Osteoporosis
Conditions
Brief summary
The aim of the study is to assess the effect of melatonin treatment in patients with osteopenia on BMD, muscle function, quality of life and calcium homeostasis.
Detailed description
Background: Melatonin is known for its regulation of circadian rhythm. The production falls with age, which explains why elderly may have disturbed sleep patterns. Laboratory study and animal experimental studies suggests that melatonin also may protect against bone loss through increased osteoblast- and inhibited osteoclast activity. However, so far human studies have not been performed. Design and patients: Double blinded randomised controlled study. Eighty post-menopausal women (aged 55-75) with osteopenia are randomized to receive 1mg, 3mg or placebo (daily - at night time) for 12 months. Methods and results: Effects of melatonin on BMD, bone- structure and mass will be assessed through DXA-scans, pQCT, and QCT. Quality of life, sleep, and activity level will be assessed though questionnaires. Calcium homeostasis will be analyzed through blood and urines samples. As safety parameters, balance and muscle function will also be performed. Conclusion: Expected improvements in BMD, quality of life and sleep.
Interventions
DRUGMelatonin
1 or 3 mg of melatonin PO each night for 12 months
Sponsors
University of Aarhus
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
FEMALE
Age
55 Years to 75 Years
Healthy volunteers
Yes
Inclusion criteria
* Postmenopausal women between 55 and 75 years. * Osteopenia verified by DXA-scans of total hip or lumbar spine (t-score between -1 and -2.5) * Written informed consent after oral and written information
Exclusion criteria
* Severely impaired renal function (plasma creatinine \>60 eGFR ml/l). * Severely impaired hepatic function (Plasma alanine aminotransferase (ALAT) and/or alkaline phosphatase more the doubled compared to upper limit of reference value). * Coagulation factors PP \<0.6 * Hypercalcemia (p-ion calcium \> 1.32 nmol/l) * Previous or present malignancies (except a treated skin cancer that is not melanoma or treated carcinoma in situ, 2 years since last therapy). * Diseases affecting the calcium homeostasis including untreated thyroid diseases. * Regular use of medicine affecting the calcium homeostasis; including diuretics, lithium, antiepileptica, glucosteroids. * SSRI-product with fluvoxamin. * Treatment with carbamazepin * Treatment with rifampicin * Severe malabsorption syndrome including gastric or intestinal resection. * Alcohol or drug abuse. * Smokers * Major medical or social problems that will be likely to preclude participation for one year.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Bone Mineral Density (BMD) | baseline and end of study (after 12 months) | Effects of melatonin on BMD will be assessed through DXA-scans |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Changes in Calcium Homeostasis | baseline, after 3, 6, 9 months, and end of study (after 12 months) | Calcium homeostasis will be analyzed through blood and urines samples |
Countries
Denmark
Participant flow
Recruitment details
We recruited 81 postmenopausal women with osteopenia to receive either melatonin (n=40) (1 or 3 mg) or similar placebo (n=41) nightly for 12 months. In addition, all women received a daily supplementation with 800mg calcium and 20ug D3
Pre-assignment details
A total of 202 women were invited to participate. 81 were included in the study
Participants by arm
| Arm | Count |
|---|---|
| Melatonin1+3 Melatonin: 1 or 3 mg of melatonin PO each night for 12 months | 40 |
| Placebo Identical placebo given nightly for 12 months | 41 |
| Total | 81 |
Baseline characteristics
| Characteristic | Melatonin1+3 | Placebo | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 8 Participants | 12 Participants | 20 Participants |
| Age, Categorical Between 18 and 65 years | 32 Participants | 29 Participants | 61 Participants |
| Region of Enrollment Denmark | 40 participants | 41 participants | 81 participants |
| Sex: Female, Male Female | 40 Participants | 41 Participants | 81 Participants |
| Sex: Female, Male Male | 0 Participants | 0 Participants | 0 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 19 / 40 | 17 / 41 |
| serious Total, serious adverse events | 5 / 40 | 7 / 41 |
Outcome results
Primary
Changes in Bone Mineral Density (BMD)
Effects of melatonin on BMD will be assessed through DXA-scans
Time frame: baseline and end of study (after 12 months)
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Melatonin1+3 | Changes in Bone Mineral Density (BMD) | -0.05 percentage of change in BMD | Standard Error 3.07 |
| Placebo | Changes in Bone Mineral Density (BMD) | -1.45 percentage of change in BMD | Standard Error 2.81 |
Comparison: The p-value was calculatedp-value: <0.05t-test, 2 sided
Secondary
Changes in Calcium Homeostasis
Calcium homeostasis will be analyzed through blood and urines samples
Time frame: baseline, after 3, 6, 9 months, and end of study (after 12 months)