title: Course of NTX changes under continuous bisphosphonate treatment in cases of NTX over-reduction due to long-term treatment with bisphosphonates.
abstract: BACKGROUND
  It has recently been suggested that long-term continuous treatment with bisphosphonates can eventually result in skeletal harm. We reported that the level of urinary cross-linked N-telopeptide of type I collagen (NTX) was over-reduced in 11 of 87 (12.7%) patients receiving long-term therapy with bisphosphonates. In this case, it is inconclusive whether treatment with bisphosphonates should be continued or not after over-reduction of bone resorption markers. In this study, we demonstrated changes in NTX levels in 13 patients who consented to continue treatment with bisphosphonates even after the over-reduction of NTX levels.
  
  
  METHODS
  We investigated 13 osteoporosis patients who wanted to continue taking bisphosphonates even after an over-reduction of their NTX levels (less than 9.3 nmolBCE/mmol Cr) caused by the long-term treatment had been recognized. We measured NTX and serum alkaline phosphatase (ALP) levels, and lumbar bone mineral density (BMD). Measurements were made at 12, 24 and 36 months before and after the recognition of NTX over-reduction.
  
  
  RESULTS
  Mean NTX levels at 42, 36, 24 and 12 months prior to recognition of NTX over-reduction (42.6 ± 38.5, 31.9 ± 16.4, 25.0 ± 10.2 and 20.4 ± 9.5 nmolBCE/mmol Cr, respectively) decreased incrementally. In contrast, mean NTX levels at 6, 12, 24 and 36 months (16.0 ± 4.6, 19.6 ± 11.9, 16.8 ± 6.4 and 18.2 ± 5.9 nmolBCE/mmol Cr, respectively) after NTX over-reduction (8.7 ± 0.9 nmolBCE/mmol Cr) returned to within the reference range. Mean ALP levels did not reveal significant change and stayed within the reference range (110-370 IU/l) during the total course of bisphosphonate treatment. Mean BMD values had a tendency to increase throughout the entire period of bisphosphonate treatment.
  
  
  CONCLUSIONS
  The NTX levels in all 13 cases returned to within the reference range even when bisphosphonate treatment was continued after the over-reduction of NTX levels because of long-term bisphosphonate treatment, and continued treatment was not observed to cause atypical fractures of the femur in any of the patients.
authors.affiliation: Department of Orthopaedic Surgery, Sapporo Medical University School of Medicine, South-1, West-16, Chuo-ku, Sapporo, 060-8543, Japan. iba@sapmed.ac.jp
authors.forename: Kousuke
authors.initials: K
authors.lastname: Iba
authors.forename: Junichi
authors.initials: J
authors.lastname: Takada
authors.forename: Koichi
authors.initials: K
authors.lastname: Sasaki
authors.forename: Takuro
authors.initials: T
authors.lastname: Wada
authors.forename: Toshihiko
authors.initials: T
authors.lastname: Yamashita
mesh_terms: D015502:Absorptiometry, Photon; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000652:urine; D015519:Bone Density; D024042:Collagen Type I / Q000652:urine*; D004164:Diphosphonates / Q000008:administration & dosage*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000175:diagnosis / Q000188:drug therapy / Q000652:urine*; D010455:Peptides / Q000652:urine*; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D024042:Collagen Type I; D004164:Diphosphonates; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide