Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate
Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN) on bone mineralization density distribution (BMDD), based o...
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| Format: | Article |
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Elsevier
2016-12-01
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| Series: | Bone Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352187216300109 |
| _version_ | 1811256189412966400 |
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| author | Barbara M. Misof Paul Roschger Charles Chen Maureen Pickarski Phaedra Messmer Klaus Klaushofer Le T. Duong |
| author_facet | Barbara M. Misof Paul Roschger Charles Chen Maureen Pickarski Phaedra Messmer Klaus Klaushofer Le T. Duong |
| author_sort | Barbara M. Misof |
| collection | DOAJ |
| description | Odanacatib (ODN) is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN) on bone mineralization density distribution (BMDD), based on quantitative backscattered electron imaging in relation to changes in histomorphometric mineralizing surface per bone surface (MS/BS) in 12–22 years old ovariectomized rhesus monkeys. Trabecular and cortical BMDD derived parameters from vertebrae and proximal tibiae were compared among vehicle (VEH, n = 8), odanacatib low dose (ODN-L, n = 8), odanacatib high dose (ODN-H, n = 8), and alendronate (ALN, n = 6) treated animals. Additionally, data from an intact, non-treated group of animals are shown (INT, n = 8). In trabecular bone from the vertebra and metaphyseal tibia, the BMDD of the ODN and ALN treatment groups was shifted toward higher mineralization densities (p < 0.001) consistent with the significant reduction of MS/BS (p < 0.05 in ODN-H and ALN) compared to VEH. Vertebral trabecular CaMean (average degree of mineralization) was significantly higher in ODN-L (+6.5%), ODN-H (+6.1%), and ALN (+6.7%, all p < 0.001). Tibial osteonal cortical bone revealed also significantly increased CaMean for ODN-L (+1.4%, p < 0.05), ODN-H (+2.2%, p < 0.05), and ALN (+3.4%, p < 0.001) versus VEH, while primary cortical bone (devoid of secondary osteons) did not show any significant differences between the study groups. The percentage of primary bone area in the tibial cross-sections (on average 45 ± 12%) was also not significantly different between the study groups (p = 0.232). No significant differences in any BMDD parameters of all studied skeletal sites between ODN and ALN treatment were found. Correlation analysis revealed that MS/BS was highly predictive for trabecular BMDD in vertebral bone. The higher MS/BS, the lower was CaMean. Our findings are consistent with the inhibition of bone resorption of ODN and ALN in trabecular and osteonal compartments. Keywords: Cathepsin K inhibitor, Odanacatib, Alendronate, Bone quality, Osteoporosis |
| first_indexed | 2024-04-12T17:36:20Z |
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| institution | Directory Open Access Journal |
| issn | 2352-1872 |
| language | English |
| last_indexed | 2024-04-12T17:36:20Z |
| publishDate | 2016-12-01 |
| publisher | Elsevier |
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| series | Bone Reports |
| spelling | doaj.art-00b5e204419c42a4b586d6915559e1d22022-12-22T03:22:58ZengElsevierBone Reports2352-18722016-12-0156269Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronateBarbara M. Misof0Paul Roschger1Charles Chen2Maureen Pickarski3Phaedra Messmer4Klaus Klaushofer5Le T. Duong6Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, Austria; Corresponding author at: Ludwig Boltzmann Institute of Osteology, UKH Meidling, Kundratstr. 37, A-1120 Vienna, Austria.Ludwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, AustriaMerck Research Laboratories, West Point, PA 19486, USAMerck Research Laboratories, West Point, PA 19486, USALudwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, AustriaLudwig Boltzmann Institute of Osteology at the Hanusch Hospital of WGKK and AUVA Trauma Centre Meidling, 1st Medical Department, Hanusch Hospital, Vienna, AustriaMerck Research Laboratories, West Point, PA 19486, USAOdanacatib (ODN) is a selective and reversible inhibitor of cathepsin K which is an important enzyme for the degradation of collagen I. Aim of the present work was the head-to-head comparison between the effects of ODN and alendronate (ALN) on bone mineralization density distribution (BMDD), based on quantitative backscattered electron imaging in relation to changes in histomorphometric mineralizing surface per bone surface (MS/BS) in 12–22 years old ovariectomized rhesus monkeys. Trabecular and cortical BMDD derived parameters from vertebrae and proximal tibiae were compared among vehicle (VEH, n = 8), odanacatib low dose (ODN-L, n = 8), odanacatib high dose (ODN-H, n = 8), and alendronate (ALN, n = 6) treated animals. Additionally, data from an intact, non-treated group of animals are shown (INT, n = 8). In trabecular bone from the vertebra and metaphyseal tibia, the BMDD of the ODN and ALN treatment groups was shifted toward higher mineralization densities (p < 0.001) consistent with the significant reduction of MS/BS (p < 0.05 in ODN-H and ALN) compared to VEH. Vertebral trabecular CaMean (average degree of mineralization) was significantly higher in ODN-L (+6.5%), ODN-H (+6.1%), and ALN (+6.7%, all p < 0.001). Tibial osteonal cortical bone revealed also significantly increased CaMean for ODN-L (+1.4%, p < 0.05), ODN-H (+2.2%, p < 0.05), and ALN (+3.4%, p < 0.001) versus VEH, while primary cortical bone (devoid of secondary osteons) did not show any significant differences between the study groups. The percentage of primary bone area in the tibial cross-sections (on average 45 ± 12%) was also not significantly different between the study groups (p = 0.232). No significant differences in any BMDD parameters of all studied skeletal sites between ODN and ALN treatment were found. Correlation analysis revealed that MS/BS was highly predictive for trabecular BMDD in vertebral bone. The higher MS/BS, the lower was CaMean. Our findings are consistent with the inhibition of bone resorption of ODN and ALN in trabecular and osteonal compartments. Keywords: Cathepsin K inhibitor, Odanacatib, Alendronate, Bone quality, Osteoporosishttp://www.sciencedirect.com/science/article/pii/S2352187216300109 |
| spellingShingle | Barbara M. Misof Paul Roschger Charles Chen Maureen Pickarski Phaedra Messmer Klaus Klaushofer Le T. Duong Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate Bone Reports |
| title | Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate |
| title_full | Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate |
| title_fullStr | Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate |
| title_full_unstemmed | Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate |
| title_short | Effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate |
| title_sort | effects of odanacatib on bone matrix mineralization in rhesus monkeys are similar to those of alendronate |
| url | http://www.sciencedirect.com/science/article/pii/S2352187216300109 |
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