Melatonin Osteoporosis Prevention Study
Condition: Osteoporosis; Osteopenia
MeSH terms: Osteoporosis; Bone Diseases, Metabolic
Intervention: melatonin; sugar pill
Intervention description: 3mg p.o. at bedtime daily; lactose p.o. at bedtime daily
Intervention MeSH terms: Melatonin
Phase: Phase 1
Study type: Interventional
Primary purpose: Prevention
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Enrollment: 19.0
Sex: Female
Minimum age: 45 Years
Maximum age: 54 Years
Healthy volunteers: Accepts Healthy Volunteers
Keywords: melatonin; menopause; perimenopause; sleep; osteoporosis; osteopenia; anxiety; depression; hypertension

Summary:

      Osteoporosis is one of the most common skeletal disorders. Today in the United States, 10
      million individuals have osteoporosis and 34 million more have low bone mass or osteopenia,
      which places them at an increased risk of some day developing osteoporosis. Of the people
      affected by this problem, 68% are women.The current thinking on the development of
      osteoporosis is that the changes in bone turnover that occur with aging play a major factor.
      Many modalities of treatment are used to prevent the bone loss and increased fracture risk
      associated with osteoporosis and osteopenia. Melatonin supplementation may be another
      treatment modality that lowers risk of hip fracture in perimenopausal women. Melatonin can
      remodel bone in animal models and in culture. Melatonin works through melatonin receptors to
      form osteoblasts from human mesenchymal stem cells and has been shown to inhibit osteoclast
      activity in rodents. Melatonin levels have been correlated with modulating bone markers; low
      nocturnal levels of melatonin correlate with in an increase in bone marker metabolism and
      osteoporosis. It is been shown that women who have worked night-shifts for greater than 20
      years have increased risk for wrist and hip fractures. Night-shift workers have lower
      nocturnal melatonin levels than people who do not work the night-shift. The addition of
      exogenous melatonin suppresses bone marker metabolism. In human stem cells taken from bone
      marrow, melatonin increases the activity of bone-forming cells called osteoblasts. It is
      hypothesized that melatonin will improve bone health, menopausal quality of life and sleep
      compared to placebo in perimenopausal women. In particular, the investigators expect
      perimenopausal women taking melatonin to show an improvement in overall bone health as
      revealed by a reduction in bone marker turnover since bone resorption increases more so than
      bone absorption in this population compared to those women taking placebo. We also expect
      that perimenopausal women taking melatonin to have better control over their menopausal
      symptoms, better quality of life and less sleep disturbances when compared to their placebo
      controls since melatonin is known to modulate estrogen levels in the body and regulate sleep.
      The data from these studies may provide novel and alternative uses for melatonin; in
      particular its use for the prevention and/or treatment of osteoporosis.
    

Eligibility criteria:

        Inclusion Criteria:

          -  Inclusion criteria include perimenopausal women,

          -  willingness to participate in the 6-month study, willingness to undergo testing of
             bone turnover markers before and after the drug therapies and willingness to provide a
             self-assessment on quality of life and sleep throughout the program.

          -  Subjects must be willing to take their treatments right before bed and to not to
             consume alcohol with this medication.

        Exclusion Criteria:

          -  Exclusion criteria will include women in whom osteopenia is a result of some other
             known process such as hyperparathyroidism, metastatic bone disease, multiple myeloma
             or chronic steroid use.

          -  Those individuals on osteoporotic drugs, hypnotics, CYP1A2 inhibiting drugs,
             fluvoxamine or those with severe sleep apnea, severe COPD and those with moderate or
             severe hepatic impairment will also be excluded.

          -  Individuals who are lactose intolerant will also be excluded because the placebo and
             melatonin capsules will contain lactose.