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Article ; Online: Early nucleolar responses differentiate mechanisms of cell death induced by oxaliplatin and cisplatin.

Sutton, Emily C / DeRose, Victoria J

2021 Volume 296, Page(s) 100633

Abstract: Recent reports provide evidence that the platinum chemotherapeutic oxaliplatin causes cell death via ribosome biogenesis stress, while cisplatin causes cell death via the DNA damage response (DDR). Underlying differences in mechanisms that might initiate ...

Abstract	Recent reports provide evidence that the platinum chemotherapeutic oxaliplatin causes cell death via ribosome biogenesis stress, while cisplatin causes cell death via the DNA damage response (DDR). Underlying differences in mechanisms that might initiate disparate routes to cell death by these two broadly used platinum compounds have not yet been carefully explored. Additionally, prior studies had demonstrated that cisplatin can also inhibit ribosome biogenesis. Therefore, we sought to directly compare the initial influences of oxaliplatin and cisplatin on nucleolar processes and on the DDR. Using pulse-chase experiments, we found that at equivalent doses, oxaliplatin but not cisplatin significantly inhibited ribosomal RNA (rRNA) synthesis by Pol I, but neither compound affected rRNA processing. Inhibition of rRNA synthesis occurred as early as 90 min after oxaliplatin treatment in A549 cells, concurrent with the initial redistribution of the nucleolar protein nucleophosmin (NPM1). We observed that the nucleolar protein fibrillarin began to redistribute by 6 h after oxaliplatin treatment and formed canonical nucleolar caps by 24 h. In cisplatin-treated cells, DNA damage, as measured by γH2AX immunofluorescence, was more extensive, whereas nucleolar organization was unaffected. Taken together, our results demonstrate that oxaliplatin causes early nucleolar disruption via inhibition of rRNA synthesis accompanied by NPM1 relocalization and subsequently causes extensive nucleolar reorganization, while cisplatin causes early DNA damage without significant nucleolar disruption. These data support a model in which, at clinically relevant doses, cisplatin kills cells via the canonical DDR, and oxaliplatin kills cells via ribosome biogenesis stress, specifically via rapid inhibition of rRNA synthesis.
MeSH term(s)	A549 Cells ; Adenocarcinoma of Lung/drug therapy ; Adenocarcinoma of Lung/metabolism ; Adenocarcinoma of Lung/pathology ; Antineoplastic Combined Chemotherapy Protocols/pharmacology ; Cell Death ; Cell Nucleolus/drug effects ; Cell Nucleolus/metabolism ; Cell Nucleolus/pathology ; Cisplatin/administration & dosage ; DNA Damage ; Humans ; Lung Neoplasms/drug therapy ; Lung Neoplasms/metabolism ; Lung Neoplasms/pathology ; Nuclear Proteins/genetics ; Nuclear Proteins/metabolism ; Oxaliplatin/administration & dosage ; Ribosomes/drug effects ; Ribosomes/metabolism
Chemical Substances	Nuclear Proteins ; Oxaliplatin (04ZR38536J) ; nucleophosmin (117896-08-9) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2021-04-03
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	2997-x
ISSN	1083-351X ; 0021-9258
ISSN (online)	1083-351X
ISSN	0021-9258
DOI	10.1016/j.jbc.2021.100633
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Article ; Online: Early infection risk in patients with systemic lupus erythematosus treated with rituximab or belimumab from the British Isles Lupus Assessment Group Biologics Register (BILAG-BR): a prospective longitudinal study.

Rodziewicz, Mia / Dyball, Sarah / Lunt, Mark / McDonald, Stephen / Sutton, Emily / Parker, Ben / Bruce, Ian N

The Lancet. Rheumatology

2023 Volume 5, Issue 5, Page(s) e284–e292

Abstract: Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE ... ...

Abstract	Background: Patients with systemic lupus erythematosus (SLE) are at an increased risk of infection relative to the general population. We aimed to describe the frequency and risk factors for serious infections in patients with moderate-to-severe SLE treated with rituximab, belimumab, and standard of care therapies in a large national observational cohort. Methods: The British Isles Lupus Assessment Group Biologics Register (BILAG-BR) is a UK-based prospective register of patients with SLE. Patients were recruited by their treating physician as part of their scheduled care from 64 centres across the UK by use of a standardised case report form. Inclusion criteria for the BILAG-BR included age older than 5 years, ability to provide informed consent, a diagnosis of SLE, and starting a new biological therapy within the last 12 months or a new standard of care drug within the last month. The primary outcome for this study was the rate of serious infections within the first 12 months of therapy. Serious infections were defined as those requiring intravenous antibiotic treatment, hospital admission, or resulting in morbidity or death. Infection and mortality data were collected from study centres and further mortality data were collected from the UK Office for National Statistics. The relationship between serious infection and drug type was analysed using a multiple-failure Cox proportional hazards model. Findings: Between July 1, 2010, and Feb 23, 2021, 1383 individuals were recruited to the BILAG-BR. 335 patients were excluded from this analysis. The remaining 1048 participants contributed 1002·7 person-years of follow-up and included 746 (71%) participants on rituximab, 119 (11%) participants on belimumab, and 183 (17%) participants on standard of care. The median age of the cohort was 39 years (IQR 30-50), 942 (90%) of 1048 patients were women and 106 (10%) were men. Of the patients with available ethnicity data, 514 (56%) of 911 were White, 169 (19%) were Asian, 161 (18%) were Black, and 67 (7%) were of multiple-mixed or other ethnic backgrounds. 118 serious infections occurred in 76 individuals during the 12-month study period, which included 92 serious infections in 58 individuals on rituximab, eight serious infections in five individuals receiving belimumab, and 18 serious infections in 13 individuals on standard of care. The overall crude incidence rate of serious infection was 117·7 (95% CI 98·3-141·0) per 1000 person-years. Compared with standard of care, the serious infection risk was similar in the rituximab (adjusted hazard ratio [HR] 1·68 [0·60-4·68]) and belimumab groups (1·01 [0·21-4·80]). Across the whole cohort in multivariate analysis, serious infection risk was associated with prednisolone dose (>10 mg; 2·38 [95%CI 1·47-3·84]), hypogammaglobulinaemia (<6 g/L; 2·16 [1·38-3·37]), and multimorbidity (1·45 [1·17-1·80]). Additional concomitant immunosuppressive use appeared to be associated with a reduced risk (0·60 [0·41-0·90]). We found no significant safety signals regarding atypical infections. Six infection-related deaths occurred at a median of 121 days (IQR 60-151) days from cohort entry. Interpretation: In patients with moderate-to-severe SLE, rituximab, belimumab, and standard immunosuppressive therapy have similar serious infection risks. Key risk factors for serious infections included multimorbidity, hypogammaglobulinaemia, and increased glucocorticoid doses. When considering the risk of serious infection, we propose that immunosupppressives, rituximab, and belimumab should be prioritised as mainstay therapies to optimise SLE management and support proactive minimisation of glucocorticoid use. Funding: None.
MeSH term(s)	Adult ; Child, Preschool ; Female ; Humans ; Male ; Middle Aged ; Agammaglobulinemia ; Antibodies, Monoclonal, Humanized ; Biological Products ; Glucocorticoids ; Immunosuppressive Agents/adverse effects ; Longitudinal Studies ; Lupus Erythematosus, Systemic/complications ; Rituximab/adverse effects ; Prospective Studies
Chemical Substances	Antibodies, Monoclonal, Humanized ; belimumab (73B0K5S26A) ; Biological Products ; Glucocorticoids ; Immunosuppressive Agents ; Rituximab (4F4X42SYQ6)
Language	English
Publishing date	2023-05-08
Publishing country	England
Document type	Journal Article
ISSN	2665-9913
ISSN (online)	2665-9913
DOI	10.1016/S2665-9913(23)00091-7
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Article ; Online: Deconvolution of whole blood transcriptomics identifies changes in immune cell composition in patients with systemic lupus erythematosus (SLE) treated with mycophenolate mofetil.

Akthar, Mumina / Nair, Nisha / Carter, Lucy M / Vital, Edward M / Sutton, Emily / McHugh, Neil / Bruce, Ian N / Reynolds, John A

Arthritis research & therapy

2023 Volume 25, Issue 1, Page(s) 111

Abstract: Background: Systemic lupus erythematosus (SLE) is a clinically and biologically heterogeneous autoimmune disease. We explored whether the deconvolution of whole blood transcriptomic data could identify differences in predicted immune cell frequency ... ...

Abstract	Background: Systemic lupus erythematosus (SLE) is a clinically and biologically heterogeneous autoimmune disease. We explored whether the deconvolution of whole blood transcriptomic data could identify differences in predicted immune cell frequency between active SLE patients, and whether these differences are associated with clinical features and/or medication use. Methods: Patients with active SLE (BILAG-2004 Index) enrolled in the BILAG-Biologics Registry (BILAG-BR), prior to change in therapy, were studied as part of the MASTERPLANS Stratified Medicine consortium. Whole blood RNA-sequencing (RNA-seq) was conducted at enrolment into the registry. Data were deconvoluted using CIBERSORTx. Predicted immune cell frequencies were compared between active and inactive disease in the nine BILAG-2004 domains and according to immunosuppressant use (current and past). Results: Predicted cell frequency varied between 109 patients. Patients currently, or previously, exposed to mycophenolate mofetil (MMF) had fewer inactivated macrophages (0.435% vs 1.391%, p = 0.001), naïve CD4 T cells (0.961% vs 2.251%, p = 0.002), and regulatory T cells (1.858% vs 3.574%, p = 0.007), as well as a higher proportion of memory activated CD4 T cells (1.826% vs 1.113%, p = 0.015), compared to patients never exposed to MMF. These differences remained statistically significant after adjusting for age, gender, ethnicity, disease duration, renal disease, and corticosteroid use. There were 2607 differentially expressed genes (DEGs) in patients exposed to MMF with over-representation of pathways relating to eosinophil function and erythrocyte development and function. Within CD4 + T cells, there were fewer predicted DEGs related to MMF exposure. No significant differences were observed for the other conventional immunosuppressants nor between patients according disease activity in any of the nine organ domains. Conclusion: MMF has a significant and persisting effect on the whole blood transcriptomic signature in patients with SLE. This highlights the need to adequately adjust for background medication use in future studies using whole blood transcriptomics.
MeSH term(s)	Humans ; Mycophenolic Acid/therapeutic use ; Transcriptome ; Gene Expression Profiling ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/genetics ; Autoimmune Diseases ; Immunosuppressive Agents/therapeutic use
Chemical Substances	Mycophenolic Acid (HU9DX48N0T) ; Immunosuppressive Agents
Language	English
Publishing date	2023-06-30
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-023-03089-5
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Article ; Online: Correction: Deconvolution of whole blood transcriptomics identifies changes in immune cell composition in patients with systemic lupus erythematosus (SLE) treated with mycophenolate mofetil.

Akthar, Mumina / Nair, Nisha / Carter, Lucy M / Vital, Edward M / Sutton, Emily / McHugh, Neil / Bruce, Ian N / Reynolds, John A

Arthritis research & therapy

2023 Volume 25, Issue 1, Page(s) 160

Language	English
Publishing date	2023-09-04
Publishing country	England
Document type	Published Erratum
ZDB-ID	2107602-9
ISSN	1478-6362 ; 1478-6354
ISSN (online)	1478-6362
ISSN	1478-6354
DOI	10.1186/s13075-023-03160-1
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Article: Lupus clinical trial eligibility in a real-world setting: results from the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR).

Dyball, Sarah / Collinson, Sophie / Sutton, Emily / McCarthy, Eoghan M / Bruce, Ian N / Parker, Ben

Lupus science & medicine

2021 Volume 8, Issue 1

Abstract: Objective: To quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort.: Methods: Literature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical ... ...

Abstract	Objective: To quantify how well phase III randomised clinical trials in both SLE and lupus nephritis (LN) represents a real-world SLE cohort. Methods: Literature reviews were performed of major published phase III SLE (n=12) and LN (n=6) clinical trials (ClinicalTrials.gov). Inclusion and exclusion criteria common across these trials were collated for non-renal SLE or LN trials, and applied to patients recruited to the British Isles Lupus Assessment Group-Biologics Register (BILAG-BR) starting either biological or standard-of-care (SOC) therapies. Results: We recruited 837 patients to the BILAG-BR from September 2010 to June 2018, starting either SOC (n=125, 15%) or a biological medication (n=712, 85%). Active LN, defined as a BILAG A in the renal domain occurred in 20% (n=166). Overall, 530 (63%) patients were ineligible to participate in non-renal SLE clinical trials and 72 (43%) patients with active LN would be ineligible for LN trials. The most common reasons for ineligibility from the non-renal lupus trials included active renal involvement (n=166, 20%) and low disease activity (n=114, 15%). For LN trials, the most common exclusion met was pre-existing renal impairment (n=15, 9%). Patients with fewer comorbidities were more likely to be eligible to participate in non-renal SLE trials. Conclusions: In this national register of patients with moderate-to-severe SLE, nearly two-thirds would not be eligible for recruitment to key SLE clinical trials nor would almost half of those with active LN. Eligibility criteria may excessively constrain enrolment and thus, how we can generalise trial results in a real-world setting.
MeSH term(s)	Biological Products ; Clinical Trials as Topic ; Cohort Studies ; Humans ; Kidney ; Lupus Nephritis/diagnosis ; United Kingdom/epidemiology
Chemical Substances	Biological Products
Language	English
Publishing date	2021-07-23
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2779620-6
ISSN	2053-8790
ISSN	2053-8790
DOI	10.1136/lupus-2021-000513
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Article ; Online: Time-Dependent Studies of Oxaliplatin and Other Nucleolar Stress-Inducing Pt(II) Derivatives.

Pigg, Hannah C / Yglesias, Matthew V / Sutton, Emily C / McDevitt, Christine E / Shaw, Michael / DeRose, Victoria J

ACS chemical biology

2022 Volume 17, Issue 8, Page(s) 2262–2271

Abstract: The properties of small molecule Pt(II) compounds that drive specific cellular responses are of interest due to their broad clinical use as chemotherapeutics as well as to provide a better mechanistic understanding of bioinorganic processes. The ... ...

Abstract	The properties of small molecule Pt(II) compounds that drive specific cellular responses are of interest due to their broad clinical use as chemotherapeutics as well as to provide a better mechanistic understanding of bioinorganic processes. The chemotherapeutic compound cisplatin causes cell death through DNA damage, while oxaliplatin may induce cell death through inhibition of ribosome biogenesis, also referred to as nucleolar stress induction. Previous work has found a subset of oxaliplatin derivatives that cause nucleolar stress at 24 h drug treatment. Here we report that these different Pt(II) derivatives exhibit a range of rates and degrees of global nucleolar stress induction as well as inhibition of rRNA transcription. Potential explanations for these variations include both the ring size and stereochemistry of the non-aquation-labile ligand. We observe that Pt(II) compounds containing a 6-membered ring show faster onset and a higher overall degree of nucleolar stress than those containing a 5-membered ring, and that compounds having the 1
MeSH term(s)	Antineoplastic Agents/chemistry ; Cisplatin/pharmacology ; DNA Damage ; Organoplatinum Compounds/pharmacology ; Oxaliplatin/pharmacology
Chemical Substances	Antineoplastic Agents ; Organoplatinum Compounds ; Oxaliplatin (04ZR38536J) ; Cisplatin (Q20Q21Q62J)
Language	English
Publishing date	2022-08-02
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S. ; Research Support, N.I.H., Extramural
ISSN	1554-8937
ISSN (online)	1554-8937
DOI	10.1021/acschembio.2c00399
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Book: Der Weihnachtsbaum

Birkenstädt, Sophie / Huddy, Delia / Sutton, Emily

2015

Title translation	The Christmas Eve tree <dt.>
Author's details	Delia Huddy. Mit Ill. von Emily Sutton. Aus dem Engl. von Sophie Birkenstädt
Keywords	Junge ; Tanne ; Weihnachtsbaum ; Obdachlosigkeit ; Kleinheit
Language	German
Size	[17] Bl, überw. Ill
Edition	1. Aufl.
Publisher	Aladin-Verl
Publishing place	Hamburg
Document type	Book
ISBN	9783848901005 ; 3848901005
Database	Former special subject collection: coastal and deep sea fishing

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Article ; Online: Gene Expression and Autoantibody Analysis Revealing Distinct Ancestry-Specific Profiles Associated With Response to Rituximab in Refractory Systemic Lupus Erythematosus.

Carter, Lucy M / Alase, Adewonuola / Wigston, Zoe / Psarras, Antonios / Burska, Agata / Sutton, Emily / Yusof, Md Yuzaiful Md / Reynolds, John A / McHugh, Neil / Emery, Paul / Wittmann, Miriam / Bruce, Ian N / Vital, Edward M

Arthritis & rheumatology (Hoboken, N.J.)

2023 Volume 75, Issue 5, Page(s) 697–710

Abstract: Objective: Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort ... ...

Abstract	Objective: Gene expression profiles are associated with the clinical heterogeneity of systemic lupus erythematosus (SLE) but are not well studied as biomarkers for therapy. We studied gene expression and response to rituximab in a multiethnic UK cohort who were refractory to standard therapy. Methods: We evaluated baseline expression levels of transcripts known to associate with clinical features of SLE using a 96-probe TaqMan array and whole blood samples from 213 patients with active SLE who had been prospectively enrolled in the British Isles Lupus Assessment Group (BILAG) Biologics Register. We measured autoantibodies using immunoprecipitation and enzyme-linked immunosorbent assays. We determined responses to first-cycle rituximab at 6 months from treatment start in 110 SLE patients by assessing BILAG 2004 disease activity. Results: Interferon gene expression scores were lower in patients of European ancestry than in all other ancestry groups. The relationship between blood interferon gene expression scores and scores annotated to plasmablasts, neutrophils, myeloid lineage, inflammation, and erythropoiesis differed between patients of European and non-European ancestries. Hierarchical clustering revealed 3 distinct non-European ancestry patient subsets with stratified responses to rituximab that were not explained by sociodemographic and clinical variables, with responses lowest in an interferon-low, neutrophil-high cluster and highest in a cluster with high expression levels across all signatures (P < 0.001). Clusters in European ancestry patients did not predict response to rituximab but segregated patients by global disease activity and renal involvement. In both ancestral groups, interferon-high clusters were associated with U1 RNP/Sm antibodies. Conclusion: Ancestry appears central to the immunologic and clinical heterogeneity in SLE. These results suggest that ancestry, disease activity, and transcriptional signatures could each assist in predicting the effectiveness of B cell depletion therapies.
MeSH term(s)	Humans ; Rituximab/therapeutic use ; Autoantibodies ; B-Lymphocytes ; Treatment Outcome ; Lupus Erythematosus, Systemic/drug therapy ; Lupus Erythematosus, Systemic/genetics ; Antibodies, Antinuclear ; Interferons ; Gene Expression
Chemical Substances	Rituximab (4F4X42SYQ6) ; Autoantibodies ; Antibodies, Antinuclear ; Interferons (9008-11-1)
Language	English
Publishing date	2023-03-22
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2756371-6
ISSN	2326-5205 ; 2326-5191
ISSN (online)	2326-5205
ISSN	2326-5191
DOI	10.1002/art.42404
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Article ; Online: Denosumab, a RANK ligand inhibitor, for postmenopausal women with osteoporosis.

Sutton, Emily E / Riche, Daniel M

The Annals of pharmacotherapy

2012 Volume 46, Issue 7-8, Page(s) 1000–1009

Abstract: Objective: To review the evidence for use of denosumab for the treatment of postmenopausal osteoporosis.: Data sources: A search of MEDLINE and EMBASE databases was conducted during January 2012, using the terms denosumab and osteoporosis, with index ...

Abstract	Objective: To review the evidence for use of denosumab for the treatment of postmenopausal osteoporosis. Data sources: A search of MEDLINE and EMBASE databases was conducted during January 2012, using the terms denosumab and osteoporosis, with index dates of 2000 to 2011. Additional information was gathered from Amgen and references cited in articles retrieved. Study selection and data extraction: English-language articles including clinical trials involving denosumab for treatment of osteoporosis and review articles were reviewed. Articles using denosumab in males or as treatment for conditions other than osteoporosis or osteopenia were excluded. Data synthesis: Many clinical trials have supported the safety and efficacy of denosumab in postmenopausal women with bone loss. It has been shown to improve bone mineral density, decrease markers of bone turnover, and prevent new vertebral fractures. It shows improvement over placebo in studies and has at least similar efficacy to alendronate in measurements of bone mineral density, with less risk for osteonecrosis of the jaw and atypical fracture, but with an increased risk of infections and neoplasms. European cost-effectiveness studies have also demonstrated that denosumab is a cost-effective choice compared to risedronate and no treatment for fracture prevention for postmenopausal women with osteoporosis. Conclusions: Denosumab has demonstrated efficacy and safety as a first-line treatment for postmenopausal osteoporosis in multiple clinical trials over at least 6 years. It may be most cost-effective for women who are unable or refuse to take bisphosphonate drugs.
MeSH term(s)	Antibodies, Monoclonal, Humanized/economics ; Antibodies, Monoclonal, Humanized/pharmacology ; Antibodies, Monoclonal, Humanized/therapeutic use ; Cost-Benefit Analysis ; Denosumab ; Female ; Humans ; Osteoporosis, Postmenopausal/drug therapy ; RANK Ligand/antagonists & inhibitors
Chemical Substances	Antibodies, Monoclonal, Humanized ; RANK Ligand ; Denosumab (4EQZ6YO2HI)
Language	English
Publishing date	2012-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1101370-9
ISSN	1542-6270 ; 1060-0280
ISSN (online)	1542-6270
ISSN	1060-0280
DOI	10.1345/aph.1Q543
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Article ; Online: Osteoporosis in men: epidemiology and treatment with denosumab.

Sidlauskas, Kristel M / Sutton, Emily E / Biddle, Michael A

Clinical interventions in aging

2014 Volume 9, Page(s) 593–601

Abstract: Osteoporosis is a major public health care concern. Although often described as a disease affecting postmenopausal women, researchers and clinicians have emphasized its prevalence in men in recent years. The National Osteoporosis Foundation has stated ... ...

Abstract	Osteoporosis is a major public health care concern. Although often described as a disease affecting postmenopausal women, researchers and clinicians have emphasized its prevalence in men in recent years. The National Osteoporosis Foundation has stated that up to 25% of men over the age of 50 years will experience a fracture due to osteoporosis. Men who suffer from a major fracture have higher mortality rates than women. Pharmacologic therapy options for treating osteoporosis are limited for men as compared with women, so each medication approved for use in this population represents an important clinical option. In September 2012, the US Food and Drug Administration approved a new indication for denosumab to increase bone mass in men with osteoporosis at high risk for fracture. Denosumab is a fully human monoclonal antibody and novel antiresorptive agent that works by binding receptor activator of nuclear factor kappa-β ligand (RANKL) and inhibiting the signaling cascade that causes osteoclast maturation, activity, and survival. Ultimately, denosumab suppresses bone turnover and increases bone mineral density in both trabecular and cortical bone. Approval for treating osteoporosis in men was based on data from the ADAMO trial which displayed efficacy in increasing bone mineral density at the lumbar spine, total hip, femoral neck, hip trochanter, and one-third radius. Studies indicate that denosumab is effective and safe, and has superior adherence rates and patient satisfaction. Although long-term data and further research on fracture reduction rates in men should be explored, at this time denosumab is one of several appropriate first-line treatment options for men with osteoporosis.
MeSH term(s)	Absorptiometry, Photon ; Antibodies, Monoclonal, Humanized/therapeutic use ; Bone Density/drug effects ; Bone Density Conservation Agents/therapeutic use ; Denosumab ; Humans ; Male ; Osteoporosis/diagnosis ; Osteoporosis/drug therapy ; Osteoporosis/epidemiology ; Osteoporosis/etiology ; Risk Factors
Chemical Substances	Antibodies, Monoclonal, Humanized ; Bone Density Conservation Agents ; Denosumab (4EQZ6YO2HI)
Language	English
Publishing date	2014-04-08
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2364924-0
ISSN	1178-1998 ; 1176-9092
ISSN (online)	1178-1998
ISSN	1176-9092
DOI	10.2147/CIA.S51940
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