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Biology and Clinical Significance of Tartrate-Resistant Acid Phosphatases: New Perspectives on an Old Enzyme

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Abstract

Type 5 tartrate-resistant acid phosphatase (TRAP) has been a clinically relevant biomarker for about 50 years. It has always been a reliable and specific cytochemical marker for hairy cell leukemia and for differentiated cells of monocytic lineage. Only recently has the test for serum TRAP activity been accepted as sensitive and specific enough for clinical use as a marker of osteoclasts and bone resorption. This has come about through steady advances in knowledge about TRAP enzymology, structure, function, and molecular regulation and a consequent appreciation that TRAP isoforms 5a and 5b have very different clinical significance. As a measure of osteoclast number and bone resorption, TRAP 5b has diagnostic and prognostic applications in osteoporosis, cancers with bone metastasis, chronic renal failure, and perhaps other metabolic and pathologic bone diseases. Serum TRAP 5a, on the other hand, has no relationship to bone metabolism but seems instead to be a measure of activated macrophages and chronic inflammation. Exploration of the real clinical usefulness of serum TRAP 5a for diagnosis and disease management in a wide variety of chronic inflammatory diseases is only now beginning. This perspective traces the important basic scientific developments that have led up to the refinement of serum TRAP isoform immunoassays and their validation as biomarkers of disease. Many unanswered questions remain, providing a wealth of opportunity for continued research of this multifaceted enzyme.

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Acknowledgments

The authors fondly acknowledge the long friendship and collaborations of Dr. Chin-Yang Li and Dr. Kwok-Wai “Bill” Lam since the initiation of our studies on TRAP. Early success was possible only through their hard work and dedication. The dedication and support of our wives, Barbara and Julia, have been equally important during long hours in the lab. The valuable contributions made in the lab and clinic over the years by colleagues, fellows, residents, students, and associates at the University of Louisville, School of Medicine, are also heartily acknowledged. We also thank Dr. Jussi Halleen and his colleagues and students from the Anatomy Department, University of Turku, who so generously shared their talents, ideas, and data about TRAP and bone metabolism. Dr. Tsu-Yi Chao and members of his Hematology/Oncology Division at the TriService General Hospital in Taipei deserve our many thanks for their tireless efforts to promote clinical research on the application of TRAP in cancer and other diseases. The authors are supported by grants from the Research Service of the U.S. Department of Veterans Affairs and by funds from the Clinical Research Foundation.

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Authors and Affiliations

  1. Special Hematology Laboratory, U.S. Department of Veterans Affairs Medical Center, 800 Zorn Ave., Louisville, KY, 40206, USA

    Anthony J. Janckila & Lung T. Yam

  2. Department of Microbiology and Immunology, University of Louisville, Louisville, KY, USA

    Anthony J. Janckila

  3. Department of Medicine, University of Louisville, Louisville, KY, USA

    Lung T. Yam

Authors
  1. Anthony J. Janckila
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  2. Lung T. Yam
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Correspondence to Anthony J. Janckila.

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Janckila, A.J., Yam, L.T. Biology and Clinical Significance of Tartrate-Resistant Acid Phosphatases: New Perspectives on an Old Enzyme. Calcif Tissue Int 85, 465–483 (2009). https://doi.org/10.1007/s00223-009-9309-8

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