall good. This study also provides encouraging data regarding lesion volume control. Further controlled studies are required to determine the place and modalities of the denosumab treatment of FD/MAS.
CONCLUSION
Denosumab significantly decreased pain in FD/MAS refractory to bisphosphonate. This study paves the way for a randomized clinical trial to validate and standardize the prescription of denosumab in FD/MAS.
Topics: Animals; Female; Diphosphonates; Denosumab; Retrospective Studies; Fibrous Dysplasia of Bone; Fibrous Dysplasia, Polyostotic; Pain
PubMed: 37301527
DOI: 10.1016/j.bone.2023.116819