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@ARTICLE{Ehnert:268774,
      author       = {Ehnert, Sabrina and Hauser, Stefan and Hengel, Holger and
                      Höflinger, Philip and Schüle, Rebecca and Lindig, Tobias
                      and Baets, Jonathan and Deconinck, Tine and de Jonghe, Peter
                      and Histing, Tina and Nüssler, Andreas K and Schöls,
                      Ludger and Rattay, Tim},
      title        = {{V}itamin {D}3 deficiency and osteopenia in spastic
                      paraplegia type 5 indicate impaired bone homeostasis.},
      journal      = {Scientific reports},
      volume       = {14},
      number       = {1},
      issn         = {2045-2322},
      address      = {[London]},
      publisher    = {Macmillan Publishers Limited, part of Springer Nature},
      reportid     = {DZNE-2024-00318},
      pages        = {7335},
      year         = {2024},
      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.},
      keywords     = {Humans / Mutation / Spastic Paraplegia, Hereditary:
                      genetics / Spastic Paraplegia, Hereditary: metabolism /
                      Oxysterols / Paraplegia / Homeostasis / Vitamin D:
                      therapeutic use / Oxysterols (NLM Chemicals) / Vitamin D
                      (NLM Chemicals)},
      cin          = {AG Gasser / AG Hauser / AG Schöls},
      ddc          = {600},
      cid          = {I:(DE-2719)1210000 / I:(DE-2719)1210016 /
                      I:(DE-2719)5000005},
      pnm          = {353 - Clinical and Health Care Research (POF4-353) / 352 -
                      Disease Mechanisms (POF4-352)},
      pid          = {G:(DE-HGF)POF4-353 / G:(DE-HGF)POF4-352},
      typ          = {PUB:(DE-HGF)16},
      pmc          = {pmc:PMC10973513},
      pubmed       = {pmid:38538623},
      doi          = {10.1038/s41598-024-53057-5},
      url          = {https://pub.dzne.de/record/268774},
}