Biological sources of variations of tartrate-resistant acid phosphatase 5b in a healthy Japanese population

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Abstract

Background

Tartrate-resistant acid phosphatase 5b (TRACP5b) is a bone resorption marker that is mainly used in clinical management of osteoporosis. For proper interpretations of test results for serum TRACP5b, we explored their biological sources of variation, esp. age-related changes, and associations with other bone-related markers in healthy Japanese adults.

Methods

During the 2009 East-Southeast Asian multicentre study for determination of reference intervals, 72 major laboratory tests were measured by centralized assays in 3541 well-defined healthy volunteers. The current study included 1980 test results in Japanese subjects for five bone-related markers: TRACP5b, bone alkaline phosphatase, intact parathyroid hormone, calcium and inorganic phosphate. Information on sources of variation, including body mass index, smoking habits and ABO-blood group, were obtained from a health status questionnaire.

Results

Gender-specific profiles of age-related changes were observed for each parameter. Increased values starting from 40 years of age in females were most prominent for TRACP5b, followed by bone alkaline phosphatase and inorganic phosphate. TRACP5b in males decreased with body mass index, bone alkaline phosphatase and TRACP5b were higher in blood type-O subjects, especially in males. TRACPT5b was closely correlated with bone alkaline phosphatase, and moderately correlated with adjusted calcium and inorganic phosphate, especially in females aged ≥45 years. Reference intervals for each analyte were determined parametrically based on gender and age.

Conclusions

This study elucidated sources of variation of TRACP5b and related bone markers in healthy Japanese subjects and demonstrated a specific age profile for each marker. These results are of relevance for better clinical usage and interpretations of serum levels of bone markers.

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Most cited references 30

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Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.

Jacques Rossouw, Garnet Anderson, Ross L Prentice … (2002)

Despite decades of accumulated observational evidence, the balance of risks and benefits for hormone use in healthy postmenopausal women remains uncertain. To assess the major health benefits and risks of the most commonly used combined hormone preparation in the United States. Estrogen plus progestin component of the Women's Health Initiative, a randomized controlled primary prevention trial (planned duration, 8.5 years) in which 16608 postmenopausal women aged 50-79 years with an intact uterus at baseline were recruited by 40 US clinical centers in 1993-1998. Participants received conjugated equine estrogens, 0.625 mg/d, plus medroxyprogesterone acetate, 2.5 mg/d, in 1 tablet (n = 8506) or placebo (n = 8102). The primary outcome was coronary heart disease (CHD) (nonfatal myocardial infarction and CHD death), with invasive breast cancer as the primary adverse outcome. A global index summarizing the balance of risks and benefits included the 2 primary outcomes plus stroke, pulmonary embolism (PE), endometrial cancer, colorectal cancer, hip fracture, and death due to other causes. On May 31, 2002, after a mean of 5.2 years of follow-up, the data and safety monitoring board recommended stopping the trial of estrogen plus progestin vs placebo because the test statistic for invasive breast cancer exceeded the stopping boundary for this adverse effect and the global index statistic supported risks exceeding benefits. This report includes data on the major clinical outcomes through April 30, 2002. Estimated hazard ratios (HRs) (nominal 95% confidence intervals [CIs]) were as follows: CHD, 1.29 (1.02-1.63) with 286 cases; breast cancer, 1.26 (1.00-1.59) with 290 cases; stroke, 1.41 (1.07-1.85) with 212 cases; PE, 2.13 (1.39-3.25) with 101 cases; colorectal cancer, 0.63 (0.43-0.92) with 112 cases; endometrial cancer, 0.83 (0.47-1.47) with 47 cases; hip fracture, 0.66 (0.45-0.98) with 106 cases; and death due to other causes, 0.92 (0.74-1.14) with 331 cases. Corresponding HRs (nominal 95% CIs) for composite outcomes were 1.22 (1.09-1.36) for total cardiovascular disease (arterial and venous disease), 1.03 (0.90-1.17) for total cancer, 0.76 (0.69-0.85) for combined fractures, 0.98 (0.82-1.18) for total mortality, and 1.15 (1.03-1.28) for the global index. Absolute excess risks per 10 000 person-years attributable to estrogen plus progestin were 7 more CHD events, 8 more strokes, 8 more PEs, and 8 more invasive breast cancers, while absolute risk reductions per 10 000 person-years were 6 fewer colorectal cancers and 5 fewer hip fractures. The absolute excess risk of events included in the global index was 19 per 10 000 person-years. Overall health risks exceeded benefits from use of combined estrogen plus progestin for an average 5.2-year follow-up among healthy postmenopausal US women. All-cause mortality was not affected during the trial. The risk-benefit profile found in this trial is not consistent with the requirements for a viable intervention for primary prevention of chronic diseases, and the results indicate that this regimen should not be initiated or continued for primary prevention of CHD.

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Coupling of bone resorption and formation by RANKL reverse signalling

Yuki Ikebuchi, Shigeki Aoki, Masashi Honma … (2018)

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Estrogen and bone health in men and women.

Jane Cauley (2015)

Estrogen is the key regulator of bone metabolism in both men and women. Menopause and the accompanying loss of ovarian estrogens are associated with declines in bone mineral density (BMD): 10-year cumulative loss was 9.1% at the femoral neck and 10.6%, lumbar spine. Estradiol concentrations also predict fractures. Total estradiol levels, <5 pg/ml were associated with a 2.5-fold increase in hip and vertebral fractures in older women, an association that was independent of age and body weight. Similar associations were found in men. Despite the lower BMD and higher fracture risk in hypogonadal men, there is little association between circulating testosterone, fracture and bone loss. Nevertheless, the combination of any low sex steroid hormone and 25-hydroxyvitamin D was associated with an increased fracture risk. Menopausal hormone therapy has been shown to reduce hip and all fractures in the Women's Health Initiative with little difference between the estrogen-alone and the estrogen plus progestin trials. The risk reductions were attenuated in both trials post intervention; however, a significant hip fracture benefit persisted over 13 years for women assigned to the combination therapy. Clinical trials of testosterone replacement in older men give tantalizing but inconclusive results. The results suggest that testosterone treatment probably improves BMD, but the results are less conclusive in older versus younger men. The Testosterone Trial is designed to test the hypothesis that testosterone treatment of men with unequivocally low serum testosterone (<275 ng/dL) will increase volumetric BMD (vBMD) of the spine. Results of the Testosterone Trials are expected in 2015.

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Author and article information

Journal

Journal ID (nlm-ta): Ann Clin Biochem

Journal ID (iso-abbrev): Ann Clin Biochem

Journal ID (publisher-id): ACB

Journal ID (hwp): spacb

Title: Annals of Clinical Biochemistry

Publisher: SAGE Publications (Sage UK: London, England )

ISSN (Print): 0004-5632

ISSN (Electronic): 1758-1001

Publication date (Electronic): 7 April 2021

Publication date (Print): July 2021

Volume: 58

Issue: 4

Pages: 358-367

Affiliations

[1 ]Research and Development Headquarters, Nitto Boseki Co., Ltd, Koriyama, Japan

[2 ]Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Ube, Japan

[3 ]Scientific & Technical Affairs Department, Nittobo Medical Co., Ltd, Tokyo, Japan

[4 ]Department of Medical Life Science, Faculty of Medical Bioscience, Kyushu University of Health and Welfare, Nobeoka, Japan

Author notes

[*]Kiyoshi Ichihara, Department of Clinical Laboratory Sciences, Faculty of Health Sciences, Yamaguchi University Graduate School of Medicine, Minami−Kogushi 1 − 1−1, Ube 755 − 8505, Japan. Email: ichihara@ 123456yamaguchi−u.ac.jp

Author information

Wataru Kikuchi https://orcid.org/0000-0002-3066-7450

Article

Publisher ID: 10.1177_00045632211003941

DOI: 10.1177/00045632211003941

PMC ID: 8258717

PubMed ID: 33715446

SO-VID: b3921b43-c552-4e22-a3a2-8ff98e265801

License:

This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License ( https://creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages ( https://us.sagepub.com/en-us/nam/open-access-at-sage).

History

Date accepted : 27 February 2021

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ScienceOpen disciplines: Biochemistry

Keywords: reference interval,bmi-related changes,calcium,inorganic phosphate,bone alkaline phosphatase,intact parathyroid hormone,abo blood group

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ScienceOpen disciplines: Biochemistry

Keywords: reference interval, bmi-related changes, calcium, inorganic phosphate, bone alkaline phosphatase, intact parathyroid hormone, abo blood group

Biological sources of variations of tartrate-resistant acid phosphatase 5b in a healthy Japanese population

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Most cited references 30

Risks and benefits of estrogen plus progestin in healthy postmenopausal women: principal results From the Women's Health Initiative randomized controlled trial.

Coupling of bone resorption and formation by RANKL reverse signalling

Estrogen and bone health in men and women.

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