OsteoPreP: The Effect of Probiotic Supplementation on Bone, Muscle, and Glucose Metabolism in Postmenopausal Women: A Randomised Placebo-controlled Trial
Trial Snapshot
- Phase
- Phase 4
- Status
- Active, not recruiting
- Enrollment
- 160
- Locations
- 2
- Primary Endpoint
- Total volumetric bone mineral density of the distal tibia
Study Overview
Brief Summary
To evaluate the effect of 12 months of supplementation with a probiotic (probiotic plus prebiotic; 2 capsules per day) on relative change (%) in total volumetric bone density (measured using high resolution peripheral quantitative computed tomography [HR-pQCT]) of the distal tibia.
Detailed Description
It is well established that bone loss occurs throughout life after the attainment of peak bone mass which is usually reached by the end of the second decade of life. During the first 5-8 years following menopause, women experience an accelerated bone loss, which is then followed by a slower phase of decline in bone mineral density (BMD). As over 40% of all women in Australia will suffer an osteoporotic (fragility) fracture in their lifetime, investigating interventions that can prevent bone loss in postmenopausal women is a critical focus. The menopausal transition is also associated with an increased risk of cardiovascular disease, diabetes, and cognitive decline. These conditions and their treatments can also affect bone health.
Previous research has indicated a potential link between the gut microbiome and bone health. Animal studies indicate that interventions affecting the gut microbiome may be successful in reducing bone loss, but human data is limited. Moreover, there is an emerging body of evidence linking the gut microbiome to cognitive, muscle and cardiometabolic function. Such studies indicate that probiotics (healthy gut bacteria) or prebiotics (food for healthy bacteria, e.g. fibre) can increase the amount of short chain fatty acids - such as butyrate -produced by the bacteria in the gut which may mediate the beneficial effects of improving gut health.
The proposed study is a double-blind, placebo-controlled randomised trial, which will investigate whether consuming a probiotic supplement containing inulin (a prebiotic soluble fibre) twice daily for 12 months will improve bone health in postmenopausal women. In addition, secondary outcomes will measure the effect of the intervention on immune system modulation and cognition as well as musculoskeletal and metabolic function as potential mediators.
One hundred and sixty postmenopausal women residing in Melbourne (Victoria, Australia) who are at least one year from their final menses will be recruited from the community via a mail out, advertisements in newspapers, social media, flyers as well as a landing page on an ACU managed website. The investigators have also applied for assisted mail outs through Services Australia for recruitment purposes. Services Australia is able to extract names and addresses of some target study demographics (females living in Melbourne aged between 40 and 65) from the Medicare database and mail them the study details on our behalf. Those wishing to participate will undergo a series of baseline assessments inclusive of bone mineral density scans, blood and stool sampling and physical activity and lifestyle questionnaires. They will then be randomised, in a blinded fashion, to consume one of the following two supplements:
- Placebo control group (n = 80): Placebo capsule - 2 capsules per day
- Probiotics group (n=80): Probiotic capsule - 2 capsules per day
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
Double-blinded
Eligibility Criteria
- Ages
- 40 Years to 65 Years (Adult, Older Adult)
- Sex
- Female
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Postmenopausal women, 40-65 years old
- •Caucasian (due to significant differences in BMD and bone remodelling between ethnicities)
- •At least one year since final menses
- •Signed informed consent
- •Up to date Covid 19 vaccination status
- •Able to walk without the use of an aid
- •Stated availability throughout the entire study period
- •Mental capacity to understand and willingness to fulfil all the details of the protocol
- •Residing in Melbourne, Victoria, Australia
Exclusion Criteria
- •Diagnosis of osteoporosis
- •T-score of -2.5 or less at the femoral neck or lumbar spine (L1-L4) on the DXA scan at screening visit
- •HbA1c ≥6.5% at screening visit
- •Blood pressure at screening visit of systolic >180 mmHg and/or diastolic >120 mmHg
- •Untreated hyperthyroidism
- •Rheumatoid arthritis
- •Diagnosed with a disease-causing secondary osteoporosis or malabsorption: chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, type 1/type 2 diabetes, or chronic liver disease
- •Bariatric surgery
- •Recently diagnosed malignancy (within the last 5 years)
- •Current or recent oral corticosteroid use (any dose within the last 3 months, or 5mg of Prednisolone (or equivalent) or a higher daily dose for 14 days or more 3-12 months prior to screening)
- •Use of antiresorptive therapy, including systemic hormone replacement therapy, bisphosphonates, strontium ranelate (current or during the last 3 years)
- •Use of teriparatide (current or during the last 3 years)
- •Participation in other clinical intervention trials
- •Antibiotics treatment 2 months prior to inclusion
- •Unwilling to cease taking other probiotic or prebiotic supplements (current use)
Outcomes
Primary Outcomes
Total volumetric bone mineral density of the distal tibia
Time Frame: 12 months
Percentage change in total volumetric bone density measured using high resolution peripheral quantitative computed tomography (HR-pQCT) of the distal tibia.
Secondary Outcomes
- Bone mineral density of the lumbar spine(12 months)
- Total volumetric bone mineral density of the distal radius(12 months)
- Bone mineral density of the hip(12 months)
- Tibia and radius trabecular bone volume(12 months)
- Tibia and radius cortical area(12 months)
- Tibia and radius cortical volumetric bone mineral density(12 months)
- Serum C-terminal cross-linking telopeptide of type I collagen (ßCTX-I) - bone turnover marker(6 months and 12 months)
- Serum osteocalcin (OC) - bone turnover marker(6 months and 12 months)
- Short-chain fatty acids (SCFAs)(6 months, 12 months, and 2 weeks post intervention)
- 16s rRNA genetic sequencing of the gut microbiota(6 months, 12 months, and 2 weeks post intervention)
- Serum procollagen type 1 N-terminal propeptide (P1NP) - bone turnover marker(6 months and 12 months)
- Fasting blood glucose(6 months and 12 months)
- Glycated haemoglobin (HbA1c)(6 months and 12 months)
- Grip strength(6 months and 12 months)
- Lower leg muscle area(12 months)
- Lean body mass(12 months)
- High-sensitivity C-reactive protein (hs-CRP)(6 months and 12 months)
- Regulatory T lymphocytes (Tregs)(12 months)
- Oral glucose tolerance test (OGTT)(6 months and 12 months)
- Muscle tissue type 1 fibre composition(6 months and 12 months)
- Muscle tissue glycogen content(6 months and 12 months)
- Cogstate One back Test Cognitive performance test(6 months and 12 months)
- Lipocalin2(6 months, 12 months, and 2 weeks post intervention)
- Muscle tissue triglyceride content(6 months and 12 months)
- Cogstate Groton Maze Learning Test Cognitive performance test(6 months and 12 months)
- Cogstate Continuous Paired Associate Learning Test Cognitive performance test(6 months and 12 months)
- Cogstate Social Emotional Cognition Test Cognitive performance test(6 months and 12 months)
- Depression, Anxiety and Stress Scale 21(6 months and 12 months)
- Gastrointestinal Symptom Rating Scale(6 months and 12 months)
- Plasma glucagon-like peptide 1(6 months and 12 months)
- Plasma peptide tyrosine-tyrosine(6 months and 12 months)
- Plasma adiponectin(6 months and 12 months)
- EuroQol Five Dimensions Quality of life Medical Outcome Survey(6 months and 12 months)
- Social Interaction Anxiety Scale(6 months and 12 months)
- The Warwick-Edinburgh Mental Wellbeing Scale(6 months and 12 months)
- Continuous blood glucose level monitoring for 10 days(6 months and 12 months)
- Fasting blood insulin(6 months and 12 months)
- Fat mass(12 months)
- Blood metabolomics(12 months)
- Office blood pressure(6 months and 12 months)
- The Visual Analogue Scale Pain Intensity(6 months and 12 months)
- Muscle mass(12 months)
- Calprotectin(6 months, 12 months, and 2 weeks post intervention)