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Osteogenesis imperfecta (OI), a heritable disorder caused by abnormalities in synthesis or processing of type I collagen, is characterized by skeletal fragility. Type I collagen interacts with multiple components of the extracellular matrix (ECM) including other collagens types. Thus, alterations in...

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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 homozygous ...

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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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September 30, 2019

Journal:
Clin Exp Rheumatol

Author:
Karsdal MA, Henriksen K, Bay-Jensen AC

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 jo...

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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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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 ag...

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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 of...

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May 28, 2019

Journal:
Bone

Author:
Bager CL, Bay F, Christiansen C, Karsdal MA

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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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 wh...

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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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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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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 women ...

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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 is...

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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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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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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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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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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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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 in po...

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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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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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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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October 27, 2015

Journal:
Climacteric

Author:
Henriksen K, Karsdal MA, Christiansen C

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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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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Abstract 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 w...

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Introduction: 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 fractu...

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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 fixed flex...

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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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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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January 15, 2014

Journal:
Calcif Tissue Int.

Author:
Henriksen K, Karsdal MA, Martin TJ

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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