Tartrate-Resistant Acid Phosphatase 5b: A Novel Serum Marker of Bone Resorption

Halleen, Jussi M.; Alatalo, Sari L.; Suominen, Harri; Cheng, Sulin; Janckila, Anthony J.; Väänänen, H. Kalervo

doi:10.1359/jbmr.2000.15.7.1337

Cited by 457 publications

(391 citation statements)

References 31 publications

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“…Four of these mediators were selected for followup: Ang-2, NTX, TRAP-5b, and CXCL13. Selection of these 4 mediators was based on pragmatic considerations: assay availability and presence (NTX, TRAP-5b) or absence (Ang-2, CXCL13) of previous studies linking the protein to bone erosion (19,20). The ability of CXCL13, Ang-2, NTX, and TRAP-5b to differentiate between virtual patients with high and low erosion is illustrated in Figure 1.…”

Section: Ra Physiolab Prediction Resultsmentioning

confidence: 99%

Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint

Meeuwisse

Linden

Rullmann

et al. 2011

Arthritis & Rheumatism

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Objective. Rheumatoid arthritis (RA) is characterized by inflammation and joint destruction, with the degree of damage varying greatly among patients. Prediction of disease severity using known clinical and serologic risk factors is inaccurate. This study was undertaken to identify new serologic markers for RA severity using an in silico model of the rheumatic joint.Methods. An in silico model of a prototypical rheumatic joint was used to predict candidate markers associated with erosiveness. The following 4 markers were chosen for validation: tartrate-resistant acid phosphatase 5b (TRAP-5b), N-telopeptide of type I collagen (NTX), angiopoietin 2 (Ang-2), and CXCL13. Serum from 74 RA patients was used to study whether radiologic joint destruction (total erosion score and total Sharp/van der Heijde score [SHS]) after 4 years of disease was associated with serum levels at the time of diagnosis. Serum marker levels were determined using enzyme-linked immunosorbent assays. For confirmation, baseline serum levels were analyzed for an association with progression of joint damage over 7 years of followup in a cohort of 155 patients with early RA.Results. Comparison of high and low quartiles of erosion score and SHS at 4 years showed a difference in baseline serum CXCL13 level (P ‫؍‬ 0.011 and P ‫؍‬ 0.018, respectively). In the confirmation cohort, elevated baseline CXCL13 levels were associated with increased rates of joint destruction during 7 years of followup (P < 0.001 unadjusted and P < 0.004 with adjustment for C-reactive protein level). Analyzing anti-CCP-2-positive and anti-CCP-2-negative RA separately yielded a significant result only in the anti-CCP-2-negative group (P < 0.001).Conclusion. Our findings indicate that CXCL13 is a novel serologic marker predictive of RA severity. This marker was identified with the help of an in silico model of the RA joint.

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Section: Ra Physiolab Prediction Resultsmentioning

confidence: 99%

Identification of CXCL13 as a marker for rheumatoid arthritis outcome using an in silico model of the rheumatic joint

Meeuwisse

Linden

Rullmann

et al. 2011

Arthritis & Rheumatism

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“…Serum TRAP (a marker of bone resorption (44) ) levels were significantly elevated in HFS mice relative to controls. Given that serum osteocalcin (a marker of bone formation (45) ) levels were not different between cohorts, it appears that ingesting an HFS diet may have disrupted the balance between bone formation and resorption, favouring resorption.…”

Section: Discussionmentioning

confidence: 98%

High-fat, sucrose diet impairs geometrical and mechanical properties of cortical bone in mice

et al. 2009

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Exposure to diets high in fat and sucrose can induce hyperinsulinaemia, affect Ca and Mg metabolism, and alter bone mineralisation and mechanical properties. The present study assessed morphological and mechanical changes in a murine model exposed to a high-fat/sucrose (HFS) diet, as well as corresponding molecular and endocrine markers of bone turnover. Female C57BL/6 mice (aged 9 weeks) consumed either a low-fat, complex carbohydrate diet or an HFS diet for 10 weeks. At the end of the 10 weeks, serum was collected for biochemical analysis. Tibiae from half the mice (n 15) were randomly selected to be micro-computed tomography scanned and tested to failure in cantilever bending, while the remaining half were prepared for real-time PCR analysis. Serum tartrate-resistant acid phosphatase was significantly elevated in HFS mice, while osteocalcin remained unchanged. Both body mass and percentage body fat were greater in mice fed HFS diet. After adjusting for body mass, tibial structural and morphological properties were adversely affected in the HFS cohort. Cortical thickness, cross-sectional area, and load at maximum were all significantly lower in mice fed HFS diet. Receptor activator of nuclear factor kb ligand (RANKL) mRNA was significantly upregulated in HFS mice, but osteoprotegerin/RANKL mRNA ratio remained unchanged between cohorts. Moreover, cyclo-oxygenase-2 mRNA tended to be increased in HFS. Thus, ingestion of an HFS diet had a significant adverse effect on mouse bone morphology and mechanics, and these effects were likely due to elevated osteoclast activity associated with the inflammatory state of obesity, and not necessarily osteoclast recruitment/ proliferation.Cortical bone: High-fat/sucrose diet: Biomechanics: C57BL/6 mice The changing face of disease aetiology over the past century has brought to the forefront the need to examine the environmental or modifiable risk factors that have influenced the epidemic of chronic disease afflicting a majority of the Western world. Nutritional status is a readily modifiable risk factor linked to numerous chronic conditions, including CHD, cancer, obesity, diabetes and osteoporosis (1,2) . Nonetheless, despite the prevalence of research linking poor dietary choices to chronic disease status, the nutritional patterns presently dominating most Western nations continue to be high in saturated fats, Na and refined carbohydrates from sugars, cereals and dairy products, and low in fruits, vegetables and lean protein (3) .Considerable effort has focused on discovering the underlying nutritional factors that predispose an individual to osteopenia or osteoporosis and subsequent fracture (4) . Much research has concentrated on the role of Ca and vitamin D metabolites influencing bone morphology and mechanics; however, macronutrients such as fat, protein and carbohydrate also play a vital role in bone health (5) . Considered independently, consumption of diets composed of large amounts of saturated fat has been documented to cause the formation of insoluble soap complexe...

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“…Recently, a new serum TRAP assay has been developed that combines enzyme capture with the monoclonal antibody O1A and isoform 5b-specific assay conditions. 42 This assay indicates that the TRAP 5b isoform is osteoclastic in origin, whereas the 5a isoform is nonosteoclastic and that isoform 5b does in fact provide an indicative marker of osteoclastic resorptive activity. 42 …”

Section: Correlation Between Trap Activity and Bone Resorptionmentioning

confidence: 95%