Rheumatology, Osteoarthritis, Biomarker position, Bone
3. Sep 2019
Associations between biomarkers of bone and cartilage turnover, gender, pain categories and radiographic severity in knee osteoarthritis.
BACKGROUND:
Excessive cartilage degradation is a known characteristic of osteoarthritis (OA). Biochemical markers, such as uCTX-II, have been shown to be associated with disease severity, yet the tissue origin of CTX-II has been disputed. This analysis investigates the association between OA knee j…
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Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Karsdal MA,
Bone, Bone
28. May 2019
Low bone turnover levels predict increased risk of cancer
BACKGROUND:
Several epidemiological studies have shown an association between bone mineral density (BMD) and risk of breast cancer in postmenopausal women, but it remains unknown whether bone turnover is associated with increased risk of cancer. The aim of this study was to investigate if markers o…
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Journal:
Authors:
- Bager CL,
- Bay F,
- Christiansen C,
- Karsdal MA,
Central Nervous System, Alzheimer’s Disease
11. Apr 2018
Two novel blood-based biomarker candidates measuring degradation of tau are associated with dementia: a prospective study
BACKGROUND:
Truncated tau appears to be specifically related to disease pathology and recent studies have shown the presence and elevation of several truncated tau species in Cerebrospinal fluid (CSF) of subjects with Alzheimer's disease (AD); however, the relevance of truncated Tau measurements in…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
Extracellular Matrix Research
29. Mar 2018
Matrix Metalloproteinase Mediated Type I Collagen Degradation is an Independent Predictor of Increased Risk of Acute Myocardial Infarction in Postmenopausal Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
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Journal:
Authors:
- Bertelsen DM,
- Neergaard JS,
- Bager CL,
- Nielsen SH,
- Secher NH,
- Svendsen JH,
- Bihlet AR,
- Andersen JR,
- Karsdal MA,
- Christiansen C,
- Nielsen HB,
Osteoarthritis
17. Jan 2018
Identification of pain categories associated with change in pain in patients receiving placebo: Data from Two Phase 3 Randomized Clinical Trials in Symptomatic Knee Osteoarthritis
BACKGROUND:
Pain is the principal clinical symptom of osteoarthritis (OA), and development of safe and effective analgesics for OA pain is needed. Drug development of new analgesics for OA pain is impaired by substantial change in pain in patients receiving placebo, and more data describing clinica…
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Journal:
Authors:
- Bihlet AR,
- Byrjalsen I,
- Bay-Jensen AC,
- Andersen JR,
- Christiansen C,
- Riis BJ,
- Valter I,
- Karsdal MA,
- Hochberg MC,
Extracellular Matrix Research
1. Dec 2017
Objective Cognitive Impairment and Progression to Dementia in Women: The Prospective Epidemiological Risk Factor Study.
BACKGROUND:
Identification of subjects with a progressive disease phenotype is an urgent need in the pharmaceutical industry where most of the recent clinical trials in Alzheimer's disease have failed.
OBJECTIVES:
The objective of this study was to identify subgroups of individuals with objecti…
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Karsdal MA,
- Brix S,
- Henriksen K,
Rheumatology, Rheumatoid Arthritis
28. Aug 2017
Suppression of active, but not total MMP-3, is associated with treatment response in a phase III clinical study of rheumatoid arthritis
OBJECTIVE:
Biologics for rheumatoid arthritis (RA) patients with moderate to severe disease may preserve joint function. Matrix metalloproteinase 3 (MMP-3), a key tissue degrading protease, is highly elevated in RA. MMP-3, which measures the total pool of circulating MMP-3 species (cMMP3), is a com…
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Journal:
Authors:
- Siebuhr AS,
- Kjelgaard-Petersen CF,
- Sun S,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
- Bay-Jensen AC,
Central Nervous System, Biomarker position
10. May 2017
Modifiable risk factors promoting neurodegeneration is associated with two novel brain degradation markers measured in serum
There has been limited success with blood-based biomarkers of neurodegeneration. One perceived reason is that blood has no direct contact to the brain. Recently developed blood-based biomarkers of tau-degradation have shown promise as potential tools for peripheral assessment of neurodegeneration; h…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Brix S,
- Workman CT,
- Nielsen HB,
- Christiansen C,
- Dragsbæk K,
- Neergaard JS,
Endocrinology, Type 2-Diabetes
7. Apr 2017
Metabolic Syndrome, Insulin Resistance, and Cognitive Dysfunction: Does Your Metabolic Profile Affect Your Brain?
Dementia and type 2 diabetes are both characterized by long prodromal phases, challenging the study of potential risk factors and their temporal relation. The progressive relation among metabolic syndrome, insulin resistance (IR), and dementia has recently been questioned, wherefore the aim of this …
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Journal:
Authors:
- Neergaard JS,
- Dragsbæk K,
- Christiansen C,
- Nielsen HB,
- Brix S,
- Karsdal MA,
- Henriksen K,
Type 2-Diabetes
6. Mar 2017
Weight change and risk of hyperglycaemia in elderly women
BACKGROUND:
Hyperglycaemia increases the risk of type 2 diabetes, heart disease and stroke, and is influenced by weight. However, the impact of preceding weight change on blood glycemia levels in late-life is less well understood.
AIM:
We studied the interplay between weight change and risk of …
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Christiansen C,
- Karsdal MA,
- Beck-Nielsen H,
- Brix S,
- Henriksen K,
Extracellular Matrix Research, Biomarker position, Oncology
11. Feb 2017
Excessive matrix metalloprotease-mediated degradation of interstitial tissue (type I collagen) independently predicts short-term survival in an observational study of postmenopausal women diagnosed with cancer
Extensive tissue remodeling mediated by matrix metalloproteases (MMPs) is an important part of cancer. The aim of this study was to investigate whether serum biomarkers reflecting MMP-mediated degradation of type I collagen (C1M), type IV collagen (C4M) and citrullinated vimentin (VICM) were predict…
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Kehlet SN,
- Dragsbaek K,
- Neergaard JS,
- Hansen HB,
- Bay-Jensen AC,
- Leeming DJ,
- Lipton A,
- Christiansen C,
- Karsdal MA,
Oncology
26. Oct 2016
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…
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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,
Hepatic System, Type 2-Diabetes
20. Oct 2016
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…
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Authors:
- Karsdal MA,
- Henriksen K,
- Nielsen MJ,
- Byrjalsen I,
- Leeming DJ,
- Gardner SD,
- Goodman ZD,
- Patel K,
- Krag A,
- Christiansen C,
- Schuppan D,
Bone, Osteoporosis
1. Oct 2016
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 …
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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,
Type 2-Diabetes
15. Sep 2016
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…
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Authors:
- Dragsbæk K,
- Neergaard JS,
- Laursen JM,
- Hansen HB,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
- Brix S,
- Henriksen K,
Type 2-Diabetes
8. Sep 2016
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…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Genovese F,
- Leeming DJ,
- Nielsen MJ,
- Riis BJ,
- Christiansen C,
- Byrjalsen I,
- Schuppan D,
Bone, Osteoporosis
16. Aug 2016
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…
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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,
Rheumatology, Osteoarthritis
2. Aug 2016
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…
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Journal:
Authors:
- Karsdal MA,
- Michaelis M,
- Ladel C,
- Siebuhr AS,
- Bihlet AR,
- Andersen JR,
- Guehring H,
- Christiansen C,
- Bay-Jensen AC,
- Kraus VB,
Oncology
13. Jul 2016
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…
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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,
Extracellular Matrix Research, Respiratory System
5. Jul 2016
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 …
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Journal:
Authors:
- Hansen NU,
- Karsdal MA,
- Brockbank S,
- Cruwys S,
- Rønnow S,
- Christiansen C,
Alzheimer’s Disease
1. Mar 2016
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.…
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Authors:
Rheumatology, Rheumatoid Arthritis
20. Jan 2016
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…
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Siebuhr AS,
- Christiansen C,
- Byrjalsen I,
- Karsdal MA,
Bone, Osteoporosis
6. Jan 2016
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…
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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,
Bone, Osteoporosis
27. Oct 2015
Role of biochemical markers in the management of osteoporosis
Estrogen and bone health form a cornerstone of osteoporosis management. Diagnosis of osteoporosis is performed using bone mineral density (BMD), despite the limitations associated with this. Within the last 25 years, numerous bone turnover markers (BTM) have been developed, and this has led to a mar…
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Rheumatology, Osteoarthritis
20. Oct 2015
Inflammation (or synovitis)-driven osteoarthritis: an opportunity for personalizing prognosis and treatment?
The disabling and painful disease osteoarthritis (OA) is the most common form of arthritis. Strong evidence suggests that a subpopulation of OA patients has a form of OA driven by inflammation. Consequently, understanding when inflammation is the driver of disease progression and which OA patients m…
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Jordan JM,
- Kjelgaard-Petersen CF,
- Christiansen C,
- Abramson SB,
- Attur M,
- Berenbaum F,
- Kraus V,
- Karsdal MA,
Bone
29. Aug 2015
Two Rare Mutations in the COL1A2 Gene Associate With Low Bone Mineral Density and Fractures in Iceland
We conducted a genome-wide association study of low bone mineral density (BMD) at the hip and spine utilizing sequence variants found through whole-genome sequencing of 2636 Icelanders. We found two rare missense mutations, p.Gly496Ala and p.Gly703Ser, in the COL1A2 gene that associate with measures…
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Journal:
Authors:
- Styrkarsdottir U,
- Thorleifsson G,
- Eiriksdottir B,
- Gudjonsson SA,
- Ingvarsson T,
- Center JR,
- Nguyen TV,
- Eisman JA,
- Christiansen C,
- Thorsteinsdottir U,
- Sigurdsson G,
- Stefansson K,
Alzheimer’s Disease, Central Nervous System
11. Jun 2015
Relationship between serum levels of tau fragments and clinical progression of Alzheimer's disease
Enzyme-generated fragments of tau have been linked to neuronal death and may serve as serum biomarkers of cognitive loss. Two competitive ELISAs detecting an ADAM10-generated fragment (Tau-A) or a caspase-3-generated fragment (Tau-C) were measured in baseline serum samples from patients with mild to…
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Authors:
Bone, Osteoporosis
10. May 2015
Novel targets for the prevention of osteoporosis - lessons learned from studies of metabolic bone disorders
Osteoporosis is a major health care problem, and whereas efficacious treatments for vertebral fracture reduction are available for osteoporosis patients, these therapies are still limited with respect to capacity for restoration of bone loss, as well as efficacy on non-vertebral fractures, such as h…
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Authors:
Endocrinology, Type 2-Diabetes
1. May 2015
Lessons learned from the clinical development of oral peptides
The oral delivery of peptides and proteins has been hampered by an array of obstacles. However, several promising novel oral delivery systems have been developed. This paper reviews the most advanced oral formulation technologies, and highlights key lessons and implications from studies undertaken t…
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Journal:
Authors:
- Karsdal MA,
- Riis BJ,
- Mehta N,
- Stern W,
- Arbit E,
- Christiansen C,
- Henriksen K,
Extracellular Matrix Research
30. Apr 2015
Matrix Metalloproteinase Mediated Type I Collagen Degradation - An Independent Risk Factor for Mortality in Women
Chronic fibro-proliferative diseases are associated with nearly 45% of all deaths in the developed world. Matrix metalloproteinase (MMP) mediated remodeling of the extracellular matrix (ECM) plays an important role in disease development. Degradation of type I collagen is considered having a major r…
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Journal:
Authors:
- Dragsbæk K,
- Neergaard JS,
- Hansen HB,
- Byrjalsen I,
- Alexandersen P,
- Kehlet SN,
- Bay-Jensen AC,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
1. Apr 2015
OA phenotypes, rather than disease stage, drive structural progression--identification of structural progressors from 2 phase III randomized clinical studies with symptomatic knee OA
BACKGROUND/PURPOSE:
The aim of this study was to identify key characteristics of disease progression through investigation of the association of radiographic progression over two years with baseline Joint Space Width (JSW), Kellgren-Lawrence (KL) grade, Western Ontario and McMaster Universities Art…
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Journal:
Authors:
- Karsdal MA,
- Bihlet A,
- Byrjalsen I,
- Alexandersen P,
- Ladel C,
- Michaels M,
- Andersen JR,
- Riis BJ,
- Kraus V,
- Bay-Jensen AC,
- Christiansen C,
Rheumatology, Osteoarthritis
1. Apr 2015
Treatment of symptomatic knee osteoarthritis with oral salmon calcitonin: results from two phase 3 trials
PURPOSE:
To evaluate the structure-modifying and symptom efficacy, as well as safety and tolerability of oral salmon calcitonin (sCT) formulated with a 5-CNAC carrier (a molecule based on Eligen(®) technology), in osteoarthritis (OA) patients with moderate to severe knee pain and joint structural d…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Alexandersen P,
- Bihlet A,
- Andersen JR,
- Riis BJ,
- Bay-Jensen AC,
- Christiansen C,
- CSMC021C2301/1 investigators,
Oncology, Lung
3. Oct 2014
Serum biomarkers reflecting specific tumor tissue remodeling processes are valuable diagnostic tools for lung cancer
Extracellular matrix (ECM) proteins, such as collagen type I and elastin, and intermediate filament (IMF) proteins, such as vimentin are modified and dysregulated as part of the malignant changes leading to disruption of tissue homeostasis. Noninvasive biomarkers that reflect such changes may have a…
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Journal:
Authors:
- Willumsen N,
- Bager CL,
- Leeming DJ,
- Smith V,
- Christiansen C,
- Karsdal MA,
- Dornan D,
- Bay-Jensen AC,
Rheumatology, Rheumatoid Arthritis
20. Sep 2014
Serological biomarkers of joint tissue turnover predict tocilizumab response at baseline
Rheumatoid arthritis (RA) is an autoimmune disease characterized by polyarticular joint inflammation resulting in massive tissue turnover. The turnover is partly mediated by an up-regulation of proteolytic enzymes, such as matrix metalloproteinases (MMPs).1 Matrix metalloproteinase 3 is 1 of the MMP…
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Journal:
Authors:
- Bay-Jensen AC,
- Byrjalsen I,
- Siebuhr AS,
- Christiansen C,
- Platt A,
- Karsdal MA,
Endocrinology, Type 2-Diabetes
14. Aug 2014
Oral salmon calcitonin enhances insulin action and glucose metabolism in diet-induced obese streptozotocin-diabetic rats
We previously reported that oral delivery of salmon calcitonin (sCT) improved energy and glucose homeostasis and attenuated diabetic progression in animal models of diet-induced obesity (DIO) and type 2 diabetes, although the glucoregulatory mode of action was not fully elucidated. In the present st…
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Journal:
Authors:
- Feigh M,
- Hjuler ST,
- Andreassen KV,
- Gydesen S,
- Ottosen I,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Endocrinology, Type 2-Diabetes
31. Jul 2014
A novel oral dual amylin and calcitonin receptor agonist (KBP-042) exerts antiobesity and antidiabetic effects in rats
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Type 2-Diabetes, Obesity, Endocrinology
6. May 2014
A Novel Oral Dual Amylin and Calcitonin Receptor Agonist (KBP-042) Exerts Anti-Obesity and Anti-Diabetic Effects in Rats
The present study investigated a novel oral dual amylin and calcitonin receptor agonist (DACRA), KBP-042, in head-to-head comparison with salmon calcitonin (sCT) with regard to in vitro receptor pharmacology, ex vivo pancreatic islet studies, and in vivo proof of concept studies in diet-induced obes…
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Journal:
Authors:
- Andreassen KV,
- Feigh M,
- Hjuler ST,
- Gydesen S,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
- Henriksen K,
Rheumatology, Osteoarthritis
1. Mar 2014
Republished: Value of biomarkers in osteoarthritis: current status and perspectives
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…
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Journal:
Authors:
- Lotz M,
- Martel-Pelletier J,
- Christiansen C,
- Brandi ML,
- Bruyère O,
- Chapurlat R,
- Collette J,
- Cooper C,
- Giacovelli G,
- Kanis JA,
- Karsdal MA,
- Kraus V,
- Lems WF,
- Meulenbelt I,
- Pelletier JP,
- Raynauld JP,
- Reiter-Niesert S,
- Rizzoli R,
- Sandell LJ,
- Van Spil WE,
- Reginster JY,
Rheumatology, Osteoarthritis
6. Feb 2014
The coupling of bone and cartilage turnover in osteoarthritis: opportunities for bone antiresorptives and anabolics as potential treatments?
Osteoarthritis (OA) is the most common form of arthritic disease, and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, affecting bone, cartilage and synovium that thereby presents multiple targets for treatment. This manuscript wil…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Lories RJ,
- Abramson S,
- Spector T,
- Pastoureau P,
- Christiansen C,
- Attur M,
- Henriksen K,
- Goldring SR,
- Kraus V,
Rheumatology, Rheumatoid Arthritis
5. Feb 2014
Effect of tocilizumab combined with methotrexate on circulating biomarkers of synovium, cartilage, and bone in the LITHE study
OBJECTIVE:
We investigated the effects of tocilizumab (TCZ) on joint tissue remodeling in patients with moderate to severely active RA by measuring tissue-specific biomarker.
METHODS:
The LITHE biomarker study (n = 740) was a phase III study of 4- and 8-mg/kg TCZ in combination with MTX. Early …
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Journal:
Authors:
- Bay-Jensen AC,
- Platt A,
- Byrjalsen I,
- Vergnoud P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
27. Jan 2014
Rheumatoid arthritis - A case for Personalized Health Care?
Ethical, clinical, and economic considerations highlight the pressing need to advance the identification of optimal treatments for each individual patient. Personalized health care (PHC) may provide a significant benefit in the treatment of a number of clinical indications characterized by costly th…
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Journal:
Authors:
- Karsdal MA,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Genant HK,
- Chamberlain C,
- Platt A,
Rheumatology, Osteoarthritis
22. Jan 2014
Osteoarthritis--a case for personalized health care?
For both economic and ethical reasons, identification of the optimal treatment for each individual patient is a pressing concern, not only for the patients and their physician, but also health care payers and the pharmaceutical industry. In the field of osteoarthritis (OA) this is of particular rele…
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Journal:
Authors:
- Karsdal MA,
- Christiansen C,
- Ladel C,
- Henriksen K,
- Kraus VB,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
7. Jan 2014
Identification and characterisation of osteoarthritis patients with inflammation derived tissue turnover
OBJECTIVES:
Osteoarthritis (OA) is a degenerative disease with a subset of patients experiencing joint inflammation, but C-reactive protein (CRP) has shown limited use in OA as a diagnostic marker. The aim was to identify subpopulations of patients with high or low levels of acute (high sensitive C…
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Journal:
Authors:
- Siebuhr AS,
- Petersen KK,
- Arendt-Nielsen L,
- Egsgaard LL,
- Eskehave T,
- Christiansen C,
- Simonsen O,
- Hoeck HC,
- Karsdal MA,
- Bay-Jensen AC,
Rheumatology, Osteoarthritis
12. Nov 2013
Value of biomarkers in osteoarthritis: current status and perspectives
Osteoarthritis affects the whole joint structure with progressive changes in cartilage, menisci, ligaments and subchondral bone, and synovial inflammation. Biomarkers are being developed to quantify joint remodelling and disease progression. This article was prepared following a working meeting of t…
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Journal:
Authors:
- Lotz M,
- Martel-Pelletier J,
- Christiansen C,
- Brandi ML,
- Bruyère O,
- Chapurlat R,
- Collette J,
- Cooper C,
- Giacovelli G,
- Kanis JA,
- Karsdal MA,
- Kraus V,
- Lems WF,
- Meulenbelt I,
- Pelletier JP,
- Raynauld JP,
- Reiter-Niesert S,
- Rizzoli R,
- Sandell LJ,
- Van Spil WE,
- Reginster JY,
Hepatic System, Alcoholic Liver Disease
5. Nov 2013
Novel serological neo-epitope markers of extracellular matrix proteins for the detection of portal hypertension
BACKGROUND:
The hepatic venous pressure gradient (HVPG) is an invasive, but important diagnostic and prognostic marker in cirrhosis with portal hypertension (PHT). During cirrhosis, remodelling of fibrotic tissue by matrix metalloproteinases (MMPs) is a permanent process generating small fragments …
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Journal:
Authors:
- Leeming D,
- Karsdal MA,
- Bendtsen F,
- Trebicka J,
- Nielsen MJ,
- Christiansen C,
- Møller S,
- Krag A,
Rheumatology
16. Oct 2013
Musculoskeletal ageing and primary prevention
Loss of musculoskeletal mass and function is a natural ageing trait, reinforced by an unhealthy life style. Loss of bone (osteoporosis) and muscle (sarcopaenia) are conditions whose prevalence are increasing because of the change in population distribution in the western world towards an older mean …
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Biomarker position
18. Aug 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways -- implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Journal:
Authors:
Rheumatology, Osteoarthritis
14. Aug 2013
Serological identification of fast progressors of structural damage with rheumatoid arthritis
INTRODUCTION:
Rheumatoid arthritis (RA) patients with structural progression are in most need of immediate treatment to maintain tissue integrity. The serum protein fingerprint, type I collagen degradation mediated by matrix metalloproteinases (MMP)-cleavage (C1M), is a biomarker of tissue destruct…
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Journal:
Authors:
- Siebuhr AS,
- Bay-Jensen AC,
- Leeming DJ,
- Plat A,
- Byrjalsen I,
- Christiansen C,
- van de Heijde D,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
1. Aug 2013
Circulating protein fragments of cartilage and connective tissue degradation are diagnostic and prognostic markers of rheumatoid arthritis and ankylosing spondylitis
Inflammation driven connective tissue turnover is key in rheumatic diseases, such as ankylosing spondylitis (AS). Few biomarkers are available for measuring disease prognosis or the efficacy of interventions applied in these tissue-related conditions. Type II collagen is the primary structural prote…
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Journal:
Authors:
- Bay-Jensen AC,
- Wichuk S,
- Byrjalsen I,
- Leeming DJ,
- Morency N,
- Christiansen C,
- Karsdal MA,
- Maksymowych WP,
Extracellular Matrix Research, Cardiovascular System, Atherosclerosis
3. Jun 2013
A MMP derived versican neo-epitope is elevated in plasma from patients with atherosclerotic heart disease
Extracellular matrix remodelling is a prerequisite for plaque rupture in atherosclerotic lesion. Versican, an extracellular matrix proteoglycan present in normal and atherosclerotic arteries is a substrate for matrix metalloproteinases (MMPs) present in macrophage rich areas. The aim of the current …
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Journal:
Authors:
- Barascuk N,
- Genovese F,
- Larsen L,
- Byrjalsen I,
- Zheng Q,
- Sun S,
- Hosbond S,
- Poulsen TS,
- Diederichsen A,
- Jensen JM,
- Mickley H,
- Register TC,
- Rasmussen LM,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Rheumatoid Arthritis
31. May 2013
Quantification of "end products" of tissue destruction in inflammation may reflect convergence of cytokine and signaling pathways - implications for modern clinical chemistry
The degree of inflammation in auto-immune diseases such as rheumatoid arthritis is often assessed in serum and used for diagnostic and prognostic purposes. The serum levels of acute inflammatory signaling molecules (C-reactive protein and serum amyloid A) in conjunction with the important pro-inflam…
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Journal:
Authors:
Endocrinology
29. May 2013
Menopause, estrogens and frailty
The controversy surrounding the results from the Women's Health Initiative (WHI) trials published a decade ago caused a significant decline in the use of menopausal hormone replacement therapy. However, these results have been vehemently contested and several lines of evidence suggest that in perime…
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Journal:
Authors:
- Nedergaard A,
- Henriksen K,
- Karsdal MA,
- Christiansen C,
Central Nervous System, Alzheimer’s Disease
22. May 2013
An enzyme-generated fragment of tau measured in serum shows an inverse correlation to cognitive function
OBJECTIVE:
Alzheimer's disease (AD) is a devastating neurological disease characterized by pathological proteolytic cleavage of tau protein, which appears to initiate death of the neurons. The objective of this study was to investigate whether a proteolytic fragment of the tau protein could serve a…
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Journal:
Authors:
- Henriksen K,
- Wang Y,
- Sørensen MG,
- Barascuk N,
- Suhy J,
- Pedersen JT,
- Duffin KL,
- Dean RA,
- Pajak M,
- Christiansen C,
- Zheng Q,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. May 2013
Role of hormones in cartilage and joint metabolism: understanding an unhealthy metabolic phenotype in osteoarthritis
OBJECTIVE:
Joint health is affected by local and systemic hormones. It is well accepted that systemic factors regulate the metabolism of joint tissues, and that substantial cross-talk between tissues actively contributes to homeostasis. In the current review, we try to define a subtype of osteoarth…
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Journal:
Authors:
- Bay-Jensen AC,
- Slagboom E,
- Chen-An P,
- Alexandersen P,
- Qvist P,
- Christiansen C,
- Meulenbelt I,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
19. Apr 2013
The neo-epitope specific PRO-C3 ELISA measures true formation of type III collagen associated with liver and muscle parameters
AIM:
The present study describes the assessment of true formation of type III collagen in different pathologies using a neo-epitope specific competitive Enzyme-linked immunosorbent assay (ELISA) towards the N-terminal propeptide of type III collagen (PRO-C3).
METHODS:
The monoclonal antibody wa…
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Journal:
Authors:
- Nielsen MJ,
- Nedergaard AF,
- Sun S,
- Veidal SS,
- Larsen L,
- Zheng Q,
- Suetta C,
- Henriksen K,
- Christiansen C,
- Karsdal MA,
- Leeming DJ,
Rheumatology, Spondyloarthropathies
4. Apr 2013
Circulating citrullinated vimentin fragments reflect disease burden in ankylosing spondylitis and have prognostic capacity for radiographic progression
OBJECTIVE:
Ankylosing spondylitis (AS) has been considered a seronegative rheumatic disease based on absent or low levels of antibodies against citrullinated proteins. The present study was undertaken to evaluate whether a citrullinated and matrix metalloproteinase-degraded fragment of vimentin (VI…
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Journal:
Authors:
- Bay-Jensen AC,
- Karsdal MA,
- Vassiliadis E,
- Marcher-Mikkelsen K,
- Lories R,
- Christiansen C,
- Maksymowych WP,
Extracellular Matrix Research
11. Mar 2013
Extracellular matrix remodeling: the common denominator in connective tissue diseases. Possibilities for evaluation and current understanding of the matrix as more than a passive architecture, but a key player in tissue failure
Increased attention is paid to the structural components of tissues. These components are mostly collagens and various proteoglycans. Emerging evidence suggests that altered components and noncoded modifications of the matrix may be both initiators and drivers of disease, exemplified by excessive ti…
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Journal:
Authors:
- Karsdal MA,
- Nielsen MJ,
- Sand JM,
- Henriksen K,
- Genovese F,
- Bay-Jensen AC,
- Adamkewicz JI,
- Christiansen C,
- Leeming DJ,
Bone
3. Mar 2013
Evaluation of the efficacy, safety and pharmacokinetic profile of oral recombinant human parathyroid hormone [rhPTH(1-31)NH(2)] in postmenopausal women with osteoporosis
CONTEXT:
Treatment of osteoporosis with subcutaneous (SC) injections of rhPTH(1-34) or rhPTH(1-84) is associated with significant improvements in BMD and reductions in osteoporotic fractures. However, subcutaneous injections can be associated with discomfort and thus deteriorating compliance.
OB…
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Journal:
Authors:
- Henriksen K,
- Andersen JR,
- Riis BJ,
- Mehta N,
- Tavakkol R,
- Alexandersen P,
- Byrjalsen I,
- Valter I,
- Nedergaard BS,
- Teglbjaerg CS,
- Stern W,
- Sturmer A,
- Mitta S,
- Nino AJ,
- Fitzpatrick LA,
- Christiansen C,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
3. Mar 2013
Protein fingerprinting of the extracellular matrix remodelling in a rat model of liver fibrosis--a serological evaluation
BACKGROUND/AIM:
We investigated nine novel biomarkers of extracellular matrix (ECM) remodelling in a rat model of liver fibrosis.
METHODS:
Liver fibrosis was induced in 52 male Wistar rats by inhalation of carbon tetrachloride and the level of hepatic fibrosis was assessed by Sirius red stainin…
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Journal:
Authors:
- Leeming DJ,
- Byrjalsen I,
- Jiménez W,
- Christiansen C,
- Karsdal MA,
Endocrinology, Type 2-Diabetes
4. Feb 2013
Oral salmon calcitonin protects against impaired fasting glycemia, glucose intolerance, and obesity induced by high-fat diet and ovariectomy in rats
OBJECTIVE:
Oral salmon calcitonin (sCT) has demonstrated clinical efficacy in treating osteoporosis in postmenopausal women. The postmenopausal state is also associated with obesity-related insulin resistance (IR) and type 2 diabetes. The aim of this study was to investigate the preventive effects …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Hjuler ST,
- Nielsen RH,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Rheumatology, Osteoarthritis
18. Dec 2012
The pathogenesis of osteoarthritis involves bone, cartilage and synovial inflammation: may estrogen be a magic bullet?
The female predominance of polyarticular osteoarthritis (OA), and in particular the marked increase of OA in women after the menopause points to a likely involvement of female sex hormones in the maintenance of cartilage homeostasis. This perception has inspired many research groups to investigate t…
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Authors:
Bone, Osteoporosis
28. Oct 2012
Recommendations on the management of fragility fracture risk in women younger than 70 years
The risk for fragility fracture represents a problem of enormous magnitude. It is estimated that only a small fraction of women with this risk take the benefit of preventive measures. The relationship between estrogen and bone mass is well known as they are the other factors related to the risk for …
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Journal:
Authors:
- Palacios S,
- Christiansen C,
- Sánchez Borrego R,
- Gambacciani M,
- Hadji P,
- Karsdal MA,
- Lambrinoudaki I,
- Lello S,
- O'Beirne B,
- Romao F,
- Rozenberg S,
- Stevenson JC,
- Ben-Rafael Z,
Endocrinology, Type 2-Diabetes
16. Sep 2012
Oral salmon calcitonin attenuates hyperglycaemia and preserves pancreatic beta-cell area and function in Zucker diabetic fatty rats
BACKGROUND AND PURPOSE:
Oral salmon calcitonin (sCT), a dual-action amylin and calcitonin receptor agonist, improved glucose homeostasis in diet-induced obese rats. Here, we have evaluated the anti-diabetic efficacy of oral sCT using parameters of glycaemic control and beta-cell morphology in male …
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Journal:
Authors:
- Feigh M,
- Andreassen KV,
- Neutzsky-Wulff AV,
- Petersen ST,
- Hansen C,
- Bay-Jensen AC,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Henriksen K,
- Karsdal MA,
Extracellular Matrix Research, Cardiovascular System, Acute Myocardial Infarct
6. Jul 2012
Clinical evaluation of a matrix metalloproteinase-12 cleaved fragment of titin as a cardiovascular serological biomarker
BACKGROUND:
Titin is a muscle-specific protein found in cardiac and skeletal muscles which is responsible for restoring passive tension. Levels and functioning of titin have been shown to be affected by cardiac damage. Due to the inherent difficulty of measuring titin levels in vivo in a clinical s…
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Journal:
Authors:
- Vassiliadis E,
- Rasmussen LM,
- Byrjalsen I,
- Larsen DV,
- Chaturvedi R,
- Hosbond S,
- Saabye L,
- Diederichsen AC,
- Genovese F,
- Duffin KL,
- Zheng Q,
- Chen X,
- Leeming DJ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Spondyloarthropathies
30. May 2012
Investigation of two novel biochemical markers of inflammation, matrix metalloproteinase and cathepsin generated fragments of C-reactive protein, in patients with ankylosing spondylitis
OBJECTIVES:
Ankylosing spondylitis (AS) is a chronic inflammation of the spine and the sacroiliac joints. Current markers of inflammation, such as C-reactive protein (CRP), are reflecting the production of an acute phase reactant rather than tissue specific inflammation, but the use of CRP as a dia…
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Journal:
Authors:
- Skjøt-Arkil H,
- Schett G,
- Zhang C,
- Larsen DV,
- Wang Y,
- Zheng Q,
- Larsen MR,
- Nawrocki A,
- Bay-Jensen AC,
- Henriksen K,
- Christiansen C,
- Alexandersen P,
- Leeming DJ,
- Karsdal MA,
Hepatic System, Alcoholic Liver Disease
5. Apr 2012
Circulating levels of citrullinated and MMP-degraded vimentin (VICM) in liver fibrosis related pathology
AIM:
To investigate whether increased levels of vimentin citrullinated peptides identified by MS in articular cartilage can be measured in pathologies other than rheumatoid arthritis and be utilised for diagnostic purposes.
METHODS:
A monoclonal antibody against the sequence RLRSSVPGV-citrullin…
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Journal:
Authors:
- Vassiliadis E,
- Oliveira CP,
- Alvares-da-Silva MR,
- Zhang C,
- Carrilho FJ,
- Stefano JT,
- Rabelo F,
- Pereira L,
- Kappel CR,
- Henriksen K,
- Veidal SS,
- Vainer B,
- Duffin KL,
- Christiansen C,
- Leeming DJ,
- Karsdal MA,
Cardiovascular System, Abdominal Aortic Aneurysm
11. Dec 2011
Abdominal aortic calcification quantified by the Morphological Atherosclerotic Calcification Distribution (MACD) index is associated with features of the metabolic syndrome
BACKGROUND:
Abdominal aortic calcifications (AAC) predict cardiovascular mortality. A new scoring model for AAC, the Morphological Atherosclerotic Calcification Distribution (MACD) index may contribute with additional information to the commonly used Aortic Calcification Severity (AC24) score, when…
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Journal:
Authors:
- Barascuk N,
- Ganz M,
- Nielsen M,
- Register TC,
- Rasmussen LM,
- Karsdal MA,
- Christiansen C,
Rheumatology, Osteoarthritis, Rheumatoid Arthritis
8. Dec 2011
Molecular serum and urine marker repertoire supporting clinical research on joint diseases
The need for improved analytical techniques in the study of slow, degenerative diseases such as rheumatoid arthritis and osteoarthritis has driven major efforts aimed at identifying biochemical markers of pathological processes in both diseases. A series of novel biochemical markers has surfaced and…
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Journal:
Authors:
- Qvist P,
- Bay-Jensen AC,
- Christiansen C,
- Sondergaard BC,
- Karsdal MA,
Extracellular Matrix Research, Biomarker position
14. Nov 2011
Protein fingerprints - relying on and understanding the information of serological protein measurements
In 2004, the FDA has articulated a Critical Path Initiative to improve the efficiency of product development industry-wide, and brought attention to the pressing needs of defining new tools to better assess safety and effectiveness of new products. A better understanding of protein subtypes, protein…
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Journal:
Authors:
- Karsdal MA,
- Delvin E,
- Christiansen C,
Bone
7. Nov 2011
Use of bone turnover markers in clinical osteoporosis assessment in women: current issues and future options
Monitoring bone turnover of the adult and aging skeleton is essential for optimal treatment of bone metabolic diseases, such as postmenopausal osteoporosis. Diagnosis of osteoporosis is based solely on dual-emission x-ray absorptiometry-based measurements of bone mineral density. However, within the…
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Authors:
Extracellular Matrix Research
16. Oct 2011
Serological biochemical markers of surrogate efficacy and safety as a novel approach to drug repositioning
How do pharmaceutical companies find new uses for old or failed drugs? Is there a way to 'manage serendipity' at the very first stage of identifying compounds that could be developed into new drugs? Several approaches are now being pursued by various companies that are dedicated to drug repositionin…
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Authors:
Endocrinology, Type 2-Diabetes
13. Oct 2011
A novel oral form of salmon calcitonin improves glucose homeostasis and reduces body weight in diet-induced obese rats
AIM:
To investigate the effects of acute and chronic administration of a novel oral formulation of salmon calcitonin (sCT) on glycaemic control, glucose homeostasis and body weight regulation in diet-induced obese (DIO) rats-an animal model of obesity-related insulin resistance and type 2 diabetes.…
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Journal:
Authors:
- Feigh M,
- Henriksen K,
- Andreassen KV,
- Hansen C,
- Henriksen JE,
- Beck-Nielsen H,
- Christiansen C,
- Karsdal MA,
Oncology, Breast
3. Aug 2011
A novel and automatic mammographic texture resemblance marker is an independent risk factor for breast cancer
OBJECTIVE:
We investigated whether breast cancer is predicted by a breast cancer risk mammographic texture resemblance (MTR) marker.
METHODS:
A previously published case-control study included 495 women of which 245 were diagnosed with breast cancer. In baseline mammograms, 2-4 years prior to d…
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Journal:
Authors:
- Nielsen M,
- Karemore G,
- Loog M,
- Raundahl J,
- Karssemeijer N,
- Otten JD,
- Karsdal MA,
- Vachon CM,
- Christiansen C,
Bone
22. Jul 2011
Vertebral fracture risk (VFR) score for fracture prediction in postmenopausal women
SUMMARY:
Early prognosis of osteoporosis risk is not only important to individual patients but is also a key factor when screening for osteoporosis drug trial populations. We present an osteoporosis fracture risk score based on vertebral heights. The score separated individuals who sustained fractu…
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Journal:
Authors:
- Lillholm M,
- Ghosh A,
- Pettersen PC,
- de Bruijne M,
- Dam EB,
- Karsdal MA,
- Christiansen C,
- Genant HK,
- Nielsen M,
Endocrinology, Type 2-Diabetes
27. May 2011
Efficacy and safety of the PPARγ partial agonist balaglitazone compared with pioglitazone and placebo: a phase III, randomized, parallel-group study in patients with type 2 diabetes on stable insulin therapy
BACKGROUND:
Treatment of patients with perioxisome proliferator-activated receptor-γ full agonists are associated with weight gain, heart failure, peripheral oedema, and bone loss. However, the safety of partial perioxisome proliferator-activated receptor-γ agonists has not been established in a cl…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Beck-Nielsen H,
- Hansen G,
- Riis BJ,
- Perrild H,
- Svendsen OL,
- Gram J,
- Karsdal MA,
- Christiansen C,
- BALLET Trial Investigators,
Bone, Osteoporosis
14. Apr 2011
Strontium ranelate effect in postmenopausal women with different clinical levels of osteoarthritis
OBJECTIVE:
The objective of this post hoc analysis was to investigate the effect of strontium ranelate on a cartilage degradation marker in postmenopausal women who participated in a randomized, placebo-controlled osteoporosis study. Women were stratified according to reported symptoms of osteoarth…
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Journal:
Authors:
- Alexandersen P,
- Karsdal MA,
- Byrjalsen I,
- Christiansen C,
Rheumatology, Spondyloarthropathies
8. Apr 2011
Biochemical markers of ongoing joint damage in rheumatoid arthritis--current and future applications, limitations and opportunities
Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease associated with potentially debilitating joint inflammation, as well as altered skeletal bone metabolism and co-morbid conditions. Early diagnosis and aggressive treatment to control disease activity offers the highest likelihood of …
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Journal:
Authors:
- Karsdal MA,
- Woodworth T,
- Henriksen K,
- Maksymowych WP,
- Genant H,
- Vergnaud P,
- Christiansen C,
- Schubert T,
- Qvist P,
- Schett G,
- Platt A,
- Bay-Jensen AC,
Bone
5. Apr 2011
Lessons learned from the development of oral calcitonin: the first tablet formulation of a protein in phase III clinical trials
Oral delivery of proteins has been hampered by an array of difficulties. However, promising novel oral delivery systems have been developed. 5-CNAC, formulated with the peptide salmon calcitonin, is in phase III clinical trials for the treatment of osteoporosis or osteoarthritis and could become the…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Bay-Jensen AC,
- Molloy B,
- Arnold M,
- John MR,
- Byrjalsen I,
- Azria M,
- Riis BJ,
- Qvist P,
- Christiansen C,
Cardiovascular System, Atherosclerosis
10. Nov 2010
Distribution, size, shape, growth potential and extent of abdominal aortic calcified deposits predict mortality in postmenopausal women
Aortic calcification is a major risk factor for death from cardiovascular disease. We investigated the relationship between mortality and the composite markers of number, size, morphology and distribution of calcified plaques in the lumbar aorta.
METHODS:
308 postmenopausal women aged 48-76 were…
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Journal:
Authors:
- Nielsen M,
- Ganz M,
- Lauze F,
- Pettersen PC,
- de Bruijne M,
- Clarkson TB,
- Dam EB,
- Christiansen C,
- Karsdal MA,
Hepatic System, Non-Alcoholic Fatty Liver Disease
30. Oct 2010
Matrix metalloproteinase-9-mediated type III collagen degradation as a novel serological biochemical marker for liver fibrogenesis
BACKGROUND:
During fibrogenesis in the liver, in which excessive remodelling of the extracellular matrix (ECM) occurs, both the quantity of type III collagen (CO3) and levels of matrix metalloproteinases (MMPs), including MMP-9, increase significantly. MMPs play major roles in ECM remodelling, via …
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Journal:
Authors:
- Veidal SS,
- Vassiliadis E,
- Barascuk N,
- Zhang C,
- Segovia-Silvestre T,
- Klickstein L,
- Larsen MR,
- Qvist P,
- Christiansen C,
- Vainer B,
- Karsdal MA,
Bone
10. Oct 2010
Oral salmon calcitonin--pharmacology in osteoporosis
IMPORTANCE OF THE FIELD:
Osteoporosis is a slow progressive disease with develops over decades, and where intervention is needed for an extended number of years. This highlights the need for safe intervention possibilities, which have sustained beneficial effects post-treatment.
AREAS COVERED IN…
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Rheumatology, Osteoarthritis
17. Jun 2010
Biochemical markers identify influences on bone and cartilage degradation in osteoarthritis--the effect of sex, Kellgren-Lawrence (KL) score, body mass index (BMI), oral salmon calcitonin (sCT) treatment and diurnal variation
BACKGROUND:
Osteoarthritis (OA) involves changes in both bone and cartilage. These processes might be associated under some circumstances. This study investigated correlations between bone and cartilage degradation in patients with OA as a function of sex, Kellgren-Lawrence (KL) score, Body Mass In…
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Authors:
Cardiovascular System, Atherosclerosis
21. Apr 2010
Human macrophage foam cells degrade atherosclerotic plaques through cathepsin K mediated processes
BACKGROUND:
Proteolytic degradation of Type I Collagen by proteases may play an important role in remodeling of atherosclerotic plaques, contributing to increased risk of plaque rupture.The aim of the current study was to investigate whether human macrophage foam cells degrade the extracellular mat…
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Journal:
Authors:
- Barascuk N,
- Skjøt-Arkil H,
- Register TC,
- Larsen L,
- Byrjalsen I,
- Christiansen C,
- Karsdal MA,
Bone
18. Feb 2010
The effect of oral salmon calcitonin delivered with 5-CNAC on bone and cartilage degradation in osteoarthritic patients: a 14-day randomized study
BACKGROUND:
The aim of this study was to investigate the pharmacokinetic and pharmacodynamic parameters of oral salmon calcitonin (oSCT) administered over 14 days to men and women presenting with osteoarthritis (OA).
MATERIALS AND METHODS:
The study was a phase-I, 2-week, placebo-controlled, do…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Henriksen K,
- Riis BJ,
- Lau EM,
- Arnold M,
- Christiansen C,
Rheumatology, Osteoarthritis
15. Feb 2010
Application of biochemical markers in development of drugs for treatment of osteoarthritis
Osteoarthritis is a chronic disease for which no efficacious medical intervention is yet available. Recent disappointments in late-stage clinical development of disease-modifying osteoarthritic drugs (DMOADs) have precipitated efforts in biomarker discovery aimed at developing an analytical tool box…
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Journal:
Authors:
- Qvist P,
- Christiansen C,
- Karsdal MA,
- Madsen SH,
- Sondergaard BC,
- Bay-Jensen AC,
Rheumatology
8. Feb 2010
Biochemical markers of joint tissue turnover
Recent disappointments in late stage developments of anti-osteoarthritic drugs have reinforced efforts to develop better biomarkers for application in both the drug development process as well as in the routine management of these patients. Here we provide a brief review of biochemical tests availab…
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Journal:
Authors:
- Bay-Jensen AC,
- Sondergaard BC,
- Christiansen C,
- Karsdal MA,
- Madsen SH,
- Qvist P,
Bone
16. Jan 2010
Investigations of inter- and intraindividual relationships between exposure to oral salmon calcitonin and a surrogate marker of pharmacodynamic efficacy
AIMS:
The aims of the study were to investigate interindividual variations in the bioavailability of salmon calcitonin (sCT) following single oral 0.8 mg doses at three different times of the day, and intraindividual variation in sCT bioavailability at each end of a 14-day treatment period. We also…
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Authors:
Cardiovascular System, Atherosclerosis
5. Nov 2009
Long-term prevention with hormone-replacement therapy after the menopause: which women should be targeted?
For decades, hormone-replacement therapy (HRT) was considered safe and was the first choice in prevention of postmenopausal osteoporosis induced by estrogen deficiency. Numerous experimental and epidemiological studies further supported a protective effect of exogenous female sex hormones on atherog…
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Journal:
Authors:
- Alexandersen P,
- Karsdal MA,
- Christiansen C,
Endocrinology, Type 2-Diabetes
15. Aug 2009
A comparison of glycemic control, water retention, and musculoskeletal effects of balaglitazone and pioglitazone in diet-induced obese rats
Agonists of Perioxisome Proliferator-Activator Receptor gamma (PPARgamma), which work as insulin sensitizers, are approved for type 2 diabetes. However, adverse effects, such as oedemas, infarctions, and increased fracture rates, limit their applicability. We performed a head-to-head comparison of e…
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Journal:
Authors:
- Henriksen K,
- Byrjalsen I,
- Nielsen RH,
- Madsen AN,
- Larsen LK,
- Christiansen C,
- Beck-Nielsen H,
- Karsdal MA,
Rheumatology, Osteoarthritis
24. Jul 2009
Identification of progressors in osteoarthritis by combining biochemical and MRI-based markers
INTRODUCTION:
At present, no disease-modifying osteoarthritis drugs (DMOADS) are approved by the FDA (US Food and Drug Administration); possibly partly due to inadequate trial design since efficacy demonstration requires disease progression in the placebo group. We investigated whether combinations…
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Journal:
Authors:
- Dam EB,
- Loog M,
- Christiansen C,
- Byrjalsen I,
- Folkesson J,
- Nielsen M,
- Qazi AA,
- Pettersen PC,
- Garnero P,
- Karsdal MA,
Oncology, Breast
16. Jul 2009
Low-dose transdermal estradiol induces breast density and heterogeneity changes comparable to those of raloxifene
The aim of this study was to investigate whether transdermal low-dose estradiol treatment induces changes in mammographic density or heterogeneity compared with raloxifene, whether if these changes relate to changes in bone formation/resorption markers, and whether these findings indicate elevation …
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Journal:
Authors:
- Nielsen M,
- Raundahl J,
- Pettersen PC,
- Loog M,
- Karemore G,
- Karsdal MA,
- Christiansen C,
Extracellular Matrix Research
14. May 2009
Biochemical markers and the FDA Critical Path: how biomarkers may contribute to the understanding of pathophysiology and provide unique and necessary tools for drug development
The aim of this review is to discuss the potential usefulness of a novel class of biochemical markers, neoepitopes, in the context of the US Food and Drug Administration (FDA) Critical Path Initiative, which emphasizes biomarkers of safety and efficacy as areas of pivotal interest. Examples of prote…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Leeming DJ,
- Mitchell P,
- Duffin K,
- Barascuk N,
- Klickstein L,
- Aggarwal P,
- Nemirovskiy O,
- Byrjalsen I,
- Qvist P,
- Bay-Jensen AC,
- Dam EB,
- Madsen SH,
- Christiansen C,
Bone
4. Apr 2009
Influence of food intake on the bioavailability and efficacy of oral calcitonin
AIMS:
To investigate the influence of food intake on the bioavailability and pharmacodynamic effects of salmon calcitonin (sCT).
METHODS:
A single-blind, randomized, partly placebo-controlled study was conducted in 36 healthy postmenopausal female volunteers aged 62-74 years. The influence of f…
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Journal:
Authors:
- Karsdal MA,
- Byrjalsen I,
- Azria M,
- Arnold M,
- Choi L,
- Riis BJ,
- Christiansen C,
Bone
2. Feb 2009
A pharmacokinetic and pharmacodynamic comparison of synthetic and recombinant oral salmon calcitonin
The aim of this study was to assess the bioavailability and pharmacodynamic efficacy of synthetic salmon calcitonin (ssCT) and recombinant salmon calcitonin (rsCT) in healthy postmenopausal women. The study was a single-blind, randomized study. Participants were 36 postmenopausal women 62 to 74 year…
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Bone
12. Jan 2009
Advances in osteoclast biology resulting from the study of osteopetrotic mutations
Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast p…
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Journal:
Authors:
- Segovia-Silvestre T,
- Neutzsky-Wulff AV,
- Sorensen MG,
- Christiansen C,
- Bollerslev J,
- Karsdal MA,
- Henriksen K,
Bone
4. Dec 2008
Investigation of the diurnal variation in bone resorption for optimal drug delivery and efficacy in osteoporosis with oral calcitonin
BACKGROUND:
Bone resorption displays marked diurnal variation. Reversible inhibition of bone resorption may result in best possible efficacy when bone resorption peaks. The aim of the study was to assess the pharmacokinetic (PK) and pharmacodynamic (PD) profiles of 0.8 mg of oral salmon calcitonin …
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Bone, Osteoporosis
18. Nov 2008
Tibolone inhibits bone resorption without secondary positive effects on cartilage degradation
BACKGROUND:
Osteoarthritis is associated with increased bone resorption and increased cartilage degradation in the subchondral bone and joint. The objective of the present study was to determine whether Tibolone, a synthetic steroid with estrogenic, androgenic, and progestogenic properties, would h…
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Bone
19. Sep 2008
The effects of oral calcitonin on bone collagen maturation: implications for bone turnover and quality
Anti-resorptive strategies may affect bone collagen maturation differently depending on the mode of action. Orally administrated calcitonin resulted in a dose dependent inhibition of bone resorption but did not change bone collagen maturation. This may reflect aspects of bone quality.
INTRODUCTIO…
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Authors:
- Karsdal MA,
- Byrjalsen I,
- Leeming DJ,
- Delmas PD,
- Christiansen C,
Bone
8. Sep 2008
Optimizing bioavailability of oral administration of small peptides through pharmacokinetic and pharmacodynamic parameters: the effect of water and timing of meal intake on oral delivery of Salmon Calcitonin
BACKGROUND:
To investigate the influence of water intake and dose timing on the pharmacokinetic and pharmacodynamic parameters of an oral formulation of salmon calcitonin (sCT).
METHODS:
The study was a randomized, partially-blind, placebo-controlled, single dose, exploratory crossover phase I …
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Oncology, Bone
27. Jun 2008
Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?
BACKGROUND:
Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in br…
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Journal:
Authors:
- Leeming DJ,
- Byrjalsen I,
- Qvist P,
- Koizumi M,
- Lynnerup N,
- Fregerslev M,
- Sørensen MG,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
16. Jun 2008
Should subchondral bone turnover be targeted when treating osteoarthritis?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of arthritic disease, and it is a major cause of disability and impaired quality of life in the elderly. OA is a complex disease of the entire joint, including bone and cartilage, thereby presenting alternative approaches for treatment. This re…
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Journal:
Authors:
- Karsdal MA,
- Leeming DJ,
- Dam EB,
- Henriksen K,
- Alexandersen P,
- Pastoureau P,
- Altman RD,
- Christiansen C,
Rheumatology, Osteoarthritis
6. Jun 2008
Automatic quantification of local and global articular cartilage surface curvature: biomarkers for osteoarthritis
The objective of this study was to quantitatively assess the surface curvature of the articular cartilage from low-field magnetic resonance imaging (MRI) data, and to investigate its role in populations with varying radiographic signs of osteoarthritis (OA), cross-sectionally and longitudinally. The…
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Journal:
Authors:
- Folkesson J,
- Dam EB,
- Olsen OF,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Rheumatology, Osteoarthritis
8. May 2008
Cartilage degradation is fully reversible in the presence of aggrecanase but not matrix metalloproteinase activity
INTRODUCTION:
Physiological and pathophysiological cartilage turnover may coexist in articular cartilage. The distinct enzymatic processes leading to irreversible cartilage damage, compared with those needed for continuous self-repair and regeneration, remain to be identified. We investigated the c…
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Journal:
Authors:
- Karsdal MA,
- Madsen SH,
- Christiansen C,
- Henriksen K,
- Fosang AJ,
- Sondergaard BC,
Rheumatology, Osteoarthritis
10. Apr 2008
Oestrogen exhibits type II collagen protective effects and attenuates collagen-induced arthritis in rats
As anti-inflammatory treatments used in rheumatoid arthritis, such as glucocorticoids, often result in secondary detrimental effects on bone health, the objective of this study was to investigate the effects of oestrogen therapy (ET) on the development and activity of collagen-induced arthritis (CIA…
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Journal:
Authors:
- Nielsen RH,
- Christiansen C,
- Stolina M,
- Karsdal MA,
Bone
22. Mar 2008
Calcitonin: a drug of the past or for the future? Physiologic inhibition of bone resorption while sustaining osteoclast numbers improves bone quality
Postmenopausal osteoporosis results from a continuous imbalance between bone resorption and bone formation, favoring bone resorption. An increasing number of treatments for osteoporosis are in development and on the market. A range of differences and similarities are found between these treatment op…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Arnold M,
- Christiansen C,
Bone, Osteoporosis
19. Mar 2008
Bone turnover and bone collagen maturation in osteoporosis: effects of antiresorptive therapies
Bone collagen maturation may be important for anti-fracture efficacy as the reduction in risk is only partly explained by a concomitant increase in BMD during anti-resorptive therapy. Different treatments caused diverse profiles in bone collagen degradation products, which may have implications for …
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Journal:
Authors:
- Byrjalsen I,
- Leeming DJ,
- Qvist P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
13. Feb 2008
Evaluation of cartilage damage by measuring collagen degradation products in joint extracts in a traumatic model of osteoarthritis
The objective of this work was to investigate whether collagen degradation products in protein extract from joints could provide quantitative information on cartilage damage. Osteoarthritis (OA) was surgically induced in rat knee joints. Joints were isolated 7, 14 and 28 days after surgery for prote…
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Journal:
Authors:
- Nielsen RH,
- Stoop R,
- Leeming DJ,
- Stolina M,
- Qvist P,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
11. Feb 2008
An update review of cellular mechanisms conferring the indirect and direct effects of estrogen on articular cartilage
OBJECTIVE:
To review cellular mechanisms that have been proposed to mediate the indirect and direct effects of estrogen on articular cartilage, and to outline the remaining clinical questions that need to be clarified before utilizing the beneficial effects of estrogen for the prevention of osteoar…
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Journal:
Authors:
- Tankó LB,
- Søndergaard BC,
- Oestergaard S,
- Karsdal MA,
- Christiansen C,
Bone
8. Feb 2008
Osteoclasts secrete non-bone derived signals that induce bone formation
Bone turnover is a highly regulated process, where bone resorption in the normal healthy individual always is followed by bone formation in a manner referred to as coupling. Patients with osteopetrosis caused by defective acidification of the resorption lacuna have severely decreased resorption, in …
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Journal:
Authors:
- Karsdal MA,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Christiansen C,
- Karsdal M,
Rheumatology, Osteoarthritis
7. Nov 2007
Calcitonin affects both bone and cartilage: a dual action treatment for osteoarthritis?
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. OA is a complex disease involving both bone and cartilage properties, and may therefore require alternative approaches for treatment. Recent lines o…
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Journal:
Authors:
- Karsdal MA,
- Sondergaard BC,
- Arnold M,
- Christiansen C,
Rheumatology, Osteoarthritis
14. Oct 2007
Osteoarthritic cartilage is more homogeneous than healthy cartilage: identification of a superior region of interest colocalized with a major risk factor for osteoarthritis
RATIONALE AND OBJECTIVES:
Cartilage loss as determined by magnetic resonance imaging (MRI) or joint space narrowing as determined by x-ray is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more sensitive assessment met…
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Journal:
Authors:
- Qazi AA,
- Dam EB,
- Nielsen M,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Rheumatology, Osteoarthritis
15. Aug 2007
The effect of oral calcitonin on cartilage turnover and surface erosion in an ovariectomized rat model
OBJECTIVE:
To investigate whether oral calcitonin treatment influences the increases in type II collagen (CII) degradation and related surface erosions of articular cartilage in ovariectomized rats.
METHODS:
Fifty rats were randomly allocated into 1 of the 5 following intervention groups: sham-…
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Journal:
Authors:
- Sondergaard BC,
- Oestergaard S,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Rheumatology, Osteoarthritis
10. Aug 2007
Bone, cartilage and hormone therapy: established concepts and future scenarios
In the aftermath of the Women's Health Initiative (WHI) study, the firm ground of postmenopausal hormone therapy (HT) has been thoroughly shaken. While there was agreement that HT is indicated for the therapy of menopause-associated vasomotor symptoms and vulvovaginal atrophy, there was a general an…
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Journal:
Authors:
- Holinka CF,
- Karsdal MA,
- Christiansen C,
Bone
18. Jun 2007
Osteoclasts prefer aged bone
We investigated whether the age of the bones endogenously exerts control over the bone resorption ability of the osteoclasts, and found that osteoclasts preferentially develop and resorb bone on aged bone. These findings indicate that the bone matrix itself plays a role in targeted remodeling of age…
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Journal:
Authors:
- Henriksen K,
- Leeming DJ,
- Byrjalsen I,
- Nielsen RH,
- Sorensen MG,
- Dziegiel MH,
- Martin TJ,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
20. May 2007
Induction of increased cAMP levels in articular chondrocytes blocks matrix metalloproteinase-mediated cartilage degradation, but not aggrecanase-mediated cartilage degradation
OBJECTIVE:
Calcitonin has been suggested to have chondroprotective effects. One signaling pathway of calcitonin is via the second messenger cAMP. We undertook this study to investigate whether increased cAMP levels in chondrocytes would be chondroprotective.
METHODS:
Cartilage degradation was i…
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Journal:
Authors:
- Karsdal MA,
- Sumer EU,
- Wulf H,
- Madsen SH,
- Christiansen C,
- Fosang AJ,
- Sondergaard BC,
Bone
18. May 2007
Assessment of osteoclast number and function: application in the development of new and improved treatment modalities for bone diseases
Numerous experimental and clinical observations suggest that overall changes in bone resorption during menopause or treatment with hormone replacement therapy (HRT) are combined effects of changes in osteoclast number and function. Moreover, due to a coupling between osteoclastic bone resorption and…
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Journal:
Authors:
- Henriksen K,
- Tankó LB,
- Qvist P,
- Delmas PD,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
10. May 2007
Separation of healthy and early osteoarthritis by automatic quantification of cartilage homogeneity
OBJECTIVE:
Cartilage loss as determined either by magnetic resonance imaging (MRI) or by joint space narrowing in X-rays is the result of cartilage erosion. However, metabolic processes within the cartilage that later result in cartilage loss may be a more accurate assessment method for early chang…
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Journal:
Authors:
- Qazi AA,
- Folkesson J,
- Karsdal MA,
- Christiansen C,
- Dam EB,
Bone
22. Apr 2007
Are nonresorbing osteoclasts sources of bone anabolic activity?
Some osteopetrotic mutations lead to low resorption, increased numbers of osteoclasts, and increased bone formation, whereas other osteopetrotic mutations lead to low resorption, low numbers of osteoclasts, and decreased bone formation. Elaborating on these findings, we discuss the possibility that …
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Journal:
Authors:
- Karsdal MA,
- Martin TJ,
- Bollerslev J,
- Christiansen C,
- Henriksen K,
Rheumatology, Osteoarthritis
15. Mar 2007
Anabolic and catabolic function of chondrocyte ex vivo is reflected by the metabolic processing of type II collagen
The aim of the present study was to investigate collagen metabolism after anabolic and catabolic stimulation of chondrocytes ex vivo.
DESIGN:
Metabolic activities in ex vivo bovine cartilage explants were stimulated with insulin-like growth factor I (IGF-I) or a combination of tumor necrosis fac…
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Journal:
Authors:
- Olsen AK,
- Sondergaard BC,
- Byrjalsen I,
- Tankó LB,
- Christiansen C,
- Müller A,
- Hein GE,
- Karsdal MA,
- Qvist P,
Rheumatology, Osteoarthritis
15. Feb 2007
MMP and non-MMP-mediated release of aggrecan and its fragments from articular cartilage: a comparative study of three different aggrecan and glycosaminoglycan assays
Aggrecan is the major proteoglycan in articular cartilage and is known to be degraded by various proteases, including matrix metalloproteinases (MMPs). The present study was undertaken to develop immunoassays detecting aggrecan and its fragments generated by MMP and non-MMP-mediated proteolysis.
…
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Journal:
Authors:
- Sumer EU,
- Sondergaard BC,
- Rousseau JC,
- Delmas PD,
- Fosang AJ,
- Karsdal MA,
- Christiansen C,
- Qvist P,
Oncology, Bone
9. Dec 2006
Biochemical approach to the detection and monitoring of metastatic bone disease: What do we know and what questions need answers?
Metastatic spread to bones frequently occurs in several types of cancer diseases, in particular breast, prostate, and lung cancer. Infiltration of bone by tumour cells is a source of several complications including severe bone pain, spinal cord compression, hypercalcemia, pathologic fractures, all r…
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Journal:
Authors:
- Tankó LB,
- Karsdal MA,
- Christiansen C,
- Leeming DJ,
Rheumatology, Osteoarthritis
14. Aug 2006
Calcitonin directly attenuates collagen type II degradation by inhibition of matrix metalloproteinase expression and activity in articular chondrocytes
OBJECTIVE:
Calcitonin was recently reported to counter progression of cartilage degradation in an experimental model of osteoarthritis, and the effects were primarily suggested to be mediated by inhibition of subchondral bone resorption. We investigated direct effects of calcitonin on chondrocytes …
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Journal:
Authors:
- Sondergaard BC,
- Wulf H,
- Henriksen K,
- Schaller S,
- Oestergaard S,
- Qvist P,
- Tankó LB,
- Bagger YZ,
- Christiansen C,
- Karsdal MA,
Rheumatology, Osteoarthritis
3. Aug 2006
Effects of ovariectomy and estrogen therapy on type II collagen degradation and structural integrity of articular cartilage in rats: implications of the time of initiation
OBJECTIVE:
To investigate how the time of initiation influences the effects of estrogen therapy on type II collagen (CII) turnover and the structural integrity of articular cartilage in ovariectomized rats and to determine whether estrogen exerts direct effects on the catabolic function of chondroc…
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Journal:
Authors:
- Oestergaard S,
- Sondergaard BC,
- Hoegh-Andersen P,
- Henriksen K,
- Qvist P,
- Christiansen C,
- Tankó LB,
- Karsdal MA,
Rheumatology, Osteoarthritis
14. Jul 2006
Calcitonin is involved in cartilage homeostasis: is calcitonin a treatment for OA?
OBJECTIVE:
Osteoarthritis (OA) is the most common form of degenerative joint diseases and a major cause of disability and impaired quality of life in the elderly. Recent observations suggest that calcitonin may act on both osteoclasts and chondrocytes. The present review was sought to summarize eme…
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Journal:
Authors:
- Karsdal MA,
- Tankó LB,
- Riis BJ,
- Sondergaard BC,
- Henriksen K,
- Altman RD,
- Qvist P,
- Christiansen C,
Bone
15. Jun 2006
Optimising antiresorptive therapies in postmenopausal women: why do we need to give due consideration to the degree of suppression?
Accelerated bone turnover with bone resorption exceeding bone formation is a major mechanism underlying postmenopausal bone loss and hence the development of osteoporosis. Accordingly, inhibition of bone resorption is a rational approach for the prevention of osteoporosis. In this context, the most …
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Journal:
Authors:
- Karsdal MA,
- Qvist P,
- Christiansen C,
- Tankó LB,
Rheumatology, Osteoarthritis
23. Mar 2006
Relative contribution of matrix metalloprotease and cysteine protease activities to cytokine-stimulated articular cartilage degradation
OBJECTIVE:
Both matrix metalloprotease (MMP) activity and cathepsin K (CK) activity have been implicated in cartilage turnover. We investigated the relative contribution of MMP activity and CK activity in cartilage degradation using ex vivo and in vivo models.
METHODS:
Bovine articular cartilag…
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Journal:
Authors:
- Søndergaard BC,
- Henriksen K,
- Wulf H,
- Oestergaard S,
- Schurigt U,
- Bräuer R,
- Danielsen I,
- Christiansen C,
- Qvist P,
- Karsdal MA,
Rheumatology, Osteoarthritis
7. Jul 2005
Oral salmon calcitonin induced suppression of urinary collagen type II degradation in postmenopausal women: a new potential treatment of osteoarthritis
OBJECTIVE:
To assess the efficacy of 3 months of oral salmon calcitonin (sCT) on cartilage degradation as estimated by the changes in the urinary excretion of C-terminal telopeptide of collagen type II (CTX-II), and to investigate whether the response of oral sCT to urinary CTX-II depends on the ba…
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Journal:
Authors:
- Bagger YZ,
- Tankó LB,
- Alexandersen P,
- Karsdal MA,
- Olson M,
- Mindeholm L,
- Azria M,
- Christiansen C,
Rheumatology, Osteoarthritis
1. Jul 2005
The clinical potential of estrogen for the prevention of osteoarthritis: what is known and what needs to be done?
Osteoarthritis (OA) remains a major epidemiological problem worldwide. The lack of established chondroprotective agents limits the clinical management of this disease to relief of symptoms, such as pain and joint stiffness. The marked increase in the prevalence and incidence of OA among women after …
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Journal:
Authors:
- Tankó LB,
- Karsdal MA,
- Christiansen C,
Bone
5. Feb 2005
Acidification of the osteoclastic resorption compartment provides insight into the coupling of bone formation to bone resorption
Patients with defective osteoclastic acidification have increased numbers of osteoclasts, with decreased resorption, but bone formation that remains unchanged. We demonstrate that osteoclast survival is increased when acidification is impaired, and that impairment of acidification results in inhibit…
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Journal:
Authors:
- Karsdal MA,
- Henriksen K,
- Sørensen MG,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Heegaard AM,
- Christophersen P,
- Martin TJ,
- Christiansen C,
- Bollerslev J,
Bone
23. Mar 2004
Matrix metalloproteinases (MMPs) safeguard osteoblasts from apoptosis during transdifferentiation into osteocytes: MT1-MMP maintains osteocyte viability
Osteoblasts undergo apoptosis or differentiate into either osteocytes or bone-lining cells after termination of bone matrix synthesis. In this study, we investigated the role of matrix metalloproteinases (MMPs) in differentiation of osteoblasts, bone formation, transdifferentiation into osteocytes, …
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Journal:
Authors:
- Karsdal MA,
- Andersen TA,
- Bonewald L,
- Christiansen C,