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Peer-reviewedCC BY-NC 4.0Osteoporosis International

Serum activin A and bone metabolism in patients undergoing hemodialysis

  • Yosuke Nakagawa1
  • Hiroo Takahashi2
  • Yuichiro Takahashi2
  • Toru Hyodo3
  • Miho Hida3
  • Takao Suga4
  • Takatoshi Kakuta1,4
  • Yusuke Tomita5
  • Michio Nakamura5
  • Hirotaka Komaba1,6
6 affiliations
  1. 1Division of Nephrology, Endocrinology and Metabolism, Tokai University School of Medicine, 143 Shimokasuya, Isehara, 259-1193 Japan
  2. 2Jinken Clinic, Ebina, Japan
  3. 3Medical Corporation Kuratakai, Hiratsuka, Japan
  4. 4Medical Corporation Showakai, Tokyo, Japan
  5. 5Department of Transplant Surgery, Tokai University School of Medicine, Isehara, Japan
  6. 6The Institute of Medical Sciences, Tokai University, Isehara, Japan
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Abstract

Activin A, which promotes osteoclast differentiation, increases with declining kidney function, but its role in bone metabolism in kidney failure remains unclear. We found that higher activin A levels were associated with increased bone turnover markers, independent of parathyroid hormone levels.

Purpose: Activin A, produced by various cells including bone marrow stromal cells, immune cells, and osteoblasts, is thought to promote osteoclast differentiation. Serum activin A levels rise with declining kidney function, but its role in bone metabolism in kidney failure remains incompletely understood.

Methods: Serum activin A levels were measured in 35 healthy individuals and 654 patients undergoing maintenance hemodialysis. Associations of serum activin A with tartrate-resistant acid phosphatase isoform 5b (TRACP5b), bone-specific alkaline phosphatase (BALP), and metacarpal bone mineral density were assessed using both unadjusted and multivariable-adjusted linear regression analyses. Serum activin A levels were also compared between patients with and without a history of fracture, and between those who developed incident fractures during follow-up and those who did not.

Results: The median serum activin A level in hemodialysis patients was 733 pg/mL (interquartile range (IQR), 591–912), approximately 2.6-fold higher than that of healthy controls (277 pg/mL; IQR, 216–289; P < 0.001). Patients with higher activin A levels had longer dialysis durations, a higher prevalence of polycystic kidney disease, and higher serum phosphorus and alkaline phosphatase levels. Higher activin A levels were significantly associated with increased TRACP5b levels independently of intact parathyroid hormone levels, with a similar trend observed for BALP. Serum activin A levels were not associated with metacarpal bone mineral density, history of fracture, or incident fractures.

Conclusion: These findings suggest that in patients with kidney failure, elevated activin A may contribute to high bone turnover, although its ability to predict fracture risk appears limited. Further studies are warranted to investigate its potential as a therapeutic target.

Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00198-026-07981-z.

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Cite

BibTeXRIS
BibTeX
@article{nakagawa2026serum,
  title = {{Serum activin A and bone metabolism in patients undergoing hemodialysis}},
  author = {Yosuke Nakagawa and Hiroo Takahashi and Yuichiro Takahashi and Toru Hyodo and Miho Hida and Takao Suga and Takatoshi Kakuta and Yusuke Tomita and Michio Nakamura and Hirotaka Komaba},
  journal = {Osteoporosis International},
  year = {2026},
  month = jul,
  doi = {10.1007/s00198-026-07981-z},
  url = {https://doi.org/10.1007/s00198-026-07981-z},
  note = {CC BY-NC 4.0},
}
RIS
TY  - JOUR
TI  - Serum activin A and bone metabolism in patients undergoing hemodialysis
AU  - Yosuke Nakagawa
AU  - Hiroo Takahashi
AU  - Yuichiro Takahashi
AU  - Toru Hyodo
AU  - Miho Hida
AU  - Takao Suga
AU  - Takatoshi Kakuta
AU  - Yusuke Tomita
AU  - Michio Nakamura
AU  - Hirotaka Komaba
PY  - 2026
DA  - 2026/07/16
JO  - Osteoporosis International
DO  - 10.1007/s00198-026-07981-z
UR  - https://doi.org/10.1007/s00198-026-07981-z
AB  - Activin A, which promotes osteoclast differentiation, increases with declining kidney function, but its role in bone metabolism in kidney failure remains unclear. We found that higher activin A levels were associated with increased bone turnover markers, independent of parathyroid hormone levels.  Purpose: Activin A, produced by various cells including bone marrow stromal cells, immune cells, and osteoblasts, is thought to promote osteoclast differentiation. Serum activin A levels rise with declining kidney function, but its role in bone metabolism in kidney failure remains incompletely understood.  Methods: Serum activin A levels were measured in 35 healthy individuals and 654 patients undergoing maintenance hemodialysis. Associations of serum activin A with tartrate-resistant acid phosphatase isoform 5b (TRACP5b), bone-specific alkaline phosphatase (BALP), and metacarpal bone mineral density were assessed using both unadjusted and multivariable-adjusted linear regression analyses. Serum activin A levels were also compared between patients with and without a history of fracture, and between those who developed incident fractures during follow-up and those who did not.  Results: The median serum activin A level in hemodialysis patients was 733 pg/mL (interquartile range (IQR), 591–912), approximately 2.6-fold higher than that of healthy controls (277 pg/mL; IQR, 216–289; P < 0.001). Patients with higher activin A levels had longer dialysis durations, a higher prevalence of polycystic kidney disease, and higher serum phosphorus and alkaline phosphatase levels. Higher activin A levels were significantly associated with increased TRACP5b levels independently of intact parathyroid hormone levels, with a similar trend observed for BALP. Serum activin A levels were not associated with metacarpal bone mineral density, history of fracture, or incident fractures.  Conclusion: These findings suggest that in patients with kidney failure, elevated activin A may contribute to high bone turnover, although its ability to predict fracture risk appears limited. Further studies are warranted to investigate its potential as a therapeutic target.  Supplementary Information: The online version contains supplementary material available at https://doi.org/10.1007/s00198-026-07981-z.
SN  - 0937-941X
SN  - 1433-2965
ER  -