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The Effect of Lactobacillus Reuteri ATCC PTA 6475 on Volumetric Bone Mineral Density in Patients With Osteopenia

Not Applicable
Completed
Conditions
Osteopenia
Interventions
Dietary Supplement: L. reuteri
Dietary Supplement: Placebo
Registration Number
NCT02422082
Lead Sponsor
Sahlgrenska University Hospital, Sweden
Brief Summary

Lactobacillus reuteri (L. reuteri) has been widely studied in clinical trials and has probiotic, health-promoting effects in both adults and children, and is safe for human consumption. Animal models indicate that treatment with L. reuteri has positive effects on bone metabolism and bone density. In other animal models of diabetes and the metabolic syndrome, positive effects on blood glucose and weight have been reported. The present double-blind, placebo-controlled, randomized study is designed to investigate if dietary supplementation with L. reuteri twice daily for 12 months has any effect on bone density, body composition, inflammation, or metabolic and endocrine markers in elderly women with osteopenia.

Detailed Description

The role of the gut microbes for human health has gained considerable interest in recent years. Lactobacillus reuteri (L.reuteri) is a naturally occurring bacterial species in the human gut. L. reuteri has been widely studied in clinical trials of adults and children and treatment with L. reuteri is safe and is associated with health-promoting effects in humans. In animal models, L. reuteri has anti-inflammatory effects and in ovariectomized mice supplementation with L. reuteri partly prevented the bone loss induced by estrogen deficiency. Furthermore, both bone density and bone formation increased in male mice in another mice model. In mice with medically induced diabetes mellitus, L. reuteri reduced blood glucose and in a mouse model mimicking the metabolic syndrome, L. reuteri prevented diet-induced obesity. The present study is a double-blind, placebo-controlled, randomized, study in 90 elderly women with osteopenia recruited from the population. These women will be treated with L. reuteri or placebo orally twice daily for 12 months. The effects on bone will be investigated with dual energy x-ray absorptiometry, high-resolution peripheral quantitative computed tomography, and bone turnover markers. Hormones and markers of inflammation and metabolism will be followed as well as changes in the gut microbiota composition.

Recruitment & Eligibility

Status
COMPLETED
Sex
Female
Target Recruitment
90
Inclusion Criteria
  • bone mineral density T-score less than -1 but more than -2.5 in the total hip or femoral neck or lumbar spine (L1-L4) by dual energy x-ray absorptiometry
  • signed informed consent
  • stated availability throughout the entire study period
  • mental ability to understand and willingness to fulfill all the details of the protocol
Exclusion Criteria
  • untreated hyperthyroidism
  • rheumatoid arthritis
  • diagnosed with disease causing secondary osteoporosis within the last year, including primary hyperparathyroidism, chronic obstructive pulmonary disease, inflammatory bowel disease, celiac disease, or diabetes
  • recently diagnosed malignancy (within the last 5 years)
  • per oral corticosteroid use
  • use of antiresorptive therapy, including systemic hormone replacement therapy, bisphosphonates, strontium ran elate
  • use of teriparatide (current or during the last 3 years)
  • participation in other clinical interventional trials
  • use of antibiotics within 2 months preceding the inclusion

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
L. reuteriL. reuteriLactobacillus reuteri (L. reuteri) ATCC PTA 6475 at a dose of 5 000 000 000 CFU as a powder in a stick-pack, orally twice daily (morning and evening) yielding a total daily dose of 10 000 000 000 CFU per day, for 12 months.
PlaceboPlaceboPlacebo product identical to the active product (L. reuteri) in taste and appearance but without the active component, orally twice daily, for 12 months.
Primary Outcome Measures
NameTimeMethod
Total tibia volumetric bone mineral density12 months

Change in percent in total tibia volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri

Secondary Outcome Measures
NameTimeMethod
Trabecular volumetric bone mineral density12 months

Change in percent in trabecular volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri

Bone material strength index12 months

Change in percent in bone material strength index compared to placebo group after 1 year of dietary supplementation with L. reuteri

Change in gut microbiota composition3-12 months

Change in percent in gut microbiota composition compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Interleukin-173-12 months

Change in percent in interleukin-17 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Bone-specific alkaline phosphatase3-12 months

Change in percent in bone-specific alkaline phosphatase in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Osteocalcin3-12 months

Change in percent in osteocalcin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Triglycerides3-12 months

Change in percent in triglycerides compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Cortical volumetric bone mineral density12 months

Change in percent in cortical volumetric bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri

Areal bone mineral density12 months

Change in percent in areal bone mineral density compared to placebo group after 1 year of dietary supplementation with L. reuteri

Ultrasensitive C-reactive protein3-12 months

Change in percent in ultrasensitive C-reactive protein in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Receptor activator of nuclear factor kappa B ligand (RANK-ligand)3-12 months

Change in percent in RANK-ligand in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Low density lipoprotein (LDL)3-12 months

Change in percent in LDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Cortical porosity12 months

Change in percent in cortical porosity compared to placebo group after 1 year of dietary supplementation with L. reuteri

Tumor-necrosis factor-alpha3-12 months

Change in percent in tumor-necrosis factor-alpha in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Tartrate-resistent alkaline phosphatase 5b3-12 months

Change in percent in tartrate-resistent alkaline phosphatase 5b in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Cross-linked N-terminal telopeptide3-12 months

Change in percent in cross-linked N-terminal telopeptide in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Receptor activator of nuclear factor kappa B (RANK)3-12 months

Change in percent in RANK in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Leptin3-12 months

Change in percent in leptin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Cortical thickness12 months

Change in percent in cortical thickness compared to placebo group after 1 year of dietary supplementation with L. reuteri

Blood pressure12 months

Change in percent in blood pressure compared to placebo group after 1 year of dietary supplementation with L. reuteri

Haemoglobin A1C3-12 months

Change in percent in haemoglobin A1C compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Cholesterol3-12 months

Change in percent in cholesterol compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Adiponectin3-12 months

Change in percent in adiponectin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Interleukin-103-12 months

Change in percent in interleukin-10 in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Blood glucose3-12 months

Change in percent in blood glucose compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Apolipoprotein B (ApoB)3-12 months

Change in percent in ApoB compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

High density lipoprotein (HDL)3-12 months

Change in percent in HDL compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Estradiol3-12 months

Change in percent in estradiol in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Apolipoprotein A1 (ApoA1)3-12 months

Change in percent in ApoA1 compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Oxytocin3-12 months

Change in percent in oxytocin in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Lean mass12 months

Change in percent in lean mass compared to placebo after 12 months of dietary supplementation with L. reuteri

Testosterone3-12 months

Change in percent in testosterone in serum compared to placebo after 3, 6, 9, and 12 months of dietary supplementation with L. reuteri

Fat mass12 months

Change in percent in fat mass compared to placebo after 12 months of dietary supplementation with L. reuteri

Trial Locations

Locations (1)

Geriatric Medicine, Mölndal Hospital

🇸🇪

Mölndal, Västra Götaland, Sweden

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