Tartrate-resistant Acid Phosphatase (TRAP) Activity in Serum: Potential Use in Assessing Bone Resorption in Patients with Multiple Myeloma

We measured serum tartrate-resistant acid phosphatase (TRAP) activity in 120 healthy subjects and 35 patients with multiple myeloma as well as urinary hydroxyproline excretion in the myeloma patients. Young subjects (0-18 years) showed higher TRAP levels (ANOVA p < 0.01) compared with the other age classes due to the more active bone remodelling processes associated with growth. Myeloma patients with bone lytic lesions (MM+) showed higher serum TRAP values than controls (p < 0.01). Hydroxyproline excretion was higher in MM + patients but the difference between patients with and without bone lesions was not statistically significant. Our data suggest that serum TRAP activity may be a suitable, simple biochemical test to assess bone turnover in patients with multiple myeloma but that its clinical usefulness as a marker of bone resorption needs further evaluation.

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A Novel Sandwich ELISA for Tartrate-Resistant Acid Phosphatase 5a and 5b Protein Reveals that Both Isoforms are Secreted by Differentiating Osteoclasts and Correlate to the Type I Collagen Degradation Marker CTX-I In Vivo and In Vitro

Calcified Tissue International ◽

10.1007/s00223-019-00618-w ◽

2019 ◽

Vol 106 (2) ◽

pp. 194-207 ◽

Cited By ~ 1

Author(s):

Laia Mira-Pascual ◽

Christina Patlaka ◽

Suchita Desai ◽

Staffan Paulie ◽

Tuomas Näreoja ◽

...

Keyword(s):

Acid Phosphatase ◽

Bone Resorption ◽

Sandwich Elisa ◽

Osteoclast Differentiation ◽

Collagen Degradation ◽

Considerable Proportion ◽

Tartrate Resistant Acid Phosphatase ◽

Osteoclast Number ◽

Serum Trap ◽

Trap 5B

Abstract Tartrate-resistant acid phosphatase type 5 (TRAP) exists as two isoforms, 5a and 5b. 5b is a marker of osteoclast number and 5a of chronic inflammation; however, its association with bone resorption is unknown. In this study, a double-TRAP 5a/5b sandwich ELISA measuring 5a and 5b protein in the same sample was developed. TRAP 5a and 5b protein levels were evaluated as osteoclast differentiation/activity markers in serum and in culture, and their correlation to the resorption marker CTX-I was examined. Serum TRAP 5a and 5b concentrations in healthy men were 4.4 ± 0.6 ng/ml and 1.3 ± 0.2 ng/ml, respectively, and they correlated moderately to each other suggesting that their secretion is coupled under healthy conditions. A correlation was also observed between serum TRAP 5a and 5b with CTX-I, suggesting that both TRAP isoforms associate with osteoclast number. During osteoclast differentiation on plastic/bone, predominantly 5b increased in media/lysate from M-CSF/RANKL-stimulated CD14+ PBMCs. However, substantial levels of 5a were detected at later stages suggesting that both isoforms are secreted from differentiating OCs. More TRAP 5b was released on bone indicating a connection to osteoclast resorptive activity, and a peak in TRAP 5b/5a-ratio coincided with rapid CTX-I release. At the end of the culture period of M-CSF + RANKL-stimulated CD14+ PBMCs, there was a correlation between the secretion of TRAP 5a and 5b proteins with CTX-I. The correlation of not only 5b but also 5a with collagen degradation, both in serum and osteoclast cultures indicates that a considerable proportion of the TRAP 5a originates from osteoclasts and may reflect a hitherto undisclosed regulatory mechanism during bone resorption and bone remodeling.

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Serum Bone Resorption Markers after Parathyroidectomy for Renal Hyperparathyroidism: Correlation Analyses for the Cross-Linked N-telopeptide of Collagen I and Tartrate-Resistant Acid Phosphatase

The Scientific World JOURNAL ◽

10.1100/2012/503945 ◽

2012 ◽

Vol 2012 ◽

pp. 1-9 ◽

Cited By ~ 3

Author(s):

Kuo-Chin Hung ◽

Chung-Yu Huang ◽

Chuan-Chieh Liu ◽

Chih-Jen Wu ◽

Shao-Yuan Chen ◽

...

Keyword(s):

Acid Phosphatase ◽

Bone Resorption ◽

Type I Collagen ◽

Bone Alkaline Phosphatase ◽

Tartrate Resistant Acid Phosphatase ◽

Type I ◽

Bone Resorption Markers ◽

Correlation Analyses ◽

Serum Trap ◽

The Cross

Patients on long-term dialysis may develop secondary hyperparathyroidism (SHPT) with increased serum concentrations of bone resorption markers such as the cross-linked N-telopeptide of type I collagen (NTX) and type-5b tartrate-resistant acid phosphatase (TRAP). When SHPT proves refractory to treatment, parathyroidectomy (PTX) may be needed. Renal patients on maintenance HD who received PTX for refractory SHPT (n=23) or who did not develop refractory SHPT (control subjects;n=25) were followed prospectively for 4 weeks. Serum intact parathyroid hormone (iPTH), NTX, TRAP, and bone alkaline phosphatase (BAP) concentrations were measured serially and correlation analyses were performed. iPTH values decreased rapidly and dramatically. BAP values increased progressively with peak increases observed at 2 weeks after surgery. NTX and TRAP values decreased concurrently and progressively through 4 weeks following PTX. A significant correlation between TRAP and NTX values was observed before PTX but not at 4 weeks after PTX. Additionally, the fractional changes in serum TRAP were larger than those in serum NTX at all times examined after PTX. Serum iPTH, TRAP, and NTX values declined rapidly following PTX for SHPT. Serum TRAP values declined to greater degrees than serum NTX values throughout the 4-week period following PTX.

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Tartrate-resistant acid phosphatase as a biomarker of bone turnover in dog

Arquivo Brasileiro de Medicina Veterinária e Zootecnia ◽

10.1590/s0102-09352011000100007 ◽

2011 ◽

Vol 63 (1) ◽

pp. 40-45 ◽

Cited By ~ 6

Author(s):

C.P Sousa ◽

F Nery ◽

J.T Azevedo ◽

C.A Viegas ◽

M.E Gomes ◽

...

Keyword(s):

Acid Phosphatase ◽

Individual Variation ◽

Bone Alkaline Phosphatase ◽

Tartrate Resistant Acid Phosphatase ◽

Biological Variability ◽

Trap Activity ◽

Non Invasive ◽

Serum Minerals ◽

Serum Trap

Values of serum tartrate-resistant acid phosphatase ( TRAP) activity were obtained in adult dogs and its biological variability was assessed. Nine healthy skeletally mature Portuguese Podengo dogs were used for the determination of TRAP, total and bone alkaline phosphatase serum activities, and also to study their relationship with serum minerals, namely calcium (Ca), phosphorous (P), and magnesium (Mg). The serum TRAP activity was 2.19±0.56IU/mL, with intra-individual variation of 18.3% and inter-individual variation of 25.6%. Significant correlations were observed between serum TRAP activity and Ca (r=-0.3431; P<0.05), Ca and Mg (r=-0.787; P<0.01), and TRAP and Mg (r=0.397; P<0.05). The results indicate that serum TRAP activity in dog could be of great value in research and in clinical practice, providing complementary non-invasive information on bone metabolism

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Intensive weight gain therapy in patients with anorexia nervosa results in improved serum tartrate-resistant acid phosphatase (TRAP) 5a and 5b isoform protein levels

Eating and Weight Disorders - Studies on Anorexia Bulimia and Obesity ◽

10.1007/s40519-019-00776-8 ◽

2019 ◽

Vol 25 (5) ◽

pp. 1387-1397

Author(s):

Christina Patlaka ◽

Bojan Tubic ◽

Pernilla Lång ◽

Staffan Paulie ◽

Diana Swolin-Eide ◽

...

Keyword(s):

Anorexia Nervosa ◽

Weight Gain ◽

Acid Phosphatase ◽

Bone Resorption ◽

Bone Metabolism ◽

High Energy ◽

Tartrate Resistant Acid Phosphatase ◽

Protein Levels ◽

Serum Trap ◽

Trap 5B

Abstract Aim Tartrate-resistant acid phosphatase (TRAP) exists as isoforms 5a and 5b. TRAP 5a is a biomarker of chronic inflammation and influences adipose tissue and 5b associates with bone metabolism/pathologies. The aim was to investigate the association of serum TRAP 5a/5b isoforms with fat and bone markers and anthropometric parameters in patients with anorexia nervosa (AN) during weight gain therapy. Methods Twenty-five Swedish female AN patients, age 16–24 years, were treated for 12 weeks with a high-energy diet with six meals daily. Serum TRAP 5a/5b, markers of fat/glucose metabolism, markers of bone resorption and formation were measured. Parameters of bone and body composition were assessed by dual-energy X-ray absorptiometry and peripheral quantitative computed tomography. Results BMI increased from median 15.4 kg/m2 to 19.0 kg/m2, p < 0.0001. TRAP 5a and 5a/5b ratio increased but TRAP 5b decreased during the study. TRAP Δ5a and Δ5b correlated with Δinsulin and Δadiponectin, respectively. TRAP 5b correlated with trabecular density at start but not at week 12. At 12 weeks, TRAP 5b correlated with CTX, and Δ decrease in TRAP 5b correlated to Δ increase in bone-specific alkaline phosphatase. Conclusions This clinical interventional study resulted in increased BMI in patients with AN. The decreased TRAP 5b protein levels confirm a role for TRAP 5b as a marker of bone resorption, whereas increased TRAP 5a seemed to derive from systemic changes in bone as well as metabolic changes. The combined detection of TRAP 5a and TRAP 5b in serum could be an indicator of improved bone metabolism. Level of evidence Level III, prospective interventional cohort study.

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BONE RESORPTION BY TARTRATE-RESISTANT ACID PHOSPHATASE-POSITIVE MULTINUCLEAR CELLS ISOLATED FROM RHEUMATOID SYNOVIUM

Rheumatology ◽

10.1093/rheumatology/35.3.213 ◽

1996 ◽

Vol 35 (3) ◽

pp. 213-217 ◽

Cited By ~ 33

Author(s):

Y. FUJIKAWA ◽

M. SHINGU ◽

T. TORISU ◽

I. ITONAGA ◽

S. MASUMI

Keyword(s):

Acid Phosphatase ◽

Bone Resorption ◽

Tartrate Resistant Acid Phosphatase ◽

Rheumatoid Synovium ◽

Multinuclear Cells

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1,25-Dihydroxy-19-nor-vitamin D2, a Vitamin D Analog with Reduced Bone Resorbing Activity In Vitro

Journal of the American Society of Nephrology ◽

10.1681/asn.v11101857 ◽

2000 ◽

Vol 11 (10) ◽

pp. 1857-1864

Author(s):

L. SHANNON HOLLIDAY ◽

STEPHEN L. GLUCK ◽

EDUARDO SLATOPOLSKY ◽

ALEX J. BROWN

Keyword(s):

Vitamin D ◽

Acid Phosphatase ◽

Bone Resorption ◽

Vitamin D Receptor ◽

Intrinsic Activity ◽

Tartrate Resistant Acid Phosphatase ◽

Mouse Bone Marrow ◽

Bone Resorbing Activity

Abstract. 1,25-Dihydroxy-19-nor-vitamin D2 (19-norD2), a new analog of 1,25(OH)2D3, suppresses parathyroid hormone in renal failure patients and in uremic rats but has less calcemic activity than 1,25(OH)2D3. Although 19-norD2 has high affinity for the vitamin D receptor and similar pharmacokinetics to those of 1,25(OH)2D3, it has much less bone resorbing activity in vivo. The intrinsic activity of 19-norD2 on osteoclastogenesis and activation of bone resorption in mouse bone marrow cultures was examined to determine the mechanism involved. 19-norD2 and 1,25(OH)2D3 (10 nM) were equivalent in stimulating the formation and maintenance of large multinucleated, tartrate-resistant acid phosphatase-positive cells. However, the amount of bone resorbed by osteoclasts stimulated by 10 nM 19-norD2, as measured by pit-forming assays, was reduced 62% compared with 10 nM 1,25(OH)2D3-stimulated osteoclasts (P < 0.05). This difference could not be attributed to enhanced catabolism or to downregulated vitamin D receptor. The rate of degradation of 19-norD2 in cultures was approximately 20% greater than 1,25(OH)2D3, not enough to account for the different effects on bone resorption. The VDR levels were identical in cultures that were treated with 19-norD2 and 1,25(OH)2D3. In summary, 19-norD2 is less effective than 1,25(OH)2D3 in stimulating mouse marrow osteoclasts to resorb bone. The reason for this difference is not clear but seems to involve the late maturation and/or activation of osteoclasts as the number of pits produced by each tartrate-resistant acid phosphatase-positive cell is reduced under stimulation by 19-norD2 compared with 1,25(OH)2D3.

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Mechanisms of bone destruction in multiple myeloma: the importance of an unbalanced process in determining the severity of lytic bone disease.

Journal of Clinical Oncology ◽

10.1200/jco.1989.7.12.1909 ◽

1989 ◽

Vol 7 (12) ◽

pp. 1909-1914 ◽

Cited By ~ 166

Author(s):

R Bataille ◽

D Chappard ◽

C Marcelli ◽

P Dessauw ◽

J Sany ◽

...

Keyword(s):

Multiple Myeloma ◽

Bone Resorption ◽

Bone Formation ◽

Bone Mass ◽

Bone Remodeling ◽

Cell Mass ◽

Bone Destruction ◽

Myeloma Cell ◽

Bone Lesions ◽

Mass Reduction

In order to clarify the mechanisms involved in the occurrence of lytic bone lesions (BL) in multiple myeloma (MM), we have compared the presenting myeloma-induced histological bone changes of 14 previously untreated MM patients with lytic BL with those of seven MM patients lacking lytic BL at presentation despite similar myeloma cell mass. A major unbalanced bone remodeling (increased bone resorption with normal to low bone formation) was the characteristic feature of patients presenting lytic BL. Furthermore, this unbalanced process was associated with a significant reduction of bone mass. Unexpectedly, a balanced bone remodeling (increase of both bone resorption and bone formation, without bone mass reduction) rather than a true lack of an excessive bone resorption was the usual feature of patients lacking lytic BL. Our current work clearly shows that a majority (72%) of patients with MM present an important unbalanced bone remodeling at diagnosis, leading to bone mass reduction and bone destruction (unbalanced MM). Some patients (20%) retain a balanced bone remodeling with initial absence of bone destruction (balanced MM). Few (8%) patients have pure osteoblastic MM without bone destruction.

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Clinical Significance of Immunoassays for Type-5 Tartrate-resistant Acid Phosphatase

Clinical Chemistry ◽

10.1093/clinchem/45.12.2150 ◽

1999 ◽

Vol 45 (12) ◽

pp. 2150-2157 ◽

Cited By ~ 38

Author(s):

Yuri R Nakasato ◽

Anthony J Janckila ◽

Jussi M Halleen ◽

H Kalervo Vaananen ◽

Stephanie P Walton ◽

...

Keyword(s):

Acid Phosphatase ◽

Rheumatic Disease ◽

Healthy Subjects ◽

Specific Activity ◽

Biological Significance ◽

Tartrate Resistant Acid Phosphatase ◽

Endstage Renal Disease ◽

Trap Activity ◽

Specificity And Sensitivity ◽

The Mean

Abstract Background: Tartrate-resistant acid phosphatase (TRAP; EC 3.1.3.2) is a product of osteoclasts and a biochemical marker of bone resorption rate. However, erythrocytes and platelets contribute to total TRAP activity in serum, reducing the specificity of direct biochemical assays in serum. Osteoclast TRAP is also known as type-5 TRAP and is antigenically unique. Immunoassays are sought to improve the specificity and sensitivity of TRAP as a bone marker. Methods: We developed two colorimetric microplate assays for type-5 TRAP: an enzyme capture immunoassay to measure antibody-bound enzymatic activity, and a two-site immunoassay to measure bound enzyme protein. Both use the same monoclonal antibody (14G6) to capture type-5 TRAP, which permits determination of specific activity of serum TRAP in health and disease. Results: Both TRAP assays were linear from one-tenth to fivefold the mean value in 18 healthy subjects. In these subjects, the mean (SD) TRAP activity was 3.2 (0.54) U/L for the enzyme capture assay and 37 (13) μg/L for the two-site assay. Mean TRAP activity was not significantly increased in 64 patients with endstage renal disease requiring hemodialysis (HD) or 99 unselected patients with rheumatic diseases. By contrast, TRAP protein was increased in both the HD and rheumatic disease groups. The specific activity of TRAP in the 17 of 64 HD sera that had increased TRAP activity (0.088 U/μg) was similar to that in healthy subjects (0.091 U/μg). By contrast, the specific activity of TRAP in the 31 of 99 rheumatic sera with increased TRAP protein (0.035 U/μg) was significantly decreased. Conclusions: Wide sample distributions for TRAP activity in HD patients and TRAP protein in rheumatic disease patients suggest the presence of subpopulations of HD patients with increased TRAP activity and of rheumatic patients with increased TRAP protein. Each assay for TRAP activity and protein may have its own biological significance and clinical applications in specific groups of patients.

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