First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma.
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 > or =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.
Institute of Hematology and Medical Oncology L. e A. Seràgnoli Bologna University, Bologna, Italy. ptosi@med.unibo.it
Patrizia
P
Tosi
Elena
E
Zamagni
Claudia
C
Cellini
Raffaele
R
Parente
Delia
D
Cangini
Paola
P
Tacchetti
Giulia
G
Perrone
Michela
M
Ceccolini
Paola
P
Boni
Sante
S
Tura
Michele
M
Baccarani
Michele
M
Cavo
D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood / Q000652:urine; D000596:Amino Acids / Q000097:blood / Q000652:urine; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood* / Q000652:urine; D016723:Bone Remodeling / Q000187:drug effects; D001862:Bone Resorption / Q000188:drug therapy* / Q000378:metabolism; D024042:Collagen Type I / Q000097:blood / Q000652:urine; D003907:Dexamethasone / Q000008:administration & dosage*; D004164:Diphosphonates / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D010146:Pain / Q000188:drug therapy; D010455:Peptides / Q000097:blood / Q000652:urine; D013792:Thalidomide / Q000008:administration & dosage*; D016896:Treatment Outcome; D000077211:Zoledronic Acid
D000596:Amino Acids; D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D015675:Osteocalcin; D013792:Thalidomide; C015484:pyridinoline; D000077211:Zoledronic Acid; D003907:Dexamethasone; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase