Bone microarchitecture and strength in men and women with PLS3 gene variants assessed with HR-pQCT

Zografia Zervou, Melissa S A M Bevers, Caroline E Wyers, Hennie T Bruggenwirth, Serwet Demirdas, Joop P van den Bergh, M Carola Zillikens

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Abstract

X-linked osteoporosis, caused by PLS3 genetic variants, is a rare bone disease, clinically affecting mainly men. Limited data are available on bone microarchitecture and genotype-phenotype correlations in this disease. Our aims were to assess bone microarchitecture and strength in adults with PLS3 variants using high-resolution peripheral quantitative computed tomography (HR-pQCT) and to explore differences in the phenotype from HR-pQCT between PLS3 variants. HR-pQCT scans were obtained from the distal radius and tibia of 13 men and three women with PLS3 variants. Results were compared with age- and sex-matched controls from a normative dataset from literature and expressed as Z-scores. Median age was 46 years for men and 48 years for women. In men, total bone area was large (median Z-score: 1.33 radius; 1.46 tibia) due to a large trabecular area (+1.73 radius; +1.87 tibia), while the cortical area was small (-2.61 radius; -2.84 tibia). Total volumetric bone mineral density (BMD) was low due to low trabecular (-3.46 radius; -3.37 tibia) and cortical BMD (-2.87 radius; -2.26 tibia). Regarding bone microarchitecture, the largest deviations were found in trabecular number (-2.18 radius; -1.64 tibia), trabecular separation (+2.32 radius; +1.65 tibia), and cortical thickness (-2.99 radius; -2.46 tibia), whereas trabecular thickness and cortical porosity were normal (-0.36 and -0.58 radius; 0.09 and -0.79 tibia). Additionally, failure load was low (-2.39 radius; -2.2 tibia). Results in the women deviated less from normative data. Men with frameshift/nonsense variants seemed to have more deviant trabecular and cortical microarchitecture and strength, at both scan locations, than those with missense/in-frame insertion variants. In conclusion, HR-pQCT provides valuable insights into bone area, BMD, microarchitecture, and strength in adults with PLS3 variants and can be used to explore genotype-phenotype relationships. Longitudinal analyses in larger groups are needed to study the natural course of the disease and treatment effects.
Original languageEnglish
JournalJournal of Bone and Mineral Research
DOIs
Publication statusE-pub ahead of print - 10 Dec 2024

Keywords

  • Bone microarchitecture
  • Bone strength
  • Hr-pqct
  • Pls3
  • X-linked osteoporosis

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