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 gears with combination chemot herapy, subdivided into two groups. Group 1 consisted of 12 patients w ith stage I and II myeloma and group 2 consisted of 13 patients with s tage III MM. Their serum biochemistry, tetracycline-labelled bone hist omorphometry and bone densitometry were compared to age- and sex-match ed controls. Patients with MM demonstrated increased indices of bone r esorption (P < 0.001 versus controls) and, to a lesser extent, increas ed indices of bone formation (P < 0.01 versus controls). No patient ha d 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 Coe f. = -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, w hereas serum paraprotein (B Coef. = -0.35; P = 0.02) and plasma cell i nfiltrate (B Coef. = -0.20; P = 0.04) were the most important predicto rs 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.