# Effects of Freeze-Dried Sake Lees and Rice Koji Extract on Osteoporosis in a Postmenopausal Mouse Model

**Authors:** Jorge Sáez-Chandía, Stephanny Castillo-Quispe, Keiichiro Okamoto, Atsushi Kurahashi, Kazuya Kodaira, Kotaro Aihara, Kiyoko Suzuki-Barrera, Masaru Kaku, Yoshikazu Mikami, Miho Terunuma, Kensuke Yamamura, Takafumi Hayashi, Makio Saeki, Yoshito Kakihara

PMC · DOI: 10.3390/nu17193077 · 2025-09-27

## TL;DR

This study shows that freeze-dried sake lees and rice koji extract may help reduce bone loss in a mouse model of postmenopausal osteoporosis.

## Contribution

The novel contribution is the demonstration of sake lees and rice koji's potential to improve bone metabolism and reduce osteoporosis in a mouse model.

## Key findings

- Sake lees and rice koji extract increased bone volume and trabecular parameters in ovariectomized mice.
- Both extracts inhibited osteoclast differentiation and promoted osteoblast activity in vitro.
- Folic acid and SAM in sake lees may contribute to collagen production by osteoblasts.

## Abstract

Background/Objectives: With the aging of the population, the number of patients with osteoporosis is increasing worldwide. Osteoporosis results from an imbalance in bone remodeling by osteoblasts and osteoclasts. This study investigated the effects of sake lees and rice koji, traditional Japanese rice-fermented products, on bone metabolism. Methods: Both sake lees extract and rice koji extract increased alkaline phosphatase (ALP) activity, extracellular collagen accumulation, and mineralization of MC3T3-E1 cells. In addition, the intracellular protein levels of Hsp47 and Sec23IP, which are required for collagen maturation and secretion, respectively, were increased during the differentiation. On the other hand, both extracts significantly inhibited osteoclastic differentiation. Furthermore, the effects of freeze-dried sake lees or rice koji extract on osteoporotic bones were examined using twelve-week-old female C3H/HeJ ovariectomized (OVX) mice. Results: The groups of mice fed 20% or 40% freeze-dried sake lees showed significant suppression of the loss in bone volume fraction (BV/TV) and trabecular volume (Tb.V) compared with those fed a normal diet as well as the 40% freeze-dried sake lees-fed group reduced in the loss of trabecular thickness (Tb.Th). Similarly, the rice koji extract-treated mice showed significant inhibition of the loss in BV/TV, Tb.V, and even trabecular number (Tb.N.). Folic acid and S-adenosylmethionine (SAM), which have been reported to be present in sake lees, promoted extracellular collagen production by osteoblasts. Conclusions: In OVX mice, the intake of freeze-dried sake lees or rice koji extract was associated with the attenuation of trabecular bone loss, suggesting potential beneficial effects on bone metabolism.

## Linked entities

- **Proteins:** SERPINH1 (serpin family H member 1), SEC23IP (SEC23 interacting protein)
- **Chemicals:** folic acid (PubChem CID 135398658), S-adenosylmethionine (PubChem CID 34755), alkaline phosphatase (PubChem CID 18985873)
- **Diseases:** osteoporosis (MONDO:0005298)

## Full-text entities

- **Diseases:** bone loss (MESH:D001847), Osteoporosis (MESH:D010024), osteoporotic bones (MESH:D058866), loss of trabecular (MESH:D000236)
- **Chemicals:** S-adenosylmethionine (MESH:D012436), Folic acid (MESH:D005492), rice koji extract (-)
- **Species:** Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606], Oryza sativa (Asian cultivated rice, species) [taxon 4530]
- **Cell lines:** MC3T3-E1 — Mus musculus (Mouse), Spontaneously immortalized cell line (CVCL_0409)

## Figures

5 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12525797/full.md

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Source: https://tomesphere.com/paper/PMC12525797