Riikka E Mäkitie1, Anders J Kämpe2, Fulya Taylan2, Outi Mäkitie3,4,5,6. 1. Folkhälsan Institute of Genetics, University of Helsinki, P. O. Box 63, FIN-00014, Helsinki, Finland. 2. Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. 3. Folkhälsan Institute of Genetics, University of Helsinki, P. O. Box 63, FIN-00014, Helsinki, Finland. outi.makitie@helsinki.fi. 4. Department of Molecular Medicine and Surgery, Center for Molecular Medicine, Karolinska Institutet, Stockholm, Sweden. outi.makitie@helsinki.fi. 5. Department of Clinical Genetics, Karolinska University Hospital, Stockholm, Sweden. outi.makitie@helsinki.fi. 6. Children's Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland. outi.makitie@helsinki.fi.
Abstract
PURPOSE OF REVIEW: This review summarizes our current knowledge on primary osteoporosis in children with focus on recent genetic findings. RECENT FINDINGS: Advances in genetic research, particularly next-generation sequencing, have found several genetic loci that associate with monogenic forms of inherited osteoporosis, widening the scope of primary osteoporosis beyond classical osteogenesis imperfecta. New forms of primary osteoporosis, such as those related to WNT1, PLS3, and XYLT2, have identified defects outside the extracellular matrix components and collagen-related pathways, in intracellular cascades directly affecting bone cell function. Primary osteoporosis can lead to severe skeletal morbidity, including abnormal longitudinal growth, compromised bone mass gain, and noticeable fracture tendency beginning at childhood. Early diagnosis and timely care are warranted to ensure the best achievable bone health. Future research will most likely broaden the spectrum of primary osteoporosis, hopefully provide more insight into the genetics governing bone health, and offer new targets for treatment.
PURPOSE OF REVIEW: This review summarizes our current knowledge on primary osteoporosis in children with focus on recent genetic findings. RECENT FINDINGS: Advances in genetic research, particularly next-generation sequencing, have found several genetic loci that associate with monogenic forms of inherited osteoporosis, widening the scope of primary osteoporosis beyond classical osteogenesis imperfecta. New forms of primary osteoporosis, such as those related to WNT1, PLS3, and XYLT2, have identified defects outside the extracellular matrix components and collagen-related pathways, in intracellular cascades directly affecting bone cell function. Primary osteoporosis can lead to severe skeletal morbidity, including abnormal longitudinal growth, compromised bone mass gain, and noticeable fracture tendency beginning at childhood. Early diagnosis and timely care are warranted to ensure the best achievable bone health. Future research will most likely broaden the spectrum of primary osteoporosis, hopefully provide more insight into the genetics governing bone health, and offer new targets for treatment.
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Authors: Johanna Korvala; Harald Jüppner; Outi Mäkitie; Etienne Sochett; Dirk Schnabel; Stefano Mora; Cynthia F Bartels; Matthew L Warman; Donald Deraska; William G Cole; Heini Hartikka; Leena Ala-Kokko; Minna Männikkö Journal: BMC Med Genet Date: 2012-04-10 Impact factor: 2.103
Authors: Isabel R Orriss; Stuart Lanham; Dawn Savery; Nicholas D E Greene; Philip Stanier; Richard Oreffo; Andrew J Copp; Gabriel L Galea Journal: Sci Rep Date: 2018-02-20 Impact factor: 4.379
Authors: Alice Costantini; Riikka E Mäkitie; Markus A Hartmann; Nadja Fratzl-Zelman; M Carola Zillikens; Uwe Kornak; Kent Søe; Outi Mäkitie Journal: J Bone Miner Res Date: 2022-09-11 Impact factor: 6.390
Authors: Riikka E Mäkitie; Petra Henning; Yaming Jiu; Anders Kämpe; Konstantin Kogan; Alice Costantini; Ville-Valtteri Välimäki; Carolina Medina-Gomez; Minna Pekkinen; Isidro B Salusky; Camilla Schalin-Jäntti; Maria K Haanpää; Fernando Rivadeneira; John H Duncan Bassett; Graham R Williams; Ulf H Lerner; Renata C Pereira; Pekka Lappalainen; Outi Mäkitie Journal: JBMR Plus Date: 2021-06-07