Rethinking the role of microbiome in age-related bone loss

Osteoporosis is a major health concern worldwide, particularly in aging populations. Despite pharmacological advancements, challenges like side effects, costs, and limited accessibility reduce adherence to treatments. Recently, the gut microbiome has gained attention for its potential role in bone metabolism. Yet, aging complicates its stability and influence, raising the need to explore alternative mechanisms behind bone loss. Given these challenges, researchers aimed to investigate non-microbial contributors to age-related bone deterioration.

A collaborative study led by Harvard Medical School, published (DOI: 10.1038/s41413-024-00366-0) in Bone Research on November 08, 2024, tackled this question. Using advanced genetic sequencing and metabolomic tools, scientists examined bone health in CB6F1 mice under germ-free and microbiome-colonized conditions to assess the microbiome's impact on bone loss during aging.

The study revealed that bone loss in germ-free mice mirrored that of their microbiome-colonized counterparts, debunking the belief that gut microbes significantly influence age-related bone deterioration. Over 21 months, both groups exhibited comparable declines in trabecular bone volume and cortical thickness, underscoring that bone loss occurs independently of gut microbiota. Although age-related shifts in microbial composition and function were observed—such as increased amino acid and protein biosynthesis—these changes did not affect bone health. Even microbiota transplants from young or old donors into germ-free mice had no discernible impact, regardless of donor age or colonization duration. These findings redirect attention to other biological pathways as potential drivers of osteoporosis.

This study overturns long-standing beliefs about the gut microbiome's role in age-related bone loss. By refocusing on other mechanisms, we aim to open new pathways for effective osteoporosis treatments."

Dr. Xiaomeng You, lead researcher

The team highlighted the microbiome's influence on other health aspects but emphasized its limited role in bone health during aging.

These results pave the way for rethinking osteoporosis interventions, suggesting that genetic, hormonal, or environmental factors may hold greater significance. Future research could leverage these insights to develop innovative therapies, ultimately improving care for aging populations. While the microbiome remains a crucial research frontier, this study underscores the importance of broadening the lens to fully understand bone health.