First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma
Patrizia Tosi
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorElena Zamagni
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorClaudia Cellini
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorRaffaele Parente
Central Laboratory, Policlinico S. Orsola, Bologna, Italy
Search for more papers by this authorDelia Cangini
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorPaola Tacchetti
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorGiulia Perrone
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorMichela Ceccolini
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorPaola Boni
Central Laboratory, Policlinico S. Orsola, Bologna, Italy
Search for more papers by this authorSante Tura
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorMichele Baccarani
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorMichele Cavo
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorPatrizia Tosi
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorElena Zamagni
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorClaudia Cellini
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorRaffaele Parente
Central Laboratory, Policlinico S. Orsola, Bologna, Italy
Search for more papers by this authorDelia Cangini
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorPaola Tacchetti
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorGiulia Perrone
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorMichela Ceccolini
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorPaola Boni
Central Laboratory, Policlinico S. Orsola, Bologna, Italy
Search for more papers by this authorSante Tura
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorMichele Baccarani
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorMichele Cavo
Institute of Hematology and Medical Oncology ‘L. e A. Seràgnoli’ Bologna University, Bologna, Italy
Search for more papers by this authorAbstract
Abstract: Background: Bone involvement is frequently observed in multiple myeloma (MM) patients both at diagnosis and during the course of the disease. The evaluation of biochemical markers of bone turnover could allow a dynamic evaluation of the effects of a given therapy on bone metabolism. Methods: In the present study, markers of bone resorption [urinary free pyridinoline (PYD), deoxypyridinoline (DPYD), N-terminal telopeptide of collagen I (NTX) and C-terminal telopeptide (serum crosslaps)] and of bone formation [bone alkaline phosphatase (BAP) and osteocalcin] were evaluated at diagnosis and after induction therapy in 40 patients (23M, 17F, median age = 53.5 yr) enrolled in the ‘Bologna 2002’ clinical trial. By study design, all patients received 4 months of combined thalidomide (100 mg/d for 2 wk then 200 mg/d), dexamethasone (40 mg/d on days 1–4, 9–12, 17–20/28 on odd cycles and on days 1–4 on even cycles) and zoledronic acid (4 mg/28 d). Results: At diagnosis, although bone resorption markers were increased in more than 40% of the patients, only NTX (P = 0.029) and crosslaps (P = 0.000) were significantly related to the extent of skeletal lesions, as assessed by X-ray. After 4 months of therapy, a significant decrease in mean (±SE) urinary NTX (52.7 ±6.9 nmol/mmol creatinine ±6.9 vs. 14 ± 1.42 nmol/mmol creatinine, P = 0.000) and serum crosslaps (6242.4 ±945 pmol/L vs. 1414.9 ± 173.8 pmol/L, P = 0.000) was observed in patients obtaining ≥partial response, at variance to what has been detected in patients showing <partial response. Conclusions: Among all bone resorption markers, urinary NTX and serum crosslaps seem to be strictly related to the extent of bone involvement in MM. Combined thalidomide + dexamethasone and zoledronic acid seem to be highly effective in reducing bone resorption in sensitive patients, although the relative contribution of each drug cannot yet be determined.
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