LONG-TERM ORAL PAMIDRONATE TREATMENT INHIBITS OSTEOCLASTIC BONE-RESORPTION AND BONE TURNOVER WITHOUT AFFECTING OSTEOBLASTIC FUNCTION IN MULTIPLE-MYELOMA

This study was performed as a cross-sectional substudy to the Danish-S wedish Pamidronate Study, a randomized placebo-controlled multicentre trial in multiple myeloma. The purpose was to evaluate the biological effects of long-term treatment with oral pamidronate 300 mg daily on b one metabolism by using histomorphometry and analysis of cytokines and biochemical markers of bone turnover. Sixteen patients were included after median 27.5 months of protocolized treatment; 10 patients receiv ed active treatment and 6 patients placebo. When compared with placebo , pamidronate treatment was associated with: (a) marked decreased oste oclastic resorption rate (0.86+/-0.59 mu m/d vs 5.7+/-5.0 mu m/d, p=0. 002), and diminished activation frequency (0.20+/-0.18 yr(-1) vs. 0.72 +/-0.55 yr(-1), p=0.014); (b) compensatory reduced volume referent bon e formation rate (0.17+/-0.21 yr(-1) vs. 0.71+/-0.54 yr(-1), p=0.007), but unaltered mineral appositional rate; (c) neutral (-0.66+/-5.6 mm) vs. negative (-2.15+/-2.2 mu m, p=0.013) bone balance per remodelling cycle; (d) higher trabecular bone volume (21.0+/-6.2% vs. 13.0+/-3.7% ,p=0.01); (e) suppressed urinary excretion and serum levels of some of the biochemical markers of bone metabolism; and (f) significant reduc tion of circulating soluble interleukin-6 receptor (IL-6sR) (25.9+/-4. 1 ng/ml vs. 32.1+/-6.6 ng/ml, p=0.04), and (g) a uniform tendency of l ower serum and marrow plasma levels of IL-6, IL-1 beta, and TNF alpha, Thus oral pamidronate was absorbed in biologically active amounts, an d reduced overall bone resorption and bone turnover without impairing osteoblastic bone formation. The observation that cytokine and cytokin e receptor levels were reduced extends the possible and potential bene ficial actions of bisphosphonates in multiple myeloma.