Probiotic (L. fermentum SRK414) Supplementation Beneficially Effects Osteocalcin and Bone Mineral Density of the Femur Neck in Post-Menopausal Women

by | May 16, 2023 | 2022, Bone Health, Probiotics

Written by Taylor Woosley, Staff Writer. Results of the double-blind randomized controlled trial with postmenopausal women supplementing with L. fermentum SRK414 showed a significant increase at 6 months post-trial in the treatment group (p = 0.030) compared to control. 

bone healthOsteoporosis is defined as a systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture1. Aging, estrogen deficiency, continuous calcium loss, and smoking are strong independent risk factors for a high risk of postmenopausal osteoporosis2. Besides the direct negative effects of estrogen-deficiency on bone, indirect effects of altered immune status in post-menopausal women might contribute to ongoing bone destruction3.

Modulation of gut microbiota has been proposed as a potential approach to the management of skeletal disorders4. Probiotics, which confer health benefits to the host, can function by modifying physiological homeostasis of the intestinal flora that can also benefit bone metabolism5. Several strains of Lactobacillus have been shown to suppress expression of osteoclastogenic factors (IL-6 and TNF-α) and induce expression of anti-osteoclastogenic factors (IL-10 and IFN-γ) leading to enhanced bone mass6.

Han et al. conducted a double-blind randomized controlled study to investigate the effects of L. fermentum SRK414 on bone health after 6 months of administration in postmenopausal women. Inclusion criteria consisted of being a postmenopausal woman defined as not having had menstruation for more than 12 months, who were older than 55 years and not on osteoporosis medication, with all the T-scores being higher than -2.5, including femur neck, femur total, and lumbar spine. Subjects were randomly assigned to 2 groups, the study group (L. fermentum SRK414, 4.0 X 109 CFU) and the control group who took a placebo capsule containing microcrystalline cellulose twice a day before meals for 6 months.

All participants underwent dual energy X-ray absorptiometry examination at pretrial and post-trial 6 months by an experienced radiologist. Bone mineral density (BMD) was measured at the femur neck, total femur, and total lumbar bar spine. BTMs were analyzed at pre-trial, post-trial 3 months, and post-trial 6 months, including serum C-terminal telopeptide (CTX), osteocalcin (OC), bone specific alkaline phosphatase, alkaline phosphatase, and estrogen. Gut microbiota concentration was measured using next-generation sequencing at pre-trial, post-trial 3 months, and post-trial 6 months.

The Shapiro-Wilk test was used to analyze data normality. The study and control groups were compared using the t-test for continuous variables using both intention to treat (ITT) and per protocol (PP) analysis. A repeated measures ANOVA test and paired t-test were adopted to identify the within-group difference between pre-trial and post-trial 3 months, and post-trial 6 months in the study and control groups.

53 subjects (27 in the study group and 26 in the control group) completed the study. Baseline characteristics of age, height, BMD, and BTMs were not significantly different between the study and control groups, except body weight and body mass index (BMI) both in ITT and PP analysis. Significant findings of the study are as follows:

  • Femur neck BMD showed a significant increase at post-trial 6 months in the study group (p = 0.030 in PP analysis, p = 0.043 in ITT analysis).
  • The control group showed a decrease in OC levels (p = 0.028), while the levels in the treatment group were maintained during the trial period.
  • At 3 months post-trial, the change in L. fermentum concentration in the gut was significantly correlated with that in OC levels (r = 0.386, p = 0.047) in the study group.

Results of the study show that L. fermentum may have a potentially beneficial effect on OC and BMD of the femur. Study limitations include the short-term follow-up period that limits the generalizability of the study results, the significant difference in BMI between the two groups, and the fact that the condition of the normal gut flora, nutrition intake, and activities could affect the action of probiotics on bone metabolism.

Source: Han, Hee Soo, Jung Geul Kim, Yoon Hyo Choi, Kyoung Min Lee, Tae Hun Kwon, and Sae Hun Kim. “Effect of Lactobacillus Fermentum as a Probiotic Agent on Bone Health in Postmenopausal Women.” Journal of Bone Metabolism 29, no. 4 (2022): 225-233.

© 2022 The Korean Society for Bone and Mineral Research

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Posted May 16, 2023.

Taylor Woosley studied biology at Purdue University before becoming a 2016 graduate of Columbia College Chicago with a major in Writing. She currently resides in Glen Ellyn, IL.

References:

  1. Kanis JA, Cooper C, Rizzoli R, Reginster JY. European guidance for the diagnosis and management of osteoporosis in postmenopausal women. Osteoporosis international : a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. Jan 2019;30(1):3-44. doi:10.1007/s00198-018-4704-5
  2. He J, Xu S, Zhang B, et al. Gut microbiota and metabolite alterations associated with reduced bone mineral density or bone metabolic indexes in postmenopausal osteoporosis. Aging (Albany NY). May 11 2020;12(9):8583-8604. doi:10.18632/aging.103168
  3. Fischer V, Haffner-Luntzer M. Interaction between bone and immune cells: Implications for postmenopausal osteoporosis. Seminars in cell & developmental biology. Mar 2022;123:14-21. doi:10.1016/j.semcdb.2021.05.014
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  6. Dar HY, Shukla P, Mishra PK, et al. Lactobacillus acidophilus inhibits bone loss and increases bone heterogeneity in osteoporotic mice via modulating Treg-Th17 cell balance. Bone Rep. Jun 2018;8:46-56. doi:10.1016/j.bonr.2018.02.001