# Update and Reassessment of Data on the Role of Osteocalcin in Bone Properties and Glucose Homeostasis in OC-/- Mice

**Authors:** Steven Tommassini, Terry Lynne Dowd

PMC · DOI: 10.3390/ijms27010170 · International Journal of Molecular Sciences · 2025-12-23

## TL;DR

This paper reviews recent studies on osteocalcin's role in bone strength and glucose metabolism, resolving earlier controversies.

## Contribution

The paper reassesses conflicting data on osteocalcin's effects and confirms its role in glucose metabolism and bone properties.

## Key findings

- Recent studies confirm osteocalcin's role in bone mineral properties and strength.
- Osteocalcin's role in glucose metabolism is supported by new data.
- Conflicting results from earlier studies are explained and resolved.

## Abstract

Osteocalcin (OC) is a small protein (49 aa) produced by the osteoblast and the most abundant noncollagenous protein in bone. Studies using the osteocalcin-depleted knock-out mouse (OC-/-) reported that osteocalcin affects bone mineral properties and bone strength. Other reports indicated osteocalcin was a hormone regulating glucose metabolism by increasing insulin secretion and sensitivity. These results were controversial. Several years ago, a couple of groups generated osteocalcin knock-out mice using different methods and failed to observe an effect of osteocalcin on bone mineral properties, bone strength or glucose metabolism. One review claimed that the previously reported results from OC-/- mouse studies were inconsistent. Within the last 2 years, additional OC-/- mouse studies have been reported, and they confirm the role of osteocalcin in glucose metabolism, bone mineral properties and strength. Some of the new data reported clears up any controversy. Published studies on the role of osteocalcin in bone and glucose metabolism using OC-/- mice will be reviewed, and results will be compared. It is shown that most of the data on the effect osteocalcin on bone properties and strength is consistent and corroborated when comparing valid data from similar techniques and similar regions of the bone. Data corroborating the role of osteocalcin in glucose metabolism will be presented, and reasons for conflicting results will be discussed. Diabetics and the elderly have reduced osteocalcin levels and are prone to bone fractures, while diabetics are glucose-intolerant. Osteocalcin may be of therapeutic use to these populations.

## Linked entities

- **Proteins:** bglap2 (bone gamma-carboxyglutamate (gla) protein (osteocalcin) 2)
- **Diseases:** diabetes (MONDO:0005015)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** Bglap2 (bone gamma-carboxyglutamate protein 2) [NCBI Gene 12097] {aka BGP2, Bglap1, Bgp, Og2, mOC-B}
- **Diseases:** glucose-intolerant (MESH:D018149), bone fractures (MESH:D050723), Diabetics (MESH:D003920)
- **Chemicals:** Glucose (MESH:D005947)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12785331/full.md

## References

65 references — full list in the complete paper: https://tomesphere.com/paper/PMC12785331/full.md

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Source: https://tomesphere.com/paper/PMC12785331