In this randomized, placebo-controlled study (named the ELBOW trial, for 'Effects of Lactobacillus reuteri on Bone in Older Women'), seventy older women (75 to 80 years-of-age) with low bone mineral density2 were randomized to receive either probiotic3 (1X1010 CFU/day) or placebo (maltodextrin powder) for 12 months. The primary outcome measure was relative change in volumetric bone mineral density (vBMD) and bone microstructure in the distal tibia; measured at baseline and at 12 months using high-resolution peripheral quantitative computed tomography (HR-pQCT). Secondary outcome measures included relative changes after 12 months in: areal BMD measured at the hip and spine; trabecular bone volume fraction; cortical vBMD; cortical thickness; serum markers for bone turnover (N-terminal telopeptide and bone-specific alkaline phosphatase); serum markers for inflammation (C-reactive protein and tumour necrosis factor alpha); serum HbA1c; and body composition (total fat and lean mass). The study subjects returned to the clinic every three months to replenish their probiotic or placebo, assess adherence and record any adverse events.
Probiotic supplementation significantly reduced loss of tibia total vBMD compared to placebo in all analyses (i.e. intention to treat4, mean difference and per protocol5). Beneficial trends were observed in secondary bone variables; but this did not achieve statistical significance, except with respect to reduction in trabecular bone volume fraction in the probiotic group compared to placebo in the per protocol population. No statistically significant differences in any markers of inflammation or bone turnover as well as other secondary outcome measures were evident at the conclusion of the study. No serious adverse events related to treatment were recorded in either group, although a few cases of gastrointestinal symptoms occurred in both groups including changes bowel habits and flatulence.
Strengths of this study include a relatively robust trial design (eg. multiple statistical analyses and rigorous exclusion criteria, state-of-art validated measurements of primary and secondary outcome measures), a well characterized study population with similar baseline characteristics (eg. ethnicity, anthropomorphic measurements and lifestyle factors) and the use of a therapeutic dose of a probiotic strain demonstrated in animal studies to positively influence BMD. Moreover, the HR-pQCT technology used to measure tibial vBMD is a highly sophisticated state-of-the-art diagnostic tool with the sensitivity to capture even small alterations in trabecular and cortical bone traits, and therefore, capable of detecting rapid or subtle changes due to probiotic treatment.
Weaknesses of this study include a relatively small sample size (N=45 per group)6. Moreover, unlike previous in vitro or animal studies with the same probiotic strain or species, no differences were detected in serum markers of inflammation, bone turnover or metabolic indices; which precludes any mechanistic explanation for the observed reduction in bone loss from probiotic treatment.
This study is the first to examine the effects of probiotic supplementation on bone metabolism in humans. Additional studies with larger sample sizes are needed to confirm these findings and help elucidate the potential mechanisms involved. However, the positive findings and relatively large effect size, "reduction in total vBMD in the distal tibia was nearly half as large in women taking 1x1010 CFU day of L. reuteri 6475 than in women taking placebo," suggest that probiotics could be considered as an adjunctive therapy to help prevent bone loss and osteoporosis during aging in postmenopausal women.
Reference: Nilsson, A.G., et al. J Intern Med 2018; 284: 307–317.