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Peer-reviewedCC BYCurrent osteoporosis reports

Osteoporosis and Alzheimer's Disease: The Role of Sclerostin.

  • Lorelé Gagiano1
  • Ziming Chen2
  • William G Blakeney3,4
  • Christopher Jones5,6,7
  • Frank Mastaglia8
  • Minghao Zheng9,10
  • Jun Yuan11,12
12 affiliations
  1. 1School of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.
  2. 2Centre for Translational Orthopaedic Research, School of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.
  3. 3Department of Orthopaedic Surgery, Royal Perth Hospital, Wellington Street, Perth, WA, 6000, Australia.
  4. 4Department of Surgery, Medical School, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia.
  5. 5Department of Orthopaedic Surgery, Fremantle and Fiona Stanley Hospitals, Perth, WA, 6150, Australia.
  6. 6Department of Orthopaedic Surgery, The Orthopaedic Research Foundation of Western Australia, Perth, WA, 6010, Australia.
  7. 7Division of Surgery, The University of Western Australia, Perth, WA, 6009, Australia.
  8. 8Perron Institute for Neurological and Translational Science, The University of Western Australia, 8 Verdun St, Nedlands, WA, 6009, Australia.
  9. 9Centre for Translational Orthopaedic Research, School of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia. [email protected].
  10. 10Perron Institute for Neurological and Translational Science, The University of Western Australia, 8 Verdun St, Nedlands, WA, 6009, Australia. [email protected].
  11. 11Centre for Translational Orthopaedic Research, School of Biomedical Sciences, The University of Western Australia, 35 Stirling Highway, Perth, WA, 6009, Australia. [email protected].
  12. 12Perron Institute for Neurological and Translational Science, The University of Western Australia, 8 Verdun St, Nedlands, WA, 6009, Australia. [email protected].
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Abstract

Purpose of review

Little is known about the underlying cause contributing to the association between Osteoporosis (OP) and Alzheimer's disease (AD). This review highlights the emerging role of sclerostin, a protein mainly produced by osteocytes, in the newly discovered crosstalk between bone and brain, with a focus on its potential contribution to the relationship between OP and AD.Recent findings

Circulating sclerostin levels increase with aging and are positively associated with brain amyloid-β burden in older adults. Studies demonstrate that elevated sclerostin can cross the blood-brain barrier, promote amyloid-β peptide deposition, and impair synaptic plasticity by suppressing Wnt/β-catenin signalling, whereas sclerostin inhibition restores neuronal plasticity and attenuates AD pathology. Sclerostin represents a promising target in the bone-brain interaction pathway. Its dual role as a measurable circulating biomarker and a modifiable component offers new opportunities for early risk assessment and therapeutic repurposing. Future longitudinal and interventional studies are essential to confirm the association between sclerostin and risk of AD, and to clarify whether targeting sclerostin can delay the onset of the disease or modify its trajectory.

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Cite

BibTeXRIS
BibTeX
@article{gagiano2026osteoporosis,
  title = {{Osteoporosis and Alzheimer's Disease: The Role of Sclerostin.}},
  author = {Lorelé Gagiano and Ziming Chen and William G Blakeney and Christopher Jones and Frank Mastaglia and Minghao Zheng and Jun Yuan},
  journal = {Current osteoporosis reports},
  year = {2026},
  month = oct,
  doi = {10.1007/s11914-026-00993-y},
  url = {https://europepmc.org/article/MED/42905237},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Osteoporosis and Alzheimer's Disease: The Role of Sclerostin.
AU  - Lorelé Gagiano
AU  - Ziming Chen
AU  - William G Blakeney
AU  - Christopher Jones
AU  - Frank Mastaglia
AU  - Minghao Zheng
AU  - Jun Yuan
PY  - 2026
DA  - 2026/10/21
JO  - Current osteoporosis reports
DO  - 10.1007/s11914-026-00993-y
UR  - https://europepmc.org/article/MED/42905237
AB  - Purpose of review  Little is known about the underlying cause contributing to the association between Osteoporosis (OP) and Alzheimer's disease (AD). This review highlights the emerging role of sclerostin, a protein mainly produced by osteocytes, in the newly discovered crosstalk between bone and brain, with a focus on its potential contribution to the relationship between OP and AD.Recent findings  Circulating sclerostin levels increase with aging and are positively associated with brain amyloid-β burden in older adults. Studies demonstrate that elevated sclerostin can cross the blood-brain barrier, promote amyloid-β peptide deposition, and impair synaptic plasticity by suppressing Wnt/β-catenin signalling, whereas sclerostin inhibition restores neuronal plasticity and attenuates AD pathology. Sclerostin represents a promising target in the bone-brain interaction pathway. Its dual role as a measurable circulating biomarker and a modifiable component offers new opportunities for early risk assessment and therapeutic repurposing. Future longitudinal and interventional studies are essential to confirm the association between sclerostin and risk of AD, and to clarify whether targeting sclerostin can delay the onset of the disease or modify its trajectory.
SN  - 1544-1873
SN  - 1544-2241
ER  -