Fracture risk remains reduced one year after discontinuation of risedronate

Osteoporos Int. 2008 Mar;19(3):365-72. doi: 10.1007/s00198-007-0460-7. Epub 2007 Oct 16.


One year after discontinuation of three year's treatment with risedronate, BMD decreased at the lumbar spine and femoral neck and bone turnover markers returned to control group levels. Despite these changes, the risk of new morphometric vertebral fractures remained lower in previous risedronate patients compared with previous control patients.

Introduction: Differences in bisphosphonate pharmacology and pharmacokinetics could influence persistence or resolution of the effects once treatment is stopped. We investigated changes in intermediate markers--bone mineral density (BMD) and bone turnover markers (BTM)--and fracture risk after discontinuation of treatment with risedronate.

Methods: Patients who received risedronate 5 mg daily (N = 398) or placebo (N = 361) during the VERT-NA study stopped therapy per protocol after 3 years but continued taking vitamin D (if levels at study entry were low) and calcium and were reassessed one year later.

Results: In the year off treatment, spine BMD decreased significantly, but remained higher than baseline (p < or = 0.001) and placebo (p < 0.001), with similar findings at the femoral neck and trochanter. Urinary NTX and bone-specific alkaline phosphatase, which decreased significantly with treatment, were not significantly different from placebo after 1 year off treatment. Despite the changes in intermediate markers, the incidence of new morphometric vertebral fractures was 46% lower in the former risedronate group compared with the former placebo group (RR 0.54 [95% CI, 0.34, 0.86, p = 0.009]).

Conclusions: Despite the apparent resolution of effect on BMD and BTM, the risk reduction of new vertebral fractures remained in the year after treatment with risedronate was stopped.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / urine
  • Bone Density / drug effects
  • Bone Density Conservation Agents / administration & dosage*
  • Bone Density Conservation Agents / therapeutic use
  • Calcium / therapeutic use
  • Collagen Type I / urine
  • Double-Blind Method
  • Drug Administration Schedule
  • Etidronic Acid / administration & dosage
  • Etidronic Acid / analogs & derivatives*
  • Etidronic Acid / therapeutic use
  • Female
  • Femur Neck / physiopathology
  • Follow-Up Studies
  • Humans
  • Lumbar Vertebrae / physiopathology
  • Middle Aged
  • Osteoporosis, Postmenopausal / complications
  • Osteoporosis, Postmenopausal / drug therapy*
  • Osteoporosis, Postmenopausal / physiopathology
  • Peptides / urine
  • Risedronic Acid
  • Spinal Fractures / etiology
  • Spinal Fractures / physiopathology
  • Spinal Fractures / prevention & control*


  • Biomarkers
  • Bone Density Conservation Agents
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Risedronic Acid
  • Etidronic Acid
  • Calcium