Targeting bone marrow pathway may curb bone loss

Researchers identify a pathway connecting bone marrow fat accumulation, inflammation, and impaired bone formation, with combined treatment preserving skeletal structure in aging mice.

By
Andrea Surnit
October 19, 2026
4 min

MDSpire News

At a Glance

Category	Detail
Condition	Age-related bone loss and deterioration of the bone marrow microenvironment
Key Mechanisms	In mice, soluble DPP4 from aging bone marrow adipocytes interacted with TLR4 on macrophages and, with accumulated mitochondrial DNA, activated STING. Downstream CD38 activity increased inflammation and depleted NMN, impairing NAD-positive metabolism and mitochondrial function in mesenchymal stem cells.
Target Population	Experimental models using genetically modified and wild-type male mice aged 3 to 24 months; human efficacy and safety were not established.
Care Setting	Preclinical research setting; the study does not establish a human clinical care setting.

Key Highlights

STING signaling in bone marrow macrophages increased with age in the mouse models.
Myeloid-specific STING deletion was associated with lower bone mass in early adulthood but attenuated bone loss from 10 to 24 months; the higher bone mass at 24 months was not statistically significant.
Macrophage-targeted STING knockdown from 12 to 18 months improved several bone microarchitecture measures and was associated with enhanced bone formation and reduced marrow adipocyte accumulation.
Combined H-151 and NMN treatment improved bone microarchitecture measures in mice; the study did not include separate treatment groups to determine each agent’s contribution.
Macrophage-targeted CD38 knockdown attenuated bone loss and improved mesenchymal stem cell mitochondrial function and osteogenic differentiation.

Guideline-Based Recommendations

Diagnosis

The study evaluated bone mineral density and trabecular bone measures using microcomputed tomography in mice.
No human diagnostic criteria or recommendations were reported.

Management

STING inhibition, combined H-151 and NMN treatment, and macrophage-targeted CD38 knockdown were investigated in mice; the findings do not establish human treatment recommendations.
The authors reported that bone microarchitecture improvements with H-151 plus NMN were comparable to those observed with alendronate sodium in the mouse experiment.

Monitoring & Follow-up

Study outcomes included bone mineral density, trabecular bone volume fraction, number, thickness and separation, bone formation, marrow adipocyte accumulation, inflammatory signaling, mitochondrial function, and NAD-positive metabolism.
No clinical monitoring recommendations for people were reported.

Risks

The findings are from preclinical models and do not establish efficacy or safety in humans.
Myeloid-specific STING deletion also affected other myeloid cells, including osteoclast precursors, so their contributions could not be excluded.
The marrow adipocyte-targeting approach could also affect stromal and adipogenic progenitor cells.
The combined H-151 and NMN experiment lacked individual treatment groups, limiting assessment of each intervention’s separate contribution.

Patient & Prescribing Data

No human patients were studied. Experiments used male mice aged 3 to 24 months.

In mice, interventions included macrophage-targeted STING knockdown, H-151 plus NMN, and macrophage-targeted CD38 knockdown. The study provides no human dosing, prescribing, efficacy, or safety data.

Clinical Best Practices

Interpret the reported interventions as preclinical findings; the study does not support prescribing them to people.
Consider the study’s stated limitations when interpreting pathway-specific effects, including effects on other myeloid and progenitor cells and the absence of separate H-151 and NMN treatment groups.