title: Long-term treatment of osteoporotic women with bisphosphonates does not impair the response to subsequently administered intravenous pamidronate.
abstract: We addressed the question whether the response of osteoporotic patients to bisphosphonate treatment is reduced with time. Bisphosphonate-treated women with postmenopausal or glucocorticoid-induced osteoporosis showed adequate and consistent changes of bone markers to subsequently administered intravenous pamidronate. Response of osteoporotic patients to bisphosphonates is not impaired during their long-term administration.
  
  
  BACKGROUND
  Inadequate response to bisphosphonate treatment has been described in patients with Paget's disease of bone but has not been addressed in osteoporosis although treatment failure is a clinically relevant problem.
  
  
  METHODS
  Twenty one women with postmenopausal osteoporosis (PMO) aged 68 ± 8.2 years and 14 women with glucocorticoid-induced osteoporosis (GIOP) aged 65 ± 10 years were treated with tri-monthly intravenous infusions of 45 mg of pamidronate for 1 year. All patients had been previously treated with bisphosphonates (alendronate, risedronate, pamidronate) for a mean period of 6.2 years (range, 1.3-14 years). Blood samples were taken for measurement of the bone resorption marker C-terminal crosslinking telopeptide of type I collagen (CTX-I) on days 1 and 4 and of the bone formation marker procollagen type I N propeptide, (P1NP) on day 1 of every tri-monthly treatment course.
  
  
  RESULTS
  With each treatment course there was a significant decrease in serum CTX-I on day 4 and an increase to baseline values 3 months after each infusion in both PMO (mean values, day 1: 291.33 ± 160.78 pg/ml vs. day 4: 131 ± 91.7 pg/ml, p < 0.001) and GIOP (day 1: 219.3 ± 114.8 pg/ml vs. day 4: 98.8 ± 51.6 pg/ml, p < 0.001). Serum P1NP remained stable during the whole year of treatment.
  
  
  CONCLUSIONS
  Long-term bisphosphonate treatment of women with either PMO or GIOP does not impair the response to subsequently administered intravenous pamidronate suggesting that inadequate response to long-term bisphosphonate treatment is not responsible for treatment failure.
authors: Department of Endocrinology and Metabolic Diseases, Leiden University Medical Center, Albinusdreef 2, 2333 ZA, Leiden, The Netherlands.
authors: M P
authors: MP
authors: Yavropoulou
authors: N A T
authors: NA
authors: Hamdy
authors: S E
authors: SE
authors: Papapoulos
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D015519:Bone Density / Q000187:drug effects; D050071:Bone Density Conservation Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D024042:Collagen Type I / Q000097:blood; D004164:Diphosphonates / Q000008:administration & dosage* / Q000627:therapeutic use; D004334:Drug Administration Schedule; D057915:Drug Substitution; D005260:Female; D005938:Glucocorticoids / Q000009:adverse effects; D006801:Humans; D007262:Infusions, Intravenous; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D015663:Osteoporosis, Postmenopausal / Q000097:blood / Q000188:drug therapy / Q000503:physiopathology; D000077268:Pamidronate; D010446:Peptide Fragments / Q000097:blood; D010455:Peptides / Q000097:blood; D011347:Procollagen / Q000097:blood; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D004164:Diphosphonates; D005938:Glucocorticoids; D010446:Peptide Fragments; D010455:Peptides; D011347:Procollagen; C052929:collagen type I trimeric cross-linked peptide; C047202:procollagen Type I N-terminal peptide; D000077268:Pamidronate