Journal Article

DZNE-2024-00318

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Vitamin D3 deficiency and osteopenia in spastic paraplegia type 5 indicate impaired bone homeostasis.

Ehnert, S. ; Hauser, S.DZNE* ; Hengel, H.DZNE* ; Höflinger, P.DZNE* ; Schüle, R.DZNE* ; Lindig, T. ; Baets, J. ; Deconinck, T. ; de Jonghe, P. ; Histing, T. ; Nüssler, A. K. ; Schöls, L.DZNE* ; Rattay, T. (Last author)DZNE*

2024
Macmillan Publishers Limited, part of Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41598-024-53057-5

Abstract: Hereditary spastic paraplegia type 5 (SPG5) is an autosomal recessively inherited movement disorder characterized by progressive spastic gait disturbance and afferent ataxia. SPG5 is caused by bi-allelic loss of function mutations in CYP7B1 resulting in accumulation of the oxysterols 25-hydroxycholesterol and 27-hydroxycholesterol in serum and cerebrospinal fluid of SPG5 patients. An effect of 27- hydroxycholesterol via the estrogen and liver X receptors was previously shown on bone homeostasis. This study analyzed bone homeostasis and osteopenia in 14 SPG5 patients as a non-motor feature leading to a potential increased risk for bone fractures. T-Scores in CT bone density measurements were reduced, indicating osteopenia in SPG5 patients. Further, we analyzed various metabolites of bone homeostasis by ELISA in serum samples of these patients. We identified a lack of vitamin D3 metabolites (Calcidiol and Calcitriol), an increase in Sclerostin as a bone formation/mineralization inhibiting factor, and a decrease in cross-linked N-telopeptide of type I collagen (NTX), a marker indicating reduced bone resorption. As statin treatment has been found to lower oxysterol levels, we evaluated its effect in samples of the STOP-SPG5 trial and found atorvastatin to normalize the increased sclerostin levels. In summary, our study identified osteopenia as a non-motor feature in SPG5 and suggests the need for vitamin D3 substitution in SPG5 patients. Sclerostin may be considered a therapeutic target and biomarker in upcoming therapeutical trials in SPG5.

Keyword(s): Humans (MeSH) ; Mutation (MeSH) ; Spastic Paraplegia, Hereditary: genetics (MeSH) ; Spastic Paraplegia, Hereditary: metabolism (MeSH) ; Oxysterols (MeSH) ; Paraplegia (MeSH) ; Homeostasis (MeSH) ; Vitamin D: therapeutic use (MeSH) ; Oxysterols ; Vitamin D

---

Contributing Institute(s):

1. Parkinson Genetics (AG Gasser)
2. Advanced cellular models of neurodegeneration (AG Hauser)
3. Clinical Neurogenetics (AG Schöls)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)
2. 352 - Disease Mechanisms (POF4-352) (POF4-352)

Appears in the scientific report 2024

---

Database coverage:
; ; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF < 5 ; JCR ; PubMed Central ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---