Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate
The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects o...
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| Veröffentlicht in: | Journal of bone and mineral research 2010-08, Vol.25 (8), p.1886-1894 |
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| creator | Seeman, Ego Delmas, Pierre D Hanley, David A Sellmeyer, Deborah Cheung, Angela M Shane, Elizabeth Kearns, Ann Thomas, Thierry Boyd, Steven K Boutroy, Stephanie Bogado, Cesar Majumdar, Sharmila Fan, Michelle Libanati, Cesar Zanchetta, Jose |
| description | The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double‐blind pilot study, 247 postmenopausal women were randomized to denosumab (60 mg subcutaneous 6 monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C‐telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to |
| doi_str_mv | 10.1002/jbmr.81 |
| format | Article |
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Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double‐blind pilot study, 247 postmenopausal women were randomized to denosumab (60 mg subcutaneous 6 monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C‐telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to <.001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. © 2010 American Society for Bone and Mineral Research</description><identifier>ISSN: 0884-0431</identifier><identifier>EISSN: 1523-4681</identifier><identifier>DOI: 10.1002/jbmr.81</identifier><identifier>PMID: 20222106</identifier><identifier>CODEN: JBMREJ</identifier><language>eng</language><publisher>Hoboken: Wiley Subscription Services, Inc., A Wiley Company</publisher><subject>Aged ; alendronate ; Alendronate - administration & dosage ; Alendronate - adverse effects ; Alendronate - pharmacology ; Antibodies, Monoclonal - administration & dosage ; Antibodies, Monoclonal - adverse effects ; Antibodies, Monoclonal - pharmacology ; Antibodies, Monoclonal, Humanized ; Biological and medical sciences ; Biomarkers - metabolism ; Bone and Bones - diagnostic imaging ; Bone and Bones - drug effects ; Bone and Bones - pathology ; Bone Density - drug effects ; Bone Density Conservation Agents - administration & dosage ; Bone Density Conservation Agents - adverse effects ; Bone Density Conservation Agents - pharmacology ; Bone Remodeling - drug effects ; cortical thickness ; Demography ; Denosumab ; Female ; Fundamental and applied biological sciences. Psychology ; HR‐pQCT ; Humans ; Middle Aged ; Original ; RANK Ligand - administration & dosage ; RANK Ligand - adverse effects ; RANK Ligand - pharmacology ; Skeleton and joints ; Tomography, X-Ray Computed ; Vertebrates: osteoarticular system, musculoskeletal system ; volumetric bone mineral density</subject><ispartof>Journal of bone and mineral research, 2010-08, Vol.25 (8), p.1886-1894</ispartof><rights>Copyright © 2010 American Society for Bone and Mineral Research</rights><rights>2015 INIST-CNRS</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5321-4aaee2f17c71b961310323c4bedca9c8aa556b0028fa2bae7baf4b653221730a3</citedby><cites>FETCH-LOGICAL-c5321-4aaee2f17c71b961310323c4bedca9c8aa556b0028fa2bae7baf4b653221730a3</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.81$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fjbmr.81$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>230,314,776,780,881,1411,27901,27902,45550,45551</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23212029$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20222106$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Seeman, Ego</creatorcontrib><creatorcontrib>Delmas, Pierre D</creatorcontrib><creatorcontrib>Hanley, David A</creatorcontrib><creatorcontrib>Sellmeyer, Deborah</creatorcontrib><creatorcontrib>Cheung, Angela M</creatorcontrib><creatorcontrib>Shane, Elizabeth</creatorcontrib><creatorcontrib>Kearns, Ann</creatorcontrib><creatorcontrib>Thomas, Thierry</creatorcontrib><creatorcontrib>Boyd, Steven K</creatorcontrib><creatorcontrib>Boutroy, Stephanie</creatorcontrib><creatorcontrib>Bogado, Cesar</creatorcontrib><creatorcontrib>Majumdar, Sharmila</creatorcontrib><creatorcontrib>Fan, Michelle</creatorcontrib><creatorcontrib>Libanati, Cesar</creatorcontrib><creatorcontrib>Zanchetta, Jose</creatorcontrib><title>Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate</title><title>Journal of bone and mineral research</title><addtitle>J Bone Miner Res</addtitle><description>The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double‐blind pilot study, 247 postmenopausal women were randomized to denosumab (60 mg subcutaneous 6 monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C‐telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to <.001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. © 2010 American Society for Bone and Mineral Research</description><subject>Aged</subject><subject>alendronate</subject><subject>Alendronate - administration & dosage</subject><subject>Alendronate - adverse effects</subject><subject>Alendronate - pharmacology</subject><subject>Antibodies, Monoclonal - administration & dosage</subject><subject>Antibodies, Monoclonal - adverse effects</subject><subject>Antibodies, Monoclonal - pharmacology</subject><subject>Antibodies, Monoclonal, Humanized</subject><subject>Biological and medical sciences</subject><subject>Biomarkers - metabolism</subject><subject>Bone and Bones - diagnostic imaging</subject><subject>Bone and Bones - drug effects</subject><subject>Bone and Bones - pathology</subject><subject>Bone Density - drug effects</subject><subject>Bone Density Conservation Agents - administration & dosage</subject><subject>Bone Density Conservation Agents - adverse effects</subject><subject>Bone Density Conservation Agents - pharmacology</subject><subject>Bone Remodeling - drug effects</subject><subject>cortical thickness</subject><subject>Demography</subject><subject>Denosumab</subject><subject>Female</subject><subject>Fundamental and applied biological sciences. Psychology</subject><subject>HR‐pQCT</subject><subject>Humans</subject><subject>Middle Aged</subject><subject>Original</subject><subject>RANK Ligand - administration & dosage</subject><subject>RANK Ligand - adverse effects</subject><subject>RANK Ligand - pharmacology</subject><subject>Skeleton and joints</subject><subject>Tomography, X-Ray Computed</subject><subject>Vertebrates: osteoarticular system, musculoskeletal system</subject><subject>volumetric bone mineral density</subject><issn>0884-0431</issn><issn>1523-4681</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp1kU1rFTEUhoMo9lrFfyCzkS5kapLJfFwXgq1alRZBdB1OMidtykxym2SU_nvPtbetLlwlcJ73fc8HY88FPxScy9eXZk6Hg3jAVqKVTa26QTxkKz4MquaqEXvsSc6XnPOu7brHbE9yKaXg3YptzrxNEZK98AVtWRJM1YgFk48Jio-hiq6yMRVvqQJhrEoCg3aZIFUmBnxTvffOER_OK6SPLXkrGTHEvMxg_mhgwjCmGKDgU_bIwZTx2e7dZz8-fvh-_Kk-_Xry-fjdaW3bRopaASBKJ3rbC7PuRCN4IxurDI4W1nYAaNvO0OiDA2kAewNOmY60UvQNh2afvb3x3SxmJhEGanzSm-RnSNc6gtf_VoK_0Ofxp1ZKtb2UZHCwM0jxasFc9OyzxWmCgHHJum9boTh1cU_SJnNO6O5SBNfb8-jtefQgiHzxd1N33O09CHi5AyDTwl2CYH2-52g1xK6Je3XD_fITXv8vT385OvtGsb8B_guplA</recordid><startdate>201008</startdate><enddate>201008</enddate><creator>Seeman, Ego</creator><creator>Delmas, Pierre D</creator><creator>Hanley, David A</creator><creator>Sellmeyer, Deborah</creator><creator>Cheung, Angela M</creator><creator>Shane, Elizabeth</creator><creator>Kearns, Ann</creator><creator>Thomas, Thierry</creator><creator>Boyd, Steven K</creator><creator>Boutroy, Stephanie</creator><creator>Bogado, Cesar</creator><creator>Majumdar, Sharmila</creator><creator>Fan, Michelle</creator><creator>Libanati, Cesar</creator><creator>Zanchetta, Jose</creator><general>Wiley Subscription Services, Inc., A Wiley Company</general><general>Wiley</general><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>7QP</scope><scope>5PM</scope></search><sort><creationdate>201008</creationdate><title>Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate</title><author>Seeman, Ego ; Delmas, Pierre D ; Hanley, David A ; Sellmeyer, Deborah ; Cheung, Angela M ; Shane, Elizabeth ; Kearns, Ann ; Thomas, Thierry ; Boyd, Steven K ; Boutroy, Stephanie ; Bogado, Cesar ; Majumdar, Sharmila ; Fan, Michelle ; Libanati, Cesar ; Zanchetta, Jose</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5321-4aaee2f17c71b961310323c4bedca9c8aa556b0028fa2bae7baf4b653221730a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Aged</topic><topic>alendronate</topic><topic>Alendronate - administration & dosage</topic><topic>Alendronate - adverse effects</topic><topic>Alendronate - pharmacology</topic><topic>Antibodies, Monoclonal - administration & dosage</topic><topic>Antibodies, Monoclonal - adverse effects</topic><topic>Antibodies, Monoclonal - pharmacology</topic><topic>Antibodies, Monoclonal, Humanized</topic><topic>Biological and medical sciences</topic><topic>Biomarkers - metabolism</topic><topic>Bone and Bones - diagnostic imaging</topic><topic>Bone and Bones - drug effects</topic><topic>Bone and Bones - pathology</topic><topic>Bone Density - drug effects</topic><topic>Bone Density Conservation Agents - administration & dosage</topic><topic>Bone Density Conservation Agents - adverse effects</topic><topic>Bone Density Conservation Agents - pharmacology</topic><topic>Bone Remodeling - drug effects</topic><topic>cortical thickness</topic><topic>Demography</topic><topic>Denosumab</topic><topic>Female</topic><topic>Fundamental and applied biological sciences. Psychology</topic><topic>HR‐pQCT</topic><topic>Humans</topic><topic>Middle Aged</topic><topic>Original</topic><topic>RANK Ligand - administration & dosage</topic><topic>RANK Ligand - adverse effects</topic><topic>RANK Ligand - pharmacology</topic><topic>Skeleton and joints</topic><topic>Tomography, X-Ray Computed</topic><topic>Vertebrates: osteoarticular system, musculoskeletal system</topic><topic>volumetric bone mineral density</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Seeman, Ego</creatorcontrib><creatorcontrib>Delmas, Pierre D</creatorcontrib><creatorcontrib>Hanley, David A</creatorcontrib><creatorcontrib>Sellmeyer, Deborah</creatorcontrib><creatorcontrib>Cheung, Angela M</creatorcontrib><creatorcontrib>Shane, Elizabeth</creatorcontrib><creatorcontrib>Kearns, Ann</creatorcontrib><creatorcontrib>Thomas, Thierry</creatorcontrib><creatorcontrib>Boyd, Steven K</creatorcontrib><creatorcontrib>Boutroy, Stephanie</creatorcontrib><creatorcontrib>Bogado, Cesar</creatorcontrib><creatorcontrib>Majumdar, Sharmila</creatorcontrib><creatorcontrib>Fan, Michelle</creatorcontrib><creatorcontrib>Libanati, Cesar</creatorcontrib><creatorcontrib>Zanchetta, Jose</creatorcontrib><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>Calcium & Calcified Tissue Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of bone and mineral research</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Seeman, Ego</au><au>Delmas, Pierre D</au><au>Hanley, David A</au><au>Sellmeyer, Deborah</au><au>Cheung, Angela M</au><au>Shane, Elizabeth</au><au>Kearns, Ann</au><au>Thomas, Thierry</au><au>Boyd, Steven K</au><au>Boutroy, Stephanie</au><au>Bogado, Cesar</au><au>Majumdar, Sharmila</au><au>Fan, Michelle</au><au>Libanati, Cesar</au><au>Zanchetta, Jose</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate</atitle><jtitle>Journal of bone and mineral research</jtitle><addtitle>J Bone Miner Res</addtitle><date>2010-08</date><risdate>2010</risdate><volume>25</volume><issue>8</issue><spage>1886</spage><epage>1894</epage><pages>1886-1894</pages><issn>0884-0431</issn><eissn>1523-4681</eissn><coden>JBMREJ</coden><abstract>The intensity of bone remodeling is a critical determinant of the decay of cortical and trabecular microstructure after menopause. Denosumab suppresses remodeling more than alendronate, leading to greater gains in areal bone mineral density (aBMD). These greater gains may reflect differing effects of each drug on bone microarchitecture and strength. In a phase 2 double‐blind pilot study, 247 postmenopausal women were randomized to denosumab (60 mg subcutaneous 6 monthly), alendronate (70 mg oral weekly), or placebo for 12 months. All received daily calcium and vitamin D. Morphologic changes were assessed using high‐resolution peripheral quantitative computed tomography (HR‐pQCT) at the distal radius and distal tibia and QCT at the distal radius. Denosumab decreased serum C‐telopeptide more rapidly and markedly than alendronate. In the placebo arm, total, cortical, and trabecular BMD and cortical thickness decreased (−2.1% to −0.8%) at the distal radius after 12 months. Alendronate prevented the decline (−0.6% to 2.4%, p = .051 to <.001 versus placebo), whereas denosumab prevented the decline or improved these variables (0.3% to 3.4%, p < .001 versus placebo). Changes in total and cortical BMD were greater with denosumab than with alendronate (p ≤ .024). Similar changes in these parameters were observed at the tibia. The polar moment of inertia also increased more in the denosumab than alendronate or placebo groups (p < .001). Adverse events did not differ by group. These data suggest that structural decay owing to bone remodeling and progression of bone fragility may be prevented more effectively with denosumab. © 2010 American Society for Bone and Mineral Research</abstract><cop>Hoboken</cop><pub>Wiley Subscription Services, Inc., A Wiley Company</pub><pmid>20222106</pmid><doi>10.1002/jbmr.81</doi><tpages>9</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Journal of bone and mineral research, 2010-08, Vol.25 (8), p.1886-1894 |
| issn | 0884-0431 1523-4681 |
| language | eng |
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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; Alma/SFX Local Collection |
| subjects | Aged alendronate Alendronate - administration & dosage Alendronate - adverse effects Alendronate - pharmacology Antibodies, Monoclonal - administration & dosage Antibodies, Monoclonal - adverse effects Antibodies, Monoclonal - pharmacology Antibodies, Monoclonal, Humanized Biological and medical sciences Biomarkers - metabolism Bone and Bones - diagnostic imaging Bone and Bones - drug effects Bone and Bones - pathology Bone Density - drug effects Bone Density Conservation Agents - administration & dosage Bone Density Conservation Agents - adverse effects Bone Density Conservation Agents - pharmacology Bone Remodeling - drug effects cortical thickness Demography Denosumab Female Fundamental and applied biological sciences. Psychology HR‐pQCT Humans Middle Aged Original RANK Ligand - administration & dosage RANK Ligand - adverse effects RANK Ligand - pharmacology Skeleton and joints Tomography, X-Ray Computed Vertebrates: osteoarticular system, musculoskeletal system volumetric bone mineral density |
| title | Microarchitectural deterioration of cortical and trabecular bone: Differing effects of denosumab and alendronate |
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