Evidence map›Paper›PMID 42151888›Full record

ArticleBMC musculoskeletal disorders2026

Role and mechanism of leptin in improving osteoporosis via the "gut-bone axis".

Lice Liu, Linjian Tong, Jia Yang, Long Sun, Jian Liu, Yu Zhu, Zhiming Sun

Abstract read
In one paragraph

Article in BMC musculoskeletal disorders, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
1citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

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2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

1 citing paper in PubMed, 1 synthesis or guideline pooled it.

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4 · The record

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PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors.

Lice LiuHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, 300070, China.
Linjian TongHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, 300070, China.
Jia YangDepartment of Orthopaedic, Jincheng General Hospital, Chang'an Road, Jincheng, Shanxi Province, 048006, China.
Long SunHuanhu Hospital Affiliated to Tianjin Medical University, Tianjin Medical University, Tianjin, 300070, China.
Jian LiuCollege of Computer Science, Nankai University, Tianjin, 300350, China.
Yu ZhuDepartment of Nutrition, Central Hospital, Tianjin Key Laboratory of Extracorporeal Life Support for Critical Diseases, Tianjin Artificial Cell Engineering Technology Research Center, Tianjin Third Central Hospital Branch, Tianjin University/Tianjin Third Central Hospital, Tianjin Institute of Geriatrics, National Medical Quality Control Center of Clinical Nutrition, Tianjin, 300170, China.
Zhiming SunNankai University Affinity the Third Central Hospital, Tianjin, 300170, China. sunzhm618@163.com.

Funding

Joint Funds of the Natural Science Foundation of Tianjin 25JCLMJC00510Natural Science Foundation of Tianjin 23JCYBJC01740Tianjin Innovation Consortium Major Science and Technology Project 24ZXKJSY00020Tianjin Key Medical Discipline Construction Project TJYXZDXK-3-002D
6 · The paper itself

Abstract

backgroundOsteoporosis is a systemic skeletal disorder characterized by reduced bone mass, microarchitectural deterioration, and increased fracture risk, particularly in postmenopausal women. Although current antiresorptive and anabolic therapies are effective in some patients, their use remains limited by safety concerns, restricted indications, and poor long-term adherence. Increasing evidence suggests that the gut-bone axis plays an important role in skeletal homeostasis, while leptin has emerged as a metabolic regulator with potential effects on bone remodeling. However, whether leptin alleviates osteoporosis through modulation of gut microbiota and microbiota-related metabolites remains unclear. Therefore, this study aimed to investigate the protective effects of leptin in ovariectomy-induced osteoporosis and to explore its potential associations with the gut microbiota-metabolite-bone regulatory mechanisms.

methodsFemale Sprague-Dawley rats were randomized into Sham, OVX, Sham+Leptin, and OVX+Leptin groups. BMD was measured by dual-energy X-ray absorptiometry, and trabecular microarchitecture was assessed by micro-CT and histology. Serum bone turnover markers were analyzed by ELISA. Gut microbiota composition was evaluated using 16 S rRNA sequencing. Serum metabolomics was performed using UHPLC-Orbitrap MS, and bile acids were quantified by LC-MS/MS. Bone protein expression was evaluated by immunohistochemistry.

resultsLeptin significantly increased BMD and improved trabecular microarchitecture in OVX rats, accompanied by normalization of ALP and OCN levels. Gut microbiota analysis showed that leptin treatment altered microbial composition, with increased relative abundances of taxa such as Akkermansia, Lachnospiraceae, and Muribaculaceae, and decreased abundance of Desulfovibrionaceae. Metabolomic profiling showed partial reversal of OVX-induced disturbances, particularly in unsaturated fatty acid and bile acids metabolism. Targeted bile acids analysis demonstrated restoration of hydrophilic bile acids following leptin treatment. Immunohistochemical analysis further showed that leptin treatment was associated with reduced RANKL expression and increased OPG expression.

conclusionsLeptin ameliorated OVX-induced osteoporosis in rats, accompanied by remodeling of the gut microbiota, partial restoration of serum metabolic and bile acids profiles, and changes in bone remodeling-related proteins. These findings suggest that the gut microbiota-metabolite-bone network may be involved in the skeletal effects of leptin, providing novel mechanistic insights and potential therapeutic strategies for osteoporosis management.

Indexed as

Bone RemodelingGastrointestinal MicrobiomeLeptinOsteoporosisAnimalsBile Acids and SaltsBone DensityDisease Models, AnimalFemaleOvariectomyRatsRats, Sprague-DawleyBile Acids and SaltsLeptinBile acidsGut-bone axisGut MicrobiotaLeptinOsteoporosis

Identifiers

PMID42151888
PMCPMC13361053

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.