The effects of the treatment of multiple myeloma (MM) with APD‐bisphosphonate on bone destruction, the dissemination pattern of the MM, and toxicity for normal and malignant cells were investigated in an animal model, the 5T2 MM. This mouse MM very closely resembles the human disease, including the typical bone lesions. It was demonstrated by radiography, microradiography, and histologic investigation that the treatment of the 5T2 MM with APD‐bisphosphonate protected the mice against a loss of bone to a significant extent. It seemed that the treatment with APD not only diminished the bone destruction by the MM but also led to the formation of new bone in already‐affected bone tissue. The growth pattern of the MM was not substantially influenced by the treatment, even though there was an indication that APD exerts some cytotoxic effect on the MM cells.

Mellstedt et al., 1984;Lokhorst et al., 1985). These findings suggested that the malignant transformation leading to the development of MM already occurred in a precursor of the plasma cell. Further support for this hypothesis was offered by the observation of chromosomal abnormalities in plasma cells as well as in cells with a B-lymphocyte phenotype of a patient with plasma cell leukaemia (MacKenzie et al., 1985). These chromosomal abnormalities showed a similarity with those reported in cases of MM. However, functional proof of the participation of idiotype-bearing B-cells in the myeloma clone has not yet been achieved. In vitro stimulation of idiotype-bearing B-cells in the presence of mitogens such as pokeweed mitogen or Staphylococcus aureus did not lead to a subsequent differentiation of these cells into a more mature Ig-secreting phenotype (Peest et al., 1984;Bloem, 1985). Moreover, it had been suggested by other investigators that the idiotype-bearing lymphocytes in MM were in fact T-lymphocytes binding the myeloma-Ig by Fc-receptors with specificity for its isotype (Hoover et al., 1981). Recently, myeloma precursors of lymphoid morphology that lacked surface and cytoplasmic Ig, but expressed the acute lymphoblastic leukaemia antigen (CALLA) were identified in the BM of patients with MM. In vitro stimulation of these cells with the phorbol ester 12-0-tetradecanoyl-phorbol-13 acetate (TPA) resulted in their transformation into plasma cells that synthesized the myeloma-specific Ig (Caligaris-Cappio et al., 1985). This observation indicated the existence of a functional relationship between more differentiated MM-cells and their precursors. However, the exact role of the idiotypebearing B-lymphocyte has not become clear in that study. A suitable experimental animal model for MM is a prerequisite for detailed studies on the basic biological mechanisms of this neoplasm. Recently, spontaneous multiple myeloma developing in a number of aging C57BL/KaLwRij mice has been observed (Radl et al., 1985a). This mouse MM resembles the human disease in several respects. In contrast with the induced mouse plasmacytomas, it is of spontaneous origin and the MM cells are predominantly located in the BM; a circulating monoclonal myeloma protein reflects the extent of the tumour load, and, in many cases, the MM is complicated by severe osteolytic bone destruction (Radl et al., 1985a). Among the different established transplantable ST MM lines, the 5T2 MM has been studied most extensively (Radl et al., 1985b MiceMale and female C57BL/KaLwRij mice from the colony of the TNO Institute for Experimental Gerontology were used in all experiments. They were maintained under conventional conditions. Detailed information on husbandry, health status, survival data, and age-associated pathology of this strain has been published elsewhere (Van Zwieten et al.,