Clodronate reduces vertebral fracture risk in women with postmenopausal or secondary osteoporosis: results of a double-blind, placebo-controlled 3-year study

J Bone Miner Res. 2004 May;19(5):728-36. doi: 10.1359/JBMR.040116. Epub 2004 Jan 19.

Abstract

The efficacy of oral clodronate 800 mg daily to reduce vertebral fractures was studied in 593 women with postmenopausal or secondary osteoporosis. The incidence of vertebral fractures was significantly reduced by 46%. The effect was not modified by the underlying cause of osteoporosis or other baseline factors including bone mineral density, QUS, weight, and smoking.

Introduction: This study aimed to determine if the bisphosphonate, clodronate (Bonefos), reduced the incidence of vertebral fractures in osteoporotic women.

Materials and methods: Women fulfilling the WHO criteria for osteoporosis at the lumbar spine (T-score </= -2.5) and/or with at least one prevalent vertebral fracture were recruited to a 3-year double-blind, placebo-controlled study. A total of 593 patients were randomized to two strata comprised of women with postmenopausal osteoporosis (I, n = 483) and secondary osteoporosis (II, n = 110). They received either clodronate 800 mg daily orally (n = 292) or an identical placebo (n = 301). All patients received a calcium supplement of 500 mg daily. BMD was measured at 6, 12, 24, and 36 months, and lateral spine radiographs were obtained at baseline and annually thereafter for vertebral morphometry.

Results: Treatment with clodronate was associated with a significant increase in mean spine BMD over 3 years (percent change from baseline, 4.35 +/- 6.34% versus 0.64 +/- 6.02% in the placebo group, p < 0.0001). At the hip, clodronate maintained total BMD, whereas a significant decrease was observed in the placebo group (percent change from baseline 0.70 +/- 5.67% versus -3.03 +/- 6.32% in the placebo group, p < 0.0001). The changes at the spine and hip were similar in both strata. Incident vertebral fractures at 3 years were observed in 63 women in the placebo group and 33 patients receiving clodronate (relative risk, 0.54; 95% CI, 0.37-0.80; p = 0.001). Clodronate significantly reduced vertebral fracture risk in both strata and in women with or without prior vertebral fracture at baseline. Nonvertebral osteoporosis-associated fractures occurred in 21 women in the placebo group and in 14 women treated with clodronate. Treatment was well tolerated, with no significant difference in adverse event rates, including esophagitis, during clodronate treatment.

Conclusion: We conclude that clodronate 800 mg daily is a safe and effective treatment to reduce fracture risk in women with osteoporosis, regardless of causation.

Publication types

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

MeSH terms

  • Aged
  • Alkaline Phosphatase / blood
  • Antimetabolites / therapeutic use
  • Bone Density / drug effects
  • Clodronic Acid / therapeutic use*
  • Collagen / blood
  • Collagen Type I
  • Double-Blind Method
  • Female
  • Humans
  • Middle Aged
  • Osteoporosis / complications*
  • Osteoporosis / etiology
  • Osteoporosis, Postmenopausal / complications*
  • Peptides / blood
  • Prospective Studies
  • Risk Factors
  • Spinal Fractures / etiology
  • Spinal Fractures / prevention & control*

Substances

  • Antimetabolites
  • Collagen Type I
  • Peptides
  • collagen type I trimeric cross-linked peptide
  • Clodronic Acid
  • Collagen
  • Alkaline Phosphatase