Most patients with multiple myeloma have lytic lesions at multiple sites in the axial skeleton. These lesions commonly give pain and are at risk of pathological fracture, and bony disease is therefore a cause of much morbidity in myeloma. Recent data indicates that the Receptor Activator of NF- κ B ligand (RANKL) and Osteoprotegerin (OPG) may be central to the local pathogenesis of these lytic lesions. Bisphosphonates may ameliorate some of these abnormalities, and clinically these agents improve the skeletal prognosis in myeloma patients. High dose chemotherapy with autologous stem cell rescue is currently under evaluation in the management of myeloma, though little is known of the effect of this therapeutic modality on the skeleton. Studies using biochemical markers of bone turnover suggest that increased osteoclast activity may be present even in apparent plateau phase of myeloma. High dose chemotherapy with autografting may normalise abnormal bone resorption, though the effect may take several weeks to emerge, and may be paralleled by increased osteoblast activity. The findings provide biochemical evidence that autografting may help normalise the abnormal bone turnover characteristic of myeloma.