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

N/ACompletedNCT02422082

Sahlgrenska University Hospital90 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

Eligibility

Sex: FEMALEMin age: 75 YearsMax age: 80 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Outcomes

Primary Outcomes

Total tibia volumetric bone mineral density

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

Time frame: 12 months

Secondary Outcomes

Trabecular volumetric bone mineral density

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

Time frame: 12 months

Cortical volumetric bone mineral density

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

Time frame: 12 months

Cortical thickness

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

Time frame: 12 months

Cortical porosity

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

Time frame: 12 months

Areal bone mineral density

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

Time frame: 12 months

Bone material strength index

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

Time frame: 12 months

Blood pressure

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

Time frame: 12 months

Change in gut microbiota composition

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

Time frame: 3-12 months

Ultrasensitive C-reactive protein

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

Time frame: 3-12 months

Interleukin-10

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

Time frame: 3-12 months

Interleukin-17

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

Time frame: 3-12 months

Tumor-necrosis factor-alpha

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

Time frame: 3-12 months

Tartrate-resistent alkaline phosphatase 5b

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

Time frame: 3-12 months

Cross-linked N-terminal telopeptide

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

Time frame: 3-12 months

Bone-specific alkaline phosphatase

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

Time frame: 3-12 months

Receptor activator of nuclear factor kappa B (RANK)

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

Time frame: 3-12 months

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

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

Time frame: 3-12 months

Osteocalcin

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

Time frame: 3-12 months

Blood glucose

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

Time frame: 3-12 months

Haemoglobin A1C

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

Time frame: 3-12 months

Apolipoprotein A1 (ApoA1)

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

Time frame: 3-12 months

Apolipoprotein B (ApoB)

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

Time frame: 3-12 months

Cholesterol

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

Time frame: 3-12 months

High density lipoprotein (HDL)

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

Time frame: 3-12 months

Low density lipoprotein (LDL)

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

Time frame: 3-12 months

Triglycerides

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

Time frame: 3-12 months

Oxytocin

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

Time frame: 3-12 months

Estradiol

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

Time frame: 3-12 months

Leptin

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

Time frame: 3-12 months

Adiponectin

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

Time frame: 3-12 months

Testosterone

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

Time frame: 3-12 months

Lean mass

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

Time frame: 12 months

Fat mass

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

Time frame: 12 months

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

Overview

Conditions

Interventions

Eligibility

Locations (1)

Outcomes

Primary Outcomes

Secondary Outcomes