Effects of Synbiotic Supplementation on Bone and Metabolic Health in Caucasian Postmenopausal Women: Rationale and Design of the OsteoPreP Trial

Abstract

Background/objectives: Correction of decreased diversity of the gut microbiome, which is characteristic of menopause, by supplementation with a synbiotic may attenuate or prevent dysbiosis processes and preserve bone mass. We describe the rationale and design of the OsteoPreP trial aimed at evaluating the effects of 12 months of supplementation with a synbiotic on bone and metabolic health in postmenopausal Caucasian women.

Methods: This is a randomized, double-blinded, placebo-controlled trial among 160 Caucasian, postmenopausal women with no current diagnosis of osteoporosis or supplementation with pro- or prebiotics, and no medical treatment affecting bone turnover. Dual-energy X-ray absorptiometry scans will be conducted at screening to confirm absence of osteoporosis. The primary outcome is the relative change (%) in total bone mineral density of the distal tibia at 12 months post-treatment between the active and placebo groups, as determined via high-resolution peripheral quantitative computed tomography. Secondary outcomes are the effects on immune system modulation and cognition, gut microbiota composition, and musculoskeletal and metabolic functions, with particular emphasis on blood glucose regulation.

Conclusions: The trial will inform on the efficacy and safety of a synbiotic containing both aerobic and anerobic bacterial strains and a prebiotic fiber on reduction in bone loss and on indices of blood glucose regulation. This trial may pave the way for an exciting field of translational research and be the underpinnings of the prevention strategy of osteoporosis and the management of metabolic dysfunction in postmenopausal women. The trial is registered with clinicaltrials.gov (NCT05348694).

Keywords: bone health; gut microbiota; metabolic health; osteoporosis; postmenopause; synbiotic.

Figure 1

Complications of gut microbiota dysbiosis. CKD = chronic kidney disease; IBD = inflammatory bowel disease.

Figure 2

Summary of OsteoPreP trial visits and activities. AE = adverse event; Ax = assessment; Hx = history; IP = investigational product; HbA1c = glycated hemoglobin; BP = blood pressure; BMI = body mass index; HWR = height-to-weight ratio; DXA = dual-energy X-ray absorptiometry; HR-pQCT = high-resolution peripheral quantitative computed tomography; CGM = continuous glucose monitor; Glu = glucose; vit B12 = vitamin B12; Treg = T regulatory cell; OGTT = oral glucose tolerance test; ^ = musculoskeletal subgroup.

Figure 3

Summary of OsteoPreP trial primary and secondary outcomes. BP = Blood pressure; DASS-21 = Depression Anxiety Stress Scale-21; EQ-5D = EuroQOL Five Dimensions quality of life scale; SIAS = Social Interaction Anxiety Scale; WEMWBS = Warwick-Edinburgh Mental Wellbeing Scale; Pain VAS = Visual Analogue Scale for pain; BMD = Bone Mineral Density; DXA = Dual-energy X-ray Absorptiometry; HR-pQCT = High-Resolution Peripheral Quantitative Computed Tomography; CGM = Continuous Glucose Monitor; OGTT = Oral Glucose Tolerance Test; HbA1c = Hemoglobin A1C blood sugar (glucose) level test; ^ = musculoskeletal subgroup at twelve months only; SCFA = Short Chain Fatty Acids; GLP-1 = Glucagon-Like Peptide-1 receptor agonist; GSRS = Gastrointestinal Symptom Rating Scale; * = musculoskeletal subgroup will undergo OGTT.

Figure 4

OsteoPreP trial inclusion and exclusion criteria and screening process. * Do not meet the inclusion criteria; ^ = DXA, BP, or HbA1c ineligible participant; Dx = diagnosis; DXA = dual-energy X-ray absorptiometry; COPD = chronic obstructive pulmonary disease; IBD = inflammatory bowel disease; CD = celiac disease; T1DM = type 1 diabetes mellitus; T2DM = type 2 diabetes mellitus; CLD = chronic liver disease; HbA1c = hemoglobin A1C blood sugar (glucose) level test; BP = blood pressure; HRT = hormone replacement therapy; RANK = receptor activator of NF-κB ligand; SERMs = selective estrogen receptor modulators.