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JBMR Plus Oct 2023Osteoporosis and cardiovascular disease are common in older adults. Treatment of osteoporosis reduces the burden of debilitating fractures; however, it is important to...
Osteoporosis and cardiovascular disease are common in older adults. Treatment of osteoporosis reduces the burden of debilitating fractures; however, it is important to understand the benefit versus risk of treatment. This study evaluates the risk of stroke (ischemic or hemorrhagic) and myocardial infarction (MI) among postmenopausal women and men initiating osteoporosis treatment with denosumab (receptor activator of nuclear factor κB ligand [RANKL] inhibitor) or zoledronic acid (bisphosphonate) between October 2010 and June 2019. A retrospective cohort study employing the new user/active comparator design was conducted. Analyses were conducted separately in two national US commercial databases, MarketScan® and Optum® for reproducibility. Inverse probability of treatment and censoring weighting was employed to control for confounding and informative censoring. Cumulative risks at 6-month, 12-month, and 36-month time points were calculated and adjusted risk ratios and differences (with 95% confidence intervals [CIs]) were estimated. In MarketScan® and Optum® databases, 96,611 and 73,127 patients met all study eligibility criteria, respectively. At 36 months, the risk ratio estimates (zoledronic acid referent group) were 1.22 (95% CI, 0.77-1.66) and 0.97 (95% CI, 0.63-1.32) for MI and 1.00 (95% CI, 0.61-1.40) and 0.87 (95% CI, 0.56-1.17) for stroke in MarketScan and Optum, respectively. Most of the treatment associations across the other time periods and outcomes also had 95% CIs including the null value. In these large samples of real-world US patients, no increased risk in MI and stroke were identified for up to 36 months of treatment in denosumab users compared with zoledronic acid users. © 2023 Amgen. published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.
PubMed: 37808402
DOI: 10.1002/jbm4.10793 -
The Lancet Regional Health. Europe Jul 2023Although age-standardised hip fracture incidence has declined in many countries during recent decades, the number of fractures is forecast to increase as the population...
BACKGROUND
Although age-standardised hip fracture incidence has declined in many countries during recent decades, the number of fractures is forecast to increase as the population ages. Understanding the drivers behind this decline is essential to inform policy for targeted preventive measures. We aimed to quantify how much of this decline could be explained by temporal trends in major risk factors and osteoporosis treatment.
METHODS
We developed a new modelling approach, Hip-IMPACT, based on the validated IMPACT coronary heart disease models. The model applied sex- and age stratified hip fracture numbers and prevalence of pharmacologic treatments and risk/preventive factors in 1999 and 2019, and best available evidence for independent relative risks of hip fracture associated with each treatment and risk/preventive factor.
FINDINGS
Hip-IMPACT explained 91% (2500/2756) of the declining hip fracture rates during 1999-2019. Two-thirds of the total decline was attributed to changes in risk/preventive factors and one-fifth to osteoporosis medication. Increased prevalence of total hip replacements explained 474/2756 (17%), increased body mass index 698/2756 (25%), and increased physical activity 434/2756 (16%). Reduced smoking explained 293/2756 (11%), and reduced benzodiazepine use explained (366/2756) 13%. Increased uptake of alendronate, zoledronic acid, and denosumab explained 307/2756 (11%), 104/2756 (4%) and 161/2756 (6%), respectively. The explained decline was partially offset by increased prevalence of type 2 diabetes and users of glucocorticoids, z-drugs, and opioids.
INTERPRETATION
Two-thirds of the decline in hip fractures from 1999 to 2019 was attributed to reductions in major risk factors and approximately one-fifth to osteoporosis medication.
FUNDING
The Research Council of Norway.
PubMed: 37215491
DOI: 10.1016/j.lanepe.2023.100643 -
JAMA Network Open Jan 2024Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for...
IMPORTANCE
Women with early breast cancer (EBC) exposed to aromatase inhibitors (AIs) may experience fragility fractures despite treatment with bone-active drugs. Risk factors for fractures in patients receiving AIs and denosumab have not been explored to date.
OBJECTIVES
To evaluate whether an association exists between dual x-ray absorptiometry (DXA)-measured fat body mass (FBM) and vertebral fracture (VF) progression in postmenopausal women with EBC undergoing adjuvant therapy with AIs in combination with denosumab and to examine whether VF was associated with common risk factors for bone fracture and parameters of body composition other than FBM.
DESIGN, SETTING, AND PARTICIPANTS
For this prospective, single-center, cohort study, 237 patients with EBC who were undergoing adjuvant treatment with AIs and denosumab (60 mg every 6 months) were enrolled at the Breast Unit of the ASST Spedali Civili of Brescia from September 2014 to June 2018. Data analysis was conducted in June 2022.
EXPOSURE
Body composition parameters, bone mineral density, and morphometric VFs were assessed by DXA at study entry and after 18 months of therapy.
MAIN OUTCOMES AND MEASURES
VF progression, defined as either new or worsening of preexisting VFs, between the 2 time points.
RESULTS
Of the 237 patients enrolled (median [range] age, 61 [28-84] years), 17 (4.4%) reported VF progression. Univariable analysis found an association between VF progression and a history of clinical fractures (odds ratio [OR], 3.22; 95% CI, 1.19-8.74; P = .02), Fracture Risk Assessment Tool (FRAX) score for major fractures (OR, 4.42; 95% CI, 1.23-13.79; P = .04), percentage of FBM (OR, 6.04; 95% CI, 1.69-21.63; P = .006), and android fat (OR, 9.58; 95% CI, 1.17-78.21; P = .04) and an inverse association with appendicular lean mass index-FBM ratio (OR, 0.25, 95% CI, 0.08-0.82; P = .02). Multivariable analysis revealed percentage of FBM (OR, 5.41; 95% CI, 1.49-19.59; P = .01) and FRAX score (OR, 3.95; 95% CI, 1.09-14.39; P = .04) as independent variables associated with VF progression.
CONCLUSIONS AND RELEVANCE
The findings of this study suggest that baseline FBM is an independent factor for VF progression in patients with EBC treated with adjuvant AIs and denosumab. This observation is new and indicates that diet and exercise may synergize with denosumab in the management of bone health in this patient setting.
Topics: Animals; Humans; Female; Middle Aged; Spinal Fractures; Breast Neoplasms; Cohort Studies; Denosumab; Fat Body; Prospective Studies; Fractures, Bone; Adjuvants, Immunologic
PubMed: 38198137
DOI: 10.1001/jamanetworkopen.2023.50950 -
European Journal of Case Reports in... 2023Organising pneumonia belongs to diffuse interstitial lung diseases; we distinguish the cryptogenic organising pneumonia, which is idiopathic, from the secondary...
INTRODUCTION
Organising pneumonia belongs to diffuse interstitial lung diseases; we distinguish the cryptogenic organising pneumonia, which is idiopathic, from the secondary organising pneumonia caused by drugs or a defined cause. Denosumab is a human monoclonal antibody, rarely inducing adverse pulmonary effects.
CASE DESCRIPTION
A 57-year-old female patient was admitted to our chest clinic for acute respiratory distress. She was treated with denosumab for severe osteoporosis. The patient described a dry cough and dyspnoea over the previous four months, increased after the last injection of denosumab. A high-resolution computed tomography scan showed bilateral basal parenchymal condensations. The aetiological investigation did not reveal any infectious or immunological origin. The favourable computed tomography imaging and clinical evolution after corticosteroid therapy led to the diagnosis of drug-induced organising pneumonia.
CONCLUSION
Denosumab could induce organising pneumonia. Therefore, clinicians should be aware of this pulmonary toxicity.
LEARNING POINTS
To the best of our knowledge denosumab, a human monoclonal antibody, may rarely induce organising pneumonia.Despite this, we advocate that clinicians be aware that exposure to this drug can cause pulmonary toxicity.The taking of denosumab by our patient does not in any way prove the causal link.
PubMed: 37789975
DOI: 10.12890/2023_004043 -
The Journal of Clinical Endocrinology... Jun 2024Denosumab is a potential therapeutic agent for osteogenesis imperfecta (OI), but its efficacy and safety remain unclear in children with OI. (Randomized Controlled Trial)
Randomized Controlled Trial Comparative Study
CONTEXT
Denosumab is a potential therapeutic agent for osteogenesis imperfecta (OI), but its efficacy and safety remain unclear in children with OI.
OBJECTIVE
We aimed to investigate the effects of denosumab on bone mineral density (BMD), spinal morphometry, and safety in children with OI compared with zoledronic acid.
METHODS
In this prospective study, 84 children or adolescents with OI were randomized to receive denosumab subcutaneous injection every 6 months or zoledronic acid intravenous infusion once. Changes of BMD and its Z-score, vertebral shape, serum levels of calcium and bone turnover biomarkers were assessed during the 1-year treatment.
RESULTS
After 12 months of treatment, BMD at the lumbar spine, femoral neck, and total hip significantly increased by 29.3%, 27.8%, and 30.2% in the denosumab group, and by 32.2%, 47.1%, and 41.1% in the zoledronic acid group (all P < .001 vs baseline). Vertebral height and projection area significantly increased after denosumab and zoledronic acid treatment. Rebound hypercalcemia was found to be a common and serious side effect of denosumab, of which 14.3% reached hypercalcemic crisis. Rebound hypercalcemia could be alleviated by switching to zoledronic acid treatment.
CONCLUSION
Treatment with denosumab or zoledronic acid is beneficial in increasing BMD and improving the spinal morphometry of children with OI. However, denosumab should be used with caution in pediatric patients with OI because of its common and dangerous side effect of rebound hypercalcemia. The appropriate dosage and dosing interval of denosumab need to be further explored in children with OI.
Topics: Humans; Denosumab; Osteogenesis Imperfecta; Child; Female; Male; Bone Density; Bone Density Conservation Agents; Zoledronic Acid; Child, Preschool; Adolescent; Prospective Studies; Treatment Outcome; Bone Remodeling
PubMed: 38198649
DOI: 10.1210/clinem/dgad732 -
BMC Cancer Oct 2023Little is known on how denosumab reduces skeletal-related events (SREs) by bone metastases from solid tumors. We sought to evaluate the effect of denosumab...
BACKGROUND
Little is known on how denosumab reduces skeletal-related events (SREs) by bone metastases from solid tumors. We sought to evaluate the effect of denosumab administration in patients with bone metastases from solid tumors.
METHODS
Data of patients treated with denosumab were collected from electronic medical charts (n = 496). Eligible participants in this study were adult patients (age ≥ 18 years) with metastatic bone lesions from solid tumors treated with denosumab. SREs, surgical interventions, the spinal instability neoplastic score (SINS) for spinal region, and Mirels' score for the appendicular region were evaluated. To assess whether denosumab could prevent SREs and associated surgery, the SINS and Mirels' score were compared between patients with and without SREs.
RESULTS
A total of 247 patients (median age, 65.5 years old; median follow-up period, 13 months) treated with denosumab for metastatic bone lesions from solid tumors were enrolled in this study. SREs occurred in 19 patients (7.7%). SREs occurred in 2 patients (0.8%) who took denosumab administration before SREs. Surgical interventions were undertaken in 14 patients (5.7%) (spinal and intradural lesions in five patients and appendicular lesions in nine patients). The mean SINS of patients without SREs compared to those with SREs were 7.5 points and 10.2 points, respectively. The mean Mirels' scores of non-SREs patients and those with SREs were 8.07 points and 10.7 points, respectively. Patients with SREs had significantly higher Mirels' score than non-SREs patients (p < 0.01). Patients with SREs had higher SINS than non-SREs patients (p = 0.09).
CONCLUSIONS
SREs occurred in patients with higher SINS or Mirels' scores. Two patients suffered from SREs though they took denosumab administration before SREs. Appropriate management of denosumab for patients with bone metastasis is significant. Surgical interventions may be needed for patients who with higher SINS or Mirel's scores.
Topics: Adult; Humans; Aged; Adolescent; Denosumab; Cross-Sectional Studies; Diphosphonates; Retrospective Studies; Bone Neoplasms; Bone Density Conservation Agents
PubMed: 37853409
DOI: 10.1186/s12885-023-11495-w -
Journal of Oral & Maxillofacial Research 2023The objective of this systematic review is to evaluate the current knowledge on the effectiveness of conservative and surgical treatment of medication-related... (Review)
Review
OBJECTIVES
The objective of this systematic review is to evaluate the current knowledge on the effectiveness of conservative and surgical treatment of medication-related osteonecrosis of the jaw.
MATERIAL AND METHODS
MEDLINE (PubMed), ScienceDirect and Cochrane Library search in combination with hand-search of relevant journals was conducted including human studies published in English between January 2017 and February 2023. Studies assessing treatment strategies for medication-related osteonecrosis of the jaw (MRONJ) were included. Quality and risk-of-bias assessment were evaluated by Joanna Briggs Institute (JBI) Risk of Bias tool.
RESULTS
A total of 4227 articles were screened from which 9 studies (7 cohort studies and 2 randomized controlled trials) met the inclusion criteria and were included in the final data synthesis. Two studies evaluate effectiveness of conservative approaches for treating MRONJ, 5 studies evaluate surgical approaches effectiveness, and 2 studies compare between those approaches. The follow-up period ranged from 6 months to 60 months. According to bias assessment, the mean JDI score of the included studies was > 9 ("low risk of bias"). The stage of the disease, the procedure performed on the patient and the results of the treatment were presented.
CONCLUSIONS
Surgical therapy seems to be superior to conservative therapy for the management of adverse stages medication-related osteonecrosis of the jaws, while conservative treatment appears to yield good outcomes at asymptomatic patients with early stages of the disease.
PubMed: 38222882
DOI: 10.5037/jomr.2023.14401 -
Frontiers in Pharmacology 2023Patients with osteoporosis are at an increased risk of cardiovascular disease (CVD). Several antiosteoporosis medications have been demonstrated with the benefit of...
Patients with osteoporosis are at an increased risk of cardiovascular disease (CVD). Several antiosteoporosis medications have been demonstrated with the benefit of preventing osteoporosis. Our aim is to assess the CVD risks associated with antiosteoporosis medications using the National Health Insurance Research Database in Taiwan between 2000 and 2016. Among 41,102 patients of 40+ years old with newly diagnosed osteoporosis, 69.1% (N = 28,387) of patients were included in the user cohort of antiosteoporosis medicines, of whom 13, 472 developed CVD by the end of 2016, while 14,915 did not. Using the nested case-control analysis in the user cohort (88.0% women and 77.4% elderly), we applied conditional logistic regression to estimate odds ratios (ORs) of eight types of CVD for the users of denosumab, bisphosphonate, teriparatide, and hormone replacement therapy (HRT). The adjusted ORs of overall CVDs were 0.13 (95% CI: 0.12-0.15) for denosumab users, 0.52 (95% CI: 0.45-0.61) for teriparatide users, and 0.80 (95% CI: 0.76-0.85) for bisphosphonate users. The HRT users were at higher odds of coronary artery and peripheral artery diseases, heart failure, pulmonary embolism, and deep vein thrombosis. Denosumab, teriparatide, and bisphosphonate may have more protective effects against CVD than hormone therapy. Physicians may take subsequent cardiovascular risks into account when choosing an adequate antiosteoporosis medication for patients with osteoporosis.
PubMed: 37881187
DOI: 10.3389/fphar.2023.1220174 -
The Journal of Clinical Endocrinology... Apr 2024Denosumab is an effective treatment for many receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated disorders but there are potential safety considerations...
CONTEXT
Denosumab is an effective treatment for many receptor activator of nuclear factor kappa-B ligand (RANKL)-mediated disorders but there are potential safety considerations and limited data to guide its use in children and adolescents.
OBJECTIVE
This document seeks to summarize the evidence and provide expert opinion on safe and appropriate use of denosumab in pediatric RANKL-mediated disorders.
PARTICIPANTS
Ten experts in pediatric bone and mineral medicine from 6 countries with experience in the use of denosumab participated in the creation of this document.
EVIDENCE
Data were sourced from the published literature, primarily consisting of case reports/series and review articles because of the lack of higher level evidence. Expert opinion of the authors was used substantially when no published data were available.
CONCLUSION
Denosumab is an effective treatment for RANKL-mediated disorders in children and adolescents but is often not curative and, in some cases, is best used in conjunction with surgical or other medical treatments. Careful multidisciplinary planning is required to define the goals of treatment and expert oversight needed to manage the risk of mineral abnormalities. Substantive, collaborative research efforts are needed to determine optimal treatment regimens and minimize risks.
Topics: Adolescent; Child; Humans; Bone and Bones; Bone Density Conservation Agents; Denosumab; Ligands; Minerals; RANK Ligand
PubMed: 38041865
DOI: 10.1210/clinem/dgad657 -
JBMR Plus Apr 2024Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).
BACKGROUND
Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).
METHODS
We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators, and calcium phosphate metabolism at baseline, month 3 and month 6. BMD was assessed at baseline and after 6 months.
RESULTS
Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab, and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8%, and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and +99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups, and Dkk1 did not change.
CONCLUSION
Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD vs denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.
PubMed: 38544922
DOI: 10.1093/jbmrpl/ziae016