Evidence map›Paper›PMID 41836579›Full record

ReviewJournal of orthopaedic translation2026

Brain-bone axis dysregulation: Biological code underlying the bidirectional association between depression and musculoskeletal disorders.

Yang Li, Sonu Ng, Keyu Kong, Minghao Jin, Wenxuan Fan, Wenjie Zhou, Zanjing Zhai, Huiwu Li

Abstract readReview
In one paragraph

Review in Journal of orthopaedic translation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.

0numbers the graph read from it
0cells of the map it votes in
3citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

3 citing papers in PubMed.

  1. Review
  2. Article
  3. Article
4 · The record

Corrections and comments

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

8 authors.

Yang LiDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.
Sonu NgDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.
Keyu KongDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.
Minghao JinDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.
Wenxuan FanDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.
Wenjie ZhouSongjiang Research Institute and Songjiang Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 201620, China.
Zanjing ZhaiDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.
Huiwu LiDepartment of Orthopedics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University, Shanghai, 200023, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Depression and musculoskeletal disorders including osteoporosis (OP), fractures, osteoarthritis (OA) and rheumatoid arthritis (RA) exhibit significant bidirectional epidemiological and pathophysiological links. Rising depression prevalence (approximately 2.7 % annually) is accompanied by the high global burden of musculoskeletal disorders. Shared mechanisms center on the neuroimmune-inflammatory axis: Depression-associated inflammation (e.g., IL-6, TNF-α) promotes bone resorption, cartilage degradation, and RA disease activity, while autonomic/endocrine dysregulation increases fracture risk through increased norepinephrine (NE) and cortisol. Contributing factors include oxidative stress, gut dysbiosis, and sex hormone imbalances. Antidepressants show divergent skeletal effects: selective serotonin reuptake inhibitors (SSRIs) may reduce bone mineral density (BMD) and increase fracture risk, while serotonin-norepinephrine reuptake inhibitors (SNRIs) can improve OA symptoms. Depression significantly worsens orthopedic outcomes, leading to increased fracture risk, pain and disability, reduced treatment response. Integrated care approaches and novel neuroimmune targets offer potential for improved comorbidity management. The Translational Potential of this Article: This review links depression with common orthopaedic disorders by synthesizing convergent neuro-immune-endocrine and metabolic pathways, and documents measurable skeletal deficits. These insights support immediate, low-cost actions: bidirectional screening, strengthened orthopaedics-psychiatry referral, and pragmatic combination care bundles. If implemented, this approach could reduce fracture risk, pain, and disability while improving recovery trajectories.

Indexed as

AntidepressantsDepressionNeuroimmune pathwaysOsteoarthritisOsteoporosisRheumatoid arthritis

Identifiers

PMID41836579
PMCPMC12988505

What OpenQuestion holds

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Registered trials

None linked

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.