Pamidronate increases markers of bone formation in patients with multiple myeloma in plateau phase under interferon-alpha treatment

Bisphosphonates are potent inhibitors of osteoclastic activity and reduce t he disease-related skeletal complications when they are used in combination with chemotherapy in patients with multiple myeloma (MM). Pamidronate also inhibits apoptosis of primary osteoblastic cells and probably induces apop tosis on human MM cells and osteoclasts. It has been reported that interfer on-alpha (IFN-alpha) decreases bone resorption and that low doses of IFN-al pha result in a significant increase in serum osteocalcin (OSC). The aim of this study was to determine the effects of pamidronate treatment on bioche mical markers of bone resorption [cross-linked N-telopeptides of type I col lagen (NTx)], bone formation [bone alkaline phosphatase (BAP) and OSC], dis ease activity [beta (2)-microglobulin, CRP, paraprotein], and interleukin-6 (IL-6) in patients with MM in plateau phase under IFN-alpha maintenance. T he above parameters were evaluated in 28 patients (13 M, 15 F, median age 7 0 years) during maintenance treatment, before the addition of pamidronate a nd after 1, 3, 6, 9, 12, and 14 months of the combined therapy. The additio n of pamidronate to maintenance treatment resulted in a significant reducti on of NTx, IL-6, beta (2)-microglobulin, CRP from the 3(rd) month and parap rotein from the 6(th) month of treatment, whereas BAP and OSC were signific antly increased from the 6th month. These changes continued during the 14-m onth follow-up of the combined treatment. Multivariate analysis showed a si gnificant negative correlation between changes of BAP and OSC and the patie nts' age. The greater increase of the bone formation markers was observed i n younger patients. These results suggest that, in addition to the inhibiti on of osteoclastic activity, pamidronate in combination with IFN-alpha was shown to induce bone formation in patients with MM in the plateau phase.