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Article ; Online: Romosozumab in the treatment of osteoporosis.

Kobza, Alexandra O / Papaioannou, Alexandra / Lau, Arthur N / Adachi, Jonathan D

2020 Volume 12, Issue 13, Page(s) 965–981

Abstract: Osteoporosis is a disease characterized by weakening of the bone architecture, which leads to an increased risk of fracture. There has been interest in the development of osteoanabolic agents that can increase bone mass and reverse the deteriorating ... ...

Abstract	Osteoporosis is a disease characterized by weakening of the bone architecture, which leads to an increased risk of fracture. There has been interest in the development of osteoanabolic agents that can increase bone mass and reverse the deteriorating architecture of osteoporotic bone. Romosozumab is a new agent for osteoporosis that both promotes bone formation and inhibits bone resorption. It is a monoclonal antibody that inhibits the activity of sclerostin, which allows the Wnt pathway to promote osteoblastogenesis and inhibit the activity of bone-resorbing osteoclasts. In clinical trials, it has proven to be superior to other agents in terms of increasing bone mineral density and reducing the incidence of fractures. This review will highlight the pharmacology, clinical efficacy and safety profile of romosozumab and suggest where this medication may fit within our current management of osteoporosis.
MeSH term(s)	Antibodies, Monoclonal/therapeutic use ; Bone Density/drug effects ; Humans ; Osteoporosis/drug therapy ; Treatment Outcome
Chemical Substances	Antibodies, Monoclonal ; romosozumab (3VHF2ZD92J)
Language	English
Publishing date	2020-08-05
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	2495964-9
ISSN	1750-7448 ; 1750-743X
ISSN (online)	1750-7448
ISSN	1750-743X
DOI	10.2217/imt-2020-0158
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Article: Understanding and Managing Corticosteroid-Induced Osteoporosis.

Kobza, Alexandra O / Herman, Deena / Papaioannou, Alexandra / Lau, Arthur N / Adachi, Jonathan D

Open access rheumatology : research and reviews

2021 Volume 13, Page(s) 177–190

Abstract: Glucocorticoids are effective immunosuppressants used in a wide variety of diseases. Their use results in secondary osteoporosis in about 30-50% of chronic glucocorticoid users. Glucocorticoids cause a rapid decline in bone strength within the first 3-6 ... ...

Abstract	Glucocorticoids are effective immunosuppressants used in a wide variety of diseases. Their use results in secondary osteoporosis in about 30-50% of chronic glucocorticoid users. Glucocorticoids cause a rapid decline in bone strength within the first 3-6 months mostly due to increased bone resorption by osteoclasts. This is followed by a more gradual loss of bone partly due to decreased osteoblastogenesis and osteoblast and osteocyte apoptosis. The loss of bone strength induced by glucocorticoids is not fully captured by bone mineral density measurements. Other tools such as the trabecular bone score and advanced imaging techniques give insight into bone quality; however, these are not used widely in clinical practice. Glucocorticoid-induced osteoporosis should be seen as a widely preventable disease. Currently, only about 15% of chronic glucocorticoid users are receiving optimal care. Glucocorticoids should be prescribed at the lowest dose and shortest duration. All patients should be counselled on lifestyle measures to maintain bone strength including nutrition and weight-bearing exercise. Pharmacological therapy should be considered for all patients at moderate to high risk of fracture as there is evidence for the prevention of bone loss and fractures with a favourable safety profile. Oral bisphosphonates are the current mainstay of therapy, whereas osteoanabolic agents may be considered for those at highest risk of fracture.
Language	English
Publishing date	2021-07-02
Publishing country	New Zealand
Document type	Journal Article ; Review
ZDB-ID	2508169-X
ISSN	1179-156X
ISSN	1179-156X
DOI	10.2147/OARRR.S282606
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Article ; Online: Dipeptidase-1 governs renal inflammation during ischemia reperfusion injury.

Lau, Arthur / Rahn, Jennifer J / Chappellaz, Mona / Chung, Hyunjae / Benediktsson, Hallgrimur / Bihan, Dominique / von Mässenhausen, Anne / Linkermann, Andreas / Jenne, Craig N / Robbins, Stephen M / Senger, Donna L / Lewis, Ian A / Chun, Justin / Muruve, Daniel A

Science advances

2022 Volume 8, Issue 5, Page(s) eabm0142

Abstract: The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia ... ...

Abstract	The mechanisms that drive leukocyte recruitment to the kidney are incompletely understood. Dipeptidase-1 (DPEP1) is a major neutrophil adhesion receptor highly expressed on proximal tubular cells and peritubular capillaries of the kidney. Renal ischemia reperfusion injury (IRI) induces robust neutrophil and monocyte recruitment and causes acute kidney injury (AKI). Renal inflammation and the AKI phenotype were attenuated in
MeSH term(s)	Acute Kidney Injury/etiology ; Animals ; Dipeptidases/metabolism ; Female ; GPI-Linked Proteins/metabolism ; Humans ; Inflammation/complications ; Male ; Mice ; Mice, Inbred C57BL ; Reperfusion Injury
Chemical Substances	GPI-Linked Proteins ; Dipeptidases (EC 3.4.13.-) ; dipeptidase (EC 3.4.13.18) ; dipeptidase 1 (EC 3.4.13.19)
Language	English
Publishing date	2022-02-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2810933-8
ISSN	2375-2548 ; 2375-2548
ISSN (online)	2375-2548
ISSN	2375-2548
DOI	10.1126/sciadv.abm0142
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Article: Evaluation of the Fracture Liaison Service within the Canadian Healthcare Setting.

Wong-Pack, Matthew / Naqvi, Nawazish / Ioannidis, George / Khalil, Ramy / Papaioannou, Alexandra / Adachi, Jonathan / Lau, Arthur N

Journal of osteoporosis

2020 Volume 2020, Page(s) 6742604

Abstract: Previous studies evaluating fracture liaison service (FLS) programs have found them to be cost-effective, efficient, and reduce the risk of fracture. However, few studies have evaluated the clinical effectiveness of these programs. We compared the ... ...

Abstract	Previous studies evaluating fracture liaison service (FLS) programs have found them to be cost-effective, efficient, and reduce the risk of fracture. However, few studies have evaluated the clinical effectiveness of these programs. We compared the patient populations of those referred for osteoporosis management by FLS to those referred by primary care physicians (PCP), within the Canadian healthcare system in the province of Ontario. Specifically, we investigated if a referral from FLS is similarly effective as PCP at identifying patients at risk for future osteoporotic fractures and if osteoporosis therapies have been previously initiated. A retrospective chart review of patients assessed by a single Ontario rheumatology practice affiliated with FLS between January 1, 2014, and December 31, 2017, was performed identifying two groups: those referred by FLS within Hamilton and those referred by their PCP for osteoporosis management. Fracture risk of each patient was determined using FRAX. A total of 573 patients (
Language	English
Publishing date	2020-03-21
Publishing country	United States
Document type	Journal Article
ISSN	2090-8059
ISSN	2090-8059
DOI	10.1155/2020/6742604
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Article: The Tissue-Selective Estrogen Complex: A Review of Current Evidence.

Pazhekattu, Rinu / Lau, Arthur N / Adachi, Jonathan D

Rheumatology and therapy

2015 Volume 2, Issue 1, Page(s) 47–58

Abstract: The tissue-selective estrogen complex (TSEC) has recently entered the market for the treatment of postmenopausal osteoporosis, and is particularly targeted to women with significant vasomotor symptoms. This review appraises the evidence behind the only ... ...

Abstract	The tissue-selective estrogen complex (TSEC) has recently entered the market for the treatment of postmenopausal osteoporosis, and is particularly targeted to women with significant vasomotor symptoms. This review appraises the evidence behind the only approved TSEC to-date, a combination of bazedoxifene and conjugated estrogens, with regards to its efficacy and relevant safety concerns. The majority of evidence that has led to its approval is derived from the SMART study. This large phase III trial with several substudies was aimed at discerning the effects of the TSEC on various estrogen-responsive tissues in comparison to raloxifene and placebo. Overall, the evidence thus far suggests a superior improvement in lumbar bone mineral density of 1.01% ± 0.28% as well as decrease in the frequency of hot flushes. Regarding safety concerns, endometrial thickness did not change over the treatment course, and investigators also identified a modest reduction in breast density. While there was no difference in rates of venous thromboembolism between treatment and placebo groups in a 2-year follow-up period, the effects of the drug on coagulation profiles are similar to those seen with hormone replacement therapy. Thus, the drug's effects on venous thromboembolism risk over a longer treatment course remain unclear. In conclusion, the actual efficacy of the TSEC for postmenopausal osteoporosis remains as yet undefined, given the lack of fracture prevention data. The evidence thus far does seem to suggest a beneficial effect on vasomotor symptoms and a generally favorable side effect profile. However, it should be noted that only one study has addressed this question thus far, and so the repeatability of the findings is still in question.
Language	English
Publishing date	2015-05-20
Publishing country	England
Document type	Review ; Journal Article
ZDB-ID	2783278-8
ISSN	2198-6584 ; 2198-6576
ISSN (online)	2198-6584
ISSN	2198-6576
DOI	10.1007/s40744-015-0013-z
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Article ; Online: Evaluation of the Fracture Liaison Service within the Canadian Healthcare Setting

Matthew Wong-Pack / Nawazish Naqvi / George Ioannidis / Ramy Khalil / Alexandra Papaioannou / Jonathan Adachi / Arthur N. Lau

Journal of Osteoporosis, Vol

2020 Volume 2020

Abstract: ... of each patient was determined using FRAX. A total of 573 patients (n = 225 (FLS group) and n = 227 (PCP group ...

Abstract	Previous studies evaluating fracture liaison service (FLS) programs have found them to be cost-effective, efficient, and reduce the risk of fracture. However, few studies have evaluated the clinical effectiveness of these programs. We compared the patient populations of those referred for osteoporosis management by FLS to those referred by primary care physicians (PCP), within the Canadian healthcare system in the province of Ontario. Specifically, we investigated if a referral from FLS is similarly effective as PCP at identifying patients at risk for future osteoporotic fractures and if osteoporosis therapies have been previously initiated. A retrospective chart review of patients assessed by a single Ontario rheumatology practice affiliated with FLS between January 1, 2014, and December 31, 2017, was performed identifying two groups: those referred by FLS within Hamilton and those referred by their PCP for osteoporosis management. Fracture risk of each patient was determined using FRAX. A total of 573 patients (n = 225 (FLS group) and n = 227 (PCP group)) were evaluated. Between the FLS and PCP groups, there were no significant differences in the absolute 10-year risk of a major osteoporotic fracture (15.6% (SD = 10.2) vs 15.3% (SD = 10.3)) and 10-year risk of hip fracture (4.7% (SD = 8.3) vs 4.7% (SD = 6.8)), respectively. 10.7% of patients referred by FLS and 40.5% of patients referred by their PCP were on osteoporosis medication prior to fracture. Our study suggests that referral from FLS is similarly effective as PCP at identifying patients at risk for future osteoporotic fractures, and clinically effective at identifying the care gap with the previous use of targeted osteoporosis therapies from referral from PCP being low and much lower in those referred by FLS. Interventional programs such as FLS can help close the treatment gap by providing appropriate care to patients that were not previously identified to be at risk for fracture by their primary care physician and initiate proper medical management.
Keywords	Medicine ; R
Subject code	610
Language	English
Publishing date	2020-01-01T00:00:00Z
Publisher	Hindawi Limited
Document type	Article ; Online
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Article: Resolution of osteonecrosis of the jaw after teriparatide [recombinant human PTH-(1-34)] therapy.

Lau, Arthur N / Adachi, Jonathan D

The Journal of rheumatology

2009 Volume 36, Issue 8, Page(s) 1835–1837

MeSH term(s)	Bone Density Conservation Agents/adverse effects ; Female ; Humans ; Jaw Diseases/chemically induced ; Jaw Diseases/diagnostic imaging ; Jaw Diseases/surgery ; Middle Aged ; Osteonecrosis/chemically induced ; Osteonecrosis/diagnostic imaging ; Osteonecrosis/surgery ; Osteoporosis, Postmenopausal/drug therapy ; Radiography ; Teriparatide/adverse effects
Chemical Substances	Bone Density Conservation Agents ; Teriparatide (10T9CSU89I)
Language	English
Publishing date	2009-08
Publishing country	Canada
Document type	Case Reports ; Letter
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.081176
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Article ; Online: Role of teriparatide in treatment of glucocorticoid-induced osteoporosis.

Lau, Arthur N / Adachi, Jonathan D

Therapeutics and clinical risk management

2010 Volume 6, Page(s) 497–503

Abstract: Glucocorticoids are commonly used in various fields within medicine. One of their most common and clinically significant side effects is glucocorticoid-induced osteoporosis (GIOP). GIOP is a disease leading to progressive decreases in bone mineral ... ...

Abstract	Glucocorticoids are commonly used in various fields within medicine. One of their most common and clinically significant side effects is glucocorticoid-induced osteoporosis (GIOP). GIOP is a disease leading to progressive decreases in bone mineral density, decreased bone strength, and increased risk of skeletal fractures. GIOP has a significant impact on the morbidity and health-related quality of life of the patients it affects. Glucocorticoids have deleterious effects on bone through promoting osteoblast apoptosis and inhibiting osteoblastogenesis. Teriparatide exerts anabolic effects on bone, so it is understandable why teriparatide is thought to be a rational treatment option. Clinical studies have indicated teriparatide is efficacious in the treatment of GIOP to improve bone mineral density values at the lumbar spine and femoral neck. Some evidence also suggests teriparatide may reduce rates of vertebral fractures in GIOP patients. Overall, this review of the current clinical evidence suggests teriparatide may be an efficacious and promising agent in the treatment of GIOP.
Language	English
Publishing date	2010-10-21
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2186560-7
ISSN	1178-203X ; 1176-6336
ISSN (online)	1178-203X
ISSN	1176-6336
DOI	10.2147/TCRM.S7776
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Article: Effect of Concomitant Disease-modifying Antirheumatic Drugs and Methotrexate Administration Route on Biologic Treatment Durability in Rheumatoid Arthritis: OBRI Cohort Results.

Lau, Arthur N / Thorne, J Carter / Movahedi, Mohammad / Rampakakis, Emmanouil / Cesta, Angela / Li, Xiuying / Couto, Sandra / Sampalis, John / Bombardier, Claire

The Journal of rheumatology

2019 Volume 46, Issue 8, Page(s) 874–886

Abstract: Objective: Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and ... ...

Abstract	Objective: Prior studies have suggested that concurrent conventional synthetic disease-modifying antirheumatic drug (csDMARD) therapy enhances the efficacy of biologic DMARD (bDMARD). Here, we assessed the effect of concomitant csDMARD use and methotrexate (MTX) route of administration on time to bDMARD discontinuation in a large Canadian (Ontario), observational, rheumatoid arthritis (RA) cohort. Methods: Patients from the Ontario Best Practices Research Initiative (OBRI) who initiated bDMARD therapy and had ≥ 1 followup assessment were included. The effect of concomitant csDMARD use (primary analysis) and MTX route of administration (secondary analysis) on bDMARD discontinuation owing to (1) any reason, (2) ineffectiveness, (3) adverse events (AE), and (4) both (2) and (3), were assessed with multivariate Cox regression. Results: Among the 814 patients included, 153 (18.8%) received bDMARD monotherapy and 661 (81.2%) combination csDMARD/bDMARD therapy. Over a mean followup of 1.9 years, bDMARD were discontinued in 38.7% of patients. In multivariate analysis, there was a nonsignificant trend toward lower discontinuation for the csDMARD/bDMARD group compared to bDMARD monotherapy for any reason (HR 0.76, 95% CI 0.55-1.05) and owing to ineffectiveness/AE (HR 0.73, 95% CI 0.50-1.06). Further, patients taking combination therapy had significantly lower risk of bDMARD discontinuation due to AE (HR 0.43, 95% CI 0.24-0.76). In the secondary analysis, no statistical association between MTX dose or route of administration and bDMARD durability was observed. Conclusion: Concomitant csDMARD use was associated with a significantly lower hazard for bDMARD discontinuation due to AE among patients with RA followed in routine clinical practice in Ontario, Canada. Neither MTX route of administration nor dose were significant predictors of bDMARD durability.
MeSH term(s)	Adult ; Aged ; Antirheumatic Agents/therapeutic use ; Arthritis, Rheumatoid/drug therapy ; Biological Products/therapeutic use ; Drug Therapy, Combination ; Female ; Humans ; Male ; Methotrexate/therapeutic use ; Middle Aged ; Treatment Outcome
Chemical Substances	Antirheumatic Agents ; Biological Products ; Methotrexate (YL5FZ2Y5U1)
Language	English
Publishing date	2019-04-15
Publishing country	Canada
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	194928-7
ISSN	1499-2752 ; 0315-162X
ISSN (online)	1499-2752
ISSN	0315-162X
DOI	10.3899/jrheum.180486
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Article: Corrigendum to "The Current Practice of Screening, Prevention, and Treatment of Androgen-Deprivation-Therapy Induced Osteoporosis in Patients with Prostate Cancer".

Al-Shamsi, Humaid O / Lau, Arthur N / Malik, Kartika / Alamri, Abdulaziz / Ioannidis, George / Corbett, Tom / Adachi, J D / Papaioannou, Alexandra

Journal of oncology

2017 Volume 2017, Page(s) 3432604

Abstract: This corrects the article DOI: 10.1155/2012/958596.]. ...

Abstract	[This corrects the article DOI: 10.1155/2012/958596.].
Language	English
Publishing date	2017-12-03
Publishing country	Egypt
Document type	Published Erratum
ZDB-ID	2461349-6
ISSN	1687-8469 ; 1687-8450
ISSN (online)	1687-8469
ISSN	1687-8450
DOI	10.1155/2017/3432604
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