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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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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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,
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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Ion transporters involved in acidification of the resorption lacuna in osteoclasts
Osteoclasts possess a large amount of ion transporters, which participate in bone resorption; of these, the vacuolar-adenosine trisphosphatase (V-ATPase) and the chloride-proton antiporter ClC-7 acidify the resorption lacuna. However, whether other ion transporters participate in this process is cur…
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Authors:
- Henriksen K,
- Sørensen MG,
- Jensen VK,
- Dziegiel MH,
- Nosjean O,
- Karsdal MA,
Characterization of metalloprotease cleavage products of human articular cartilage
OBJECTIVE:
To identify, characterize, and compare proteolysis peptide products generated by metalloprotease digests of human articular cartilage.
METHODS:
Human articular cartilage was digested by the addition of exogenous metalloproteases, including matrix metalloproteinases 2, 3, 8, 9, 12, an…
Journal:
Authors:
- Zhen EY,
- Brittain IJ,
- Laska DA,
- Mitchell PG,
- Sumer EU,
- Karsdal MA,
- Duffin KL,
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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Authors:
- Leeming DJ,
- Byrjalsen I,
- Qvist P,
- Koizumi M,
- Lynnerup N,
- Fregerslev M,
- Sørensen MG,
- Christiansen C,
- Karsdal MA,
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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Authors:
- Karsdal MA,
- Leeming DJ,
- Dam EB,
- Henriksen K,
- Alexandersen P,
- Pastoureau P,
- Altman RD,
- Christiansen C,
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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Authors:
- Folkesson J,
- Dam EB,
- Olsen OF,
- Karsdal MA,
- Pettersen PC,
- Christiansen C,
Characterization of the bone phenotype in ClC-7-deficient mice
Mice deficient in the chloride channel ClC-7, which is likely involved in acidification of the resorption lacuna, display severe osteopetrosis. To fully characterize the osteopetrotic phenotype, the phenotypes of osteoclasts and osteoblasts were evaluated. ClC-7(-/-) mice and their corresponding wil…
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Authors:
- Neutzsky-Wulff AV,
- Karsdal MA,
- Henriksen K,
Biochemical markers for monitoring response to therapy: evidence for higher bone specificity by a novel marker compared with routine markers
The aim of the present study was to compare a novel marker for high bone turnover with two routine markers for screening in prostate cancer patients. The markers were evaluated in two studies: (a) a cross-sectional study of 170 prostate cancer patients with local disease stratified by +/-lymph node …
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Authors:
- Leeming DJ,
- Hegele A,
- Byrjalsen I,
- Hofmann R,
- Qvist P,
- Karsdal MA,
- Schrader AJ,
- Wagner R,
- Olbert P,
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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Authors:
- Karsdal MA,
- Madsen SH,
- Christiansen C,
- Henriksen K,
- Fosang AJ,
- Sondergaard BC,
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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Authors:
- Nielsen RH,
- Christiansen C,
- Stolina M,
- Karsdal MA,
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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Authors:
- Karsdal MA,
- Henriksen K,
- Arnold M,
- Christiansen C,
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 …
Journal:
Authors:
- Byrjalsen I,
- Leeming DJ,
- Qvist P,
- Christiansen C,
- Karsdal MA,
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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Authors:
- Nielsen RH,
- Stoop R,
- Leeming DJ,
- Stolina M,
- Qvist P,
- Christiansen C,
- Karsdal MA,
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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Authors:
- Tankó LB,
- Søndergaard BC,
- Oestergaard S,
- Karsdal MA,
- Christiansen C,
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 …
Journal:
Authors:
- Karsdal MA,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Christiansen C,
- Karsdal M,