Bone Abstracts

Objectives: A heterozygous missense mutation p. C218G in WNT1 was recently identified as the cause of severe primary osteoporosis (Laine et al., New engl J Med 2013). The mutation has thus far been identified in two large Finnish families presenting with dominantly inherited, early-onset osteoporosis, with affected adult patients showing reduced bone mineral density (BMD), vertebral compression fractures, kyphosis and height loss. This study examined characteristics of WNT1 osteoporosis in the axial skeleton using magnetic resonance imaging (MRI). The study was approved by the Research Ethics Committee.

Methods: This study included 17 adults (12 females) with a heterozygous p. C218G WNT1 mutation. MRI scans were taken of the axial skeleton with a focus from Th5 to L5. All scans were reviewed independently by an experienced radiologist and an orthopedic surgeon. Images were assessed for vertebral morphology and signal intensity, vertebral endplates, vertebral corner defects, intervertebral disc shape and intensity, spinal canal width as well as overall spinal stature and scoliosis.

Results: The 17 subjects ranged in age from 11 to 76 years (median 49 years). Overall the MRI scans showed several changes, especially in the thoracic spine; mildly to severely collapsed vertebrae (in 9/17 subjects), elongation of vertebral shape (in 4/17), and defects in vertebral endplates (in 10/17). Intervertebral discs were abnormally high with degenerative signal loss. All changes were more common in older subjects; thoracic kyphosis was evident already in young adults and 7/8 of those over 50 years had vertebral compression fractures.

Conclusions: This study confirms that the mutated WNT1 alters thoracic vertebral shape and intervertebral discs, causes changes to endplates and predisposes to vertebral collapse and compression fractures, particularly in thoracic spine. Changes are apparent already in young adults and gradually increase with age resulting in severe spinal pathology. Children are rarely affected.