Bones are living tissue, continually renewed through a balance of removal and rebuilding. When rebuilding fails to keep pace, structure can deteriorate. Understanding that imbalance requires looking beyond mineral content to the cells sharing the marrow.
A proposed connection inside aging marrow
Zhichao Li and colleagues’ October 15, 2026 study in Advanced Science used male mice, rat marrow protein screening and cell experiments. Animal groups generally contained six to nine mice.
Aged marrow fat cells released soluble DPP4, a signaling protein. DPP4 engaged TLR4 on macrophages, immune cells, and cooperated with mitochondrial DNA to activate STING, an immune alarm pathway. Downstream CD38 activity depleted NMN available to neighbouring stem cells, reducing NAD+ and bone-forming capacity.
NAD+ is a molecule cells use in energy metabolism and other essential reactions. NMN is a precursor used to make it. The proposed problem involves both inflammatory signaling and competition over a local biochemical resource.
What the interventions showed
Reducing macrophage STING from middle age improved mouse bone measures. Lifelong deletion had age-dependent effects, with some endpoint differences not statistically significant. H-151, a STING inhibitor, plus NMN from 12 to 18 months improved bone density, trabecular structure and formation measures while reducing inflammatory markers.
Trabecular bone is the internal, lattice-like structure visible in a bone cutaway. Density and architecture provide complementary information: the amount of mineral and the arrangement of the supporting framework are different features.
Why the treatment claim needs restraint
The combination experiment lacked separate H-151-only and NMN-only groups, so it cannot establish each component’s contribution or synergy. Genetic targeting was imperfectly cell-specific; marrow injections could introduce injury effects. No human osteoporosis treatment was established.
A combination that outperforms a control is not automatically evidence that both ingredients are necessary. Nor does a biological explanation provide a clinical dose, a safe delivery method or proof that fracture risk would fall in people.
The age dependence also poses a practical research question. If an immune pathway has different functions at different stages of life, the useful target may be a particular cell population and time window. Broad suppression could have consequences that a bone measurement alone would miss.
What the work may mean
Our interpretation is that this is a useful route for investigating how the marrow environment affects rebuilding, rather than a reason to start NMN for osteoporosis. The distinction between carefully timed inhibition and complete removal also features in our earlier discussion of STING regulation, which covers different research.
The next clinical question is whether this mechanism can be targeted safely enough to improve outcomes that matter to patients. Until that is tested, a plausible mechanism remains a research lead.
Research classification: Early Research. Original research: Li Z et al. doi:10.1002/advs.77571. Full text is freely accessible.
Featured image: AI-generated conceptual illustration, not microscopy or experimental data.