INCLUSION CRITERIA:
1. Women who have elected to undergo, or who have undergone (within 8 weeks), a surgical procedure that results, at a minimum, in the absence of both ovaries. Patients enrolled in the screening arm of GOG-0199 who decide to undergo surgery are potentially eligible for GOG-0215.
2. Patients who are pre-menopausal as determined at the time of enrollment (Fast Fact Sheet), Women whose last menstrual cycle occurred less than 12 months prior to study enrollment will be considered pre-menopausal.
In unclear cases (e.g. women under the age of 60 with at least one inact ovary who have had a hysterectomy), premenopausal status may be determined by follicle stimulating hormone (FSH) level less than or equal to 20 U/L. Women with FSH levels greater than 20 will not be eligible for this trial.
3. Patients with normal renal function as evidenced by a calculated creatinine clearance of greater than 60 ml/minute (Cockcroft-Gault).
4. Patients who have met the pre-entry requirements.
5. Patients who have signed an approved informed consent and authorization permitting release of personal health information.
6. Patients with a baseline BMD T-Score at or above minus 1.5 (no more than 1.5 standard deviation below the mean value for young adults) on both the total lumbar spine (L1-L4 region, not individual bones) and bilateral hip. Thus, for example, patients with T-scores of minus 1.5, minus 1, minus 0.5, zero, plus one, etc, will be eligible, while those with scores such as minus 1.9., minus 2.0, minus 2.5, etc, will not be eligible.
7. Patients with GOG Performance Grade of 0, 1, or 2.
8. Women, who had/have at least one intact ovary at the time of surgery.
EXCLUSION CRITERIA:
1. Patients with clinical or radiological evidence of existing fracture of the lumbar spine or bilateral hip.
2. Patients with history of fracture with low intensity trauma or no associated trauma. This includes patients with a history of surgery to the hip or spine.
3. Uncontrolled seizure disorder associated with falls.
4. Patients with prior history of treatment for osteoporosis.
5. Patients with diseases that influence bone metabolism such as Paget's disease, osteogenesis imperfecta, and uncontrolled thyroid or parathyroid dysfunction within 12 months prior to study entry.
6. Patients with other non-malignant systemic diseases including uncontrolled infections, uncontrolled type 2 diabetes mellitus, cardiovascular, renal, hepatic, and lung diseases which would prevent prolonged follow-up. Patients with previous history of thrombosis or thromboembolism can be included only if medically suitable.
7. Patients with a known history of HIV are excluded.
8. Patients with known hypersensitivity to Zometa or other bisphosphonates.
9. Patients who have had any current or prior bisphosphonate treatment (oral or intravenous) during the 12 months prior to study entry.
10. Patients who have taken estrogen or hormone replacement therapy (estrogen plus, progesterone or estrogrn alone). for 30 days or greater within the past 12 months. Current or prior use of oral contraceptives at enrollment is acceptable.
Women who, at the time of enrollment, are planning to take systemic (oral) hormone replacement therapy (estrogen plus progesterone or estrogen alone) following are ot eligible. Vaginal (non-systemic) estrogens are acceptable.
11. Patients who have received current or prior endocrine therapy within the past 12 months (other than insulin and/or oral anti-diabetic medications, and thyroid hormone replacement).
12. Patients who have received current or prior treatment with systemic corticosteroids within the past 12 months (short term corticosteroid therapy, e.g. to prevent/treat chemotherapy-induced nausea/vomiting, is acceptable).
13. Patients with current or prior exposure to anabolic steroids or growth hormone within the past 6 months.
14. Patients currently taking Tibolone or prior use within the last 6 months before randomization.
15. Prior use of systemic sodium fluoride for greater than 3 months during the past 2 years.
16. Patients currently treated with any drugs known to affect the skeleton (e.g., calcitonin, mithramycin, or gallium nitrate) within 2 weeks prior to randomization.
17. Patients who are currently using or have used within the past 12 months tamoxifen or raloxifene or any other selective estrogen receptor modulator (SERM).
18. Women with psychiatric, psychological or other conditions which prevent fully informed consent.
19. Women with current active malignancy (excluding non-melanoma skin cancer).
20. Women with adjuvant radiation therapy or chemotherapy within the past 1 month (31 days).
21. Women who have been treated for prior metastatic malignant disease within the past 5 years.
22. Women with a history of any medical condition which places the subject at risk for donating blood for research purposes, e.g., chronic infectious diseases, severe anemia, or hemophilia.
23. Women whose last menstrual cycle occurred 12 or more months prior to study enrollment will be considered post-menopausal and are not eligible.
For women under the age of 60 with at least one intact ovary who have had a hysterectomy, menopausal status may be determined by follicle stimulating hormone (FSH) level. Women with FSH levels greater than 20 will not be eligible for this trial.
24. Patients who are pregnant.
25. Current active dental problems including infection of the teeth or jawbone (maxilla or mandibular); dental or fixture trauma, or a current or prior diagnosis of osteonecrosis of the jaw (ONJ), of exposed bone in the mouth, or of slow healing after dental procedures.
26. Recent (within six weeks) or planned dental or jaw surgery (e.g. extraction, implants).
National Institutes of Health Clinical Center
Bethesda, Maryland 20892. Last update: 09/20/2008