Prevention of Early Postmenopausal Bone Loss With Lactobacillus Reuteri

Not Applicable

Completed

• Conditions: Postmenopausal Osteoporosis

• Registration Number: NCT04169789
• Lead Sponsor: Sahlgrenska University Hospital, Sweden

Brief Summary

This study evaluates the effect of two different doses of Lactobacillus reuteri ATCC PTA 6475 (L.reuteri 6475) on bone loss in early postmenopausal women. One third of the participants will be randomised to the lower dose, one third to the higher dose and one third to placebo.

Detailed Description

We have previously shown that daily supplementation of the probiotic Lactobacillus reuteri ATCC PTA 6475 (10E10 colony-forming units (CFU)) was able to reduce bone loss over 12 months in 76-year-old women compared to placebo.

It is not known if the probiotic is effective over longer time periods or if the effect is dose-dependent. The aim of this study is to investigate if two different doses of Lactobacillus reuteri ATCC PTA 6475 (total daily dose of either 1x10E9 or 1x10E10 CFU/day) can prevent or reduce bone loss, compared to placebo, in early (1-4 years since last menses) postmenopausal women over 24 months. All women will receive 400 IU of vitamin D (cholecalciferol) per day. Changes in bone mineral density, bone geometry and microstructure will be measured using dual x-ray absorptiometry and high resolution peripheral computed tomography.

Study Timeline

• Study First Submitted: 2019-11-18
• Study First Submitted QC: 2019-11-18
• Study First Posted: 2019-11-20
• Study Start: 2019-12-04
• Primary Completion: 2022-10-18
• Study Completion: 2022-10-18
• Status Verified: 2023-02
• Last Update Submitted: 2023-02-03
• Last Update Posted: 2023-02-06

Recruitment & Eligibility

• Status: COMPLETED
• Sex: Female
• Target Recruitment: 239

Inclusion Criteria

• Postmenopausal women, 45 years or older, within 1-4 years from their last menses.
• Vitamin D levels above 25 nmol/L.
• Signed informed consent.
• Stated availability throughout the entire study period.
• Ability to understand study instructions and willingness to adhere to the protocol.

Exclusion Criteria

• Bone mineral density of < -2.5 combined with a fracture risk assessment tool (FRAX) score of 20% or higher for major osteoporotic fracture.
• Severe osteoporosis, defined as bone mineral density of < -3.0 in either the total hip, femur neck or lumbar spine L1-L4.
• Vertebral fracture (grade II or III) diagnosed using lateral spine imaging with DXA.
• Untreated hyperthyroidism or hyperthyroidism within the last 5 years.
• Known untreated hyperparathyroidism.
• Rheumatoid arthritis.
• Diagnosed with disease causing secondary osteoporosis, including chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, or diabetes mellitus.
• Recently diagnosed malignancy (within the last 5 years).
• Oral corticosteroid use.
• Previous (within the last 5 years) use of antiresorptive therapy, including systemic hormone therapy (estrogen), bisphosphonates, strontium ranelate or denosumab.
• Systemic skeletal disease (including e.g. Paget's disease and osteogenesis imperfecta).
• Any systemic disease that could affect bone loss, as judged by the investigator.
• Use of teriparatide (current or during the last 3 years).
• Participation in other clinical trials.
• Current antibiotics treatment or within the last 2 months prior to inclusion.
• Current and within the past 2 months use of probiotic supplement
• Vitamin D deficiency (25-OH vitamin D<25 nmol/l)
• Hypo- or hypercalcemia.
• Osteosynthesis materials in both lower legs (tibia).

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Total tibia volumetric bone mineral density	24 months	Measured using high resolution peripheral computed tomography (HRpQCT), relative change 0-24 months

Secondary Outcome Measures

Name	Time	Method
Serum Wnt10b concentration	0-24 months and 0-12 months	Relative change 0-24 months and 0-12 months
Tibia trabecular bone volume fraction	0-24 months and 0-12 months	Measured using HRpQCT, relative change 0-24 months and 0-12 months
Tibia cortical volumetric BMD	0-24 months and 0-12 months	Measured using HRpQCT, relative change 0-24 months and 0-12 months
Total tibia volumetric bone mineral density	12 months	Measured using HRpQCT, relative change 0-12 months
Blood bone formation marker procollagen type 1N propeptide (P1NP)	0-24 months and 0-12 months	Relative change 0-24 months and 0-12 months
Fecal calprotectin	0-24 months and 0-12 months	Relative change 0-24 months and 0-12 months
Fecal lipocalin-2	0-24 months and 0-12 months	Relative change 0-24 months and 0-12 months
Blood bone resorption marker C-terminal cross-linking telopeptide of type I collagen (CTX)	0-24 months and 0-12 months	Relative change 0-24 months and 0-12 months
Areal bone mineral density (aBMD) at the lumbar spine	24 months	Measured using dual x-ray absorptiometry (DXA), relative change 0-24 months and 0-12 months
Areal BMD of the total hip (DXA)	0-24 months and 0-12 months	Measured using DXA, relative change 0-24 months and 0-12 months
Tibia cortical area	0-24 months and 0-12 months	Measured using HRpQCT, relative change 0-24 months and 0-12 months
Serum butyrate concentration	0-24 months and 0-12 months	Relative change 0-24 months and 0-12 months

Trial Locations

Locations (1)

Geriatric Medicine, Sahlgrenska University Hospital, Mölndal; 🇸🇪 Gothenburg, Västra Götaland, Sweden