Document Detail


A phase II clinical trial does not show that high dose simvastatin has beneficial effect on markers of bone turnover in multiple myeloma.
MedLine Citation:
PMID:  18668701     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Several studies have evaluated the impact of low dose statin (20-80 mg/day) on bone metabolism with inconclusive results despite promising data of preclinical studies. In this study, we investigated the effect of high dose simvastatin (HD-Sim) on biochemical markers of bone turnover and disease activity in six heavily pretreated patients with multiple myeloma (MM). These patients were treated with simvastatin (15 mg/kg/day) for 7 days followed by a rest period of 21 days in two 4-week cycles. Endpoints were changes in the level of biochemical markers of (i) osteoclast activity (tartrate resistant acid phosphatase, TRACP); (ii) bone resorption (collagen fragments CTX and NTX); (iii) bone formation (osteocalcin and aminoterminal propeptide of type I collagen PINP); (iv) cholesterol; (v) regulators of bone metabolism [osteoprotegerin (OPG) and Dickkopf-1 (DKK-1)] and (vi) disease activity (monoclonal proteins or free light chains in serum). TRACP activity in serum and levels of collagen fragments (NTX) in urine increased for all patients temporarily during the 7 days of treatment with HD-Sim indicating that osteoclasts may have been stimulated rather than inhibited. The other markers of bone metabolism showed no change. None of the patients showed any reduction in free monoclonal light chains or monoclonal proteins in serum during treatment with HD-Sim. In spite of the fact that bone turn over effects of HD-Sim may have been blunted by concomitant treatment of patients with other drugs we observed a transient increase in markers of osteoclast activity. This sign of a transient stimulation of osteoclast activity suggests that HD-Sim may be harmful rather than beneficial for MM patients. For this reason and because of gastro-intestinal side effects the study was stopped prematurely.
Authors:
T E Sondergaard; P T Pedersen; T L Andersen; K Søe; T Lund; B Ostergaard; P Garnero; J-M Delaisse; T Plesner
Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Hematological oncology     Volume:  27     ISSN:  1099-1069     ISO Abbreviation:  Hematol Oncol     Publication Date:  2009 Mar 
Date Detail:
Created Date:  2009-03-03     Completed Date:  2009-04-27     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8307268     Medline TA:  Hematol Oncol     Country:  England    
Other Details:
Languages:  eng     Pagination:  17-22     Citation Subset:  IM    
Copyright Information:
Copyright 2009 John Wiley & Sons, Ltd.
Affiliation:
Department of Clinical Cell Biology, IRS-CSFU, University of Southern Denmark, Vejle Hospital, Vejle, Denmark.
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MeSH Terms
Descriptor/Qualifier:
Aged
Aged, 80 and over
Antilipemic Agents / therapeutic use,  toxicity
Bone and Bones / drug effects,  metabolism*
Drug Administration Schedule
Drug Therapy, Combination
Female
Humans
Male
Middle Aged
Multiple Myeloma / drug therapy*,  metabolism*
Osteoclasts / drug effects,  metabolism
Patient Selection
Simvastatin / therapeutic use*,  toxicity*
Chemical
Reg. No./Substance:
0/Antilipemic Agents; 79902-63-9/Simvastatin

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