title: Association between sclerostin and bone density in chronic spinal cord injury.
abstract: Spinal cord injury (SCI) results in profound bone loss due to muscle paralysis and the inability to ambulate. Sclerostin, a Wnt signaling pathway antagonist produced by osteocytes, is a potent inhibitor of bone formation. Short-term studies in rodent models have shown increased sclerostin in response to mechanical unloading that is reversed with reloading. These studies suggest that complete spinal cord injury, a condition resulting in mechanical unloading of the paralyzed lower extremities, will be associated with high sclerostin levels. We assessed the relationship between circulating sclerostin and bone density in 39 subjects with chronic SCI and 10 without SCI. We found that greater total limb bone mineral content was significantly associated with greater circulating levels of sclerostin. Sclerostin levels were reduced, not elevated, in subjects with SCI who use a wheelchair compared with those with SCI who walk regularly. Similarly, sclerostin levels were lower in subjects with SCI who use a wheelchair compared with persons without SCI who walk regularly. These findings suggest that circulating sclerostin is a biomarker of osteoporosis severity, not a mediator of ongoing bone loss, in long-term, chronic paraplegia. This is in contrast to the acute sclerostin-mediated bone loss shown in animal models of mechanical unloading in which high sclerostin levels suppress bone formation. Because these data indicate important differences in the relationship between mechanical unloading, sclerostin, and bone in chronic SCI compared with short-term rodent models, it is likely that sclerostin is not a good therapeutic target to treat chronic SCI-induced osteoporosis.
authors: Department of Physical Medicine and Rehabilitation, Harvard Medical School, Boston, MA, USA.
authors: Leslie R
authors: LR
authors: Morse
authors: Supreetha
authors: S
authors: Sudhakar
authors: Valery
authors: V
authors: Danilack
authors: Carlos
authors: C
authors: Tun
authors: Antonio
authors: A
authors: Lazzari
authors: David R
authors: DR
authors: Gagnon
authors: Eric
authors: E
authors: Garshick
authors: Ricardo A
authors: RA
authors: Battaglino
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D000375:Aging / Q000473:pathology; D015519:Bone Density / Q000502:physiology*; D019485:Bone Morphogenetic Proteins / Q000097:blood*; D002908:Chronic Disease; D005819:Genetic Markers; D006801:Humans; D008297:Male; D008875:Middle Aged; D012720:Severity of Illness Index; D013119:Spinal Cord Injuries / Q000097:blood* / Q000503:physiopathology*; D014910:Wheelchairs
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019485:Bone Morphogenetic Proteins; D005819:Genetic Markers; C422903:SOST protein, human