A randomized, placebo-controlled study on the effect of cyclic intermittent etidronate therapy on the bone mineral density changes associated with six months of gonadotropin-releasing hormone agonist treatment

Am J Obstet Gynecol. 1996 Jul;175(1):105-9. doi: 10.1016/s0002-9378(96)70258-2.


Objective: Our purpose was to determine whether intermittent cyclic etidronate therapy blocks the decline in bone density associated with gonadotropin-releasing hormone agonist therapy.

Study design: Thirty-one premenopausal subjects who needed treatment with leuprolide (Lupron) 3.75 mg monthly for 6 months were randomized to etidronate or placebo. Bone turnover was assessed by measurement of serum calcium, phosphorus, alkaline phosphatase, and fasting urinary calcium/creatinine ratios. Bone density was measured by dual energy x-ray absorptiometry.

Results: Gonadotropin-releasing hormone treatment produced a significant decrease (4% to 10%) in bone density at the anteroposterior and lateral spine in placebo-treated patients (11). No significant change was demonstrated in etidronate-treated patients (15). Significant increases in serum calcium, phosphorus, alkaline phosphatase, and urinary calcium/creatinine ratios were noted in the placebo group. No significant change in these parameters were evident in the etidronate group.

Conclusion: Etidronate blocks bone mineral density changes associated with gonadotropin-releasing hormone agonist therapy and normalizes serum and urine indicators of bone turnover.

Publication types

  • Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Bone Density / drug effects*
  • Bone Remodeling / drug effects
  • Double-Blind Method
  • Endometriosis / blood
  • Endometriosis / physiopathology
  • Endometriosis / therapy*
  • Estradiol / blood
  • Etidronic Acid / administration & dosage*
  • Female
  • Gonadotropin-Releasing Hormone / agonists
  • Gonadotropin-Releasing Hormone / therapeutic use*
  • Humans
  • Leiomyoma / blood
  • Leiomyoma / physiopathology
  • Leiomyoma / therapy*
  • Middle Aged
  • Prospective Studies
  • Uterine Neoplasms / blood
  • Uterine Neoplasms / physiopathology
  • Uterine Neoplasms / therapy*


  • Gonadotropin-Releasing Hormone
  • Estradiol
  • Etidronic Acid