Bone, Osteoporosis
15. May 2020
Generation of Gene-Corrected Functional Osteoclasts From Osteopetrotic Induced Pluripotent Stem Cells
Background: Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by non-functional osteoclasts and a fatal outcome early in childhood. About 50% of patients have mutations in the TCIRG1 gene.
Methods: IMO iPSCs were generated from a patient carrying a homozygou…
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Journal:
Authors:
- Xian X,
- Moraghebi R,
- Löfvall H,
- Fasth A,
- Henriksen K,
- Richter J,
- Woods NB,
- Moscatelli I,
Rheumatology, Bone, Osteoporosis, Osteoarthritis, Biomarker position
30. Sep 2019
Biochemical markers in osteoarthritis with lessons learned from osteoporosis.
Osteoarthritis (OA) is a disease of the whole joint, including synovium, bone and cartilage. OA is a slow degenerative and very heterogeneous disease, with both varying levels of disease activity and progression. Biomarkers are urgently needed to assist drug developers in selecting and developing th…
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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,
Osteoporosis, Bone
10. Jun 2019
Hematopoietic stem cell-targeted neonatal gene therapy with a clinically applicable lentiviral vector corrects osteopetrosis in oc/oc mice.
Infantile malignant osteopetrosis (IMO) is an autosomal recessive disorder characterized by nonfunctional osteoclasts. Approximately 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. Gene therapy represents a potential alternative treatment …
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Journal:
Authors:
- Löfvall H,
- Rothe M,
- Schambach A,
- Henriksen K,
- Richter J,
- Moscatelli I,
Bone, Rheumatology, Osteoarthritis
5. Jun 2019
A dual amylin and calcitonin receptor agonist inhibits pain behavior and reduces cartilage pathology in an osteoarthritis rat model
OBJECTIVES:
Pain and disability are the main clinical manifestations of osteoarthritis, for which only symptomatic therapies are available. Hence, there is a need for therapies that can simultaneously alter disease progression and provide pain relief. KBP is a dual amylin- and calcitonin-receptor a…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Lövfall H,
- Karsdal MA,
- Andreassen KV,
- Thudium CS,
- Henriksen K,
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,
Rheumatology, Bone
28. Feb 2019
GPDPLQ1237-A Type II Collagen Neo-Epitope Biomarker of Osteoclast- and Inflammation-Derived Cartilage Degradation in vitro
C-telopeptide of type II collagen (CTX-II) has been shown to be a highly relevant biomarker of cartilage degradation in human rheumatic diseases, if measured in synovial fluid or urine. However, serum or plasma CTX-II have not been demonstrated to have any clinical utility to date. Here, we describe…
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Journal:
Authors:
- Löfvall H,
- Katri A,
- Dabrowska A,
- Karsdal MA,
- Luo Y,
- He Y,
- Manon-Jensen T,
- Dziegiel MH,
- Bay-Jensen AC,
- Thudium CS,
- Henriksen K,
Rheumatology, Rheumatoid Arthritis, Bone
22. Feb 2019
Combining Naproxen and a Dual Amylin and Calcitonin Receptor Agonist improves pain and structural outcomes in the Collagen-Induced Arthritis rat model
BACKGROUND:
Pain is a debilitating symptom of rheumatoid arthritis (RA), caused by joint inflammation and cartilage and bone destruction. Nonsteroidal anti-inflammatory drugs (NSAIDs) are used to treat pain and inflammation in RA, but are not disease-modifying and do not prevent joint destruction w…
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Journal:
Authors:
- Katri A,
- Dabrowska A,
- Löfvall H,
- Ding M,
- Karsdal MA,
- Andreassen KV,
- Schneider Thudium C,
- Henriksen K,
Bone, Extracellular Matrix Research
2. Oct 2018
Alterations in non-type I collagen biomarkers in osteogenesis imperfecta.
Osteogenesis imperfecta (OI) is a rare disorder of connective tissue caused by abnormalities in the synthesis or processing of type I collagen. Type I collagen is the most abundant type of collagen and is expressed in almost all connective tissues. Given that type I collagen interacts with other col…
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Journal:
Authors:
- Nicol L,
- Morar P,
- Wang Y,
- Henriksen K,
- Sun S,
- Karsdal MA,
- Smith R,
- Nagamani SCS,
- Shapiro J,
- Lee B,
- Orwoll E,
Bone, Extracellular Matrix Research, Biomarker position
14. Jul 2018
Bone and soft tissue turnover in relation to all-cause mortality in postmenopausal women.
BACKGROUND:
The relationship between levels of extracellular matrix (ECM) turnover and mortality is currently unknown. The study aimed to determine if levels of ECM turnover are predictors of all-cause mortality in a large cohort of post-menopausal women.
METHODS:
5,855 postmenopausal Danish wo…
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Journal:
Authors:
- Bager CL,
- Willumsen N,
- Bay-Jensen AC,
- Nielsen HB,
- Karsdal MA,
Bone, Extracellular Matrix Research, Osteoarthritis
10. Apr 2018
Osteoclasts degrade bone and cartilage knee joint compartments through different resorption processes
BACKGROUND:
Osteoclasts have been strongly implicated in osteoarthritic cartilage degradation, at least indirectly via bone resorption, and have been shown to degrade cartilage in vitro. The osteoclast resorption processes required to degrade subchondral bone and cartilage-the remodeling of which i…
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Journal:
Authors:
- Löfvall H,
- Newbould H,
- Karsdal MA,
- Dziegiel MH,
- Richter J,
- Henriksen K,
- Thudium CS,
Bone, Osteoporosis
20. Jul 2017
Targeting NSG mice-engrafting cells with a clinically applicable lentiviral vector corrects osteoclasts in Infantile Malignant Osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by nonfunctional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to develop a clinically…
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Journal:
Authors:
- Moscatelli I,
- Löfvall H,
- Schneider Thudium C,
- Rothe M,
- Montano C,
- Kertész Z,
- Sirin M,
- Schulz A,
- Schambach A,
- Henriksen K,
- Richter J,
Bone
15. Jul 2017
Preventive effects of kudzu root on bone loss and cartilage degradation in ovariectomized rat
The clinical utility of Traditional Chinese Medicine (TCM) herbs/roots extracts in osteoporosis (OP) and osteoarthritis (OA) has been described in multiple reports, but there have been few studies of TCM for preventing bone loss and cartilage degradation simultaneously. Six-month-old female Sprague-…
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Authors:
- Luo Y,
- Zheng S,
- Ding Y,
- Dai Y,
- Zhou Y,
- Xiang R,
- Qvist P,
- Zheng Q,
- Bay-Jensen AC,
- Karsdal MA,
Osteoporosis
3. Feb 2017
Forced expression of human M-CSF in CD34+ cells promotes monocyte differentiation in vitro and in vivo but blunts osteoclastogenesis in vitro
OBJECTIVES:
Here, we tested the hypothesis that human M-CSF (hM-CSF) overexpressed in cord blood (CB) CD34+ cells would induce differentiation and survival of monocytes and osteoclasts in vitro and in vivo.
METHODS:
Human M-CSF was overexpressed in cord blood CD34+ cells using a lentiviral vect…
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Journal:
Authors:
- Montano Almendras CP,
- Thudium CS,
- Löfvall H,
- Moscatelli I,
- Schambach A,
- Henriksen K,
- Richter J,
Bone
14. Dec 2016
High throughput, quantitative analysis of human osteoclast differentiation and activity
Osteoclasts are multinuclear cells that degrade bone under both physiological and pathophysiological conditions. Osteoclasts are therefore a major target of osteoporosis therapeutics aimed at preserving bone. Consequently, analytical methods for osteoclast activity are useful for the development of …
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Journal:
Authors:
- Diepenhorst NA,
- Nowell CJ,
- Rueda P,
- Henriksen K,
- Pierce T,
- Cook AE,
- Pastoureau P,
- Sabatini M,
- Charman WN,
- Christopoulos A,
- Summers RJ,
- Sexton PM,
- Langmead CJ,
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,
Bone
30. Aug 2016
Neo-epitope Peptides as Biomarkers of Disease Progression for Muscular Dystrophies and Other Myopathies
For several decades, serological biomarkers of neuromuscular diseases as dystrophies, myopathies and myositis have been limited to routine clinical biochemistry panels. Gauging the pathological progression is a prerequisite for proper treatment and therefore identifying accessible, easy to monitor b…
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Journal:
Authors:
- Arvanitidis A,
- Henriksen K,
- Karsdal MA,
- Nedergaard AF,
Bone
19. Aug 2016
Regulation and Function of Lentiviral Vector-Mediated TCIRG1 Expression in Osteoclasts from Patients with Infantile Malignant Osteopetrosis: Implications for Gene Therapy
Infantile malignant osteopetrosis (IMO) is a rare, recessive disorder characterized by increased bone mass caused by dysfunctional osteoclasts. The disease is most often caused by mutations in the TCIRG1 gene encoding a subunit of the V-ATPase involved in the osteoclasts capacity to resorb bone. We …
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Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Löfvall H,
- Kertész Z,
- Montano C,
- Bjurström CF,
- Karsdal MA,
- Schulz AS,
- Richter J,
- Henriksen K,
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,
Osteoporosis, Bone
1. Jun 2016
Zoledronate prevents lactation induced bone loss and results in additional post-lactation bone mass in mice
In rodents, lactation is associated with a considerable and very rapid bone loss, which almost completely recovers after weaning. The aim of the present study was to investigate whether the bisphosphonate Zoledronate (Zln) can inhibit lactation induced bone loss, and if Zln interferes with recovery …
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Journal:
Authors:
- Wendelboe MH,
- Thomsen JS,
- Henriksen K,
- Vegger JB,
- Brüel A,
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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Bone, Osteoporosis
8. Sep 2015
Null mutation of chloride channel 7 (Clcn7) impairs dental root formation but does not affect enamel mineralization
ClC-7, located in late endosomes and lysosomes, is critical for the function of osteoclasts. Secretion of Cl(-) by the ruffled border of osteoclasts enables H(+) secretion by v-H(+)-ATPases to dissolve bone mineral. Mice lacking ClC-7 show altered lysosomal function that leads to severe lysosomal st…
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Journal:
Authors:
- Guo J,
- Bervoets TJ,
- Henriksen K,
- Everts V,
- Bronckers AL,
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,
Bone, Osteoporosis
1. Jul 2015
Suppressed bone remodeling in black bears conserves energy and bone mass during hibernation
Decreased physical activity in mammals increases bone turnover and uncouples bone formation from bone resorption, leading to hypercalcemia, hypercalcuria, bone loss and increased fracture risk. Black bears, however, are physically inactive for up to 6 months annually during hibernation without losin…
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Journal:
Authors:
- McGee-Lawrence M,
- Buckendahl P,
- Carpenter C,
- Henriksen K,
- Vaughan M,
- Donahue S,
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:
Bone
22. Jul 2014
A comparison of osteoclast-rich and osteoclast-poor osteopetrosis in adult mice sheds light on the role of the osteoclast in coupling bone resorption and bone formation
Osteopetrosis due to lack of acid secretion by osteoclasts is characterized by abolished bone resorption, increased osteoclast numbers, but normal or even increased bone formation. In contrast, osteoclast-poor osteopetrosis appears to have less osteoblasts and reduced bone formation, indicating that…
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Journal:
Authors:
- Thudium CS,
- Moscatelli I,
- Flores C,
- Thomsen JS,
- Brüel A,
- Gudmann NS,
- Hauge EM,
- Karsdal MA,
- Richter J,
- Henriksen K,
Bone, Rheumatology, Osteoarthritis
6. Jun 2014
ALPHA-CTX is associated with subchondral bone turnover and predicts progression of joint space narrowing and osteophytes in osteoarthritis
OBJECTIVE:
To evaluate joint tissue remodeling, with urinary collagen biomarkers, uALPHA CTX and uCTXII, and their association with osteoarthritis (OA) severity, progression, and localized knee bone turnover.
METHODS:
Participants (N=149) with symptomatic and radiographic knee OA underwent fixe…
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Journal:
Authors:
- Huebner JL,
- Bay-Jensen AC,
- Huffman KM,
- He Y,
- Leeming DJ,
- McDaniel GE,
- Karsdal MA,
- Kraus VB,
Bone
22. Apr 2014
Decline in calcitonin receptor expression in osteocytes with age
We have previously shown that co-administration of the transient osteoclast inhibitor, salmon calcitonin (sCT), blunts the anabolic effect of parathyroid hormone (PTH) in young rats and increases osteocytic expression of the bone formation inhibitor sclerostin (Sost). To determine whether this also …
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Journal:
Authors:
- Gooi JH,
- Chia LY,
- Walsh NC,
- Karsdal MA,
- Quinn JM,
- Martin TJ,
- Sims NA,
Bone
15. Jan 2014
Osteoclast-derived coupling factors in bone remodeling
In the bone remodeling process that takes place throughout the skeleton at bone multicellular units, intercellular communication processes are crucial. The osteoblast lineage has long been known to program osteoclast formation and hence resorption, but the preservation of bone mass and integrity req…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Martin TJ,
Bone
11. Dec 2013
Osteoclasts are not crucial for hematopoietic stem cell maintenance in adult mice
The osteoclast is vital for establishment of normal hematopoiesis in the developing animal. However, its role for maintenance of hematopoiesis in adulthood is more controversial. To shed more light on this process, we transplanted hematopoietic stem cells from two osteopetrotic mouse models, with la…
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Journal:
Authors:
- Flores C,
- Moscatelli I,
- Thudium CS,
- Gudmann NS,
- Thomsen JS,
- Brüel A,
- Karsdal MA,
- Henriksen K,
- Richter J,
Bone
5. Nov 2013
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34(+) cells restores osteoclast function in infantile malignant osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…
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Journal:
Authors:
- Moscatelli I,
- Thudium CS,
- Flores C,
- Schulz A,
- Askmyr M,
- Gudmann NS,
- Andersen NM,
- Porras O,
- Karsdal MA,
- Villa A,
- Fasth A,
- Henriksen K,
- Richter J,
Bone
29. Jul 2013
Lentiviral gene transfer of TCIRG1 into peripheral blood CD34+ cells restores osteoclast function in infantile malignant osteopetrosis
Infantile malignant osteopetrosis (IMO) is a rare, lethal, autosomal recessive disorder characterized by non-functional osteoclasts. More than 50% of the patients have mutations in the TCIRG1 gene, encoding for a subunit of the osteoclast proton pump. The aim of this study was to restore the resorpt…
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Journal:
Authors:
- Moscatelli I,
- Thudium CS,
- Flores C,
- Schulz A,
- Askmyr M,
- Gudmann KN,
- Andersen NM,
- Porras O,
- Karsdal MA,
- Villa A,
- Fasth A,
- Henriksen K,
- Richter J,
Bone
13. Jul 2013
Autosomal dominant osteopetrosis revisited: lessons from recent studies
Systematic studies of autosomal dominant osteopetrosis (ADO) were followed by the identification of underlying mutations giving unique possibilities to perform translational studies. What was previously designated ADO1 turned out to be a high bone mass phenotype caused by a missense mutation in the …
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Journal:
Authors:
- Bollerslev J,
- Henriksen K,
- Nielsen MF,
- Brixen K,
- Van Hul W,
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,
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,
Bone
16. Sep 2012
A specific subtype of osteoclasts secretes factors inducing nodule formation by osteoblasts
Osteoclasts are known to be important for the coupling process between bone resorption and formation. The aim of this study was to address when osteoclasts are anabolically active. Human monocytes were differentiated into mature osteoclasts by treatment with M-CSF and RANKL. Conditioned medium was c…
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Journal:
Authors:
- Henriksen K,
- Andreassen KV,
- Thudium CS,
- Gudmann KN,
- Moscatelli I,
- Crüger-Hansen CE,
- Schulz AS,
- Dziegiel MH,
- Richter J,
- Karsdal MA,
- Neutzsky-Wulff AV,
Bone
5. Apr 2012
Generation of human osteoclasts from peripheral blood
Osteoclasts are multi-nucleated cells that have the unique ability to resorb calcified bone matrix. They derive from haematopoietic precursor cells, and can be generated in vitro by stimulation of peripheral blood mononuclear cells with the cytokines M-CSF and RANKL. In this chapter, we describe the…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Taylor A,
- Tosh D,
- Coxon FP,
Bone, Osteoporosis
13. Mar 2012
Disruption of the V-ATPase functionality as a way to uncouple bone formation and resorption - a novel target for treatment of osteoporosis
The unique ability of the osteoclasts to resorb the calcified bone matrix is dependent on secretion of hydrochloric acid. This process is mediated by a vacuolar H+ ATPase (V-ATPase) and a chloride-proton antiporter. The structural subunit of the V-ATPase, a3, is highly specific for osteoclasts, and …
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Journal:
Authors:
- Thudium CS,
- Jensen VK,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
11. Dec 2011
Glucocorticoids exert context-dependent effects on cells of the joint in vitro
INTRODUCTION:
Glucocorticoids are known to attenuate bone formation in vivo leading to decreased bone volume and increased risk of fractures, whereas effects on the joint tissue are less characterized. However, glucocorticoids appear to have a reducing effect on inflammation and pain in osteoarthri…
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Journal:
Authors:
- Madsen SH,
- Andreassen KV,
- Christensen ST,
- Karsdal MA,
- Sverdrup FM,
- Bay-Jensen AC,
- Henriksen K,
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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Journal:
Authors:
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,
Bone
15. Jun 2011
Degradation of the organic phase of bone by osteoclasts: a secondary role for lysosomal acidification
Osteoclasts degrade bone matrix by secretion of hydrochloric acid and proteases. We studied the processes involved in the degradation of the organic matrix of bone in detail and found that lysosomal acidification is involved in this process and that MMPs are capable of degrading the organic matrix i…
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Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Nielsen RH,
- Gram J,
- Schaller S,
- Dziegiel MH,
- Everts V,
- Bollerslev J,
- Karsdal MA,
Bone
11. Jun 2011
Dissociation of bone resorption and bone formation in adult mice with a non-functional V-ATPase in osteoclasts leads to increased bone strength
Osteopetrosis caused by defective acid secretion by the osteoclast, is characterized by defective bone resorption, increased osteoclast numbers, while bone formation is normal or increased. In contrast the bones are of poor quality, despite this uncoupling of formation from resorption.To shed light …
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Journal:
Authors:
- Henriksen K,
- Flores C,
- Thomsen JS,
- Brüel AM,
- Thudium CS,
- Neutzsky-Wulff AV,
- Langenbach GE,
- Sims N,
- Askmyr M,
- Martin TJ,
- Everts V,
- Karsdal MA,
- Richter J,
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,
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,
Bone
15. Feb 2011
Osteoclast activity and subtypes as a function of physiology and pathology--implications for future treatments of osteoporosis
Osteoclasts have traditionally been associated exclusively with catabolic functions that are a prerequisite for bone resorption. However, emerging data suggest that osteoclasts also carry out functions that are important for optimal bone formation and bone quality. Moreover, recent findings indicate…
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Authors:
- Henriksen K,
- Bollerslev J,
- Everts V,
- Karsdal MA,
Bone
10. Jan 2011
Imatinib mesylate does not increase bone volume in vivo
Imatinib mesylate is a tyrosine kinase inhibitor used in the management of disorders in which activation of c-Abl, PDGFR, or c-Kit signaling plays a critical role. In vitro, imatinib stimulates osteoblast differentiation, inhibits osteoblast proliferation and survival, and decreases osteoclast devel…
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Journal:
Authors:
- O'Sullivan S,
- Naot D,
- Callon KE,
- Watson M,
- Gamble GD,
- Ladefoged M,
- Karsdal MA,
- Browett P,
- Cornish J,
- Grey A,
Bone
4. Nov 2010
A quantitative assay for lysosomal acidification rates in human osteoclasts
The osteoclast initiates resorption by creating a resorption lacuna. The ruffled border surrounding the lacunae arises from exocytosis of lysosomes. To dissolve the inorganic phase of the bone, the vacuolar adenosine triphosphatase, located in the ruffled border, pumps protons into the resorption la…
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Journal:
Authors:
- Jensen VK,
- Nosjean O,
- Dziegiel MH,
- Boutin JA,
- Sørensen MG,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
26. Oct 2010
Screening of protein kinase inhibitors identifies PKC inhibitors as inhibitors of osteoclastic acid secretion and bone resorption
BACKGROUND:
Bone resorption is initiated by osteoclastic acidification of the resorption lacunae. This process is mediated by secretion of protons through the V-ATPase and chloride through the chloride antiporter ClC-7. To shed light on the intracellular signalling controlling extracellular acidifi…
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Journal:
Authors:
- Sørensen MG,
- Karsdal MA,
- Dziegiel MH,
- Boutin JA,
- Nosjean O,
- Henriksen K,
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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Bone, Osteoporosis
5. Oct 2010
Enzyme-linked immunosorbent serum assays (ELISAs) for rat and human N-terminal pro-peptide of collagen type I (PINP)--assessment of corresponding epitopes
OBJECTIVES:
The present study describes two newly developed N-terminal pro-peptides of collagen type I (PINP) competitive enzyme-linked immunosorbent assays (ELISAs) for the assessment of corresponding PINP epitopes in the rat- and human species.
METHODS:
Monoclonal antibodies were raised again…
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Journal:
Authors:
- Leeming DJ,
- Larsen DV,
- Zhang C,
- Hi Y,
- Veidal SS,
- Nielsen RH,
- Henriksen K,
- Zheng Q,
- Barkholt V,
- Riis BJ,
- Byrjalsen I,
- Qvist P,
- Karsdal MA,
Bone
15. Aug 2010
Severe developmental bone phenotype in ClC-7 deficient mice
Bone development is dependent on the functionality of three essential cell types: chondrocytes, osteoclasts and osteoblasts. If any of these cell types is dysfunctional, a developmental bone phenotype can result. The bone disease osteopetrosis is caused by osteoclast dysfunction or impaired osteocla…
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Sims NA,
- Supanchart C,
- Kornak U,
- Felsenberg D,
- Poulton IJ,
- Martin TJ,
- Karsdal MA,
- Henriksen K,
Bone
6. Jun 2010
Calcitonin impairs the anabolic effect of PTH in young rats and stimulates expression of sclerostin by osteocytes
The therapeutic goal of increasing bone mass by co-treatment of parathyroid hormone (PTH) and an osteoclast inhibitor has been complicated by the undefined contribution of osteoclasts to the anabolic activity of PTH. To determine whether active osteoclasts are required at the time of PTH administrat…
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Journal:
Authors:
- Gooi JH,
- Pompolo S,
- Karsdal MA,
- Kulkarni NH,
- Kalajzic I,
- McAhren SH,
- Han B,
- Onyia JE,
- Ho PW,
- Walsh NC,
- Chia LY,
- Quinn JM,
- Martin TJ,
- Sims NA,
Bone, Osteoporosis
1. Jun 2010
Alterations in osteoclast function and phenotype induced by different inhibitors of bone resorption--implications for osteoclast quality
BACKGROUND:
Normal osteoclasts resorb bone by secretion of acid and proteases. Recent studies of patients with loss of function mutations affecting either of these processes have indicated a divergence in osteoclastic phenotypes. These difference in osteoclast phenotypes may directly or indirectly …
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Journal:
Authors:
- Neutzsky-Wulff AV,
- Sørensen MG,
- Kocijancic D,
- Leeming DJ,
- Dziegiel MH,
- Karsdal MA,
- Henriksen K,
Bone
15. May 2010
Should biochemical markers of bone turnover be considered standard practice for safety pharmacology
The success in biomedical sciences such as genomics and proteomics is not paralleled in the medical product development methods. The consequence of this is a lack of translation into improved drug safety and efficacy. Therefore the US Food and Drug Administration (FDA) introduced the Critical Path I…
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Journal:
Authors:
- Henriksen K,
- Bohren KM,
- Bay-Jensen AC,
- 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,
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:
Bone
10. Dec 2009
PLCL1 rs7595412 variation is not associated with hip bone size variation in postmenopausal Danish women
BACKGROUND:
Bone size (BS) variation is under strong genetic control and plays an important role in determining bone strength and fracture risk. Recently, a genome-wide association study identified polymorphisms associated with hip BS variation in the PLCL1 (phospholipase c-like 1) locus. Carriers …
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Journal:
Authors:
- Cauchi S,
- Byrjalsen I,
- Durand E,
- Karsdal MA,
- Froguel P,
Bone, Osteoporosis
20. Sep 2009
Is bone quality associated with collagen age?
The World Health Organization defines osteoporosis as a systemic disease characterized by decreased bone tissue mass and microarchitectural deterioration, resulting in increased fracture risk. Since this statement, a significant amount of data has been generated showing that these two factors do not…
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Journal:
Authors:
- Leeming DJ,
- Henriksen K,
- Byrjalsen I,
- Qvist P,
- Madsen SH,
- Garnero P,
- Karsdal MA,
Bone
4. Jun 2009
Local communication on and within bone controls bone remodeling
Bone remodeling is required for healthy calcium homeostasis and for repair of damage occurring with stress and age. Osteoclasts resorb bone and osteoblasts form bone. These processes normally occur in a tightly regulated sequence of events, where the amount of formed bone equals the amount of resorb…
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Journal:
Authors:
- Henriksen K,
- Neutzsky-Wulff AV,
- Bonewald LF,
- Karsdal MA,
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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Authors:
Bone
23. Jan 2009
Characterization of acid flux in osteoclasts from patients harboring a G215R mutation in ClC-7
The chloride-proton antiporter ClC-7 has been speculated to be involved in acidification of the lysosomes and the resorption lacunae in osteoclasts; however, neither direct measurements of chloride transport nor acidification have been performed. Human osteoclasts harboring a dominant negative mutat…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Neutzsky-Wulff AV,
- Jensen VK,
- Dziegiel MH,
- Bollerslev J,
- Karsdal MA,
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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Authors:
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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Authors:
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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Journal:
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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Authors:
Bone
4. Sep 2008
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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Journal:
Authors:
- Henriksen K,
- Sørensen MG,
- Jensen VK,
- Dziegiel MH,
- Nosjean O,
- Karsdal MA,
Bone
3. Jun 2008
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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Journal:
Authors:
- Neutzsky-Wulff AV,
- Karsdal MA,
- Henriksen K,
Bone, Osteoporosis
17. May 2008
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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Journal:
Authors:
- Leeming DJ,
- Hegele A,
- Byrjalsen I,
- Hofmann R,
- Qvist P,
- Karsdal MA,
- Schrader AJ,
- Wagner R,
- Olbert P,
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,
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,
Bone
22. Oct 2007
Diphyllin, a novel and naturally potent V-ATPase inhibitor, abrogates acidification of the osteoclastic resorption lacunae and bone resorption
Dissolution of the inorganic phase of bone by the osteoclasts mediated by V-ATPase and ClC-7 is a prerequisite for bone resorption. Inhibitors of osteoclastic V-ATPase or ClC-7 are novel approaches for inhibition of osteoclastic bone resorption. By testing natural compounds in acidification assays, …
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Neutzsky-Wulff AV,
- Dziegiel MH,
- Karsdal MA,
Bone
7. Sep 2007
Dissolution of the inorganic phase of bone leading to release of calcium regulates osteoclast survival
Osteoclasts are the sole cells possessing the ability to resorb calcified bone matrix. This occurs via secretion of hydrochloric acid mediated by the V-ATPase and the chloride channel ClC-7. Loss of acidification leads to osteopetrosis characterized by ablation of bone resorption and increased osteo…
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Journal:
Authors:
- Nielsen RH,
- Karsdal MA,
- Sørensen MG,
- Dziegiel MH,
- Henriksen K,
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,
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,
Bone
15. May 2007
Characterization of osteoclasts derived from CD14+ monocytes isolated from peripheral blood
Bone resorption is solely mediated by osteoclasts. Therefore, a pure osteoclast population is of high interest for the investigation of biological aspects of the osteoclasts, such as the direct effect of growth factors and hormones, as well as for testing and characterizing inhibitors of bone resorp…
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Henriksen DB,
- Nielsen FC,
- Dziegiel MH,
- Karsdal MA,
Bone
12. May 2007
Biochemical markers in preclinical models of osteoporosis
Although several treatments for osteoporosis exist, further understanding of the mode of action of current treatments, as well as development of novel treatments, are of interest. Thus, preclinical models of osteoporosis are very useful, as they provide the possibility for gaining knowledge about th…
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Schaller S,
- Karsdal MA,
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,
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,
Bone
25. Aug 2006
Estrogen directly attenuates human osteoclastogenesis, but has no effect on resorption by mature osteoclasts
Estrogen deficiency arising with the menopause promotes marked acceleration of bone resorption, which can be restored by hormone replacement therapy. The inhibitory effects of estrogen seem to involve indirect cytokine- mediated effects via supporting bone marrow cells, but direct estrogen-receptor …
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Journal:
Authors:
- Sørensen MG,
- Henriksen K,
- Dziegiel MH,
- Tankó LB,
- Karsdal MA,
Bone, Osteoporosis
16. Aug 2006
An update on biomarkers of bone turnover and their utility in biomedical research and clinical practice
BACKGROUND:
Maintenance of the structural and functional integrity of the skeleton is a critical function of a continuous remodeling driven by highly associated processes of bone resorption and synthetic activities driven by osteoclasts and osteoblasts, respectively. Acceleration of bone turnover, …
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Journal:
Authors:
- Leeming DJ,
- Alexandersen P,
- Karsdal MA,
- Qvist P,
- Schaller S,
- Tankó LB,
Oncology, Bone
15. Jul 2006
Alpha CTX as a biomarker of skeletal invasion of breast cancer: immunolocalization and the load dependency of urinary excretion
We recently showed that increased urinary excretion of the cross-linked, nonisomerized form of the C-telopeptide of collagen type I (alphaalphaCTX) could be a sensitive indicator of the presence of bone metastases in breast cancer patients. The present study was sought to investigate (a) the localiz…
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Journal:
Authors:
- Leeming DJ,
- Delling G,
- Koizumi M,
- Henriksen K,
- Karsdal MA,
- Li B,
- Qvist P,
- Tankó LB,
- Byrjalsen I,
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,
Bone
10. Apr 2006
Mechanisms involved in skeletal anabolic therapies
Since parathyroid hormone (PTH) is the only proven anabolic therapy for bone, it becomes the benchmark by which new treatments will be evaluated. The anabolic effect of PTH is dependent upon intermittent administration, but when an elevated PTH level is maintained even for a few hours it initiates p…
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Journal:
Authors:
- Martin TJ,
- Quinn JM,
- Gillespie MT,
- Ng KW,
- Karsdal M,
- Sims NA,
Bone
5. Nov 2005
Osteoclasts from patients with autosomal dominant osteopetrosis type I caused by a T253I mutation in low-density lipoprotein receptor-related protein 5 are normal in vitro, but have decreased resorption capacity in vivo
Autosomal dominant osteopetrosis type I (ADOI) is presumably caused by gain-of-function mutations in the LRP5 gene. Patients with a T253I mutation in LRP5 have a high bone mass phenotype, characterized by increased mineralizing surface index but abnormally low numbers of small osteoclasts. To invest…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Høegh-Andersen P,
- Jemtland R,
- Ueland T,
- Dziegiel MH,
- Schaller S,
- Bollerslev J,
- Karsdal MA,
Bone
18. Oct 2005
The role of chloride channels in osteoclasts: ClC-7 as a target for osteoporosis treatment
Chloride ions play a major role in osteoclast biology and bone homeostasis. In addition to its general cellular roles, chloride is involved in the specific bone resorption activity of osteoclasts. The chloride channel ClC-7 has been shown to be mandatory for bone resorption. It is necessary for the …
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Sørensen MG,
- Karsdal MA,
Bone
2. Jun 2005
In vitro, ex vivo, and in vivo methodological approaches for studying therapeutic targets of osteoporosis and degenerative joint diseases: how biomarkers can assist
Although our approach to the clinical management of osteoporosis (OP) and degenerative joint diseases (DJD)-major causes of disability and morbidity in the elderly-has greatly advanced in the past decades, curative treatments that could bring ultimate solutions have yet to be found or developed. Eff…
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Hoegh-Andersen P,
- Søndergaard BC,
- Sumer EU,
- Tankó LB,
- Qvist P,
- Karsdal MA,
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
16. May 2004
Characterization of osteoclasts from patients harboring a G215R mutation in ClC-7 causing autosomal dominant osteopetrosis type II
Autosomal dominant osteopetrosis II (ADOII) is a relatively benign disorder caused by a missense mutation in the ClCN7 gene. In this study, we characterize the osteoclasts from patients with ADOII, caused by a G215R mutation, and investigate the effect on osteoclast function in vitro. Osteoclasts fr…
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Journal:
Authors:
- Henriksen K,
- Gram J,
- Schaller S,
- Dahl BH,
- Dziegiel MH,
- Bollerslev J,
- Karsdal MA,
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,
Bone
1. Mar 2004
The chloride channel inhibitor NS3736 [corrected] prevents bone resorption in ovariectomized rats without changing bone formation
Chloride channel activity is essential for osteoclast function. Consequently, inhibition of the osteoclastic chloride channel should prevent bone resorption. Accordingly, we tested a chloride channel inhibitor on bone turnover and found that it inhibits bone resorption without affecting bone formati…
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Journal:
Authors:
- Schaller S,
- Henriksen K,
- Sveigaard C,
- Heegaard AM,
- Hélix N,
- Stahlhut M,
- Ovejero MC,
- Johansen JV,
- Solberg H,
- Andersen TL,
- Hougaard D,
- Berryman M,
- Shiødt CB,
- Sørensen BH,
- Lichtenberg J,
- Christophersen P,
- Foged NT,
- Delaissé JM,
- Engsig MT,,
- Karsdal MA,
Bone
21. Jan 2004
Measurement of tumor load and distribution in a model of cancer-induced osteolysis: a necessary precaution when testing novel anti-resorptive therapies
The Arguello model of cancer metastasis to bone has been used extensively to study breast cancer-induced osteolytic disease. The effects of therapy on skeletal disease and on tumour burden in soft organs are traditionally measured using radiography and/or time-consuming histomorphometry, respectivel…
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Journal:
Authors:
- Amhlaoibh RN,
- Hoegh-Andersen P,
- Brünner N,
- Sørensen A,
- Winding B,
- Holst-Hansen C,
- Karsdal MA,
- Engsig MT,
- Delaissé JM,
- Heegaard AM,
Bone
23. Sep 2003
RANKL and vascular endothelial growth factor (VEGF) induce osteoclast chemotaxis through an ERK1/2-dependent mechanism
Development of bone depends on a continuous supply of bone-degrading osteoclasts. Although several factors such as the matrix metalloproteinases and the integrins have been shown to be important for osteoclast recruitment, the mechanism of action remains poorly understood. In this study we investiga…
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Journal:
Authors:
- Henriksen K,
- Karsdal MA,
- Delaisse JM,
- Engsig MT,
Bone
20. Aug 2003
Transforming growth factor-beta controls human osteoclastogenesis through the p38 MAPK and regulation of RANK expression
Although RANK-L is essential for osteoclast formation, factors such as transforming growth factor-beta (TGF-beta) are potent modulators of osteoclastogenic stimuli. To systematically investigate the role of TGF-beta in human osteoclastogenesis, monocytes were isolated from peripheral blood by three …
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Journal:
Authors:
- Karsdal MA,
- Hjorth P,
- Henriksen K,
- Kirkegaard T,
- Nielsen KL,
- Lou H,
- Delaissé JM,
- Foged NT,
Bone
1. May 2003
The type I collagen fragments ICTP and CTX reveal distinct enzymatic pathways of bone collagen degradation
Bone resorption may generate collagen fragments such as ICTP and CTX, which can be quantified in serum and/or urine by using specific immunoassays, and which are used as clinical markers. However, the relative abundance of ICTP and CTX varies according to the type of bone pathology, suggesting that …
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Authors:
- Garnero P,
- Ferreras M,
- Karsdal MA,
- Nicamhlaoibh R,
- Risteli J,
- Borel O,
- Qvist P,
- Delmas PD,
- Foged NT,
- Delaissé JM,
Bone
10. Sep 2002
Matrix metalloproteinase-dependent activation of latent transforming growth factor-beta controls the conversion of osteoblasts into osteocytes by blocking osteoblast apoptosis
Upon termination of bone matrix synthesis, osteoblasts either undergo apoptosis or differentiate into osteocytes or bone lining cells. In this study, we investigated the role of matrix metalloproteinases (MMPs) and growth factors in the differentiation of osteoblasts into osteocytes and in osteoblas…
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Journal:
Authors:
- Karsdal MA,
- Larsen L,
- Engsig MT,
- Lou H,
- Ferreras M,
- Lochter A,
- Delaissé JM,
- Foged NT,
Bone
27. Jul 2001
Transforming growth factor-beta-induced osteoblast elongation regulates osteoclastic bone resorption through a p38 mitogen-activated protein kinase- and matrix metalloproteinase-dependent pathway
Transforming growth factor-beta (TGF-beta) is a powerful modulator of bone metabolism, and both its anabolic and catabolic effects on bone have been described. Here we have tested the hypothesis that TGF-beta-induced changes in osteoblast shape promote bone resorption by increasing the surface area …
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Journal:
Authors:
- Karsdal MA,
- Fjording MS,
- Delaissé JM,
- Lochter A,
Bone
15. Feb 2000
Proteinases in bone resorption: obvious and less obvious roles
Bone resorption is critical for the development and the maintenance of the skeleton, and improper regulation of bone resorption leads to pathological situations. Proteinases are necessary for this process. In this review, we show that this need of proteinases is not only because they are required fo…
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Journal:
Authors:
- Delaissé JM,
- Engsig MT,
- Everts V,
- del Carmen Ovejero M,
- Ferreras M,
- Lund L,
- Vu TH,
- Werb Z,
- Winding B,
- Lochter A,
- Karsdal MA,
- Troen T,
- Kirkegaard T,
- Lenhard T,
- Heegaard AM,
- Neff L,
- Baron R,
- Foged NT,