title: Circulating sclerostin is elevated in short-term and reduced in long-term SCI.
abstract: Spinal cord injury (SCI) causes profound bone loss due to muscle paralysis resulting in the inability to walk. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have demonstrated increased sclerostin in response to mechanical unloading that is reversed with reloading. Although sclerostin inhibition has been proposed as a potential therapy for bone loss, it is not known if sclerostin levels vary with duration of SCI in humans. We analyzed circulating sclerostin in 155 men with varying degrees of SCI who were 1 year or more post-injury. We report that sclerostin levels are greatest in subjects with short-term SCI (≤5 years post-injury) and decrease significantly over the first 5 years post-injury. There was no association between sclerostin and injury duration in subjects with long-term SCI (>5 years post-injury). In subjects with long-term SCI, sclerostin levels were positively associated with lower extremity bone density and bone mineral content. These data suggest that sclerostin levels are initially increased after SCI in response to mechanical unloading. This response is time-limited and as bone loss progresses, circulating sclerostin is lowest in subjects with severe osteoporosis. These findings support a dual role for sclerostin after SCI: a therapeutic target in acute SCI, and a biomarker of osteoporosis severity in chronic SCI.
authors.affiliation: The Forsyth Institute, Cambridge, MA, USA.
authors.forename: Ricardo A
authors.initials: RA
authors.lastname: Battaglino
authors.forename: Supreetha
authors.initials: S
authors.lastname: Sudhakar
authors.forename: Antonio A
authors.initials: AA
authors.lastname: Lazzari
authors.forename: Eric
authors.initials: E
authors.lastname: Garshick
authors.forename: Ross
authors.initials: R
authors.lastname: Zafonte
authors.forename: Leslie R
authors.initials: LR
authors.lastname: Morse
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000097:blood / Q000473:pathology; D015519:Bone Density; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D001842:Bone and Bones / Q000473:pathology / Q000503:physiopathology; D005260:Female; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000097:blood / Q000175:diagnosis / Q000503:physiopathology; D013119:Spinal Cord Injuries / Q000097:blood* / Q000473:pathology / Q000503:physiopathology; D013997:Time Factors; D014807:Vitamin D / Q000097:blood
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human; D014807:Vitamin D