The prevalence of ENPP1 deficiency in humans with Ossification of the Posterior Longitudinal Ligament and the preclinical efficacy of ENPP1 enzyme therapy in murine Ossification of the Posterior Longitudinal Ligament
Authors' conclusion
Our findings establish a clear link between decreased plasma PPi, ENPP1 deficiency, and OPLL, unveiling additional therapeutic targets to more effectively manage this poorly treated condition.
Study context
- Population
- Patients presenting for surgical correction of of the posterior longitudinal ligament (OPLL) or cervical osteoarthritis; Enpp1-deficient mice (Enpp1asj)
- Participants
- 50 vs 25
- Exposure
- OPLL vs cervical osteoarthritis; ENPP1 enzyme replacement therapies in Enpp1asj mice
- OPLLn = 50
- Cervical osteoarthritisn = 25reference
- Outcome
- ENPP1 deficiency in OPLL
Methodological detailsconsecutive patients, Exome sequencing of 19 genes associated with phosphate wasting and spinal ligament enthesopathy/ossification
- Consecutive patients
- Exome sequencing of 19 genes associated with phosphate wasting and spinal ligament enthesopathy/ossification
Main finding
As reported in the abstract
OPLL
14%
- OPLL patients harboring monoallelic pathogenic ENPP1 variants
- 14%
Observational data: associations, not effects.
Further findings
Enpp1asj mouse phenotype · 17 wk of age
- Pathologic mineralization of spine, long bones and tendons, with increased long bone and spinal fracture risk
Bone-targeted ENPP1 in Enpp1asj mice
- Significantly ameliorated spinal hyperostosis, improved or normalized spinal and long bone fragility, ameliorated tendon enthesopathies, improved trabecular microarchitecture
Soluble ENPP1 in Enpp1asj mice
- Prevented tendon enthesopathies, normalized cortical bone microarchitecture, improved long bone fragility
Original publication
The prevalence of ENPP1 deficiency in humans with Ossification of the Posterior Longitudinal Ligament and the preclinical efficacy of ENPP1 enzyme therapy in murine Ossification of the Posterior Longitudinal Ligament. J Bone Miner Res. Published 18 November 2025. doi:10.
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