Bone Resorption in Multiple Myeloma and in Monoclonal Gammopathy of Undetermined Significance: Quantification by Urinary Pyridinium Cross-Links of Collagen
To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patie...
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| Veröffentlicht in: | Blood 1997-11, Vol.90 (9), p.3743-3750 |
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| creator | Pecherstorfer, Martin Seibel, Markus J. Woitge, Henning W. Horn, Eva Schuster, Judith Neuda, Jane Sagaster, Peter Köhn, Horst Bayer, Peter Thiébaud, Daniel Ludwig, Heinz |
| description | To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low ( |
| doi_str_mv | 10.1182/blood.V90.9.3743 |
| format | Article |
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Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low (<50%), but it was between 78% (h-DPD) and 93% (i-DPD) in stage III MM. Specificity in patients with MGUS was between 87% (h-PYD) and 97% (h-DPD). In conclusion, determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for evaluating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of i-DPD levels may contribute importantly to clinical guidance, since increased i-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DPD levels did not change in parallel but instead diverged strongly after chemotherapy might explain the observation that bone lesions sometimes progress even in patients who achieve complete remission.</description><identifier>ISSN: 0006-4971</identifier><identifier>EISSN: 1528-0020</identifier><identifier>DOI: 10.1182/blood.V90.9.3743</identifier><identifier>PMID: 9345061</identifier><language>eng</language><publisher>Washington, DC: Elsevier Inc</publisher><subject>Adult ; Aged ; Aged, 80 and over ; Biological and medical sciences ; Biomarkers ; Bone Resorption - urine ; Collagen - urine ; Cross-Linking Reagents ; Female ; Humans ; Immunodeficiencies. Immunoglobulinopathies ; Immunoglobulinopathies ; Immunopathology ; Male ; Medical sciences ; Middle Aged ; Multiple Myeloma - physiopathology ; Multiple Myeloma - urine ; Paraproteinemias - physiopathology ; Paraproteinemias - urine ; Pyridinium Compounds - urine</subject><ispartof>Blood, 1997-11, Vol.90 (9), p.3743-3750</ispartof><rights>1997 American Society of Hematology</rights><rights>1998 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c482t-6d064985ad3a3a2040750de6d6b9bb2ad6e717dd6a04cae338d4b5478fc223013</citedby><cites>FETCH-LOGICAL-c482t-6d064985ad3a3a2040750de6d6b9bb2ad6e717dd6a04cae338d4b5478fc223013</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=2054002$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9345061$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pecherstorfer, Martin</creatorcontrib><creatorcontrib>Seibel, Markus J.</creatorcontrib><creatorcontrib>Woitge, Henning W.</creatorcontrib><creatorcontrib>Horn, Eva</creatorcontrib><creatorcontrib>Schuster, Judith</creatorcontrib><creatorcontrib>Neuda, Jane</creatorcontrib><creatorcontrib>Sagaster, Peter</creatorcontrib><creatorcontrib>Köhn, Horst</creatorcontrib><creatorcontrib>Bayer, Peter</creatorcontrib><creatorcontrib>Thiébaud, Daniel</creatorcontrib><creatorcontrib>Ludwig, Heinz</creatorcontrib><title>Bone Resorption in Multiple Myeloma and in Monoclonal Gammopathy of Undetermined Significance: Quantification by Urinary Pyridinium Cross-Links of Collagen</title><title>Blood</title><addtitle>Blood</addtitle><description>To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low (<50%), but it was between 78% (h-DPD) and 93% (i-DPD) in stage III MM. Specificity in patients with MGUS was between 87% (h-PYD) and 97% (h-DPD). In conclusion, determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for evaluating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of i-DPD levels may contribute importantly to clinical guidance, since increased i-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DPD levels did not change in parallel but instead diverged strongly after chemotherapy might explain the observation that bone lesions sometimes progress even in patients who achieve complete remission.</description><subject>Adult</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Biological and medical sciences</subject><subject>Biomarkers</subject><subject>Bone Resorption - urine</subject><subject>Collagen - urine</subject><subject>Cross-Linking Reagents</subject><subject>Female</subject><subject>Humans</subject><subject>Immunodeficiencies. Immunoglobulinopathies</subject><subject>Immunoglobulinopathies</subject><subject>Immunopathology</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>Multiple Myeloma - physiopathology</subject><subject>Multiple Myeloma - urine</subject><subject>Paraproteinemias - physiopathology</subject><subject>Paraproteinemias - urine</subject><subject>Pyridinium Compounds - urine</subject><issn>0006-4971</issn><issn>1528-0020</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1997</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kUlvFDEQhS0ECpOBOxckHxC3Hrz1lhsZkYA0Eetwtdx2dTC47cbuRurfwp_Fsyg3LrZc9eqp_D6EXlCyobRhbzoXgtl8b8mm3fBa8EdoRUvWFIQw8hitCCFVIdqaPkWXKf0khArOygt00XJRkoqu0N_r4AF_gRTiONngsfX4bnaTHR3guwVcGBRW3hzrwQftglcO36phCKOafiw49HjvDUwQB-vB4K_23tveauU1XOHPs_LT8Xl07xa8j9aruOBPS7TGejsPeBtDSsXO-l_pYLcNzql78M_Qk165BM_P9xrtb959274vdh9vP2zf7gotGjYVlSGVaJtSGa64YkSQuiQGKlN1bdcxZSqoaW1MpYjQCjhvjOhKUTe9ZowTytfo9cl3jOH3DGmSg00a8hIewpxk3fKKtflcI3IS6sPCEXo5Rjvkz0hK5IGHPPKQmYds5YFHHnl59p67AczDwBlA7r8691XSyvUxx2bTg4yRUmSWWXZ1kkHO4Y-FKJO2kBM2NoKepAn2_zv8Az-Uq1g</recordid><startdate>19971101</startdate><enddate>19971101</enddate><creator>Pecherstorfer, Martin</creator><creator>Seibel, Markus J.</creator><creator>Woitge, Henning W.</creator><creator>Horn, Eva</creator><creator>Schuster, Judith</creator><creator>Neuda, Jane</creator><creator>Sagaster, Peter</creator><creator>Köhn, Horst</creator><creator>Bayer, Peter</creator><creator>Thiébaud, Daniel</creator><creator>Ludwig, Heinz</creator><general>Elsevier Inc</general><general>The Americain Society of Hematology</general><scope>6I.</scope><scope>AAFTH</scope><scope>IQODW</scope><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>7X8</scope></search><sort><creationdate>19971101</creationdate><title>Bone Resorption in Multiple Myeloma and in Monoclonal Gammopathy of Undetermined Significance: Quantification by Urinary Pyridinium Cross-Links of Collagen</title><author>Pecherstorfer, Martin ; Seibel, Markus J. ; Woitge, Henning W. ; Horn, Eva ; Schuster, Judith ; Neuda, Jane ; Sagaster, Peter ; Köhn, Horst ; Bayer, Peter ; Thiébaud, Daniel ; Ludwig, Heinz</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c482t-6d064985ad3a3a2040750de6d6b9bb2ad6e717dd6a04cae338d4b5478fc223013</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1997</creationdate><topic>Adult</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Biological and medical sciences</topic><topic>Biomarkers</topic><topic>Bone Resorption - urine</topic><topic>Collagen - urine</topic><topic>Cross-Linking Reagents</topic><topic>Female</topic><topic>Humans</topic><topic>Immunodeficiencies. Immunoglobulinopathies</topic><topic>Immunoglobulinopathies</topic><topic>Immunopathology</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>Multiple Myeloma - physiopathology</topic><topic>Multiple Myeloma - urine</topic><topic>Paraproteinemias - physiopathology</topic><topic>Paraproteinemias - urine</topic><topic>Pyridinium Compounds - urine</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pecherstorfer, Martin</creatorcontrib><creatorcontrib>Seibel, Markus J.</creatorcontrib><creatorcontrib>Woitge, Henning W.</creatorcontrib><creatorcontrib>Horn, Eva</creatorcontrib><creatorcontrib>Schuster, Judith</creatorcontrib><creatorcontrib>Neuda, Jane</creatorcontrib><creatorcontrib>Sagaster, Peter</creatorcontrib><creatorcontrib>Köhn, Horst</creatorcontrib><creatorcontrib>Bayer, Peter</creatorcontrib><creatorcontrib>Thiébaud, Daniel</creatorcontrib><creatorcontrib>Ludwig, Heinz</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Blood</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pecherstorfer, Martin</au><au>Seibel, Markus J.</au><au>Woitge, Henning W.</au><au>Horn, Eva</au><au>Schuster, Judith</au><au>Neuda, Jane</au><au>Sagaster, Peter</au><au>Köhn, Horst</au><au>Bayer, Peter</au><au>Thiébaud, Daniel</au><au>Ludwig, Heinz</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Resorption in Multiple Myeloma and in Monoclonal Gammopathy of Undetermined Significance: Quantification by Urinary Pyridinium Cross-Links of Collagen</atitle><jtitle>Blood</jtitle><addtitle>Blood</addtitle><date>1997-11-01</date><risdate>1997</risdate><volume>90</volume><issue>9</issue><spage>3743</spage><epage>3750</epage><pages>3743-3750</pages><issn>0006-4971</issn><eissn>1528-0020</eissn><abstract>To quantify osseous breakdown in multiple myeloma (MM), monoclonal gammopathy of undetermined significance (MGUS), and benign osteoporosis, we measured urinary levels of pyridinium cross-links of collagen in 50 patients with newly diagnosed and untreated MM, 40 patients with MGUS, 40 untreated patients with osteoporotic vertebral fractures, and 64 healthy adults. Ion-paired, reverse-phase high-performance liquid chromatography (HPLC) was used to measure total urinary excretion of pyridinoline (h-PYD) and deoxypyridinoline (h-DPD). Urinary excretion of free immunoreactive deoxypyridinoline (i-DPD) was determined with an enzyme immunoassay. MM patients had significantly (P < .0001) higher levels of h-PYD, h-DPD, and i-DPD than the healthy adults, patients with MGUS, or patients with osteoporosis. The MGUS and osteoporosis groups presented with elevated (P < .05) levels of urinary pyridinium cross-links when compared with healthy controls. In 20 MM patients who subsequently received chemotherapy, the percent changes in i-DPD did not correlate with the changes in the monoclonal protein. In one of three patients experiencing a transition of initial MGUS into stage I MM, i-DPD increased above the upper limit of the normal range. In 13 patients with stable MGUS, i-DPD remained normal in repeated measurements. Based on the upper limits of the normal range, the sensitivity of urinary pyridinium cross-links in stage I and II MM was low (<50%), but it was between 78% (h-DPD) and 93% (i-DPD) in stage III MM. Specificity in patients with MGUS was between 87% (h-PYD) and 97% (h-DPD). In conclusion, determining the urinary excretion of pyridinium cross-links seems to be a promising noninvasive and thus easily repeatable method for evaluating the actual degree of osseous breakdown. Although measurement of pyridinium cross-link levels is not useful in discriminating patients with MGUS from early-stage myeloma patients, determination of i-DPD levels may contribute importantly to clinical guidance, since increased i-DPD levels seem to identify patients who are particularly likely to benefit from osteoclast-inhibiting drugs such as bisphosphonates. The fact that in a number of patients paraprotein concentrations and i-DPD levels did not change in parallel but instead diverged strongly after chemotherapy might explain the observation that bone lesions sometimes progress even in patients who achieve complete remission.</abstract><cop>Washington, DC</cop><pub>Elsevier Inc</pub><pmid>9345061</pmid><doi>10.1182/blood.V90.9.3743</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection |
| subjects | Adult Aged Aged, 80 and over Biological and medical sciences Biomarkers Bone Resorption - urine Collagen - urine Cross-Linking Reagents Female Humans Immunodeficiencies. Immunoglobulinopathies Immunoglobulinopathies Immunopathology Male Medical sciences Middle Aged Multiple Myeloma - physiopathology Multiple Myeloma - urine Paraproteinemias - physiopathology Paraproteinemias - urine Pyridinium Compounds - urine |
| title | Bone Resorption in Multiple Myeloma and in Monoclonal Gammopathy of Undetermined Significance: Quantification by Urinary Pyridinium Cross-Links of Collagen |
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