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Gestational Protein Restriction Promotes Osteoporotic Phenotype During Aging
Bruno Calsa1, Saul Lindo-Samanamud2,3, Giovani Vinhato Breanza4
1Fetal Programming and Hydroelectrolyte Metabolism Laboratory, Department of Internal Medicine, School of Medical Sciences, Campinas State University (UNICAMP), Campinas, SP, Brazil.
Calcified Tissue International
|July 24, 2026
Summary
Gestational protein restriction impairs bone health in aging mice by altering the immune microenvironment. This early-life nutritional stress leads to weaker bones and increased fracture risk later in life.
Area of Science:
- Bone biology and skeletal health
- Nutritional science and metabolism
- Immunology and inflammation
Background:
- Osteoporosis is characterized by impaired bone remodeling and microarchitecture deterioration, increasing fracture risk.
- Early-life nutritional stress is linked to long-term health issues, but its skeletal effects are not fully understood.
- The impact of gestational nutrition on the skeletal immune microenvironment and age-related bone fragility requires investigation.
Purpose of the Study:
- To investigate if gestational protein restriction causes lasting changes in the skeletal immune microenvironment.
- To determine if these changes contribute to age-related bone fragility in offspring.
- To elucidate the molecular mechanisms linking nutritional stress to bone health.
Main Methods:
- Gestational protein restriction model in C57BL/6J mice.
- Microcomputed tomography and three-point bending tests for bone structural and mechanical analysis.
- RNA sequencing, RT-qPCR, and immunohistochemistry for molecular and cellular profiling of the skeletal immune microenvironment.
Main Results:
- Low-protein offspring exhibited reduced bone mineral density, trabecular bone volume, and cortical thickness with aging.
- Compromised bone mechanical strength, increased cortical porosity, and disrupted collagen organization were observed in aged low-protein offspring.
- Gestational protein restriction led to altered gene expression in immune pathways, increased macrophage markers (CD68+ cells), and enhanced osteoclast-related signaling.
Conclusions:
- Gestational protein restriction induces persistent reprogramming of the skeletal immune microenvironment.
- This reprogramming is associated with enhanced osteoclast-related signaling and impaired bone mechanical competence during aging.
- Early-life nutrition significantly impacts long-term skeletal health and immune function.
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