scholarly journals The effect of previous treatment with bisphosphonate and renal impairment on the response to denosumab in osteoporosis: a ‘real-life’ study

2019 ◽  
Vol 43 (4) ◽  
pp. 469-475 ◽  
Author(s):  
T. R. Fraser ◽  
I. Flogaitis ◽  
A. E. Moore ◽  
G. Hampson
Keyword(s):  
Real Life ◽  
Previous Treatment ◽  
Bisphosphonate Therapy ◽  
Bisphosphonate Treatment ◽  
Mineral Density ◽  
Life Study ◽  
Group A ◽  
Real Life Study ◽  
Group B ◽  
The Impact

Abstract Purpose To investigate changes in bone mineral density (BMD) following denosumab after previous bisphosphonate therapy and the impact of chronic kidney disease (CKD) on response. Methods A retrospective study of 134 patients (11 M, 123 F) aged [mean (SD)] 72 [11] years on denosumab was undertaken. Ninety-five patients had previously been on oral and 28 on iv bisphosphonate. Lumbar spine (LS), total hip (TH) and femoral neck (FN) BMD were measured before treatment and at 2.7 [1.2] years. GFR was < 35 ml/min in 24 patients (18%). Ninety-four (18 M, 76 F) patients aged 71 [11] years transitioning to zoledronate were also studied. Results BMD improved following denosumab [mean (SEM) % change LS: 6.0 (0.62) p < 0.001, TH: 2.28 (0.64) p < 0.001, FN: 1.9 (0.77) p = 0.045]. Changes at the TH and FN were lower in patients with GFR < 35 ml/min (Group B) compared to those with GFR > 35 ml/min (Group A) [% change TH; Group A: 2.9 (0.72), Group B: − 0.84 (1.28), p = 0.015, FN; Group A: 2.76 (0.86), Group B: − 1.47 (1.53), p = 0.025]. % change in BMD at the FN and PTH were negatively associated (r = − 0.25, p = 0.013). BMD changes were not different at 12–18 months between patients on denosumab compared to zoledronate [% change at LS: denosumab: 3.97% (0.85), zoledronate: 2.6% (0.5), p = 0.19 TH: denosumab: 0.97% (0.58), zoledronate: 0.92% (0.6), p = 0.95). Conclusion Denosumab increases BMD following previous bisphosphonate treatment and is comparable to zoledronate. Lower response seen at the hip in CKD is related to PTH concentrations.

scholarly journals Efficacy of Denosumab Therapy Following Treatment with Bisphosphonates in Women with Osteoporosis: A Cohort Study

2021 ◽  
Vol 18 (4) ◽  
pp. 1728
Author(s):  
Chiara Marocco ◽  
Giovanna Zimatore ◽  
Edoardo Mocini ◽  
Rachele Fornari ◽  
Giovanni Iolascon ◽  
...  
Keyword(s):  
Biochemical Markers ◽  
Human Monoclonal Antibody ◽  
Real Life ◽  
Mineral Density ◽  
Life Study ◽  
Positive Therapeutic Effect ◽  
Specialized Center ◽  
Previously Treated ◽  
Real Life Study ◽  
Post Menopausal

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy and assess its efficacy in increasing bone mineral density (BMD) and modulating biochemical skeletal markers following previous treatments with bisphosphonates in a group of post-menopausal women with osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased efficacy in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

scholarly journals Reduction of arrhythmias in primary hyperparathyroidism, by parathyroidectomy, evaluated with 24-h ECG monitoring

2018 ◽  
Vol 179 (2) ◽  
pp. 117-124 ◽  
Author(s):  
Jessica Pepe ◽  
Cristiana Cipriani ◽  
Mario Curione ◽  
Federica Biamonte ◽  
Luciano Colangelo ◽  
...  
Keyword(s):  
Primary Hyperparathyroidism ◽  
Mineral Metabolism ◽  
Randomized Study ◽  
Density Measurement ◽  
Mean Value ◽  
Ecg Monitoring ◽  
Mineral Density ◽  
Group A ◽  
Group B ◽  
The Impact

ObjectiveHypercalcemia may induce arrhythmias. There are no data on the prevalence of arrhythmias in primary hyperparathyroidism (PHPT) in daily life. Aim of the study was to investigate both the prevalence of arrhythmias in patients with PHPT compared to controls and the impact of parathyroidectomy, evaluated by 24-h electrocardiogram (ECG) monitoring.DesignThis is a randomized study.MethodsTwenty-six postmenopausal women with PHPT and 26 controls were enrolled. PHPT patients were randomized to two groups: 13 underwent parathyroidectomy (Group A) and 13 were followed up conservatively (Group B). After 6 months, patients were studied again. Each patient underwent mineral metabolism biochemical evaluation, bone mineral density measurement, standard ECG and 24-h ECG monitoring.ResultsPHPT patients showed higher calcium and parathyroid hormone compared to controls and a higher prevalence of both supraventricular (SVBPs) and ventricular premature beats (VPBs) during 24-h ECG monitoring. Groups A and B showed no differences in mean baseline biochemical values and ECG parameters. Mean value of QTc in PHPT groups was in the normal range at baseline, but significantly shorter than controls. A negative correlation was found between QTc and ionized calcium levels (r = −0.48,P < 0.05). After parathyroidectomy, Group A had a significant reduction in SVPBs and VPBs compared to baseline and restored normal QTc. Group B showed no significant changes after a 6-month period.ConclusionsThe increased prevalence of SVPBs and VPBs is significantly reduced by parathyroidectomy, and it is mainly related to the short QTc caused by hypercalcemia.

Multicentric Real Life Evaluation of the Impact of Next-Generation Sequencing on the Clinical Management of Chronic Myeloid Malignancies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5771-5771
Author(s):  
Sophie Vantyghem ◽  
Pierre Peterlin ◽  
Sylvain Thepot ◽  
Audrey Ménard ◽  
Viviane Dubruille ◽  
...  
Keyword(s):  
Poor Prognosis ◽  
Myeloproliferative Neoplasm ◽  
Real Life ◽  
Good Prognosis ◽  
Advisory Committees ◽  
Therapeutic Decisions ◽  
Group A ◽  
Molecular Assessment ◽  
Group B ◽  
The Impact

Introduction Next generation sequencing (NGS) has allowed to improve knowledge about the genomic landscape of hematological malignancies. Somatic mutations (SM) are valuable new biomarkers but the utility of incorporating routine sequencing to guide diagnosis and therapeutic decisions remains challenging. We report here an observational multicentric study aimed at assessing the impact of SM testing by NGS in a real-life setting on the diagnosis and treatment of chronic myeloid malignancies (CMM). Patients and Method All patients who benefited from molecular assessment, between 10/2014 and 03/2019 in our University Hospital were included. All provided informed consent for data collection. All NGS requests were validated during a regional multidisciplinary concertation meeting. A custom targeted panel of 34 genes (145kbp i.e. ASXL1,BCOR, BCORL1, CBL, CSF3R, DNMT3A, ETV6, EZH2, GATA2, IDH1, IDH2, JAK2, KDM6A, KIT, KRAS, MPL, NPM1, NRAS, PIGA, PTEN, PTPN11, RAD21, RUNX1, SETBP1, SF3B1, SMC1A, SMC3, SRSF2, STAG2, TET2, TNFAIP3, TP53, U2AF1, ZRSR2) was applied on DNA extracted from peripheral blood or bone marrow samples. DNA libraries, built with the Haloplex® target enrichment protocol (Agilent Technologies, Santa Clara, CA), were paired-end sequenced (150bp reads) with a MiSeq® Instrument (Illumina, San Diego, CA). Data analysis used an in-house pipeline including three variant callings (GATK HaplotypeCaller, VarScan and SAMTools). In a first group (A), NGS indication was to search for clonal hematopoiesis (CH), defined by the presence of at least one SM, in order to confirm or rule out a diagnosis of Idiopathic Cytopenia of Undetermined Significance (ICUS), Clonal Cytopenia of Undetermined Significance (CCUS), myelodysplastic syndrome (MDS), mixed myelodysplastic/myeloproliferative neoplasm (MDS/MPN), aplastic anemia (AA)/hypoplastic myelodysplasia (hMDS) or myeloproliferative neoplasm (MPN), based on recommendations of the WHO classification. In a second group (B), the theranostic impact of SM was studied. Prognostic SMs according to Bejar (2011) were used for MDS and MDS/MPN excluding chronic myelomonocytic leukemia that were analyzed with Itzykson score (2013) and/or CPSS-Mol score (Elena 2016). Prognostic SMs according to Vannucchi (2013) were used for myelofibrosis. Results The median age of the cohort was 60 years old (range: 10-87) with a median follow up of 1.1 years from molecular assessment to last follow-up. Within group A (94 patients), the most frequent blood count anomalies were cytopenia (68%), thrombocytosis (16%), and monocytosis (13%). The karyotype was normal in 77% and failed in 5% of the cases. Non-specific abnormalities (i.e. loss of chr Y, del 20q), were found in 8% of the cases. Before molecular assessment, the diagnoses proposed were ICUS (n=37), suspicion of MDS/MPN (n=16), AA/hMDS (n=16), or MPN (n=25). CH was detected in 31 patients comforting the diagnosis of CMM for 33% of group A (8 CCUS, 3 MDS, 7 MDS/MPN, 6 medullary hypoplasia, 7 MPN) patients. Considering the patients for whom no CH was detected (n=63), the initial suspected diagnosis of CMM was ruled out in 47 patients (i.e. 50% of group A). For the 16 remaining (i.e. 17% of group A), no firm diagnosis could be retained. Within group B (95 patients), NGS identified prognosis SM in 33% of the patients, i.e. poor prognosis SM in 24, including 8/40 MDS, 10/29 MDS/MPN and 6/17 myelofibrosis and good prognosis SM(SF3B1) in 7 of them, respectively 6/40 MDS and 1/29 MDS/MPN. Prognostic SMs had a therapeutic impact in 18/95 pts (19%). Indeed 13 patients with poor prognosis SM had a therapeutic change including 12 allogeneic stem-cell transplantation and 1 hypomethylating agent. Conversely, 5 patients with a good prognosis SM or absence of poor prognosis SM had a de-escalation of treatment intensity. Conclusion The use of NGS in daily practice had a clinical impact in both diagnostic and therapeutic decisions provided that the prescription is made in a critically explored context and not as a systematic test. In this "real life" cohort, the presence or absence of SM was a useful complement for integrated diagnoses in 83% of the patients, allowing to confirm (33%), or exclude (50%) a suspected condition. Moreover, in this cohort 34% of the patients had a SM with a reported prognostic impact and the treatment was modified in 19% of the cases. Yet, it remains necessary to integrate these results with other diagnostic criteria. Disclosures Peterlin: AbbVie Inc: Consultancy; Jazz Pharma: Consultancy; Astellas: Consultancy; Daiichi-Sankyo: Consultancy. Moreau:Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; AbbVie: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Le Gouill:Celgene: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support; Roche-Genentech: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Travel support. Chevallier:Daiichi Sankyo: Honoraria; Incyte: Consultancy, Honoraria; Jazz Pharmaceuticals: Honoraria.

scholarly journals Effectiveness of Denosumab Therapy after Treatment with Bisphosphonates in Women Affected by Osteoporosis: A Real-Life Study

2020 ◽  
Author(s):  
Chiara Marocco ◽  
Giovanna Zimatore ◽  
Edoardo Mocini ◽  
Rachele Fornari ◽  
Giovanni Iolascon ◽  
...  
Keyword(s):  
Biochemical Markers ◽  
Human Monoclonal Antibody ◽  
Real Life ◽  
Mineral Density ◽  
Life Study ◽  
Positive Therapeutic Effect ◽  
Specialized Center ◽  
Previously Treated ◽  
Real Life Study ◽  
Post Menopausal

Denosumab is a human monoclonal antibody that neutralizes RANKL, a cytokine able to interact with the RANK receptor on preosteoclasts and osteoclasts, decreasing their recruitment and differentiation, leading to a decreased bone resorption. The aim of this observational real-life study was to analyze adherence to denosumab therapy, its effectiveness in increasing bone mineral density (BMD) and in modulating biochemical skeletal markers upon previous treatments with bisphosphonates in a group of post-menopausal women affected by osteoporosis. Women were recruited in the specialized center from March 2012 to September 2019. Biochemical markers were recorded at baseline and every six months prior to subsequent drug injection. Dual X-ray Absorptiometry was requested at baseline and after 18/24 months. Comparing BMD at baseline and after denosumab therapy in naive patients and in those previously treated with bisphosphonates, a positive therapeutic effect was observed in both groups. The results of our real-life study demonstrate, as expected, that BMD values significantly increased upon denosumab treatment. Interestingly, denosumab showed an increased effectiveness in patients previously treated with bisphosphonates. Moreover, biochemical markers data indicate that osteoporotic patients, without other concomitant unstable health conditions, could be evaluated once a year, decreasing the number of specialistic center access.

scholarly journals Post-Hoc Analysis Evaluating the Impact of Antihyperglycemic Background Therapies on Attainment of A1C Targets Without Hypoglycemia in the ACHIEVE Control Pragmatic, Real-Life Study

2021 ◽  
pp. ds200079
Author(s):  
Timothy S. Bailey ◽  
Pierre Evenou ◽  
Jasvinder Gill ◽  
Paulos Berhanu ◽  
Romain Raymond ◽  
...  
Keyword(s):  
Real Life ◽  
Life Study ◽  
Post Hoc Analysis ◽  
Real Life Study ◽  
Post Hoc ◽  
The Impact

scholarly journals Impact of Cumulative Dose of Carfilzomib in Combination with Lenalidomide and Desamethasone in Relapsed Refractory Myeloma Patients: A Retrospective Real Life Survey of the Sicilian Myeloma Network

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5636-5636
Author(s):  
Concetta Conticello ◽  
Enrica Antonia Martino ◽  
Vittorio Del Fabro ◽  
Giuseppe Sapienza ◽  
Valeria Calafiore ◽  
...  
Keyword(s):  
Adverse Events ◽  
Cumulative Dose ◽  
Overall Response Rate ◽  
Response Rate ◽  
Real Life ◽  
Previous Treatment ◽  
Complete Response ◽  
Overall Response ◽  
Group A ◽  
Group B

Abstract Background: Triplet-based lenalidomide plus dexamethasone (Rd) combinations have become the new standard of care for early relapse and refractory multiple myeloma (RRMM). Carfilzomib is a novel selective proteasome inhibitor (PI) with high efficacy in RRMM. The ASPIRE phase 3 trial showed the superiority of carfilzomib-based triplet (KRd compared to Rd), leading to approval of K for RRMM. However, little is known about safety and efficacy of KRd outside a clinical trial context. Experimental design and aims: In 11 Sicilian Centers belonging to the Sicilian Myeloma Network, from November 2016, when KRd regimen was approved in Italy, to June 2018, 103 consecutive RRMM patients (previous lines 1-10) have received KRd regimen, according to ASPIRE schedule. Lenalidomide dosage was reduced in patients with a low count of platelet and/or renal failure according to manufacturer guidelines. Since previous studies have demonstrated that increased cumulative dose of first generation PI bortezomib significantly improved overall survival of patients treated with VMP regimen, we studied the effect of cumulative dose of Carfilzomib in RRMM patients receiving KRd. Results: Clinical and demographic characteristics of patients included in the study are summarized in Table 1. Median age was 65 years (range 33-86), most patients were males (54%). About half of the patients included in the survey were refractory to previous treatment (54%); Sixty-five (63%) patients received at least 5 cycles of KRd and 38 (36%) received at least 10 cycles. Overall response rate was 34% (35 patients); 18 patients (17%) achieved a complete response (CR), 6 patients minimal response (MR), 13 (12%) patients achieved PR, 16 patients achieved MR and then progressed; progression occurred in 20 patients, among them 3 did not reached any response. Delays due to adverse events were 33%, mainly due to febrile neutropenia (22%), thromboembolic events (4.5%), heart failure (3%), or thrombocytopenia (4.5%). To prevent hematological toxicities, 24% of patients received granulocyte growth factors, 15% erythropoietin. In 30 patients treatment was reduced (mainly due to lenalidomide toxicity) and in 5 patients discontinued for toxicity. Thus, median cumulative carfizomib doses at 2, 3, 4 and 6 cycles were respectively 480 mg (282 mg/m2), 735 mg (435 mg/m2), 995 mg (589 mg/m2) and 1522mg (890 mg/m2). After a median follow up of 16.2 months, PFS at 12 months was 67.3%. We found that median PFS was significantly longer in patients who received at least 480 mg (282 mg/m2) within first two months of treatment compared to those that could not receive full-dose KRd (respectively, undefined vs 11 months p=0.04). To identify patients that could obtain the most advantage by KRd treatment, 65 patients who had received at least six cycles were distinguished in two groups, based on previous treatments. In group A, 27 patients were heavily pretreated (median previous lines 4, range 2-10) and had previously received lenalidomide while 38 patients included in group B were less pretreated (median previous lines 3, range 1-5) and lenalidomide- naïve. We found that group A had lower PFS than group B although duration of PFS from the previous treatment was similar in both groups. Conclusions: In our cohort of patients rate of VGPR or better obtained with KRd combination was high with an overall response rate of 34%, with an acceptable safety profile. It is therefore reasonable that approaches to achieve a higher cumulative dose, such as continuing therapy in responding patients and/or proactive adverse events management, influence efficacy. In addition, it is likely that patients not previously exposed to several lines of treatment including lenalidomide are the best candidate for a favorable outcome with KRd regimen. Disclosures Di Raimondo: Celgene: Honoraria; Takeda: Honoraria, Research Funding.

scholarly journals Impact of a double-layer cementing technique on the homogeneity of cementation and the generation of loose bone cement fragments in tibial unicompartmental knee arthroplasty

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Christian B. Scheele ◽  
Matthias F. Pietschmann ◽  
Christian Schröder ◽  
Christian Suren ◽  
Thomas M. Grupp ◽  
...  
Keyword(s):  
Bone Cement ◽  
Double Layer ◽  
Knee Arthroplasty ◽  
Unicompartmental Knee Arthroplasty ◽  
Cementing Technique ◽  
Mineral Density ◽  
Unicompartmental Knee ◽  
Group A ◽  
Group B ◽  
The Impact

Abstract Background The objective of this study was to evaluate the impact of a single- vs. double-layer cementing technique on morphological cementation and the generation of microscopic cement layers or loose cement fragments in unicompartmental knee arthroplasty (UKA). Methods UKAs were implanted in 12 cadaver knees. The specimens were divided into two groups of comparable bone mineral density. Six UKAs were implanted using a single-layer cementing technique (group A) and six UKAs were implanted using a double-layer cementing technique (group B). Morphological cementation was assessed on nine cuts through the implant–cement–bone interface in the frontal plane. Loose bone cement fragments and the microscopically quality of layer formation were evaluated. Results Contact between bone and prosthesis was observed in 45.4% of interfaces in group A and 27.8% in group B (p = 0.126). The significant increase of areas without visible cement interlocking in the anteroposterior direction in group A (p = 0.005) was not evident in group B (p = 0.262). Penetration around the peg tended to occur more frequently in group B (67.5% vs. 90.6% p = 0.091). Scanning electron microscopy identified no evidence of fissure formations within the bilaminar cement mantle. Free bone cement fragments were documented in 66.7% in both groups with no difference concerning mass (p = 1.0). Conclusions This in-vitro study showed a tendency towards a more homogenous cementation of tibial UKAs using a double-layer cementing technique, although most of the differences did not reach the level of significance. However, theoretical downsides of the double-layer cementing technique such as an increased formation of free bone fragments or a microscopically fissure formation within the cement layer could not be detected either.

scholarly journals The Impact of Seropositivity on Bone Mineral Density in Rheumatoid Arthritis - A 3-year Prospective Observational Study

2021 ◽  
Author(s):  
Shan-Fu Yu ◽  
Jia-Feng Chen ◽  
Ying-Chou Chen ◽  
Yu-Wei Wang ◽  
Chung-Yuan Hsu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Bone Mineral Density ◽  
Bone Loss ◽  
Bone Mineral ◽  
Mineral Density ◽  
Group Iii ◽  
Group I ◽  
Group A ◽  
Group B ◽  
The Impact

Abstract Background:To explore the impact of seropositivity on systemic bone loss in rheumatoid arthritis (RA).Methods:This was an interim analysis of the RA registry. Clinical characteristics in the registry were documented, and bone mineral density (BMD) was measured; this was repeated 3 years later. Participants were grouped into seropositive (SPRA) and seronegative (SNRA) based on the presence or absence of rheumatoid factor (RF) and/or anti-cyclic citrullinated peptide antibodies (ACPA). After matching (1:2) for age and sex, SNRA and SPRA were regrouped into A and B. To elucidate the impact of number of antibodies on BMD changes, the matched group was sub-divided according to the number of antibodies present (0, group I; 1, group II; 2, group III). The changes in BMD were compared for each group at baseline and 3 years later. Results:A total of 477 participants who completed a 3-year observation period were included. After matching, 312 participants were enrolled (group A, 104; group B, 208). Three years later, group B had significant bone loss in the femoral neck (FN) (p <0.001), total hip (TH) (p = 0.001), and 1st–4th lumbar vertebrae (L1–4) (p = 0.006), while group A has bone loss only at FN (p = 0.002). Groups I, II, and III included 104, 52, and 156 participants, respectively. Significant bone loss was recorded at FN (p = 0.002) in group I, FN (p <0.001) in group II, and FN (p <0.001), TH (p = 0.002), and L1–4 (p = 0.016) in group III. In terms of percent change in BMD (△BMD%), more significantly negative changes were found at TH in group B (p = 0.027) and within groups I-III (p for trend = 0.021). Logistic regression showed that seropositivity is a significant predictor of △BMD≧–5% at TH (odds ratio 1.85, 95% confidence interval 1.03-3.33, p = 0.039).Conclusions:SPRA lost more bone than SNRA after 3 years. More attention should be paid to SPRA patients, especially those with double-positive antibodies, with vigorous evaluation of BMD and fracture risk.

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