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Frontiers in Endocrinology 2023To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients... (Meta-Analysis)
Meta-Analysis
PURPOSE
To assess the alterations in bone mineral density and bone turnover marker concentrations following the administration of denosumab and romosozumab therapies in patients with osteoporosis.
METHODS
PubMed was searched for studies published until January 28, 2023, that investigated the clinical efficacy and bone turnover marker changes of denosumab and romosozumab in the treatment of osteoporosis, with a minimum follow-up of 3 months in each study. Studies were screened, and data on changes in bone mineral density (BMD), P1NP, and TRACP-5b levels after treatment were extracted and included in the analysis.
RESULTS
Six studies were analyzed. At 3 months after treatment, the romosozumab group showed greater changes in lumbar BMD and bone turnover markers. BMD of total hip and femoral neck was relatively delayed. Beginning at 6 to 12 months, romosozumab showed greater changes in bone mineral density and markers of bone turnover.
CONCLUSION
Both romosozumab and denosumab have antiosteoporotic effects, with greater effects on BMD and bone turnover markers observed within 12 months of romosozumab treatment.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42023395034.
Topics: Humans; Bone Density; Denosumab; Bone Density Conservation Agents; Osteoporosis
PubMed: 37529613
DOI: 10.3389/fendo.2023.1188969 -
Journal of Orthopaedic Surgery and... Jun 2023Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Continuous use of glucocorticoids (GCs) has become the primary cause of secondary osteoporosis. Bisphosphonate drugs were given priority over denosumab and teriparatide in the 2017 American College of Rheumatology (ACR) guidelines but have a series of shortcomings. This study aims to explore the efficacy and safety of teriparatide and denosumab compared with those of oral bisphosphonate drugs.
METHODS
We systematically searched studies included in the PubMed, Web of Science, Embase, and Cochrane library databases and included randomized controlled trials that compared denosumab or teriparatide with oral bisphosphonates. Risk estimates were pooled using both fixed and random effects models.
RESULTS
We included 10 studies involving 2923 patients who received GCs for meta-analysis, including two drug base analyses and four sensitivity analyses. Teriparatide and denosumab were superior to bisphosphonates in increasing the bone mineral density (BMD) of the lumbar vertebrae [teriparatide: mean difference [MD] 3.98%, 95% confidence interval [CI] 3.61-4.175%, P = 0.00001; denosumab: MD 2.07%, 95% CI 0.97-3.17%, P = 0.0002]. Teriparatide was superior to bisphosphonates in preventing vertebral fractures and increasing hip BMD [MD 2.39%, 95% CI 1.47-3.32, P < 0.00001]. There was no statistically significant difference between serious adverse events, adverse events, and nonvertebral fracture prevention drugs.
CONCLUSIONS
Teriparatide and denosumab exhibited similar or even superior characteristics to bisphosphonates in our study, and we believe that they have the potential to become first-line GC-induced osteoporosis treatments, especially for patients who have previously received other anti-osteoporotic drugs with poor efficacy.
Topics: Humans; Teriparatide; Glucocorticoids; Denosumab; Bone Density Conservation Agents; Osteoporosis; Diphosphonates; Bone Density; Treatment Outcome
PubMed: 37349750
DOI: 10.1186/s13018-023-03920-4 -
Journal of Musculoskeletal & Neuronal... Dec 2022Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM)... (Meta-Analysis)
Meta-Analysis Review
Bisphosphonates (BPs) and denosumab (DENOS), due to their ability to inhibit osteoclast activity, are used to prevent skeletal complications in multiple myeloma (MM) patients. The NCBI PubMed, Web of Science, Scopus and ClinicalTrials.gov databases, were systematically searched for interventional studies, assessing the use of BP and DENOS in MM patients. Overall survival, disease progression, skeletal-related events, bone pain, osteonecrosis of the jaw (ONJ) and renal toxicity were the outcomes of interest. A total of 993 studies were retrieved and 43 were used for qualitative synthesis. Clodronate (CLOD) and zoledronic acid (ZOL) were effective in reducing skeletal complications compared to placebo. Results are mixed regarding the efficacy of pamidronate in reducing skeletal related events. ONJ rates were higher for ZOL, but under 5%, with CLOD having the safest profile. DENOS demonstrated non-inferiority to ZOL, in improving overall survival [pooled Hazard Ratio(HR) 1.02(95% CI 0.72,1.44)], progression free survival [pooled HR 0.92(95% CI 0.76,1.11)] and in reducing skeletal related events [pooled HR 1.03(95% CI 0.92,1.16)], with similar rates of ONJ and better safety profile regarding renal toxicity. Denosumab has comparable efficacy and safety with ZOL and may even replace BPs in the future, in the management of myeloma bone disease.
Topics: Humans; Diphosphonates; Multiple Myeloma; Denosumab; Zoledronic Acid; Clodronic Acid
PubMed: 36458395
DOI: No ID Found -
Journal of the American Board of Family... Feb 2023There are multiple classes of pharmacologic agents approved for treatment of osteoporosis, but their costs vary widely, and systematic data on their efficacy compared... (Meta-Analysis)
Meta-Analysis
BACKGROUND
There are multiple classes of pharmacologic agents approved for treatment of osteoporosis, but their costs vary widely, and systematic data on their efficacy compared with the traditional standard, bisphosphonates, for reducing fractures in postmenopausal women are lacking. The objective was to perform a systematic review and meta-analysis assessing the efficacy of denosumab compared with bisphosphonates.
METHODS
Researchers selected randomized controlled trials (RCTs) comparing denosumab to bisphosphonates that included information on clinical and/or osteoporotic fracture events over the follow-up period. Each clinical outcome was meta-analyzed using a fixed-effects analysis, with clinical and osteoporotic fractures as the outcomes of interest. A meta-regression was performed using change in bone mineral density (BMD) as the moderator variable.
RESULTS
Seven RCTs were included. Denosumab was not associated with a reduction in clinical or osteoporotic fractures compared with bisphosphonates. There was no association between the change in BMD with denosumab and bisphosphonates and denosumab's effect on both osteoporotic and clinical fractures.
DISCUSSION
Existing data do not support the use of the more expensive denosumab as a first-line agent over bisphosphonates for reduction of fractures in postmenopausal women with osteoporosis. One limitation in this study was each RCT was not individually powered for fracture incidences.
Topics: Female; Humans; Diphosphonates; Osteoporotic Fractures; Bone Density Conservation Agents; Postmenopause; Osteoporosis, Postmenopausal; Osteoporosis; Bone Density
PubMed: 36653115
DOI: 10.3122/jabfm.2022.220099R1 -
Frontiers in Pharmacology 2024Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian...
Several medications have been used for glucocorticoids-induced osteoporosis (GIO). However, the best therapeutic option for GIO is still controversial. A Bayesian network meta-analysis was conducted to compare the efficacy and safety of denosumab, teriparatide and bisphosphonates for patients with GIO. Relevant randomized controlled trials published in PubMed, Embase, Cochrane Library and ClinicalTrials.gov up to August 2023 were searched. The following efficiency and safety outcomes were extracted for comparison: bone mineral density (BMD) percentage changes in lumbar spine, femur neck and total hip, and incidences of adverse events (AEs), serious adverse events (SAEs), vertebrae and non-vertebrae fracture. Bayesian random effects models were used for multiple treatment comparisons. 11 eligible RCTs involving 2,877 patients were identified. All the six medications including alendronate, risedronate, etidronate, zoledronate, teriparatide, and denosumab and were effective in increasing BMD. Teriparatide and denosumab were more effective in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. Alendronate and denosumab were more effective in improving total hip BMD. Alendronate and teriparatide had the lowest incidences of AEs and SAEs. Teriparatide denosumab and the bisphosphonates are all effective in improving BMD for GIO patients. Based on this network meta-analysis, teriparatide and denosumab have higher efficiency in improving lumbar spine and femur neck BMD, and reducing vertebrae fracture. 10.17605/OSF.IO/2G8YA, identifier CRD42023456305.
PubMed: 38313307
DOI: 10.3389/fphar.2024.1336075 -
Rheumatology Advances in Practice 2021Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion...
OBJECTIVES
Denosumab is used for osteoporosis because it inhibits osteoclast maturation and suppresses bone resorption. Although denosumab is expected to inhibit the bone erosion in RA, its therapeutic efficacy is not well established. The aim of this study was to estimate the effects of denosumab on RA through a meta-analysis.
METHODS
A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. PubMed, Web of Science and Scopus were searched for original studies providing information on BMD, joint destruction and disease activity in denosumab-treated RA. A random-effects model was used in the meta-analysis.
RESULTS
Of the 367 studies identified, 18 met the selection criteria. The BMDs of the lumbar spine, total hip and femoral neck at 12 months after denosumab treatment increased by 5.27% (95% CI: 4.37, 6.18), 2.82% (2.46, 3.18) and 3.07% (2.66, 3.48), respectively. In the sensitivity analysis, age and sex tended to influence the effect of denosumab therapy on the rate of variation of BMD, but not glucocorticoid use. The changes in the modified total sharp, erosion and joint space narrowing scores at 12 months after denosumab treatment were significantly smaller with denosumab than with placebo, although the DAS did not change after denosumab treatment.
CONCLUSION
Although denosumab has an inhibitory effect on the bone resorption in RA, its effects might be influenced by the age and sex of RA patients, but not by glucocorticoid use.
PubMed: 34988358
DOI: 10.1093/rap/rkab099 -
The Cochrane Database of Systematic... May 2023Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with... (Review)
Review
BACKGROUND
Osteoporosis is characterized by low bone mass and micro-architectural deterioration of bone tissue leading to increased bone fragility. In people with beta-thalassaemia, osteoporosis represents an important cause of morbidity and is due to a number of factors. First, ineffective erythropoiesis causes bone marrow expansion, leading to reduced trabecular bone tissue with cortical thinning. Second, excessive iron loading causes endocrine dysfunction, leading to increased bone turnover. Lastly, disease complications can result in physical inactivity, with a subsequent reduction in optimal bone mineralization. Treatments for osteoporosis in people with beta-thalassaemia include bisphosphonates (e.g. clodronate, pamidronate, alendronate; with or without hormone replacement therapy (HRT)), calcitonin, calcium, zinc supplementation, hydroxyurea, and HRT alone (for preventing hypogonadism). Denosumab, a fully human monoclonal antibody, inhibits bone resorption and increases bone mineral density (BMD). Finally, strontium ranelate simultaneously promotes bone formation and inhibits bone resorption, thus contributing to a net gain in BMD, increased bone strength, and reduced fracture risk. This is an update of a previously published Cochrane Review.
OBJECTIVES
To review the evidence on the efficacy and safety of treatment for osteoporosis in people with beta-thalassaemia.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Haemoglobinopathies Trials Register, which includes references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. We also searched online trial registries. Date of most recent search: 4 August 2022.
SELECTION CRITERIA
Randomized controlled trials (RCTs) in people with beta-thalassaemia with: a BMD Z score below -2 standard deviations (SDs) for children aged under 15 years, adult males (aged 15 to 50 years) and premenopausal females aged over 15 years; or a BMD T score below -2.5 SDs for postmenopausal females and males aged over 50 years.
DATA COLLECTION AND ANALYSIS
Two review authors assessed the eligibility and risk of bias of the included RCTs, and extracted and analysed data. We assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included six RCTs (298 participants). Active interventions included bisphosphonates (3 trials, 169 participants), zinc supplementation (1 trial, 42 participants), denosumab (1 trial, 63 participants), and strontium ranelate (1 trial, 24 participants). The certainty of the evidence ranged from moderate to very low and was downgraded mainly due to concerns surrounding imprecision (low participant numbers), but also risk of bias issues related to randomization, allocation concealment, and blinding. Bisphosphonates versus placebo or no treatment Two RCTs compared bisphosphonates to placebo or no treatment. After two years, one trial (25 participants) found that alendronate and clodronate may increase BMD Z score compared to placebo at the femoral neck (mean difference (MD) 0.40, 95% confidence interval (CI) 0.22 to 0.58) and the lumbar spine (MD 0.14, 95% CI 0.05 to 0.23). One trial (118 participants) reported that neridronate compared to no treatment may increase BMD at the lumbar spine and total hip at six and 12 months; for the femoral neck, the study found increased BMD in the neridronate group at 12 months only. All results were of very low-certainty. There were no major adverse effects of treatment. Participants in the neridronate group reported less back pain; we considered this representative of improved quality of life (QoL), though the certainty of the evidence was very low. One participant in the neridronate trial (116 participants) sustained multiple fractures as a result of a traffic accident. No trials reported BMD at the wrist or mobility. Different doses of bisphosphonate compared One 12-month trial (26 participants) assessed different doses of pamidronate (60 mg versus 30 mg) and found a difference in BMD Z score favouring the 60 mg dose at the lumbar spine (MD 0.43, 95% CI 0.10 to 0.76) and forearm (MD 0.87, 95% CI 0.23 to 1.51), but no difference at the femoral neck (very low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment. Zinc versus placebo One trial (42 participants) showed zinc supplementation probably increased BMD Z score compared to placebo at the lumbar spine after 12 months (MD 0.15, 95% CI 0.10 to 0.20; 37 participants) and 18 months (MD 0.34, 95% CI 0.28 to 0.40; 32 participants); the same was true for BMD at the hip after 12 months (MD 0.15, 95% CI 0.11 to 0.19; 37 participants) and 18 months (MD 0.26, 95% CI 0.21 to 0.31; 32 participants). The evidence for these results was of moderate certainty. The trial did not report BMD at the wrist, fracture incidence, mobility, QoL, or adverse effects of treatment. Denosumab versus placebo Based on one trial (63 participants), we are unsure about the effect of denosumab on BMD Z score at the lumbar spine, femoral neck, and wrist joint after 12 months compared to placebo (low-certainty evidence). This trial did not report fracture incidence, mobility, QoL, or adverse effects of treatment, but the investigators reported a reduction in bone pain measured on a visual analogue scale in the denosumab group after 12 months of treatment compared to placebo (MD -2.40 cm, 95% CI -3.80 to -1.00). Strontium ranelate One trial (24 participants) only narratively reported an increase in BMD Z score at the lumbar spine in the intervention group and no corresponding change in the control group (very low-certainty evidence). This trial also found a reduction in back pain measured on a visual analogue scale after 24 months in the strontium ranelate group compared to the placebo group (MD -0.70 cm (95% CI -1.30 to -0.10); we considered this measure representative of improved quality of life.
AUTHORS' CONCLUSIONS
Bisphosphonates may increase BMD at the femoral neck, lumbar spine, and forearm compared to placebo after two years' therapy. Zinc supplementation probably increases BMD at the lumbar spine and hip after 12 months. Denosumab may make little or no difference to BMD, and we are uncertain about the effect of strontium on BMD. We recommend further long-term RCTs on different bisphosphonates and zinc supplementation therapies in people with beta-thalassaemia-associated osteoporosis.
Topics: Adult; Child; Female; Male; Humans; Middle Aged; beta-Thalassemia; Alendronate; Pamidronate; Clodronic Acid; Denosumab; Osteoporosis; Diphosphonates; Fractures, Bone
PubMed: 37159055
DOI: 10.1002/14651858.CD010429.pub3 -
Calcified Tissue International Oct 2021It is acknowledged that the COVID-19 pandemic has caused profound disruption to the delivery of healthcare services globally. This has affected the management of many... (Review)
Review
It is acknowledged that the COVID-19 pandemic has caused profound disruption to the delivery of healthcare services globally. This has affected the management of many long-term conditions including osteoporosis as resources are diverted to cover urgent care. Osteoporosis is a public health concern worldwide and treatment is required for the prevention of further bone loss, deterioration of skeletal micro-architecture, and fragility fractures. This review provides information on how the COVID-19 pandemic has impacted the diagnosis and management of osteoporosis. We also provide clinical recommendations on the adaptation of care pathways based on experience from five referral centres to ensure that patients with osteoporosis are still treated and to reduce the risk of fractures both for the individual patient and on a societal basis. We address the use of the FRAX tool for risk stratification and initiation of osteoporosis treatment and discuss the potential adaptations to treatment pathways in view of limitations on the availability of DXA. We focus on the issues surrounding initiation and maintenance of treatment for patients on parenteral therapies such as zoledronate, denosumab, teriparatide, and romosozumab during the pandemic. The design of these innovative care pathways for the management of patients with osteoporosis may also provide a platform for future improvement to osteoporosis services when routine clinical care resumes.
Topics: Bone Density Conservation Agents; COVID-19; Humans; Osteoporosis; Osteoporotic Fractures; Pandemics; SARS-CoV-2; Teriparatide
PubMed: 34003337
DOI: 10.1007/s00223-021-00858-9 -
Iranian Journal of Public Health Jul 2022We aimed to review the systematic economic evaluation of denosumab versus than alternative drugs and oral bisphosphonates of postmenopausal osteoporosis in women and... (Review)
Review
BACKGROUND
We aimed to review the systematic economic evaluation of denosumab versus than alternative drugs and oral bisphosphonates of postmenopausal osteoporosis in women and help health system policy makers for prioritizing and optimally allocate limited health resources.
METHODS
We examined the databases of PubMed, Web of Science, Embase, Scopus, Cochrane Library, ProQuest. Strategy search was designed based on keywords. Inclusion criteria were: studies that conducted economic evaluation denosumab compared to oral bisphosphonates for the treatment of osteoporosis in postmenopausal women. Cost-effectiveness studies conducted using decision analysis models based on the economic evaluation approach; studies with available full-text papers; and studies written in English and published between 2010 and 2020. After selecting articles based on inclusion and exclusion criteria, data were extracted and the results were summarized. The quality of the articles was evaluated using the CHEERS checklist.
RESULTS
Among 214 initial studies, 8 studies met the inclusion criteria. Most studies focused on the cost-effectiveness of denosumab compared with oral bisphosphonates for the treatment of osteoporosis. The study agreed interval ranged from 3 months to 5 years. The costs investigated in the studies were direct medical costs. In most studies, the use of denosumab significantly prevented fractures.
CONCLUSION
Denosumab is generally more cost-effective than alternative drugs and oral bisphosphonates (alendronate, risedronate, strontium ranelate, ibandronate, and untreated).
PubMed: 36248303
DOI: 10.18502/ijph.v51i7.10084 -
Frontiers in Endocrinology 2023Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended... (Meta-Analysis)
Meta-Analysis
Efficacy of antiresorptive agents bisphosphonates and denosumab in mitigating hypercalcemia and bone loss in primary hyperparathyroidism: A systematic review and meta-analysis.
PURPOSE
Primary hyperparathyroidism (PHPT) is characterized by increased bone remodeling and hypercalcemia. Parathyroidectomy (PTX), the current standard of care, is recommended in all symptomatic and some groups of asymptomatic patients. Anti-resorptive therapies (bisphosphonates and denosumab) have been used in patients where PTX is refused or contraindicated. In this meta-analysis, we investigated the effectiveness of anti-resorptives in preventing/treating PHPT-induced bone loss and mitigating hypercalcemia.
METHOD
PubMed, Scopus, and Cochrane Library databases were searched for articles with keywords containing PHPT, bisphosphonates, and denosumab in various combinations. We extracted and tabulated areal BMD (aBMD), serum mineral, and bone turnover parameters from the qualified studies and used comprehensive meta-analysis software for analysis.
RESULTS
Of the 1,914 articles screened, 13 were eligible for meta-analysis. In the pooled analysis, 12 months of anti-resoptives (bisphosphonates and denosumab) therapy significantly increased aBMD at the lumbar spine (Standard difference in means (SDM)=0.447, 95% CI=0.230 to 0.664, p=0.0001), femoral neck (SDM=0.270, 95% CI=0.049 to 0.491, p=0.017) and increased serum PTH (SDM=0.489, 95% CI=0.139 to 0.839, p=0.006), and decreased serum calcium (SDM=-0.545, 95% CI=-0.937 to -0.154, p=0.006) compared with baseline. 12 months of bisphosphonate use significantly increased aBMD only at the lumbar spine (SDM=0.330, 95% CI=0.088 to 0.571, p=0.007) with a significant increased in serum PTH levels (SDM=0.546, 95% CI= 0.162 to 0.930, p=0.005), and a decreased in serum calcium (SDM=-0.608, 95% CI=-1.048 to -0.169, p=0.007) and bone-turnover markers (BTMs) compared with baseline. Denosumab use for 12 months significantly increased aBMD at both the lumbar spine (SDM=0.828, 95% CI=0.378 to 1.278, p=0.0001) and femur neck (SDM=0.575, 95% CI=0.135 to 1.015, p=0.010) compared with baseline. Mean lumbar spine aBMD (SDM=0.350, 95% CI=0.041 to 0.659, p=0.027) and serum PTH (SDM=0.602, 95% CI= 0.145 to 1.059, p=0.010) were significantly increased after 12 months of alendronate use compared with placebo. When compared with baseline, alendronate significantly decreased BTMs after 12 months and increased aBMD without altering the PTH and calcium levels after 24 months.
CONCLUSION
Anti-resorptives are effective in mitigating bone loss and hypercalcemia in PHPT while maintaining or increasing aBMD. PTX reversed all changes in PHPT and normalized PTH levels.
Topics: Humans; Bone Density Conservation Agents; Diphosphonates; Alendronate; Denosumab; Hypercalcemia; Calcium; Hyperparathyroidism, Primary; Bone Density; Parathyroid Hormone; Bone Diseases, Metabolic; Lumbar Vertebrae
PubMed: 36817591
DOI: 10.3389/fendo.2023.1098841