Biochemical, histomorphometric and densitometric changes in patients with multiple myeloma: effects of glucocorticoid therapy and disease activity.

It is unknown whether bone changes which can occur in multiple myeloma (MM) are due to cytokine-induced osteoclastic bone resorption from a clone of abnormal plasma cells or high-dose glucocorticoid therapy. We studied 25 MM patients treated for 1-12 years with combination chemotherapy, subdivided into two groups. Group 1 consisted of 12 patients with stage I and II myeloma and group 2 consisted of 13 patients with stage III MM. Their serum biochemistry, tetracycline-labelled bone histomorphometry and bone densitometry were compared to age- and sex-matched controls. Patients with MM demonstrated increased indices of bone resorption (P < 0.001 versus controls) and, to a lesser extent, increased indices of bone formation (P < 0.01 versus controls). No patient had evidence of a mineralization defect. Lumbar spine, femoral neck and total body bone mineral density measurements (BMD) were significantly lower in group 2 compared with group 1 (P < 0.05). Following 12 months of therapy, lumbar spine BMD decreased by 6.6% (95% CI, 2.7% to -9.3%) and femoral neck BMD decreased by 9.5% (95% CI, -3.2% to -15.9%). In a stepwise regression analysis, cumulative prednisolone dosage (B Coef. = -0.39; P = 0.03) and plasma cell infiltrate (B Coef. = -0.08; P = 0.05) were the most important predictors of lumbar spine bone loss, whereas serum paraprotein (B Coef.= -0.35; P = 0.02) and plasma cell infiltrate (B Coef. = -0.20; P = 0.04) were the most important predictors of femoral neck bone loss. We conclude that MM is characterized by high bone turnover with osteoblast-osteoclast uncoupling. Both disease activity and high-dose glucocorticoid therapy may be responsible for the ongoing bone loss seen with MM.