Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet
Tibolone is a synthetic steroid with tissue-specific estrogenic, progestogenic, and androgenic properties. The therapeutic effects of tibolone on bone mass and strength, bone metabolic markers, and indices of histomorphometry were investigated in ovariectomized (ovx) rats on a low (0.1%)-calcium die...
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| Veröffentlicht in: | Bone (New York, N.Y.) N.Y.), 1999-09, Vol.25 (3), p.311-319 |
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| creator | Yoshitake, K Yokota, K Kasugai, Y Kagawa, M Sukamoto, T Nakamura, T |
| description | Tibolone is a synthetic steroid with tissue-specific estrogenic, progestogenic, and androgenic properties. The therapeutic effects of tibolone on bone mass and strength, bone metabolic markers, and indices of histomorphometry were investigated in ovariectomized (ovx) rats on a low (0.1%)-calcium diet in comparison with 17α-ethynylestradiol (EE) or 1α-hydroxyvitamin D
3 [1α(OH)D
3]. Tibolone (0.1–3 mg/kg/day), EE (0.1 mg/kg/day), or 1α(OH)D
3 (0.5 μg/kg/day) was administered orally once a day for 16 weeks, starting 12 weeks after ovariectomy, when the bone mineral density (BMD) of lumbar vertebrae (L4–5) and femur (global, proximal, and distal regions) had already been decreased by the combination of ovariectomy and low dietary calcium. The BMD of the lumbar vertebrae and the femur were higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. The BMD of the mid-diaphysial regions of femur and tibia, which consist mainly of cortical bone, were decreased 28 weeks after ovariectomy in the ovx control group. The BMD of the mid-diaphysial femur was higher in the groups treated with 1α(OH)D
3, and the BMD of mid-diaphysial tibia was higher in the groups treated with tibolone or 1α(OH)D
3 than in the ovx control group. Like BMD, the compressive strength of the vertebral body of L2, corrected for the volume of each individual vertebra tested, was higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. Trabecular bone volume and trabecular number were reduced 12 and 28 weeks after ovariectomy but there was no change in trabecular thickness. These reduced indices were increased in the groups treated with tibolone, EE, or 1α(OH)D
3 when compared with the ovx control group. Tibolone or EE decreased serum levels of osteocalcin and bone alkaline phosphatase and urinary levels of deoxypyridinoline and pyridinoline compared with the ovx control group. Furthermore, tibolone or EE decreased the mineralizing surface and bone formation rate as well as the osteoclast surface and osteoclast numbers. 1α(OH)D
3, however, did not affect these serum and urinary parameters. These data suggest that tibolone suppresses the accelerated bone turnover induced by a combination of ovariectomy and low dietary calcium, and indicate that tibolone may be a potentially useful drug for the treatment of postmenopausal osteoporosis. |
| doi_str_mv | 10.1016/S8756-3282(99)00172-6 |
| format | Article |
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3 [1α(OH)D
3]. Tibolone (0.1–3 mg/kg/day), EE (0.1 mg/kg/day), or 1α(OH)D
3 (0.5 μg/kg/day) was administered orally once a day for 16 weeks, starting 12 weeks after ovariectomy, when the bone mineral density (BMD) of lumbar vertebrae (L4–5) and femur (global, proximal, and distal regions) had already been decreased by the combination of ovariectomy and low dietary calcium. The BMD of the lumbar vertebrae and the femur were higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. The BMD of the mid-diaphysial regions of femur and tibia, which consist mainly of cortical bone, were decreased 28 weeks after ovariectomy in the ovx control group. The BMD of the mid-diaphysial femur was higher in the groups treated with 1α(OH)D
3, and the BMD of mid-diaphysial tibia was higher in the groups treated with tibolone or 1α(OH)D
3 than in the ovx control group. Like BMD, the compressive strength of the vertebral body of L2, corrected for the volume of each individual vertebra tested, was higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. Trabecular bone volume and trabecular number were reduced 12 and 28 weeks after ovariectomy but there was no change in trabecular thickness. These reduced indices were increased in the groups treated with tibolone, EE, or 1α(OH)D
3 when compared with the ovx control group. Tibolone or EE decreased serum levels of osteocalcin and bone alkaline phosphatase and urinary levels of deoxypyridinoline and pyridinoline compared with the ovx control group. Furthermore, tibolone or EE decreased the mineralizing surface and bone formation rate as well as the osteoclast surface and osteoclast numbers. 1α(OH)D
3, however, did not affect these serum and urinary parameters. These data suggest that tibolone suppresses the accelerated bone turnover induced by a combination of ovariectomy and low dietary calcium, and indicate that tibolone may be a potentially useful drug for the treatment of postmenopausal osteoporosis.</description><identifier>ISSN: 8756-3282</identifier><identifier>EISSN: 1873-2763</identifier><identifier>DOI: 10.1016/S8756-3282(99)00172-6</identifier><identifier>PMID: 10495135</identifier><language>eng</language><publisher>New York, NY: Elsevier Inc</publisher><subject>17α-ethynylestradiol ; 1α-hydroxyvitamin D 3 ; Absorptiometry, Photon ; Alkaline Phosphatase - blood ; Amino Acids - urine ; Anabolic Agents - therapeutic use ; Animals ; Biological and medical sciences ; Bone and Bones - diagnostic imaging ; Bone and Bones - drug effects ; Bone and Bones - pathology ; Bone Density - drug effects ; Bone Density - physiology ; Bone Diseases, Metabolic - drug therapy ; Bone Diseases, Metabolic - metabolism ; Bones, joints and connective tissue. Antiinflammatory agents ; Calcium - blood ; Calcium - deficiency ; Calcium, Dietary - administration & dosage ; Cholecalciferol - therapeutic use ; Ethinyl Estradiol - therapeutic use ; Female ; Histomorphometry ; Medical sciences ; Norpregnenes - therapeutic use ; Osteocalcin - blood ; Osteopenia ; Ovariectomy ; Pharmacology. Drug treatments ; Rats ; Rats, Sprague-Dawley ; Space life sciences ; Tibolone ; Weight-Bearing - physiology</subject><ispartof>Bone (New York, N.Y.), 1999-09, Vol.25 (3), p.311-319</ispartof><rights>1999 Elsevier Science Inc.</rights><rights>1999 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c390t-c8c7b1b8fa77b54898f6708046226cd08ec100b4cb0a721edf395fb9f2cf6fd13</citedby><cites>FETCH-LOGICAL-c390t-c8c7b1b8fa77b54898f6708046226cd08ec100b4cb0a721edf395fb9f2cf6fd13</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S8756328299001726$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=1960526$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/10495135$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Yoshitake, K</creatorcontrib><creatorcontrib>Yokota, K</creatorcontrib><creatorcontrib>Kasugai, Y</creatorcontrib><creatorcontrib>Kagawa, M</creatorcontrib><creatorcontrib>Sukamoto, T</creatorcontrib><creatorcontrib>Nakamura, T</creatorcontrib><title>Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet</title><title>Bone (New York, N.Y.)</title><addtitle>Bone</addtitle><description>Tibolone is a synthetic steroid with tissue-specific estrogenic, progestogenic, and androgenic properties. The therapeutic effects of tibolone on bone mass and strength, bone metabolic markers, and indices of histomorphometry were investigated in ovariectomized (ovx) rats on a low (0.1%)-calcium diet in comparison with 17α-ethynylestradiol (EE) or 1α-hydroxyvitamin D
3 [1α(OH)D
3]. Tibolone (0.1–3 mg/kg/day), EE (0.1 mg/kg/day), or 1α(OH)D
3 (0.5 μg/kg/day) was administered orally once a day for 16 weeks, starting 12 weeks after ovariectomy, when the bone mineral density (BMD) of lumbar vertebrae (L4–5) and femur (global, proximal, and distal regions) had already been decreased by the combination of ovariectomy and low dietary calcium. The BMD of the lumbar vertebrae and the femur were higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. The BMD of the mid-diaphysial regions of femur and tibia, which consist mainly of cortical bone, were decreased 28 weeks after ovariectomy in the ovx control group. The BMD of the mid-diaphysial femur was higher in the groups treated with 1α(OH)D
3, and the BMD of mid-diaphysial tibia was higher in the groups treated with tibolone or 1α(OH)D
3 than in the ovx control group. Like BMD, the compressive strength of the vertebral body of L2, corrected for the volume of each individual vertebra tested, was higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. Trabecular bone volume and trabecular number were reduced 12 and 28 weeks after ovariectomy but there was no change in trabecular thickness. These reduced indices were increased in the groups treated with tibolone, EE, or 1α(OH)D
3 when compared with the ovx control group. Tibolone or EE decreased serum levels of osteocalcin and bone alkaline phosphatase and urinary levels of deoxypyridinoline and pyridinoline compared with the ovx control group. Furthermore, tibolone or EE decreased the mineralizing surface and bone formation rate as well as the osteoclast surface and osteoclast numbers. 1α(OH)D
3, however, did not affect these serum and urinary parameters. These data suggest that tibolone suppresses the accelerated bone turnover induced by a combination of ovariectomy and low dietary calcium, and indicate that tibolone may be a potentially useful drug for the treatment of postmenopausal osteoporosis.</description><subject>17α-ethynylestradiol</subject><subject>1α-hydroxyvitamin D 3</subject><subject>Absorptiometry, Photon</subject><subject>Alkaline Phosphatase - blood</subject><subject>Amino Acids - urine</subject><subject>Anabolic Agents - therapeutic use</subject><subject>Animals</subject><subject>Biological and medical sciences</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 - physiology</subject><subject>Bone Diseases, Metabolic - drug therapy</subject><subject>Bone Diseases, Metabolic - metabolism</subject><subject>Bones, joints and connective tissue. Antiinflammatory agents</subject><subject>Calcium - blood</subject><subject>Calcium - deficiency</subject><subject>Calcium, Dietary - administration & dosage</subject><subject>Cholecalciferol - therapeutic use</subject><subject>Ethinyl Estradiol - therapeutic use</subject><subject>Female</subject><subject>Histomorphometry</subject><subject>Medical sciences</subject><subject>Norpregnenes - therapeutic use</subject><subject>Osteocalcin - blood</subject><subject>Osteopenia</subject><subject>Ovariectomy</subject><subject>Pharmacology. Drug treatments</subject><subject>Rats</subject><subject>Rats, Sprague-Dawley</subject><subject>Space life sciences</subject><subject>Tibolone</subject><subject>Weight-Bearing - physiology</subject><issn>8756-3282</issn><issn>1873-2763</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1999</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkcuO1DAQRS0EYpqBTwB5gRAsAnbSseMVQqPhIY3EAlhbfpQVQ2I3tjMt-Df-DSfdAnasyi6dqlu6F6HHlLykhLJXnwbes6Zrh_a5EC8Iobxt2B20owPvmpaz7i7a_UEu0IOcvxJCOsHpfXRByV70tOt36Ne1c2BKxtFhyvAR4Nv2LglUmSEUfPRlxMXrOMUAOAas1zqrnLEK9vwDM6rgjZq23uhziXNMhzHOUJI32AfrDeRa62RZUl10q5KvynH2P8HipOoNmxTkovTk81i7MReIBwhercIKT_HYVBHjlxlbD-UhuufUlOHRuV6iL2-vP1-9b24-vvtw9eamMZ0gpTGD4ZrqwSnOdb8fxOAYJwPZs7ZlxpIBDCVE740mircUrOtE77RwrXHMWdpdomenvYcUvy_1Qjn7bGCaVIC4ZMlXZ_d8BfsTaFLMOYGTh-RnlX5ISuSam9xyk2soUgi55SZZnXtyFlj0DPafqVNQFXh6BlSuDrikgvH5LycY6dt1z-sTBtWNWw9JZuMhGLA-VbOljf4_l_wG5jS5Tg</recordid><startdate>19990901</startdate><enddate>19990901</enddate><creator>Yoshitake, K</creator><creator>Yokota, K</creator><creator>Kasugai, Y</creator><creator>Kagawa, M</creator><creator>Sukamoto, T</creator><creator>Nakamura, T</creator><general>Elsevier Inc</general><general>Elsevier Science</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>7X8</scope></search><sort><creationdate>19990901</creationdate><title>Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet</title><author>Yoshitake, K ; Yokota, K ; Kasugai, Y ; Kagawa, M ; Sukamoto, T ; Nakamura, T</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c390t-c8c7b1b8fa77b54898f6708046226cd08ec100b4cb0a721edf395fb9f2cf6fd13</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>1999</creationdate><topic>17α-ethynylestradiol</topic><topic>1α-hydroxyvitamin D 3</topic><topic>Absorptiometry, Photon</topic><topic>Alkaline Phosphatase - blood</topic><topic>Amino Acids - urine</topic><topic>Anabolic Agents - therapeutic use</topic><topic>Animals</topic><topic>Biological and medical sciences</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 - physiology</topic><topic>Bone Diseases, Metabolic - drug therapy</topic><topic>Bone Diseases, Metabolic - metabolism</topic><topic>Bones, joints and connective tissue. Antiinflammatory agents</topic><topic>Calcium - blood</topic><topic>Calcium - deficiency</topic><topic>Calcium, Dietary - administration & dosage</topic><topic>Cholecalciferol - therapeutic use</topic><topic>Ethinyl Estradiol - therapeutic use</topic><topic>Female</topic><topic>Histomorphometry</topic><topic>Medical sciences</topic><topic>Norpregnenes - therapeutic use</topic><topic>Osteocalcin - blood</topic><topic>Osteopenia</topic><topic>Ovariectomy</topic><topic>Pharmacology. Drug treatments</topic><topic>Rats</topic><topic>Rats, Sprague-Dawley</topic><topic>Space life sciences</topic><topic>Tibolone</topic><topic>Weight-Bearing - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Yoshitake, K</creatorcontrib><creatorcontrib>Yokota, K</creatorcontrib><creatorcontrib>Kasugai, Y</creatorcontrib><creatorcontrib>Kagawa, M</creatorcontrib><creatorcontrib>Sukamoto, T</creatorcontrib><creatorcontrib>Nakamura, T</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>MEDLINE - Academic</collection><jtitle>Bone (New York, N.Y.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Yoshitake, K</au><au>Yokota, K</au><au>Kasugai, Y</au><au>Kagawa, M</au><au>Sukamoto, T</au><au>Nakamura, T</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet</atitle><jtitle>Bone (New York, N.Y.)</jtitle><addtitle>Bone</addtitle><date>1999-09-01</date><risdate>1999</risdate><volume>25</volume><issue>3</issue><spage>311</spage><epage>319</epage><pages>311-319</pages><issn>8756-3282</issn><eissn>1873-2763</eissn><abstract>Tibolone is a synthetic steroid with tissue-specific estrogenic, progestogenic, and androgenic properties. The therapeutic effects of tibolone on bone mass and strength, bone metabolic markers, and indices of histomorphometry were investigated in ovariectomized (ovx) rats on a low (0.1%)-calcium diet in comparison with 17α-ethynylestradiol (EE) or 1α-hydroxyvitamin D
3 [1α(OH)D
3]. Tibolone (0.1–3 mg/kg/day), EE (0.1 mg/kg/day), or 1α(OH)D
3 (0.5 μg/kg/day) was administered orally once a day for 16 weeks, starting 12 weeks after ovariectomy, when the bone mineral density (BMD) of lumbar vertebrae (L4–5) and femur (global, proximal, and distal regions) had already been decreased by the combination of ovariectomy and low dietary calcium. The BMD of the lumbar vertebrae and the femur were higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. The BMD of the mid-diaphysial regions of femur and tibia, which consist mainly of cortical bone, were decreased 28 weeks after ovariectomy in the ovx control group. The BMD of the mid-diaphysial femur was higher in the groups treated with 1α(OH)D
3, and the BMD of mid-diaphysial tibia was higher in the groups treated with tibolone or 1α(OH)D
3 than in the ovx control group. Like BMD, the compressive strength of the vertebral body of L2, corrected for the volume of each individual vertebra tested, was higher in the groups treated with tibolone, EE, or 1α(OH)D
3 than in the ovx control group. Trabecular bone volume and trabecular number were reduced 12 and 28 weeks after ovariectomy but there was no change in trabecular thickness. These reduced indices were increased in the groups treated with tibolone, EE, or 1α(OH)D
3 when compared with the ovx control group. Tibolone or EE decreased serum levels of osteocalcin and bone alkaline phosphatase and urinary levels of deoxypyridinoline and pyridinoline compared with the ovx control group. Furthermore, tibolone or EE decreased the mineralizing surface and bone formation rate as well as the osteoclast surface and osteoclast numbers. 1α(OH)D
3, however, did not affect these serum and urinary parameters. These data suggest that tibolone suppresses the accelerated bone turnover induced by a combination of ovariectomy and low dietary calcium, and indicate that tibolone may be a potentially useful drug for the treatment of postmenopausal osteoporosis.</abstract><cop>New York, NY</cop><pub>Elsevier Inc</pub><pmid>10495135</pmid><doi>10.1016/S8756-3282(99)00172-6</doi><tpages>9</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 8756-3282 |
| ispartof | Bone (New York, N.Y.), 1999-09, Vol.25 (3), p.311-319 |
| issn | 8756-3282 1873-2763 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_70039471 |
| source | MEDLINE; Elsevier ScienceDirect Journals |
| subjects | 17α-ethynylestradiol 1α-hydroxyvitamin D 3 Absorptiometry, Photon Alkaline Phosphatase - blood Amino Acids - urine Anabolic Agents - therapeutic use Animals Biological and medical sciences Bone and Bones - diagnostic imaging Bone and Bones - drug effects Bone and Bones - pathology Bone Density - drug effects Bone Density - physiology Bone Diseases, Metabolic - drug therapy Bone Diseases, Metabolic - metabolism Bones, joints and connective tissue. Antiinflammatory agents Calcium - blood Calcium - deficiency Calcium, Dietary - administration & dosage Cholecalciferol - therapeutic use Ethinyl Estradiol - therapeutic use Female Histomorphometry Medical sciences Norpregnenes - therapeutic use Osteocalcin - blood Osteopenia Ovariectomy Pharmacology. Drug treatments Rats Rats, Sprague-Dawley Space life sciences Tibolone Weight-Bearing - physiology |
| title | Effects of 16 weeks of treatment with tibolone on bone mass and bone mechanical and histomorphometric indices in mature ovariectomized rats with established osteopenia on a low-calcium diet |
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