Abnormally High and Heterogeneous Bone Matrix Mineralization After Childhood Solid Organ Transplantation: A Complex Pathology of Low Bone Turnover and Local Defects in Mineralization
ABSTRACT Chronic renal, liver, and heart failure in children associates with multiple skeletal complications. Increased fracture incidence often persists after transplantation and could be related to alterations in bone material properties. In the present cohort study we evaluated bone mineralizatio...
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| Veröffentlicht in: | Journal of bone and mineral research 2017-05, Vol.32 (5), p.1116-1125 |
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| creator | Fratzl‐Zelman, Nadja Valta, Helena Pereira, Renata C Misof, Barbara M Roschger, Paul Jalanko, Hannu Wesseling‐Perry, Katherine Klaushofer, Klaus Mäkitie, Outi |
| description | ABSTRACT
Chronic renal, liver, and heart failure in children associates with multiple skeletal complications. Increased fracture incidence often persists after transplantation and could be related to alterations in bone material properties. In the present cohort study we evaluated bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) in 23 pediatric solid organ allograft recipients with suspected osteoporosis. We measured BMDD in the entire cross‐sectional area of transiliac bone biopsies obtained from kidney (n = 9), liver (n = 9), and heart (n = 5) transplant recipients (aged 7.6 to 19.7 years; 6.0 ± 5.6 years posttransplantation, patients with a history of clinical fractures: n = 14). The BMDD findings were compared with age‐appropriate references and with a previously presented cohort of children with chronic kidney disease on dialysis (CKD5D, n = 18). Furthermore, we related the BMDD parameters with patients’ clinical and bone histomorphometric outcomes. Compared to healthy children, qBEI results for cancellous and cortical bone in transplant recipients revealed an increase in the most frequently occurring calcium concentration (+2.9%, p = 0.001; +3.5%, p = 0.014), in the portion of fully mineralized bone (fivefold; 10‐fold, both p |
| doi_str_mv | 10.1002/jbmr.3087 |
| format | Article |
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Chronic renal, liver, and heart failure in children associates with multiple skeletal complications. Increased fracture incidence often persists after transplantation and could be related to alterations in bone material properties. In the present cohort study we evaluated bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) in 23 pediatric solid organ allograft recipients with suspected osteoporosis. We measured BMDD in the entire cross‐sectional area of transiliac bone biopsies obtained from kidney (n = 9), liver (n = 9), and heart (n = 5) transplant recipients (aged 7.6 to 19.7 years; 6.0 ± 5.6 years posttransplantation, patients with a history of clinical fractures: n = 14). The BMDD findings were compared with age‐appropriate references and with a previously presented cohort of children with chronic kidney disease on dialysis (CKD5D, n = 18). Furthermore, we related the BMDD parameters with patients’ clinical and bone histomorphometric outcomes. Compared to healthy children, qBEI results for cancellous and cortical bone in transplant recipients revealed an increase in the most frequently occurring calcium concentration (+2.9%, p = 0.001; +3.5%, p = 0.014), in the portion of fully mineralized bone (fivefold; 10‐fold, both p < 0.0001) and in heterogeneity of mineralization (+26,5% and +27.8%, both p < 0.0001), respectively. Moreover, the BMDD parameters were nonsignificantly distinct from CKD5D cohort except that the heterogeneity in mineralization was higher posttransplantation. There was a strong inverse correlation between the average calcium content of the bone matrix and patients’ biochemical ALP levels, histomorphometric indices of bone formation and resorption. The abnormally high bone matrix mineralization in transplant recipients, consistent with serum and histomorphometric outcomes, suggests a history of low bone turnover with accumulation of fully mineralized bone packets. Additionally, the increased heterogeneity of mineralization suggests local alterations in mineralization kinetics, which may be linked to dysfunctional osteocytes that were recently shown to accumulate within the bone matrix during organ failure and concomitant glucocorticoid and immunosuppressive medication. © 2017 American Society for Bone and Mineral Research.</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.3087</identifier><identifier>PMID: 28214296</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Adolescent ; Adult ; Age ; Age Factors ; Allografts ; BMDD ; Bone density ; Bone Density - drug effects ; Bone growth ; Bone imaging ; Bone matrix ; BONE MINERALIZATION DENSITY DISTRIBUTION ; Bone Remodeling - drug effects ; Bone resorption ; Bone turnover ; Calcium ; Cancellous bone ; Child ; Child, Preschool ; Childhood ; CHILDREN ; Cortical bone ; Dialysis ; Female ; Finland ; Fractures ; Glucocorticoids ; Glucocorticoids - administration & dosage ; Glucocorticoids - adverse effects ; Heart diseases ; Heart transplantation ; Humans ; Immunosuppression ; Immunosuppressive Agents - administration & dosage ; Immunosuppressive Agents - adverse effects ; Infant ; Kidney transplantation ; Liver diseases ; Male ; Mineralization ; Organ Transplantation ; Osteocytes ; Osteogenesis ; Osteoporosis ; QBEI ; QUANTITATIVE BACKSCATTERED ELECTRON IMAGING ; Renal failure ; SOLID ORGAN TRANSPLANTATION ; TRANSILIAC BONE BIOPSIES ; Transplantation ; Transplants & implants</subject><ispartof>Journal of bone and mineral research, 2017-05, Vol.32 (5), p.1116-1125</ispartof><rights>2017 American Society for Bone and Mineral Research</rights><rights>2017 American Society for Bone and Mineral Research.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4267-13ecee459bf637e8ce30a950ed2b45e56cb501202643d67fe2358a062c14ade3</citedby><cites>FETCH-LOGICAL-c4267-13ecee459bf637e8ce30a950ed2b45e56cb501202643d67fe2358a062c14ade3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fjbmr.3087$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.3087$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/28214296$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttp://kipublications.ki.se/Default.aspx?queryparsed=id:135769449$$DView record from Swedish Publication Index$$Hfree_for_read</backlink></links><search><creatorcontrib>Fratzl‐Zelman, Nadja</creatorcontrib><creatorcontrib>Valta, Helena</creatorcontrib><creatorcontrib>Pereira, Renata C</creatorcontrib><creatorcontrib>Misof, Barbara M</creatorcontrib><creatorcontrib>Roschger, Paul</creatorcontrib><creatorcontrib>Jalanko, Hannu</creatorcontrib><creatorcontrib>Wesseling‐Perry, Katherine</creatorcontrib><creatorcontrib>Klaushofer, Klaus</creatorcontrib><creatorcontrib>Mäkitie, Outi</creatorcontrib><title>Abnormally High and Heterogeneous Bone Matrix Mineralization After Childhood Solid Organ Transplantation: A Complex Pathology of Low Bone Turnover and Local Defects in Mineralization</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>ABSTRACT
Chronic renal, liver, and heart failure in children associates with multiple skeletal complications. Increased fracture incidence often persists after transplantation and could be related to alterations in bone material properties. In the present cohort study we evaluated bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) in 23 pediatric solid organ allograft recipients with suspected osteoporosis. We measured BMDD in the entire cross‐sectional area of transiliac bone biopsies obtained from kidney (n = 9), liver (n = 9), and heart (n = 5) transplant recipients (aged 7.6 to 19.7 years; 6.0 ± 5.6 years posttransplantation, patients with a history of clinical fractures: n = 14). The BMDD findings were compared with age‐appropriate references and with a previously presented cohort of children with chronic kidney disease on dialysis (CKD5D, n = 18). Furthermore, we related the BMDD parameters with patients’ clinical and bone histomorphometric outcomes. Compared to healthy children, qBEI results for cancellous and cortical bone in transplant recipients revealed an increase in the most frequently occurring calcium concentration (+2.9%, p = 0.001; +3.5%, p = 0.014), in the portion of fully mineralized bone (fivefold; 10‐fold, both p < 0.0001) and in heterogeneity of mineralization (+26,5% and +27.8%, both p < 0.0001), respectively. Moreover, the BMDD parameters were nonsignificantly distinct from CKD5D cohort except that the heterogeneity in mineralization was higher posttransplantation. There was a strong inverse correlation between the average calcium content of the bone matrix and patients’ biochemical ALP levels, histomorphometric indices of bone formation and resorption. The abnormally high bone matrix mineralization in transplant recipients, consistent with serum and histomorphometric outcomes, suggests a history of low bone turnover with accumulation of fully mineralized bone packets. Additionally, the increased heterogeneity of mineralization suggests local alterations in mineralization kinetics, which may be linked to dysfunctional osteocytes that were recently shown to accumulate within the bone matrix during organ failure and concomitant glucocorticoid and immunosuppressive medication. © 2017 American Society for Bone and Mineral Research.</description><subject>Adolescent</subject><subject>Adult</subject><subject>Age</subject><subject>Age Factors</subject><subject>Allografts</subject><subject>BMDD</subject><subject>Bone density</subject><subject>Bone Density - drug effects</subject><subject>Bone growth</subject><subject>Bone imaging</subject><subject>Bone matrix</subject><subject>BONE MINERALIZATION DENSITY DISTRIBUTION</subject><subject>Bone Remodeling - drug effects</subject><subject>Bone resorption</subject><subject>Bone turnover</subject><subject>Calcium</subject><subject>Cancellous bone</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Childhood</subject><subject>CHILDREN</subject><subject>Cortical bone</subject><subject>Dialysis</subject><subject>Female</subject><subject>Finland</subject><subject>Fractures</subject><subject>Glucocorticoids</subject><subject>Glucocorticoids - administration & dosage</subject><subject>Glucocorticoids - adverse effects</subject><subject>Heart diseases</subject><subject>Heart transplantation</subject><subject>Humans</subject><subject>Immunosuppression</subject><subject>Immunosuppressive Agents - administration & dosage</subject><subject>Immunosuppressive Agents - adverse effects</subject><subject>Infant</subject><subject>Kidney transplantation</subject><subject>Liver diseases</subject><subject>Male</subject><subject>Mineralization</subject><subject>Organ Transplantation</subject><subject>Osteocytes</subject><subject>Osteogenesis</subject><subject>Osteoporosis</subject><subject>QBEI</subject><subject>QUANTITATIVE BACKSCATTERED ELECTRON IMAGING</subject><subject>Renal failure</subject><subject>SOLID ORGAN TRANSPLANTATION</subject><subject>TRANSILIAC BONE BIOPSIES</subject><subject>Transplantation</subject><subject>Transplants & implants</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2017</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp10U9v0zAYBnALgVg3OPAFkCUu7JDNdhIn4daVPwW1GoLeLSd507o4drATuvLB-Hw4S9lhEidH1k-P37wPQq8ouaKEsOt92bqrmOTZEzSjKYujhOf0KZqRPE8iksT0DJ17vyeE8JTz5-iM5YwmrOAz9GdeGutaqfURL9V2h6Wp8RJ6cHYLBuzg8Y01gNeyd-oOr5UBJ7X6LXtlDZ43AeLFTul6Z22Nv1utanzrttLgjZPGd1qa_t6-w3O8sG2n4Q5_lf3Oars9YtvglT1MT2wGZ-yvkDeOsLKV1Pg9NFD1Hivz6OUX6FkjtYeXp_MCbT5-2CyW0er20-fFfBVVCeNZRGOoAJK0KBseZ5BXEBNZpARqViYppLwqU0IZYTyJa541wOI0l4SziiayhvgCRVOsP0A3lKJzqpXuKKxU4nT1I3yBSIq8yEnwbyffOftzAN-LVvkKdNjCuEpBc14UPCtYFuibR3RvwwLCzwQVRkzH8oK6nFTlrPcOmocRKBFj92LsXozdB_v6lDiULdQP8l_ZAVxP4KA0HP-fJL7crL_dR_4Fqse8HA</recordid><startdate>201705</startdate><enddate>201705</enddate><creator>Fratzl‐Zelman, Nadja</creator><creator>Valta, Helena</creator><creator>Pereira, Renata C</creator><creator>Misof, Barbara M</creator><creator>Roschger, Paul</creator><creator>Jalanko, Hannu</creator><creator>Wesseling‐Perry, Katherine</creator><creator>Klaushofer, Klaus</creator><creator>Mäkitie, Outi</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TS</scope><scope>K9.</scope><scope>7X8</scope><scope>ADTPV</scope><scope>AOWAS</scope></search><sort><creationdate>201705</creationdate><title>Abnormally High and Heterogeneous Bone Matrix Mineralization After Childhood Solid Organ Transplantation: A Complex Pathology of Low Bone Turnover and Local Defects in Mineralization</title><author>Fratzl‐Zelman, Nadja ; Valta, Helena ; Pereira, Renata C ; Misof, Barbara M ; Roschger, Paul ; Jalanko, Hannu ; Wesseling‐Perry, Katherine ; Klaushofer, Klaus ; Mäkitie, Outi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4267-13ecee459bf637e8ce30a950ed2b45e56cb501202643d67fe2358a062c14ade3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2017</creationdate><topic>Adolescent</topic><topic>Adult</topic><topic>Age</topic><topic>Age Factors</topic><topic>Allografts</topic><topic>BMDD</topic><topic>Bone density</topic><topic>Bone Density - drug effects</topic><topic>Bone growth</topic><topic>Bone imaging</topic><topic>Bone matrix</topic><topic>BONE MINERALIZATION DENSITY DISTRIBUTION</topic><topic>Bone Remodeling - drug effects</topic><topic>Bone resorption</topic><topic>Bone turnover</topic><topic>Calcium</topic><topic>Cancellous bone</topic><topic>Child</topic><topic>Child, Preschool</topic><topic>Childhood</topic><topic>CHILDREN</topic><topic>Cortical bone</topic><topic>Dialysis</topic><topic>Female</topic><topic>Finland</topic><topic>Fractures</topic><topic>Glucocorticoids</topic><topic>Glucocorticoids - administration & dosage</topic><topic>Glucocorticoids - adverse effects</topic><topic>Heart diseases</topic><topic>Heart transplantation</topic><topic>Humans</topic><topic>Immunosuppression</topic><topic>Immunosuppressive Agents - administration & dosage</topic><topic>Immunosuppressive Agents - adverse effects</topic><topic>Infant</topic><topic>Kidney transplantation</topic><topic>Liver diseases</topic><topic>Male</topic><topic>Mineralization</topic><topic>Organ Transplantation</topic><topic>Osteocytes</topic><topic>Osteogenesis</topic><topic>Osteoporosis</topic><topic>QBEI</topic><topic>QUANTITATIVE BACKSCATTERED ELECTRON IMAGING</topic><topic>Renal failure</topic><topic>SOLID ORGAN TRANSPLANTATION</topic><topic>TRANSILIAC BONE BIOPSIES</topic><topic>Transplantation</topic><topic>Transplants & implants</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Fratzl‐Zelman, Nadja</creatorcontrib><creatorcontrib>Valta, Helena</creatorcontrib><creatorcontrib>Pereira, Renata C</creatorcontrib><creatorcontrib>Misof, Barbara M</creatorcontrib><creatorcontrib>Roschger, Paul</creatorcontrib><creatorcontrib>Jalanko, Hannu</creatorcontrib><creatorcontrib>Wesseling‐Perry, Katherine</creatorcontrib><creatorcontrib>Klaushofer, Klaus</creatorcontrib><creatorcontrib>Mäkitie, Outi</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Physical Education Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>SwePub</collection><collection>SwePub Articles</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fratzl‐Zelman, Nadja</au><au>Valta, Helena</au><au>Pereira, Renata C</au><au>Misof, Barbara M</au><au>Roschger, Paul</au><au>Jalanko, Hannu</au><au>Wesseling‐Perry, Katherine</au><au>Klaushofer, Klaus</au><au>Mäkitie, Outi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Abnormally High and Heterogeneous Bone Matrix Mineralization After Childhood Solid Organ Transplantation: A Complex Pathology of Low Bone Turnover and Local Defects in Mineralization</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2017-05</date><risdate>2017</risdate><volume>32</volume><issue>5</issue><spage>1116</spage><epage>1125</epage><pages>1116-1125</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><abstract>ABSTRACT
Chronic renal, liver, and heart failure in children associates with multiple skeletal complications. Increased fracture incidence often persists after transplantation and could be related to alterations in bone material properties. In the present cohort study we evaluated bone mineralization density distribution (BMDD) by quantitative backscattered electron imaging (qBEI) in 23 pediatric solid organ allograft recipients with suspected osteoporosis. We measured BMDD in the entire cross‐sectional area of transiliac bone biopsies obtained from kidney (n = 9), liver (n = 9), and heart (n = 5) transplant recipients (aged 7.6 to 19.7 years; 6.0 ± 5.6 years posttransplantation, patients with a history of clinical fractures: n = 14). The BMDD findings were compared with age‐appropriate references and with a previously presented cohort of children with chronic kidney disease on dialysis (CKD5D, n = 18). Furthermore, we related the BMDD parameters with patients’ clinical and bone histomorphometric outcomes. Compared to healthy children, qBEI results for cancellous and cortical bone in transplant recipients revealed an increase in the most frequently occurring calcium concentration (+2.9%, p = 0.001; +3.5%, p = 0.014), in the portion of fully mineralized bone (fivefold; 10‐fold, both p < 0.0001) and in heterogeneity of mineralization (+26,5% and +27.8%, both p < 0.0001), respectively. Moreover, the BMDD parameters were nonsignificantly distinct from CKD5D cohort except that the heterogeneity in mineralization was higher posttransplantation. There was a strong inverse correlation between the average calcium content of the bone matrix and patients’ biochemical ALP levels, histomorphometric indices of bone formation and resorption. The abnormally high bone matrix mineralization in transplant recipients, consistent with serum and histomorphometric outcomes, suggests a history of low bone turnover with accumulation of fully mineralized bone packets. Additionally, the increased heterogeneity of mineralization suggests local alterations in mineralization kinetics, which may be linked to dysfunctional osteocytes that were recently shown to accumulate within the bone matrix during organ failure and concomitant glucocorticoid and immunosuppressive medication. © 2017 American Society for Bone and Mineral Research.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>28214296</pmid><doi>10.1002/jbmr.3087</doi><tpages>10</tpages><oa>free_for_read</oa></addata></record> |
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| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Wiley Online Library Journals Frontfile Complete; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals |
| subjects | Adolescent Adult Age Age Factors Allografts BMDD Bone density Bone Density - drug effects Bone growth Bone imaging Bone matrix BONE MINERALIZATION DENSITY DISTRIBUTION Bone Remodeling - drug effects Bone resorption Bone turnover Calcium Cancellous bone Child Child, Preschool Childhood CHILDREN Cortical bone Dialysis Female Finland Fractures Glucocorticoids Glucocorticoids - administration & dosage Glucocorticoids - adverse effects Heart diseases Heart transplantation Humans Immunosuppression Immunosuppressive Agents - administration & dosage Immunosuppressive Agents - adverse effects Infant Kidney transplantation Liver diseases Male Mineralization Organ Transplantation Osteocytes Osteogenesis Osteoporosis QBEI QUANTITATIVE BACKSCATTERED ELECTRON IMAGING Renal failure SOLID ORGAN TRANSPLANTATION TRANSILIAC BONE BIOPSIES Transplantation Transplants & implants |
| title | Abnormally High and Heterogeneous Bone Matrix Mineralization After Childhood Solid Organ Transplantation: A Complex Pathology of Low Bone Turnover and Local Defects in Mineralization |
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