Comparison of different treatment modalities for postmenopausal patients with osteopenia: hormone replacement therapy, calcitonin and clodronate

Climacteric. 2000 Jun;3(2):92-101. doi: 10.3109/13697130009167610.


Objective: To evaluate the effectiveness of hormone replacement therapy (HRT), clodronate, calcitonin and a clodronate plus calcitonin combination in postmenopausal patients with osteopenia.

Methods: One hundred postmenopausal patients with osteopenia, with bone mineral density (BMD) measurements at least one standard deviation below the mean value for young premenopausal subjects (T score < -1), were studied. They had no contraindications to HRT, clodronate or calcitonin use and were randomized to four different treatment groups. Patients in group I were treated with transdermal estradiol 50 micrograms/day and oral medroxyprogesterone acetate 10 mg/day during the last 12 days of the month; group II received oral clodronate 400 mg/day for 1 month out of every 3 months; group III received calcitonin nasal spray 100 IU/day; and patients in group IV were treated with oral clodronate 400 mg/day for 1 month out of every 3 months plus calcitonin nasal spray 100 IU/day. Elementary calcium 1000 mg/day was supplemented to patients in all groups. Spinal and femoral neck BMD measurements and markers of bone mineral metabolism were measured in each patient before treatment and 6, 12 and 18 months after treatment in 86 patients.

Results: Significant increases in mean lumbar spine BMD were found in the group receiving HRT, and at the end of 18 months there was a 2.69 +/- 0.76% increase, compared with baseline. Mean femoral neck BMD also increased by 2.22 +/- 0.57% in the HRT group; this was significantly different from baseline, resulting in a higher bone mass gain than in the other three groups. Increases in both lumbar spine and femoral neck BMD were found in patients treated with clodronate, although the only significant increase was observed in lumbar spine BMD at the end of 18 months. The mean changes in BMD were not significantly different, compared with the other groups, and at the end of 18 months there was a 2.20 +/- 0.58% increase at the lumbar spine. The mean vertebral and femoral neck BMD did not change significantly throughout the study period in patients receiving calcitonin. At the end of 18 months, there was a 0.13 +/- 0.52% decrease and a 0.11 +/- 0.49% increase in mean lumbar spine and femoral neck BMD, respectively, compared with baseline. The combination of clodronate plus calcitonin increased mean lumbar spine and femoral neck BMD by 2.08 +/- 1.05% and 1.46 +/- 1.09%, respectively, at the end of 18 months, but these increases were not significantly different from those in the groups where these agents were used alone. Significant decreases in bone resorption and in markers of bone formation were observed in all groups.

Conclusion: HRT was found to be the most effective treatment regimen in postmenopausal patients with osteopenia, compared with clodronate, calcitonin and a clodronate plus calcitonin combination. Clodronate or calcitonin might be alternatives when HRT is contraindicated or refused by the patient; although calcitonin was found to be less effective. The clodronate plus calcitonin combination was not superior to either of these agents when used alone.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Alkaline Phosphatase / blood
  • Bone Density
  • Calcitonin / administration & dosage
  • Calcitonin / therapeutic use*
  • Calcium / blood
  • Clodronic Acid / administration & dosage
  • Clodronic Acid / therapeutic use*
  • Drug Therapy, Combination
  • Estrogen Replacement Therapy*
  • Female
  • Femur
  • Humans
  • Lumbar Vertebrae
  • Middle Aged
  • Osteocalcin / blood
  • Osteoporosis, Postmenopausal / drug therapy*
  • Phosphorus / blood
  • Treatment Outcome


  • Clodronic Acid
  • Osteocalcin
  • Phosphorus
  • Calcitonin
  • Alkaline Phosphatase
  • Calcium