Romosozumab for Bone Density in Functional Hypothalamic Amenorrhea
This study is looking at whether a medication called romosozumab can improve bone density in young women and girls (ages 14-30) who have functional hypothalamic amenorrhea (FHA). FHA is when your period stops due to things like intense exercise, stress, or an eating disorder, and it can lead to low bone density. You would be randomly assigned to receive either romosozumab or an inactive placebo for six months, given as monthly shots. Everyone in the study will also receive estrogen (transdermal estradiol) and progesterone, plus one IV infusion of zoledronic acid at the six-month mark. Researchers will compare bone density improvements between the romosozumab and placebo groups after one year.
- Study design
- This is an interventional study with an unclear status, planning to enroll 114 participants. Participants will be randomly assigned to receive either romosozumab or a placebo.
- What's involved
- You would receive six monthly subcutaneous injections of either romosozumab or placebo. You would also apply a transdermal estradiol patch twice weekly and take oral progesterone for 12 days each month, plus receive one intravenous infusion of zoledronic acid at the 6-month visit. Bone density will be measured at 0 and 6 months.
- Compensation
- Not stated in the trial record.
- Follow-up
- Bone density and tibial measurements will be taken at 0 and 6 months. The study aims to investigate improvements at one year.
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NCT06533865
Romosozumab as an Adjunct to Physiologic Estrogen Replacement in Functional Hypothalamic Amenorrhea
Recruiting
PHASE3Ages 14–30InterventionalTreatmentMassachusetts General HospitalInvestigator-initiated
~114 participants
Updated 2026-04-23 on ClinicalTrials.gov
What's tested:RomosozumabPlaceboZoledronic acid
At a glance
Recruiting sites
2 of 2 listed sites are recruiting right now
RecruitingSuspended, closed, or not yet open
What they're measuring
Lumbar spine bone density
Measured over 0 and 6 months
+2 more outcomes measured
Conditions
Where it's being run
2 sites across 2 statesMassachusetts1
Virginia1
Who to contact
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Do you actually qualify for this trial?
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Eligibility criteria
Inclusion
Female, age 14-30 years, skeletally mature with bone age ≥ 12 years
For women of reproductive age, agree to use one of the following for the study duration:
Biochemical criteria:
Negative βHCG (pregnancy test)
TSH within twice the upper limit of normal; potassium, magnesium within the normal range; prolactin \<10 ng/mL above the upper limit of normal; FSH not elevated.
Serum ALT ≤ 3 times upper limit of normal, LDL ≤ 190 mg/dl
eGFR ≥ 30ml/minute
If the diagnosis of FHA is unclear, we may check additional labs (e.g., testosterone and sex hormone binding globulin if there is a suspicion of PCOS based on clinical hyperandrogenism).
Less than 3 menses in the preceding 6 months
BMD Z-score ≤ -1.0 at ≥ 1 skeletal site (for subjects \<18 years old, we will use the height Z-score-adjusted BMD Z-score using the pediatric bone density calculator developed by the National Institutes of Health and currently maintained by the Children's Hospital of Philadelphia)
Dental check-up within the past year
If the menstrual status of the subject is unclear due to the presence of a progestin-releasing IUD, serum estradiol levels will be checked twice, at least one week apart. Both estradiol levels must be \< 50 pg/mL.At the discretion of the study clinician, subjects with a diagnosis of PCOS may undergo one to two serum estradiol levels, at least one week apart. The estradiol level(s) must be \< 50 pg/mL
Exclusion
Disease other than FHA known to affect bone, including untreated thyroid dysfunction, Cushing's disease, renal failure, diabetes mellitus
Use of bisphosphonates in the past year
Use of other medications known to affect bone metabolism within 3 months of the study (other than calcium and vitamin D supplementation).
Current use of systemic corticosteroids
Migraine with aura as classified in IHS Classification ICHD-3.
Personal history of or first-degree relative with unprovoked thromboembolism (unless the subject has been tested and ruled out for a hypercoagulable state).
Active substance use disorder; currently smokes or vapes
History of malignancy or Paget disease of bone
Pregnant, planning to become pregnant within 12 months after the end of treatment and/or breastfeeding
Cardiovascular: History of myocardial infarction or stroke; history of hypertension or use of anti-hypertensive medications
Immunodeficiency or taking immunosuppressive therapy
Other conditions that can cause oligo-amenorrhea such as PCOS, primary ovarian insufficiency. A participant with PCOS may be included if a study clinician determines that missed menstrual periods are more likely a consequence of FHA.
Dental: Osteonecrosis of the jaw (ONJ) or risk factor for ONJ, such as invasive dental procedures (tooth extraction, dental implants, oral surgery in the past 3 months), poor oral hygiene, periodontal and/or pre-existing dental disease
Planned invasive dental procedure or other planned major surgery for 18 months after the baseline visit
Known sensitivity or absolute contraindication to any of the products or components of the medications to be administered (romosozumab, zoledronic acid, transdermal estradiol, micronized progesterone, calcium or vitamin D supplements)
BMD Z-score \<-2.5 (who we will refer for evaluation)
What this trial measures
- Lumbar spine bone density0 and 6 months
6-month change in lumbar spine bone density
- Tibial cortical thickness0 and 6 months
6-month change in tibial cortical thickness
- Tibial failure load0 and 6 months
6-month change in tibial failure load