Amenorrhea, or not having menstrual periods, is correlated with a loss of bone density. Right now, there are no FDA-approved therapies to treat bone loss in young adult women who have stopped having menstrual periods or who are having too few periods. This research study is testing whether two medications, in combination with estrogen and progesterone, can increase bone density and strength in young adult women who have stopped having periods or have very few periods.

You (or your teen) may be eligible for this study if you meet the following criteria.

Inclusion Criteria:

• Women ages 14-30 who have had less than 3 periods in the past 6 months
• Have had a dental check-up within the past year
• Not currently pregnant, breastfeeding, or planning to become pregnant in the future
• Have below-average bone density (will be tested for this as part of the study)
• Willing to use birth control for the study’s duration
• Willing to commit to a 12-month study including 9 visits, blood draws, bone scans, questionnaires, and taking study medications and supplements
• Willing to commit to 9 visits at UVA in Charlottesville, VA
• Do not smoke cigarettes (or vape)
• Have no planned invasive dental procedures or major surgeries within the next 18 months
• No medical history of cardiac problems, strokes, kidney disease, liver disease, Cushing’s disease, diabetes, thyroid disease, blood clots or clotting disorders, migraines with aura, cancer, Paget’s disease, eating disorders, PCOS, primary ovarian insufficiencies, osteonecrosis of the jaw, substance abuse, immunodeficiency disorders, immunosuppressive therapy, oral steroid use

Visits

This study involves 9 visits over the course of 12 months. These visits will include history and physical exams, blood draws, questionnaires about your exercise and eating habits, DXA scans (which measure bone health and body composition), and XCT scans (which evaluate the structure of the bones in your wrist and leg).

Treatments

If you’re eligible and choose to participate, you will be randomly assigned to either the romosozumab or placebo group (in a 2:1 ratio, meaning you are two times more likely to receive the active medication than the placebo, or inactive medication).

You will receive monthly subcutaneous injections of romosozumab or placebo, which will be administered at your study visits at UVA. These injections are given from a pen device similar to an insulin pen.

You’ll also receive self-adhesive estrogen patches (100 micrograms/day) to apply twice weekly. These patches can be worn while doing your daily activities, including showering. We will also provide oral progesterone pills for 12 days each month (to balance the effects of estrogen and prevent thickening of the uterine lining), as well as daily calcium and vitamin D supplements. In addition, all participants will receive a single infusion of zoledronic acid at the 6-month visit.

As a participant, you may receive up to $1,550 for completing the entire study. In addition, we will help cover transportation costs. For local participants, transportation costs will be reimbursed up to $25 per visit (such as Uber fares or gas mileage). For participants traveling from farther away, compensation will be provided at 70 cents per mile, up to $150 per visit.

There is no cost for you to participate in our research study.