Effect of oral clodronate on bone mass, bone turnover and subsequent metastases in women with primary breast cancer.
Breast cancer treatments have been associated with accelerated bone loss and increased osteoporosis risk. In a subgroup analysis of a randomised, double-blind, placebo-controlled study, we compared the changes in spine and total hip bone mineral density (BMD) and biochemical markers of bone turnover in women with primary breast cancer who had received standard therapy plus either oral clodronate 1600 mg/d (n=419) or placebo (n=432) for 2 years. After 2 years, spine BMD was 1.92% higher in patients who received clodronate instead of placebo (P<0.0001) and total hip BMD was 1.29% higher (P=0.002 versus placebo). Patients who received clodronate had a median 26% reduction in levels of serum N-terminal pro-peptide of type I procollagen (PINP)--a marker of bone turnover--after 2 years of therapy. This compares with a median 5% increase in patients who received placebo (P<0.0001). Effects on BMD, but not biochemical markers, persisted for up to 3 years post-treatment. Early changes in PINP were associated with changes in BMD and the likelihood of developing bone metastases. This study shows the use of oral clodronate during primary breast cancer treatment is associated with reduced bone turnover and protection against bone metastases.
McCloskey
Eugene
E
WHO Collaborating Centre for Metabolic Bone Diseases, University of Sheffield Medical School, Sheffield, UK. e.v.mccloskey@shef.ac.uk
Paterson
Alexander
A
Kanis
John
J
Tähtelä
Rita
R
Powles
Trevor
T
D000284:Administration, Oral; D000328:Adult; D015415:Biomarkers / Q000378:metabolism; D015519:Bone Density / Q000187:drug effects*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001859:Bone Neoplasms / Q000517:prevention & control / Q000556:secondary; D016723:Bone Remodeling / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy / Q000503:physiopathology*; D017024:Chemotherapy, Adjuvant; D004002:Clodronic Acid / Q000008:administration & dosage / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D006621:Hip Joint / Q000503:physiopathology; D006801:Humans; D008159:Lumbar Vertebrae / Q000503:physiopathology; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood
D015415:Biomarkers; D050071:Bone Density Conservation Agents; D010446:Peptide Fragments; D011347:Procollagen; C047202:procollagen Type I N-terminal peptide; D004002:Clodronic Acid