INTERMITTENT ETIDRONATE PARTIALLY PREVENTS BONE LOSS IN HIRSUTE HYPERANDROGENIC WOMEN TREATED WITH GNRH AGONIST

Treatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced bone turnover and accelerated bone loss in premenopausal wome n with endometriosis, uterine leiomyomatomas and hirsutism. Sodium eti dronate is a powerful inhibitor of bone resorption which has been prov en efficacious in the prevention and treatment of postmenopausal osteo porosis. The objective of this study was to evaluate the skeletal effe cts of 6 months of therapy with the depot preparation of the GnRH agon ist triptorelin (decapeptil 3.75 mg intramuscularly every 4 weeks) in 24 hirsute patients, aged 24-33 years, with hyperandrogenic chronic an ovulation. Ten patients also received cyclical etidronate in an oral d ose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg /day elemental oral calcium (one cycle). The remaining 14 patients rec eived 500 mg/day of elemental calcium continuously. After 6 months all treatments were discontinued for at least a further 6 months. Bone mi neral density (BMD) at lumbar spine and hip (dual-energy X-ray absorpt iometry, Sophos LXRA, France) and biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N-telopeptide and hydroxyproline/cre atinine ratio) were evaluated at baseline, 6 months and 12 months. In the group given GnRH agonist alone BMD fell significantly at all measu red skeletal sites during the first 6 months. In the patients treated with etidronate a significant decrease in BMD was observed at lumbar s pine but not in the femoral neck and trochanter, and the changes at lu mbar spine and trochanter were significantly smaller than those in the control group. At 6 months bone turnover was also increased in patien ts treated with GnRH and calcium. Cyclical etidronate prevented the in crease in biochemical markers of bone formation and resorption, with t he exception of calcium/creatinine excretion, which was significantly increased in both groups. Six months after treatment withdrawal BMD di d not recover in either group. Biochemical markers (N-telopeptide, ser um alkaline phosphatase) remained increased in those patients previous ly treated with calcium alone while they remained close to baseline va lues in the patients treated with cyclical etidronate. Our study indic ates that: (1) GnRH agonist therapy causes remarkable bone loss in you ng individuals with androgen excess who are expected to have increased bone mass; (2) this bone loss can be partially prevented by intermitt ent cyclical etidronate therapy.