Effect of Recent Spinal Cord Injury on Wnt Signaling Antagonists (Sclerostin and Dkk‐1) and Their Relationship With Bone Loss. A 12‐Month Prospective Study

Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short‐term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the...

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Published in:Journal of bone and mineral research 2015-06, Vol.30 (6), p.1014-1021
Main Authors: Gifre, Laia, Vidal, Joan, Carrasco, Josep L, Filella, Xavier, Ruiz‐Gaspà, Silvia, Muxi, Africa, Portell, Enric, Monegal, Ana, Guañabens, Nuria, Peris, Pilar
Format: Article
Language:English
Subjects:
Adolescent
Adult
Aged
Biomarkers - blood
Bone Morphogenetic Proteins - blood
Bone Resorption - blood
Bone Resorption - etiology
DKK‐1
Female
Follow-Up Studies
Genetic Markers
Humans
Intercellular Signaling Peptides and Proteins - blood
Male
Middle Aged
OSTEOPOROSIS
Prospective Studies
SCLEROSTIN
Spinal Cord Injuries - blood
Spinal Cord Injuries - complications
SPINAL CORD INJURY
WNT SIGNALING
Wnt Signaling Pathway
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creator Gifre, Laia
Vidal, Joan
Carrasco, Josep L
Filella, Xavier
Ruiz‐Gaspà, Silvia
Muxi, Africa
Portell, Enric
Monegal, Ana
Guañabens, Nuria
Peris, Pilar
description Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short‐term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk‐1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty‐two patients (aged 35 ± 14yrs) with a recent (
doi_str_mv 10.1002/jbmr.2423
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A 12‐Month Prospective Study</title><source>Wiley</source><creator>Gifre, Laia ; Vidal, Joan ; Carrasco, Josep L ; Filella, Xavier ; Ruiz‐Gaspà, Silvia ; Muxi, Africa ; Portell, Enric ; Monegal, Ana ; Guañabens, Nuria ; Peris, Pilar</creator><creatorcontrib>Gifre, Laia ; Vidal, Joan ; Carrasco, Josep L ; Filella, Xavier ; Ruiz‐Gaspà, Silvia ; Muxi, Africa ; Portell, Enric ; Monegal, Ana ; Guañabens, Nuria ; Peris, Pilar</creatorcontrib><description>Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short‐term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk‐1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty‐two patients (aged 35 ± 14yrs) with a recent (&lt;6months) complete SCI were prospectively included. Sclerostin and Dkk‐1, bone turnover markers (bone formation: PINP, bone ALP; resorption: sCTx) and BMD (lumbar spine, proximal femur, total body and lower extremities [DXA]) were assessed at baseline and at 6 and 12 months. The results were compared with a healthy control group. 22/42 patients completed the 12‐month follow‐up. At baseline, SCI patients showed a marked increase in bone markers (PINP and sCTx), remaining significantly increased at up to 6 months of follow‐up. Additionally, they presented significantly increased Dkk‐1 values throughout the study, whereas sclerostin values did not significantly change. BMD markedly decreased at the proximal femur (‐20.2 ± 5.4%, p &lt; 0.01), total body (‐5.7 ± 2.2%, p = 0.02) and lower extremities (‐13.1 ± 4.5%, p = 0.01) at 12 months. Consequently, 59% of patients developed densitometric osteoporosis at 12 months. Patients with higher Dkk‐1 values (&gt;58 pmol/L) at baseline showed higher sublesional BMD loss. In conclusion, this study shows that short‐term after SCI there is a marked increase in bone turnover and bone loss, the latter associated with an increase in Dkk‐1 serum levels. 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A 12‐Month Prospective Study</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short‐term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk‐1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty‐two patients (aged 35 ± 14yrs) with a recent (&lt;6months) complete SCI were prospectively included. Sclerostin and Dkk‐1, bone turnover markers (bone formation: PINP, bone ALP; resorption: sCTx) and BMD (lumbar spine, proximal femur, total body and lower extremities [DXA]) were assessed at baseline and at 6 and 12 months. The results were compared with a healthy control group. 22/42 patients completed the 12‐month follow‐up. At baseline, SCI patients showed a marked increase in bone markers (PINP and sCTx), remaining significantly increased at up to 6 months of follow‐up. Additionally, they presented significantly increased Dkk‐1 values throughout the study, whereas sclerostin values did not significantly change. BMD markedly decreased at the proximal femur (‐20.2 ± 5.4%, p &lt; 0.01), total body (‐5.7 ± 2.2%, p = 0.02) and lower extremities (‐13.1 ± 4.5%, p = 0.01) at 12 months. Consequently, 59% of patients developed densitometric osteoporosis at 12 months. Patients with higher Dkk‐1 values (&gt;58 pmol/L) at baseline showed higher sublesional BMD loss. 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A 12‐Month Prospective Study</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2015-06</date><risdate>2015</risdate><volume>30</volume><issue>6</issue><spage>1014</spage><epage>1021</epage><pages>1014-1021</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><notes>ObjectType-Article-1</notes><notes>SourceType-Scholarly Journals-1</notes><notes>ObjectType-Feature-3</notes><notes>content type line 23</notes><notes>ObjectType-Undefined-2</notes><abstract>Spinal cord injury (SCI) has been associated with a marked increase in bone loss and bone remodeling, especially short‐term after injury. The absence of mechanical load, mediated by osteocyte mechanosensory function, seems to be a causative factor related to bone loss in this condition. However, the pathogenesis and clinical management of this process remain unclear. Therefore, the aim of the study was to analyze the effect of recent SCI on the Wnt pathway antagonists, sclerostin and Dickkopf (Dkk‐1), and their relationship with bone turnover and bone mineral density (BMD) evolution. Forty‐two patients (aged 35 ± 14yrs) with a recent (&lt;6months) complete SCI were prospectively included. Sclerostin and Dkk‐1, bone turnover markers (bone formation: PINP, bone ALP; resorption: sCTx) and BMD (lumbar spine, proximal femur, total body and lower extremities [DXA]) were assessed at baseline and at 6 and 12 months. The results were compared with a healthy control group. 22/42 patients completed the 12‐month follow‐up. At baseline, SCI patients showed a marked increase in bone markers (PINP and sCTx), remaining significantly increased at up to 6 months of follow‐up. Additionally, they presented significantly increased Dkk‐1 values throughout the study, whereas sclerostin values did not significantly change. BMD markedly decreased at the proximal femur (‐20.2 ± 5.4%, p &lt; 0.01), total body (‐5.7 ± 2.2%, p = 0.02) and lower extremities (‐13.1 ± 4.5%, p = 0.01) at 12 months. Consequently, 59% of patients developed densitometric osteoporosis at 12 months. Patients with higher Dkk‐1 values (&gt;58 pmol/L) at baseline showed higher sublesional BMD loss. In conclusion, this study shows that short‐term after SCI there is a marked increase in bone turnover and bone loss, the latter associated with an increase in Dkk‐1 serum levels. The persistence of increased levels of this Wnt antagonist throughout the study and their relationship with the magnitude of bone loss suggests a contributory role of this mediator in this process. © 2014 American Society for Bone and Mineral Research.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>25484108</pmid><doi>10.1002/jbmr.2423</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adolescent
Adult
Aged
Biomarkers - blood
Bone Morphogenetic Proteins - blood
Bone Resorption - blood
Bone Resorption - etiology
DKK‐1
Female
Follow-Up Studies
Genetic Markers
Humans
Intercellular Signaling Peptides and Proteins - blood
Male
Middle Aged
OSTEOPOROSIS
Prospective Studies
SCLEROSTIN
Spinal Cord Injuries - blood
Spinal Cord Injuries - complications
SPINAL CORD INJURY
WNT SIGNALING
Wnt Signaling Pathway
title Effect of Recent Spinal Cord Injury on Wnt Signaling Antagonists (Sclerostin and Dkk‐1) and Their Relationship With Bone Loss. A 12‐Month Prospective Study
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