The Impact of Bisphosphonates on Bone Loss in Patients Undergoing Surgery and Postoperative Chemotherapy for Gynecologic Malignancies.

Objectives:

1. To evaluate the impact of bisphosphonates on bone mineral density (BMD=primary endpoint) in women with gynecologic malignancies undergoing chemotherapy.
2. To determine if bone loss in women with gynecologic malignancies undergoing chemotherapy is correlated with any of the clinicopathologic parameters gathered in this investigation i.e., race, tumor stage.

Introduction:

Dramatic bone loss in women during the first five years following cessation of ovarian function has been well documented (1). It is estimated that greater than 1.5 million fractures related to osteoporosis (OP) will occur in the US annually (2) and that 33% of women will have sustained hip fractures by age of 90 years(3). With increasing age also comes increasing risk of many cancers, including ovarian, uterine, breast, lung, and colon cancers. 23,500 new cases of ovarian cancer and 38,400 new cases of uterine cancer were diagnosed in the US last year (4). Many of these patients are postmenopausal at the time of diagnosis, and many enter menopause secondary to surgical resection of the ovaries or chemotherapy prompting ovarian failure. This population of women therefore, is at significant risk for osteoporosis.

To the author's knowledge, there has only been one study examining bone loss in menopausal women with gynecologic cancers undergoing chemotherapy (5). This was a small (n=25) prospective observational study with no controlled treatment arm. The authors observed a higher incidence of baseline bone loss and significant additional loss during chemotherapy treatment. Bone loss has also been described in breast cancer patients undergoing chemotherapy (6,7). Laboratory and animal studies demonstrate a deleterious effect of cytotoxic chemotherapy on protein synthesis and DNA replication, resulting in altered or diminished bone formation (8-10). We know of no intervention studies in postmenopausal women with cancer undergoing chemotherapy i.e., comparing different osteoporosis prevention strategies. Estrogen therapy is often contraindicated in gynecologic malignancies and alternative treatments for bone loss prevention are not routinely used by gynecologic oncologists. At present there are no guidelines and/or recommendations in the Gynecologic Oncology community for preventative treatment of bone loss in individuals undergoing chemotherapy (not even calcium and/or vitamin D supplementation recommendations).