In vivo effect of beta 2-microglobulin on bone resorption

beta 2-Microglobulin (beta 2-M) deposits have been found in the destructive bone lesions associated with dialysis-related amyloidosis. To examine whether beta 2-M can cause bone resorption in vivo, doses of beta 2-M alone were compared with parathyroid hormone (PTH), aluminum, and vehicle alone. Eleven injections of 10 micrograms each were made over a period of 56 hours into the subcutaneous tissue overlying the occipital region of mice. Using a computerized image analysis system we measured (1) periosteal and inner bone length, (2) bone marrow interface length, and (3) the extent of resorption along these surfaces expressed as percentage of total length. Injections of either beta 2-M or PTH were associated with 22% +/- 4% and 25% +/- 4% resorption of periosteal surface, respectively, and 15.9% +/- 2% and 19.9% +/- 5% resorption of marrow bone surfaces, respectively, compared with control. In contrast, aluminum did not increase bone resorption over controls. The simultaneous injection of calcitonin, an osteoclast inhibitor, with beta 2-M or PTH did not increase periosteal resorption over controls. The resorption of inner bone surface was similar in all groups. These studies show that beta 2-M and PTH cause bone resorption in the bone surfaces proximate to the site of injection. This suggests that beta 2-M may contribute to the development of the bone cysts in dialysis-related amyloidosis.