Clinical Drug Investigation

, Volume 33, Issue 3, pp 193–198 | Cite as

Improved Efficacy of Intramuscular Weekly Administration of Clodronate 200 mg (100 mg Twice Weekly) Compared with 100 mg (Once Weekly) for Increasing Bone Mineral Density in Postmenopausal Osteoporosis

  • Bruno Frediani
  • Ilaria Bertoldi
  • Serena Pierguidi
  • Antonella Nicosia
  • Valentina Picerno
  • Georgios Filippou
  • Luca Cantarini
  • Mauro Galeazzi
Original Research Article
  • 165 Downloads

Abstract

Background

Clodronate is a bisphosphonate used for the treatment of postmenopausal osteoporosis and all conditions characterized by excess bone resorption. We have previously reported that intramuscular (IM) therapy with clodronate at a dose of 100 mg/week displays significant effects on bone mineral density (BMD) although a plateau effect is observed after 1 year of treatment. Previous reports indicate that the densitometric effects of bisphosphonates directly correlate with the drug dosage and suggest that using IM clodronate at doses higher than 100 mg/week may result in improved efficacy. However, to the best of our knowledge, this has never been proved.

Objective

The primary endpoint of the study was the effect on BMD of IM clodronate 100 mg once weekly or 100 mg twice weekly in patients with postmenopausal osteoporosis. The incidence of non-traumatic vertebral fractures and adverse events was also reported.

Methods

The present study was a randomized, open-label, parallel-group trial conducted between January 2007 and December 2009 in the Osteoporosis and Osteoarticular Instrumental Diagnosis Centre (University of Siena, Siena, Italy). The study involved 60 women, aged 57–78 years, with a history of postmenopausal osteoporosis for more than 5 years. Patients were randomized to receive IM clodronate 100 mg once weekly (Group A, 30 patients) or 100 mg twice weekly (Group B, 30 patients), for 2 years.

Results

Significant increases compared with baseline in BMD were observed for both groups at 1 and 2 years, with significantly higher increases for Group B compared with Group A. Group B displayed a BMD increase (±SD) at the lumbar spine of +4.0 % (±2.1) and +5.9 % (±2.0) at 1 and 2 year(s), respectively, compared with +2.8 % (±1.7) and +3.5 % (±2.2), respectively, observed for Group A. Similarly, Group B showed better performance compared with Group A for BMD increase at the femoral neck, with an observed increase of +3.5 % (±1.7) and +5.4 % (±1.8) at 1 and 2 year(s), respectively, compared with a change of +2.3 % (±1.9) and +2.5 % (±1.9), respectively, registered in Group A. Consistently, the BMD increase measured at the total femur was significantly higher for Group B [+3.4 % (±1.9) and +4.9 % (±2.1) at years 1 and 2, respectively] compared with Group A [+1.6 % (±0.9) and +2.4 % (±1.9) at years 1 and 2, respectively]. When the change in BMD from year 1 to year 2 was compared, a significant increase of BMD was seen in Group B in all the analysed regions, contrary to that observed for Group A where a plateau effect resulted in no significant change from year 1 to year 2. Three non-traumatic vertebral fractures occurred during the study: two in Group A and one in Group B.

Conclusion

The present study indicates the superior performance of IM clodronate 200 mg weekly (100 mg twice weekly) compared with 100 mg once weekly in BMD in women with postmenopausal osteoporosis. This work demonstrated that administration of twice the drug dosage in a week significantly improved the efficacy of the treatment without inducing serious adverse events. Therefore, IM clodronate 200 mg weekly may be considered a valid therapeutic choice for the treatment of postmenopausal osteoporosis.

Notes

Acknowledgements

Prof. Frediani wishes to thank his entire group for their important contribution in performing the assessments and in collecting data. The authors declare no conflicts of interest. Editorial assistance was provided by inScience Communications, Springer Healthcare, and funded by Prof. Frediani.

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Copyright information

© Springer International Publishing Switzerland 2013

Authors and Affiliations

  • Bruno Frediani
    • 1
    • 2
  • Ilaria Bertoldi
    • 1
  • Serena Pierguidi
    • 1
  • Antonella Nicosia
    • 1
  • Valentina Picerno
    • 1
  • Georgios Filippou
    • 1
  • Luca Cantarini
    • 1
  • Mauro Galeazzi
    • 1
  1. 1.Rheumatology Department, Osteoporosis and Osteoarticular Instrumental Diagnosis CentreUniversity of SienaSienaItaly
  2. 2.Rheumatology Department, Osteoporosis and Rheumatologic Instrumental Diagnosis Centre, Ospedale ‘Le Scotte’University of SienaSienaItaly

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