ORIGINAL RESEARCH article
Front. Endocrinol.
Sec. Bone Research
Pathogenic SGMS2 variants are not a common cause of early-onset osteoporosis among Finnish patients
Provisionally accepted
Petra Loid1,2,3,4*
Sampo Richardt1,2
Tuukka Niinimaki5,6
Minna Pekkinen1,2,3
Outi Mäkitie1,2,3,4,7
Riikka Mäkitie1,2,8- 1University of Helsinki, Helsinki, Finland
- 2Folkhälsan Research Center, Helsinki, Finland
- 3Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland
- 4Department of Molecular Medicine and Surgery and Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden
- 5Research Unit of Clinical Medicine, University of Oulu, Oulu, Finland
- 6Department of Surgery, Oulu University Hospital, Oulu, Finland
- 7Clinical genetics, Karolinska University Hospital, Stockholm, Sweden
- 8Department of Otorhinolaryngology - Head and Neck Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland
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Primary osteoporosis can be caused by pathogenic variants in multiple genes. Recently, rare heterozygous variants in SGMS2, encoding SMS2, have been identified to cause early-onset osteoporosis or more severe skeletal dysplasia. The incidence of pathogenic SGMS2 variants and their consequent clinical features, however, remain limited. This study aimed to identify the prevalence and nature of SGMS2 variants in Finnish patients with genetically undiagnosed idiopathic early-onset osteoporosis. All eleven exons and exon-intron boundaries of SGMS2 were sequenced. In a cohort of 44 patients (42 females and two males, median age at the time of recruitment 60 years, range 25–76 years), we identified one rare heterozygous missense variant (c.715T>C, p.Phe239Leu) and three intronic variants with unknown functional consequences; no pathogenic or likely pathogenic variants were found. Our results suggest that pathogenic variants in SGMS2 are not a common cause of early-onset idiopathic osteoporosis in Finnish patients. Further studies in larger cohorts and variable skeletal phenotypes are needed to increase our understanding of the role of SGMS2 in skeletal fragility.
Keywords: Early-onset osteoporosis, monogenicosteoporosis, Sequencing, SGMS2, Single nucleotide variants
Received: 06 Oct 2025; Accepted: 03 Feb 2026.
Copyright: © 2026 Loid, Richardt, Niinimaki, Pekkinen, Mäkitie and Mäkitie. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Petra Loid
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