High throughput, quantitative analysis of human osteoclast differentiation and activity
Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of …
Journal:
Authors:
- Diepenhorst NA,
- Nowell CJ,
- Rueda P,
- Henriksen K,
- Pierce T,
- Cook AE,
- Pastoureau P,
- Sabatini M,
- Charman WN,
- Christopoulos A,
- Summers RJ,
- Sexton PM,
- Langmead CJ,
Blood-based biomarkers in Alzheimer disease: Current state of the science and a novel collaborative paradigm for advancing from discovery to clinic
The last decade has seen a substantial increase in research focused on the identification of blood-based biomarkers that have utility in Alzheimer's disease (AD). Blood-based biomarkers have significant advantages of being time- and cost-efficient as well as reduced invasiveness and increased patien…
Journal:
Authors:
- O'Bryant SE,
- Mielke MM,
- Rissman RA,
- Lista S,
- Vanderstichele H,
- Zetterberg H,
- Lewczuk P,
- Posner H,
- Hall J,
- Johnson L,
- Fong YL,
- Luthman J,
- Jeromin A,
- Batrla-Utermann R,
- Villarreal A,
- Britton G,
- Snyder PJ,
- Henriksen K,
- Grammas P,
- Gupta V,
- Martins R,
- Hampel H,
Serum tau fragments predict return to play in concussed professional ice hockey players
INTRODUCTION:
The diagnosis of sports-related concussion is mainly based on subjective clinical symptoms and neuropsychological tests. Thus, reliable brain injury biomarkers to assess when it is safe to return to play are highly desirable. The overall objective of this study was to evaluate the uti…
Journal:
Authors:
- Shahim P,
- Linemann T,
- Inekci D,
- Karsdal MA,
- Blennow K,
- Tegner Y,
- Zetterberg H,
- Henriksen K,
Nitrite and S-Nitrosohemoglobin Exchange Across the Human Cerebral and Femoral Circulation: Relationship to Basal and Exercise Blood Flow Responses to Hypoxia
BACKGROUND:
The mechanisms underlying red blood cell (RBC)-mediated hypoxic vasodilation remain controversial, with separate roles for nitrite () and S-nitrosohemoglobin (SNO-Hb) widely contested given their ability to transduce nitric oxide bioactivity within the microcirculation. To establish the…
Journal:
Authors:
- Bailey DM,
- Rasmussen P,
- Overgaard M,
- Evans KA,
- Bohm AM,
- Seifert T,
- Brassard P,
- Zaar M,
- Nielsen HB,
- Raven PB,
- Secher NH,
Altered collagen turnover in factor VIII-deficient rats with hemophilic arthropathy identifies potential novel serological biomarkers in hemophilia
ESSENTIALS:
Joint bleeding in hemophilia may induce significant remodeling of the extracellular matrix. Biomarkers of collagen turnover were investigated in a F8-/- rat model of hemophilic arthropathy. Biomarkers of cartilage degradation increased significantly during development of arthropathy. B…
Journal:
Authors:
- Manon-Jensen T,
- Karsdal MA,
- Nielsen LN,
- Kjelgaard-Hansen M,
- Vandahl B,
- Olsen EHN,
- Enoksson M,
- Roepstorff K,
Cohort Profile: The Prospective Epidemiological Risk Factor (PERF) study
The world’s population is ageing. In Europe alone, the elderly population over age 65 will double from 88 to 153 million and the fastest growing segment of the population will be those over 80, tripling in number from 24 to 60 million in 2060. Low birth rates and increasing longevity are the key fac…
Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Kehlet SN,
- Hansen HB,
- Hansen G,
- Byrjalsen I,
- Alexandersen P,
- Lindgren LM,
- Bihlet AR,
- Riis BJ,
- Andersen JR,
- Qvist P,
- Karsdal MA,
- Christiansen C,
Fibrogenesis assessed by serological type III collagen formation identifies patients with progressive liver fibrosis and responders to anti-fibrotic therapy
There are no approved treatments for liver fibrosis. To aid development of antifibrotic therapies, noninvasive biomarkers that can identify patients with progressive fibrosis and that permit monitoring of the response to antifibrotic therapy are much needed. Samples from a phase II antifibrotic tria…
Authors:
- Karsdal MA,
- Henriksen K,
- Nielsen MJ,
- Byrjalsen I,
- Leeming DJ,
- Gardner SD,
- Goodman ZD,
- Patel K,
- Krag A,
- Christiansen C,
- Schuppan D,
The association between histological, macroscopic and magnetic resonance imaging assessed synovitis in end-stage knee osteoarthritis: a cross-sectional study
OBJECTIVES:
To investigate the association between magnetic resonance imaging (MRI), macroscopic and histological assessments of synovitis in end-stage knee osteoarthritis (KOA).
METHODS:
Synovitis of end-stage osteoarthritic knees was assessed using non-contrast-enhanced (CE), contrast-enhance…
Journal:
Authors:
- Riis RG,
- Gudbergsen H,
- Simonsen O,
- Henriksen M,
- Al-Mashkur N,
- Eld M,
- Petersen KK,
- Kubassova O,
- Bay Jensen AC,
- Damm J,
- Bliddal H,
- Arendt-Nielsen L,
- Boesen MP,
High levels of biomarkers of collagen remodeling are associated with increased mortality in COPD - results from the ECLIPSE study
BACKGROUND:
There is a need to identify individuals with COPD at risk for disease progression and mortality. Lung tissue remodeling is associated with the release of extracellular matrix (ECM) fragments into the peripheral circulation. We hypothesized that ECM remodeling was associated with mortali…
Journal:
Authors:
- Sand JM,
- Leeming DJ,
- Byrjalsen I,
- Bihlet AR,
- Lange P,
- Tal-Singer R,
- Miller BE,
- Karsdal MA,
- Vestbo J,
Fibrosis is not just fibrosis - basement membrane modelling and collagen metabolism differs between hepatitis B- and C-induced injury
BACKGROUND:
While morphological patterns differ, the molecular phenotype of liver fibrosis is considered a stereotypical response to chronic liver injury. However, with different cellular triggers and networks regulating fibrosis, the molecular responses of the injured liver may not be identical.
…
Journal:
Authors:
- Nielsen MJ,
- Karsdal MA,
- Kazankov K,
- Krag A,
- Grønbæk H,
- Leeming DJ,
- Schuppan D,
- George J,
A randomized, double-blind, multicenter, placebo-controlled study to evaluate the efficacy and safety of oral salmon calcitonin in the treatment of osteoporosis in postmenopausal women taking calcium and vitamin D
This randomized, double-blind, placebo-controlled phase III study was conducted to assess the efficacy and safety of oral calcitonin (SMC021) for the treatment of postmenopausal osteoporosis. A total of 4665 postmenopausal women with osteoporosis were randomized 1:1 to receive calcium and vitamin D …
Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Andersen JR,
- Bihlet AR,
- Russo LA,
- Alexandersen P,
- Valter I,
- Qvist P,
- Lau E,
- Riis BJ,
- Christiansen C,
- Karsdal MA,
- SMC021 investigators,
Metabolic syndrome and subsequent risk of type 2 diabetes and cardiovascular disease in elderly women: Challenging the current definition
The prognostic value of the metabolic syndrome (MetS) is believed to vary with age. With an elderly population expecting to triple by 2060, it is important to evaluate the validity of MetS in this age group. We examined the association of MetS risk factors with later risk of type 2 diabetes (T2DM) a…
Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Laursen JM,
- Hansen HB,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
- Brix S,
- Henriksen K,
Serum endotrophin identifies optimal responders to PPARγ agonists in type 2 diabetes
AIMS/HYPOTHESIS:
The treatment of type 2 diabetes with full peroxisome proliferator-activated receptor gamma (PPARγ) agonists improves insulin sensitivity, but is associated with weight gain, heart failure, peripheral oedema and bone loss. Endotrophin, the C-terminal fragment of the α3 chain of pro…
Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Genovese F,
- Leeming DJ,
- Nielsen MJ,
- Riis BJ,
- Christiansen C,
- Byrjalsen I,
- Schuppan D,
Characterization of serological neo-epitope biomarkers reflecting collagen remodeling in clinically stable chronic obstructive pulmonary disease
OBJECTIVES:
Chronic obstructive pulmonary disease (COPD) is characterized by chronic inflammation that leads to excessive remodeling of the lung extracellular matrix (ECM), resulting in release of protein fragments (neo-epitopes) to the blood. Serological markers assessing this have previously been…
Journal:
Authors:
- Lange P,
- Leeming DJ,
- Karsdal MA,
- Midjord AK,
- Martinez G,
- Sand JM,
Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies
For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor b…
Journal:
Authors:
- Arvanitidis A,
- Henriksen K,
- Karsdal MA,
- Nedergaard AF,
Systemic Biomarkers of Collagen and Elastin Turnover Are Associated With Clinically Relevant Outcomes in COPD
BACKGROUND:
Extracellular matrix (ECM) remodeling of the lung tissue releases protein fragments into the blood, where they may be detected as serologic surrogate markers of disease activity in COPD. Our goal was to assess the association of ECM turnover with severity and outcome of COPD.
METHODS…
Journal:
Authors:
- Leeming DJ,
- Kristensen JH,
- Karsdal MA,
- Sand JM,
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy
Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …
Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Löfvall H,
- Kertész Z,
- Montano C,
- Bjurström CF,
- Karsdal MA,
- Schulz AS,
- Richter J,
- Henriksen K,
Effect of Abaloparatide vs Placebo on New Vertebral Fractures in Postmenopausal Women With Osteoporosis: A Randomized Clinical Trial
IMPORTANCE:
Additional therapies are needed for prevention of osteoporotic fractures. Abaloparatide is a selective activator of the parathyroid hormone type 1 receptor.
OBJECTIVE:
To determine the efficacy and safety of abaloparatide, 80 μg, vs placebo for prevention of new vertebral fracture i…
Journal:
Authors:
- Miller PD,
- Hattersley G,
- Riis BJ,
- Williams GC,
- Lau E,
- Russo LA,
- Alexandersen P,
- Zerbini CA,
- Hu MY,
- Harris AG,
- Fitzpatrick LA,
- Cosman F,
- Christiansen C,
Disease-modifying treatments for osteoarthritis (DMOADs) of the knee and hip: lessons learned from failures and opportunities for the future
Osteoarthritis (OA) is the biggest unmet medical need among the many musculoskeletal conditions and the most common form of arthritis. It is a major cause of disability and impaired quality of life in the elderly. We review several ambitious but failed attempts to develop joint structure-modifying t…
Journal:
Authors:
- Karsdal MA,
- Michaelis M,
- Ladel C,
- Siebuhr AS,
- Bihlet AR,
- Andersen JR,
- Guehring H,
- Christiansen C,
- Bay-Jensen AC,
- Kraus VB,
Type VIII collagen is elevated in diseases associated with angiogenesis and vascular remodeling
OBJECTIVES:
Type VIII collagen is involved in angiogenesis and remodeling of arteries. We hypothesized that type VIII collagen was upregulated in diseases associated with vascular remodeling, e.g. pulmonary fibrosis and cancer. In this paper we present the development and validation of a competiti…
Journal:
Authors:
- Hansen NU,
- Willumsen N,
- Sand JM,
- Larsen L,
- Karsdal MA,
- Leeming DJ,
Exploration of a potent PI3 kinase/mTOR inhibitor as a novel anti-fibrotic agent in IPF
RATIONALE:
Idiopathic pulmonary fibrosis (IPF) is the most rapidly progressive and fatal of all fibrotic conditions with no curative therapies. Common pathomechanisms between IPF and cancer are increasingly recognised, including dysfunctional pan-PI3 kinase (PI3K) signalling as a driver of aberran…
Journal:
Authors:
- Mercer PF,
- Woodcock HV,
- Eley JD,
- Platé M,
- Sulikowski MG,
- Durrenberger PF,
- Franklin L,
- Nanthakumar CB,
- Man Y2,
- Genovese F,
- McAnulty RJ,
- Yang S,
- Maher TM,
- Nicholson AG,
- Arbit E,
- Marshall RP,
- Lukey PT,
- Chambers RC,
The dual amylin- and calcitonin-receptor agonist KBP-042 increases insulin sensitivity and induces weight loss in rats with obesity
OBJECTIVE:
In this study, KBP-042, a dual amylin- and calcitonin-receptor agonist, was investigated as a treatment of obesity and insulin resistance in five different doses (0.625 µg/kg-10 µg/kg) compared with saline-treated and pair-fed controls.
METHODS:
Rats with obesity received daily s.c…
Journal:
Authors:
- Hjuler ST,
- Gydesen S,
- Andreassen KV,
- Pedersen SL,
- Hellgren LI,
- Karsdal MA,
- Henriksen K,
Excessive collagen turnover products are released during colorectal cancer progression and elevated in serum from metastatic colorectal cancer patients
During cancer progression, the homeostasis of the extracellular matrix becomes imbalanced with an excessive collagen remodeling by matrix metalloproteinases. As a consequence, small protein fragments of degraded collagens are released into the circulation. We have investigated the potential of prote…
Journal:
Authors:
- Kehlet SN,
- Sanz-Pamplona R,
- Brix S,
- Leeming DJ,
- Karsdal MA,
- Moreno V,
Quantification of fibronectin as a method to assess ex vivo extracellular matrix remodeling
Altered architecture, composition and quality of the extracellular matrix (ECM) are pathological hallmarks of several inflammatory and fibro-proliferative pathological processes such as osteoarthritis (OA), rheumatoid arthritis (RA), fibrosis and cancer. One of the most important components of the E…
Journal:
Authors:
- Bager CL,
- Gudmann NS,
- Willumsen N,
- Leeming DJ,
- Karsdal MA,
- Bay-Jensen AC,
- Høgdall E,
- Balslev I,
- He Y,
Remodeling of the Tumor Microenvironment Predicts Increased Risk of Cancer in Postmenopausal Women: The Prospective Epidemiologic Risk Factor (PERF I) Study
BACKGROUND:
An altered tumor microenvironment is one of the earliest signs of cancer and an important driver of the disease. We have seen previously that biomarkers reflecting tumor microenvironment modifications, such as matrix metalloproteinase (MMP)-degraded type 1 collagen (C1M), MMP-degraded t…
Journal:
Authors:
- Bager CL,
- Willumsen N,
- Kehlet SN,
- Hansen HB,
- Bay-Jensen AC,
- Leeming DJ,
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Høgdall E,
- Karsdal MA,
Tissue turnover of collagen type I, III and elastin is elevated in the PCLS model of IPF and can be restored back to vehicle levels using a phosphodiesterase inhibitor
BACKGROUND:
The aim of this study was to develop and validate a model for pulmonary fibrosis, using ex vivo tissue cultures of lungs from bleomycin treated animals, enabling the investigation of fibrosis remodeling using novel biomarkers for the detection of ECM protein fragments. The combination …
Journal:
Authors:
- Hansen NU,
- Karsdal MA,
- Brockbank S,
- Cruwys S,
- Rønnow S,
- Christiansen C,
Chondrocyte activity is increased in psoriatic arthritis and axial spondyloarthritis
BACKGROUND:
Psoriatic arthritis (PsA) and axial spondyloarthritis (axSpA) are chronic inflammatory rheumatic diseases with complex origins. Both are characterized by altered extracellular matrix remodeling in joints and entheses that results in destructive and osteochondral proliferative lesions. T…
Journal:
Authors:
- Gudmann NS,
- Munk HL,
- Christensen AF,
- Ejstrup L,
- Sørensen GL,
- Loft AG,
- Karsdal MA,
- Bay-Jensen AC,
- He Y,
- Siebuhr AS,
- Junker P,
Intercritical circulating levels of neo-epitopes reflecting matrixmetalloprotease-driven degradation as markers of gout and frequent gout attacks
OBJECTIVE:
Recurrent flares constitute the main clinical burden of gout. Our aim was to assess whether biomarkers measuring MMP tissue degradation could be used as markers of frequent gout flares.
METHODS:
Fasting plasma samples from 112 men with gout and 170 controls, along with serum samples …
Journal:
Authors:
- Valdes AM,
- Manon-Jensen T,
- Abhishek A,
- Jenkins W,
- Siebuhr AS,
- Karsdal MA,
- Doherty S,
- Zhang W,
- Richardson H,
- Doherty M,
- Bay-Jensen AC,
Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice
In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery …
Journal:
Authors:
- Wendelboe MH,
- Thomsen JS,
- Henriksen K,
- Vegger JB,
- Brüel A,
Precision-Cut Kidney Slices as a Tool to Understand the Dynamics of Extracellular Matrix Remodeling in Renal Fibrosis
The aim of this study was to set up an ex vivo model for renal interstitial fibrosis in order to investigate the extracellular matrix (ECM) turnover profile in the fibrotic kidney. We induced kidney fibrosis in fourteen 12-week-old male Sprague Dawley rats by unilateral ureteral obstruction (UUO) su…
Journal:
Authors:
- Genovese F,
- Kàrpàti ZS,
- Nielsen SH,
- Karsdal MA,
The Need for Predictive, Prognostic, Objective and Complementary Blood-Based Biomarkers in Osteoarthritis (OA)
Osteoarthritis (OA) has traditionally been viewed as a non-inflammatory arthropathy and has not been considered a ‘serious disease’. However, this view has radically changed in recent years, due to the complexity and heterogeneity of the patient populations, spiralling socio-economical costs and lon…
Journal:
Authors:
- Bay-Jensen AC,
- Henrotin Y,
- Karsdal MA,
- Mobasheri A,
KBP-088, a novel DACRA with prolonged receptor activation, is superior to davalintide in terms of efficacy on body weight
This study aims to elucidate the mechanism behind the potent weight loss induced by dual amylin and calcitonin receptor agonists (DACRA) through comparison of the novel DACRA KBP-088 with the amylinomimetic davalintide with regard to in vitro receptor pharmacology and in vivo efficacy on food intake…
Journal:
Authors:
- Gydesen S,
- Hjuler ST,
- Christensen JM,
- Karsdal MA,
- Arbit E,
- Andreassen KV,
Osteoarthritis biomarkers derived from cartilage extracellular matrix: Current status and future perspectives
Specific soluble biomarkers can be powerful tools for the diagnosis, prognosis and personalized management of osteoarthritis (OA). Biomarkers are potential indicators of the effect of a drug on cartilage metabolism and provide crucial information about the mechanisms of drug action. In this review, …
Journal:
Authors:
- Henrotin Y,
- Sanchez C,
- Bay-Jensen AC,
- Mobasheri A,
Abdominal wall hernias - A local manifestation of systemically impaired quality of the extracellular matrix
BACKGROUND:
Throughout life, inguinal hernia develops in approximately every fourth man, some of whom develop multiple hernias. If patients at risk of developing multiple hernias could be identified by a serologic biomarker, treatment might be able to be tailored and improved. Evidence suggests tha…
Journal:
Authors:
- Henriksen NA,
- Mortensen JH,
- Lorentzen L,
- Ågren MS,
- Bay-Jensen AC,
- Jorgensen LN,
- Karsdal MA,
Association between biomarkers of tissue inflammation and progression of osteoarthritis: evidence from the Rotterdam study cohort
BACKGROUND:
We aimed to investigate the prognostic value of two biomarkers of tissue inflammation, matrix metalloproteinase-dependent degradation of C-reactive protein (CRPM) and connective tissue type I collagen turnover (C1M), on the incidence and progression of radiographic osteoarthritis (OA) i…
Journal:
Authors:
- Saberi Hosnijeh F,
- Siebuhr AS,
- Uitterlinden AG,
- Oei EH,
- Hofman A,
- Karsdal MA,
- Bierma-Zeinstra SM,
- Bay-Jensen AC,
- van Meurs JB,
Neo-Epitopes-Fragments of Cartilage and Connective Tissue Degradation in Early Rheumatoid Arthritis and Unclassified Arthritis
OBJECTIVE:
Tissue destruction in rheumatoid arthritis (RA) is predominantly mediated by matrix metalloproteinases (MMPs), thereby generating protein fragments. Previous studies have revealed that these fragments include MMP-mediated collagen type I, II, and III degradation, citrullinated and MMP-de…
Journal:
Authors:
- Maijer KI,
- Gudmann NS,
- Karsdal MA,
- Gerlag DM,
- Tak PP,
- Bay-Jensen AC,
Collagen-mediated hemostasis
Collagens mediate essential hemostasis by maintaining the integrity and stability of the vascular wall. Imbalanced turnover of collagens by uncontrolled formation and/or degradation may result in pathologic conditions such as fibrosis. Thickening of the vessel wall because of accumulation of collage…
Journal:
Authors:
- Manon-Jensen T,
- Kjeld NG,
- Karsdal MA,
Late-Life Risk Factors for All-Cause Dementia and Differential Dementia Diagnoses in Women: A Prospective Cohort Study
Since the first evidence of a decline in dementia incidence was reported in 2011, the focus on modifiable risk factors has increased. The possibility of risk factor intervention as a prevention strategy has been widely discussed; however, further evidence in relation to risk factors is still needed.…
Journal:
Authors:
CRP and a biomarker of type I collagen degradation, C1M, can differentiate anti-inflammatory treatment response in ankylosing spondylitis
AIM:
To investigate if tissue turnover biomarkers were efficacy biomarkers in ankylosing spondylitis and if the biomarkers at baseline predicted a good outcome (BASDAI50).
PATIENTS & METHODS:
Twenty-two etanercept treated ankylosing spondylitis patients were investigated for inflammation (CRP, …
Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Karsdal MA,
- Lories RJ,
- de Vlam K,
Synovitis biomarkers: ex vivo characterization of three biomarkers for identification of inflammatory osteoarthritis
OBJECTIVE:
Characterize biomarkers measuring extracellular matrix turnover of inflamed osteoarthritis synovium.
METHODS:
Human primary fibroblast-like synoviocytes and synovial membrane explants (SMEs) treated with various cytokines and growth factors were assessed by C1M, C3M, and acMMP3 in …
Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Ladel C,
- Christiansen TG,
- Siebuhr AS,
- Kjelgaard-Petersen CF,
Inhibition of lysosomal protease cathepsin D reduces renal fibrosis in murine chronic kidney disease
During chronic kidney disease (CKD) there is a dysregulation of extracellular matrix (ECM) homeostasis leading to renal fibrosis. Lysosomal proteases such as cathepsins (Cts) regulate this process in other organs, however, their role in CKD is still unknown. Here we describe a novel role for catheps…
Journal:
Authors:
- Fox C,
- Cocchiaro P,
- Oakley F,
- Howarth R,
- Callaghan K,
- Leslie J,
- Luli S,
- Wood KM,
- Sheerin NS,
- Genovese F,
- Moles A,
Osteoarthritis year in review 2015: soluble biomarkers and the BIPED criteria
OBJECTIVE:
To review and summarize biomarker data published from April 2014 to May 2015 to provide insight to the ongoing work in the field of osteoarthritis (OA). Furthermore, to summarize the BIPED criteria and set it in context of the medical needs of 2015.
METHODS:
PubMed was used as search…
Journal:
Authors:
- Bay-Jensen AC,
- Reker D,
- Kjelgaard-Petersen CF,
- Mobasheri A,
- Karsdal MA,
- Ladel C,
- Henrotin Y,
- Thudium CS,
Early changes in blood-based joint tissue destruction biomarkers are predictive of response to tocilizumab in the LITHE study
BACKGROUND:
Rheumatoid arthritis (RA) is characterized by gradual joint destruction. Tocilizumab (TCZ) significantly suppresses symptoms, however not all patients are protected from joint damage. We investigated whether early measurement of specific biomarkers could predict early joint protection r…
Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Siebuhr AS,
- Christiansen C,
- Byrjalsen I,
- Karsdal MA,
Sequence variants in the PTCH1 gene associate with spine bone mineral density and osteoporotic fractures
Bone mineral density (BMD) is a measure of osteoporosis and is useful in evaluating the risk of fracture. In a genome-wide association study of BMD among 20,100 Icelanders, with follow-up in 10,091 subjects of European and East-Asian descent, we found a new BMD locus that harbours the PTCH1 gene, re…
Journal:
Authors:
- Styrkarsdottir U,
- Thorleifsson G,
- Gudjonsson SA,
- Sigurdsson A,
- Center JR,
- Lee SH,
- Nguyen TV,
- Kwok TC,
- Lee JS,
- Ho SC,
- Woo J,
- Leung PC,
- Kim BJ,
- Rafnar T,
- Kiemeney LA,
- Ingvarsson T,
- Koh JM,
- Tang NL,
- Eisman JA,
- Christiansen C,
- Sigurdsson G,
- Thorsteinsdottir U,
- Stefansson K,
The impact of clinical trial monitoring approaches on data integrity and cost-a review of current literature
PURPOSE:
Monitoring is a costly requirement when conducting clinical trials. New regulatory guidance encourages the industry to consider alternative monitoring methods to the traditional 100 % source data verification (SDV) approach. The purpose of this literature review is to provide an overview o…