The use of alkaline phosphatase as a bone turnover marker after spinal cord injury: A scoping review of human and animal studies

Abstract

Background:

Serum alkaline phosphatase (ALP) is measured as an indicator of bone or liver disease. Bone-specific alkaline phosphatase (B-ALP) is an isoform of ALP found in the bone tissue which can predict fractures and heterotopic ossification.

Objective:

The aim of this scoping review was to explore the current use of ALP and B-ALP in studies using humans or animal models of SCI, and to identify ways to advance future research using ALP and B-ALP as a bone marker after SCI.

Results:

HUMAN STUDIES: 42 studies were included. The evidence regarding changes or differences in ALP levels in individuals with SCI compared to controls is conflicting. For example, a negative correlation between B-ALP and total femur BMD was observed in only one of three studies examining the association. B-ALP seemed to increase after administration of teriparatide, and to decrease after treatment with denosumab. The effects of exercise on ALP and B-ALP levels are heterogeneous and depend on the type of exercise performed. ANIMAL STUDIES: 11 studies were included. There is uncertainty regarding the response of ALP or B-ALP levels after SCI; levels increased after some interventions, including vibration protocols, curcumin supplementation, cycles in electromagnetic field or hyperbaric chamber. Calcitonin or bisphosphonate administration did not affect ALP levels.

Conclusion:

Researchers are encouraged to measure the bone-specific isoform of ALP rather than total ALP in future studies in humans of animal models of SCI.

Keywords:

• Spinal Injury
• Biomarkers
• Bone metabolism
• Phosphate homeostasis

Acknowledgements

We would like to acknowledge the direct and indirect support of the Rehabilitation Translational Continuum (ReCon) team: Armstrong K., Balbinot G., Battaglino R., Cayer L., Cesarz G., Chan B., Coleman A., Cowley K., Craven B.C., Fouad K., Furlan J., Giangregorio L., Gilbert P.M., Habib-Perez O., Houston D., Jeji T., Kalsi-Ryan S., Kwon B., Li G., Magnuson D.S.K., Masani K., Morse L., Musselman K., Newton E., Park A., Patsakos E., Petrie S., Ponzano M., and Shepherd J., Wiest M.J., Ye G., Zariffa J. Only the main authors are responsible for the content of this manuscript.

Availability of data and material

The data being reported are accurate and are coming from the official source.

Disclaimer statements

Contributors Conceptualization: B. Catharine Craven, Lora M. Giangregorio, David S.K. Magnuson; Methodology: B. Catharine Craven, Lora M. Giangregorio, David S.K. Magnuson, Matteo Ponzano, Matheus J. Wiest; Formal analysis and investigation: André Coleman, Emily Newton, Maureen Pakosh, Eleni M. Patsakos, Matteo Ponzano, Matheus J. Wiest; Writing – original draft preparation: Matteo Ponzano; Writing – review and editing: André Coleman, B. Catharine Craven, Lora M. Giangregorio, David S.K. Magnuson, Emily Newton, Maureen Pakosh, Eleni M. Patsakos, Matteo Ponzano, Matheus J. Wiest; Funding acquisition: B. Catharine Craven; Resources: B. Catharine Craven, Lora M. Giangregorio, David S.K. Magnuson, Matheus J. Wiest; Supervision: B. Catharine Craven, Lora M. Giangregorio.

Conflicts of interest Matteo Ponzano, Matheus J. Wiest, André Coleman, Emily Newton, Maureen Pakosh, Eleni M. Patsakos, David S.K. Magnuson, Lora M. Giangregorio and B. Catharine Craven declare that they have no conflict of interest.

Additional information

Funding

This study was supported by the Ontario Neurotrauma Foundation (#2017-SCI-RECON-1037). We acknowledge the support of the Natural Sciences and Engineering Research Council of Canada, CREATE 509950–2018 Training in Global Biomedical Technology Research and Innovation.