Synbiotic Treatment for Osteoporosis

(STARS Trial)

Overseen By Shivani Sahni, PhD

Age: 18+

Sex: Female

Trial Phase: Academic

Sponsor: Hebrew SeniorLife

Must not be taking: Antibiotics, Bisphosphonates, Glucocorticoids, others

Disqualifiers: Obesity, Cancer, Diabetes, Smoking, others

Compensation: Varies

Number of Visits: 9

Duration: 18 months

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests whether a synbiotic, a mix of probiotics and prebiotics, can improve bone health in older women with osteoporosis. Participants will receive either the synbiotic or a placebo over 18 months to determine its effect on bone strength. Women with osteoporosis who have opted not to take standard osteoporosis medications during the trial period might be suitable candidates. As an unphased trial, this study provides a unique opportunity to explore alternative treatments for osteoporosis.

Will I have to stop taking my current medications?

The trial requires that participants do not take osteoporosis medications during the study. Additionally, you must avoid certain dietary supplements like fish oil, probiotics, prebiotics, and fiber. If you are on antibiotics, you must not have used them in the past 3 months before joining the trial.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that SBD111, a synbiotic medical food, is generally safe for use. In a study involving 286 postmenopausal women over a year, participants tolerated the treatment well. Most side effects were mild, related to stomach and digestion issues, and not serious. Another study found that negative effects were rare and mild. Overall, this evidence suggests that SBD111 is safe for consumption. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard treatments for osteoporosis, which often include medications like bisphosphonates or hormone-related therapies, the synbiotic treatment SBD111 is unique because it combines probiotics and prebiotics to support bone health. Researchers are excited about this approach because it targets the gut microbiome, which is an emerging area of interest for its potential role in bone density and overall bone health. This novel mechanism of action could offer a more holistic and natural alternative for managing osteoporosis, potentially improving bone strength without the side effects commonly associated with current medications.

What evidence suggests that this synbiotic treatment might be effective for osteoporosis?

Research has shown that the synbiotic treatment, SBD111, which participants in this trial may receive, might help slow bone loss in some women. One study found that SBD111 did not significantly reduce bone loss for everyone, but it showed promise in women with early signs of bone weakening, known as osteopenia. Another study found that SBD111 could improve gut health, reduce immune responses, and decrease the activity of cells that break down bones. These early findings suggest that SBD111 may support bone health, especially in older women at risk of osteoporosis. ^{1 6 7 8 9}

Who Is on the Research Team?

Shivani Sahni, PhD

Principal Investigator

Hebrew SeniorLife

Are You a Good Fit for This Trial?

This trial is for women over 60 with healthy vitamin D levels and normal kidney function, who haven't had certain surgeries or conditions that affect bone health. They should not be on specific medications, have a history of substance abuse, or plan to change their diet/exercise during the study.

Inclusion Criteria

Willing to comply with protocol and report on compliance and side effects during study period

I am 60 years old or older.

25-hydroxy vitamin D ≥ 20 ng/mL

Exclusion Criteria

Indwelling catheter, implanted hardware/prosthetic device or feeding tube

Any other condition that in the opinion of the investigator or study clinician would jeopardize the safety or rights of the volunteer participating in the study or would make it unlikely the volunteer could complete the study

I have had weight loss surgery in the past.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive SBD111 medical food or placebo capsules daily for 18 months

18 months

In-person visits at baseline, 9 months, and 18 months; monthly telephone calls

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Synbiotic

Trial Overview The trial tests a 'synbiotic' (a combo of probiotics and prebiotics) against a placebo to see if it helps maintain bone health in older women. It's randomized and double-blind, meaning neither participants nor researchers know who gets the real treatment.

How Is the Trial Designed?

Group I: SBD111 medical food Experimental Treatment 1 Intervention

This group will receive SBD111 medical food capsules to be consumed over 18 months.

Group II: Placebo Placebo Group 1 Intervention

This group will receive placebo capsules to be consumed over 18 months.

Who Is Running the Clinical Trial?

Hebrew SeniorLife

Lead Sponsor

Trials

52

Recruited

273,000+

Solarea Bio, Inc

Industry Sponsor

Trials

5

Recruited

720+

Beth Israel Deaconess Medical Center

Collaborator

Trials

872

Recruited

12,930,000+

Tufts University

Collaborator

Trials

271

Recruited

595,000+

MaineHealth

Collaborator

Trials

76

Recruited

43,800+

Published Research Related to This Trial

Lactobacillus rhamnosus GG (LGG) treatment in ovariectomized rats showed protective effects against osteoporosis by improving bone microarchitecture and biomechanics, as well as regulating key biomarkers related to bone health.

LGG also positively influenced the gut microbiome and intestinal barrier, restoring the balance of Th17 and Treg cells, which are important for immune regulation, thereby alleviating inflammation and promoting osteogenesis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus rhamnosus GG ameliorates osteoporosis in ovariectomized rats by regulating the Th17/Treg balance and gut microbiota structure. Guo, M., Liu, H., Yu, Y., et al.[2023]

In a systematic review of 10 randomized controlled trials involving 1156 participants, probiotics showed a statistically significant improvement in the percentage of lumbar spine bone mineral density (BMD) compared to placebo, suggesting they may help in managing osteoporosis and osteopenia.

The safety analysis indicated that probiotics did not lead to a higher rate of adverse events compared to the control group, highlighting their potential as a safe supplement for bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Improving Effect and Safety of Probiotic Supplements on Patients with Osteoporosis and Osteopenia: A Systematic Review and Meta-Analysis of 10 Randomized Controlled Trials. Zeng, L., Yu, G., Yang, K., et al.[2022]

A 2-week study involving 51 healthy elderly volunteers showed that synbiotic supplementation (Lactobacillus acidophilus and lactitol) led to an increase in beneficial bifidobacteria levels in the gut microbiota.

The synbiotic intervention appeared to halt the decline of certain bacterial groups (Blautia coccoides-Eubacterium rectale and Clostridium cluster XIVab), suggesting potential protective effects on gut health in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Gut microbiota of healthy elderly NSAID users is selectively modified with the administration of Lactobacillus acidophilus NCFM and lactitol. Björklund, M., Ouwehand, AC., Forssten, SD., et al.[2021]

Probiotics have shown promise in preventing bone loss in animal models and can slightly reduce bone loss in elderly postmenopausal women, potentially offering benefits similar to calcium and vitamin D supplements.

Probiotics may influence calcium absorption and vitamin D levels, suggesting they could be a complementary treatment alongside traditional osteoporosis therapies, but more research is needed to confirm their effectiveness in humans.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Are Probiotics the New Calcium and Vitamin D for Bone Health? Rizzoli, R., Biver, E.[2021]

In a study using a rat model of glucocorticoid-induced osteoporosis, the probiotic Lactobacillus plantarum LP45 was shown to significantly improve bone structure and density over 8 weeks, indicating its potential as a dietary supplement for osteoporosis prevention.

LP45 administration restored key biochemical markers related to bone health, such as osteocalcin and RANKL, suggesting that its protective effects against osteoporosis may involve the RANKL/OPG signaling pathway.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Lactobacillus plantarum LP45 inhibits the RANKL/OPG signaling pathway and prevents glucocorticoid-induced osteoporosis. Jiang, X., Qi, X., Xie, C.[2023]

In a study involving 28 ovariectomized female Wistar rats, the genetically modified Lactobacillus plantarum expressing BMP-2 helped maintain trabecular bone structure and showed potential to inhibit bone loss compared to standard probiotics.

The BMP-2-expressing probiotics led to significant differences in serum levels of osteocalcin and C-telopeptide of type I collagen, indicating a positive effect on bone metabolism in the osteoporosis model.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effect of Genetically Modified Lactobacillus plantarum Carrying Bone Morphogenetic Protein 2 Gene on an Ovariectomized Rat. Jin, ES., Kim, JY., Yang, JM., et al.[2022]

Probiotic supplementation has shown promise in increasing bone density and protecting against both primary and secondary osteoporosis, as demonstrated in recent murine studies.

The review highlights the role of intestinal microbiota in modulating bone health, suggesting that probiotics may influence the bone remodeling process and help counteract the effects of osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Potential of Probiotics as a Therapy for Osteoporosis. Collins, FL., Rios-Arce, ND., Schepper, JD., et al.[2019]

The synbiotic food product SBD111, designed to promote bone health through its probiotic and prebiotic components, showed no signs of toxicity in a 28-day study with female rats, indicating it is safe for consumption at high doses.

The study established a no-observable adverse effect level (NOAEL) for SBD111 at 2.0 x 10^11 CFU/kg-bw, with no significant changes in health markers or behavior observed in the rats, suggesting its potential for safe use in promoting bone health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food safety assessment and toxicity study of the synbiotic consortium SBD111. Easson, DD., Murphy, VA., Ballok, AE., et al.[2022]

The postbiotic L. plantarum MD35 has been shown to inhibit osteoclast differentiation and activity in mouse bone marrow-derived macrophages, suggesting a mechanism for its anti-osteoporotic effects.

In an ovariectomized mouse model of postmenopausal osteoporosis, oral administration of MD35 significantly reduced bone loss and improved bone structure, indicating its potential as a therapeutic option for treating osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Protective Effects of the Postbiotic Lactobacillus plantarum MD35 on Bone Loss in an Ovariectomized Mice Model. Myeong, JY., Jung, HY., Chae, HS., et al.[2023]

Osteoporosis affects around 200 million people globally and is linked to decreased bone mineral density and fragility fractures, with emerging evidence suggesting that gut health may play a significant role in bone health.

Alterations in gut microbiota can influence bone health by affecting osteoclast activity and calcium absorption, leading to the hypothesis that dietary supplements, prebiotics, and probiotics could be potential therapeutic agents for improving bone health and managing osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Role of Dietary Supplements and Probiotics in Modulating Microbiota and Bone Health: The Gut-Bone Axis. de Sire, A., de Sire, R., Curci, C., et al.[2022]

A study involving 37 healthy elderly Korean women showed that a 3-week intake of a synbiotic drink significantly altered their gut microbiome, with 30 bacterial taxa changing during this period.

The intake of synbiotics not only improved fecal shape and activity but also introduced new bacteria like Ellagibacter, indicating potential benefits for gut health in the elderly.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Association between Altered Blood Parameters and Gut Microbiota after Synbiotic Intake in Healthy, Elderly Korean Women. Lee, SH., You, HS., Kang, HG., et al.[2021]

Bifidobacterium longum (BL) has shown promising effects in enhancing bone health in a mouse model of post-menopausal osteoporosis, significantly increasing bone mass and strength while improving bone microarchitecture.

BL works by suppressing the formation of osteoclasts (cells that break down bone) and modulating immune responses, as evidenced by changes in specific immune cell populations and cytokine levels, indicating its potential as a novel treatment for osteoporosis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Bifidobacterium longum Ameliorates Ovariectomy-Induced Bone Loss via Enhancing Anti-Osteoclastogenic and Immunomodulatory Potential of Regulatory B Cells (Bregs). Sapra, L., Shokeen, N., Porwal, K., et al.[2022]

A study involving 100 chronically constipated women showed that a synbiotic supplement (LACTOFOS®) significantly improved stool frequency and consistency compared to a placebo over 30 days.

The synbiotic treatment led to better constipation intensity scores, indicating its efficacy in managing constipation, while not affecting abdominal symptoms like pain or bloating.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of synbiotic in constipated adult women - a randomized, double-blind, placebo-controlled study of clinical response. Waitzberg, DL., Logullo, LC., Bittencourt, AF., et al.[2022]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40815418/

A randomized, double-blind, placebo-controlled clinical ... SBD111 did not significantly reduce bone loss for the full cohort, but did produce evidence of reduced bone loss in women with osteopenia and ...

2. medrxiv.org medrxiv.org/content/10.1101/2025.05.20.25325893v1

A randomized, double-blind, placebo-controlled clinical ... This 12-month study in 286 early postmenopausal women evaluated the efficacy and safety of SBD111, a synbiotic medical food, in reducing bone loss.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06389539

Study Details | NCT06389539 | Synbiotic to Attenuate ... Aim 1: To determine the effect of 18 months of daily intake of SBD111 medical food on the primary outcome of lumbar spine dual energy x-ray absorptiometry (DXA) ...

4. marcusinstituteforaging.org marcusinstituteforaging.org/news/3m-grant-supports-study-probioticprebiotic-synbiotic-medical-food-bone-health-older-women

$3M Grant Supports Study of Probiotic/Prebiotic (Synbiotic) ... The study will support an 18-month clinical trial of a synbiotic medical food in 220 older women to test whether it maintains lumbar spine bone mineral density ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40832188/

A synbiotic medical food improves gut barrier function, ... A synbiotic medical food improves gut barrier function, reduces immune responses, and inhibits osteoclast activity in models of postmenopausal ...

6. sciencedirect.com sciencedirect.com/science/article/pii/S0278691522005270

Food safety assessment and toxicity study of the synbiotic ... SBD111 is a consortium of probiotic microbes designed to promote bone health. SBD111 was evaluated in rats at 2.0 x 10 10 , 9.8 x 10 10 , or 2.0 x 10 11 CFU

7. link.springer.com link.springer.com/article/10.1007/s00198-025-07650-7

A randomized, double-blind, placebo-controlled clinical ... This 12-month study in 286 early postmenopausal women evaluated the efficacy and safety of SBD111, a synbiotic medical food, in reducing bone ...

8. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11649316/

Randomized clinical trial to test the safety and tolerability of ... The relatively low frequency and mild severity of GI symptoms and AEs suggests that SBD111 at the level tested is safe for human consumption.

9. cdn.nutrition.org cdn.nutrition.org/article/S2475-2991(23)13066-6/fulltext

Safety and Tolerability of SBD111 an Optimized Probiotic ... The relatively low frequency and mild severity of GI symptoms and AEs suggests that SBD111 at the level tested is safe for human consumption and that SBD111 ...