acid-phosphatase and Paraproteinemias

Bone destruction, caused by aberrant production and activation of osteoclasts, is a prominent feature of multiple myeloma. We demonstrate that myeloma stimulates osteoclastogenesis by triggering a coordinated increase in the tumor necrosis factor-related activation-induced cytokine (TRANCE) and decrease in its decoy receptor, osteoprotegerin (OPG). Immunohistochemistry and in situ hybridization studies of bone marrow specimens indicate that in vivo, deregulation of the TRANCE-OPG cytokine axis occurs in myeloma, but not in the limited plasma cell disorder monoclonal gammopathy of unknown significance or in nonmyeloma hematologic malignancies. In coculture, myeloma cell lines stimulate expression of TRANCE and inhibit expression of OPG by stromal cells. Osteoclastogenesis, the functional consequence of increased TRANCE expression, is counteracted by addition of a recombinant TRANCE inhibitor, RANK-Fc, to marrow/myeloma cocultures. Myeloma-stroma interaction also has been postulated to support progression of the malignant clone. In the SCID-hu murine model of human myeloma, administration of RANK-Fc both prevents myeloma-induced bone destruction and interferes with myeloma progression. Our data identify TRANCE and OPG as key cytokines whose deregulation promotes bone destruction and supports myeloma growth.

Topics: Acid Phosphatase; Animals; Carrier Proteins; Disease Progression; Glycoproteins; Hodgkin Disease; Humans; Isoenzymes; Leukemia, Lymphocytic, Chronic, B-Cell; Membrane Glycoproteins; Mice; Mice, SCID; Osteoprotegerin; Paraproteinemias; RANK Ligand; Receptor Activator of Nuclear Factor-kappa B; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Reference Values; Reverse Transcriptase Polymerase Chain Reaction; Tartrate-Resistant Acid Phosphatase; Time Factors

Amyloidosis primarily involving bone is described in a 59-year-old male pateint. Well circumscribed lytic lesions of the skeleton raised the possibility of myelomatosis. The prolonged insidious course of the disease was uncomplicated by hypercalcemia, pathological fracture, or hematologic abnormalities. The clinical course, together with histological findings and strongly positive bone scan, were the distinguishing features. The osseous manifestations without plasma cell tumor appears to be a rare occurrence in amyloidosis.

Topics: Acid Phosphatase; Amyloidosis; Bone and Bones; Bone Resorption; Humans; Male; Middle Aged; Osteolysis; Paraproteinemias; Serum Amyloid A Protein; Technetium