Serum Tartrate-resistant Acid Phosphatase 5b Is a Specific and Sensitive Marker of Bone Resorption

Abstract

Bone-resorbing osteoclasts and activated macrophages express high amounts of type 5 tartrate-resistant acid phosphatase (TRACP; EC 3.1.3.2) (1). Osteoclasts secrete TRACP into the circulation, and serum TRACP has been considered a potentially useful marker of bone resorption. Several technical problems have prevented the use of serum TRACP as a specific marker of bone resorption. Early enzymatic assays lacked specificity because of the presence of interfering acid phosphatases derived from platelets and erythrocytes (2)(3). Serum TRACP can be determined by use of fluoride (4) or by immunoassays with antibodies specific for TRACP (5)(6)(7)(8)(9). However, there are two forms of TRACP in the serum, namely TRACP 5a and TRACP 5b. Of these, TRACP 5b is derived from osteoclasts, whereas TRACP 5a originates from other, as yet unidentified sources (10)(11)(12). Two diagnostic assays have been developed recently for serum TRACP 5b: a kinetic assay based on the use of specific inhibitors (13), and an immunoassay based on a highly characterized specific monoclonal antibody (12). The TRACP 5b-specific immunoassay has been shown to be a useful method for monitoring antiresorptive therapy (12). We have now further characterized the immunoassay by studying the clinical specificity and clinical sensitivity of serum TRACP 5b in various bone diseases and nonskeletal diseases. We obtained serum samples from 303 individuals after written informed consent. At the time of sampling, none of the subjects was receiving antiosteoporotic treatment. Healthy premenopausal women, healthy postmenopausal women, and breast cancer (BC) patients without evidence of bone metastases (BC−) were included as control populations. Patients with bone …