{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,22]],"date-time":"2026-08-22T08:50:12Z","timestamp":1787388612844,"version":"build-2736575974"},"reference-count":51,"publisher":"The Endocrine Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2003,5,1]]},"abstract":"<jats:p>With the ready availability of several osteoporosis therapies, teriparatide [human PTH-(1\u201334)] is likely to be prescribed to postmenopausal women with prior exposure to agents that prevent bone loss, such as bisphosphonates, estrogen, or selective estrogen receptor modulators. Therefore, we evaluated the ability of once daily teriparatide to induce bone formation in ovariectomized (Ovx) rats with extended prior exposure to various antiresorptive agents, such as alendronate (ABP), 17\u03b1-ethinyl estradiol (EE), or raloxifene (Ral). Sprague Dawley rats were Ovx and treated with ABP (28 \u03bcg\/kg, twice weekly), EE (0.1 mg\/kg\u00b7d), or Ral (1 mg\/kg\u00b7d) for 10 months before switching to teriparatide 30 \u03bcg\/kg\u00b7d for another 2 months. Analysis of the proximal tibial metaphysis showed that all three antiresorptive agents prevented ovariectomy-induced bone loss after 10 months, but were mechanistically distinct, as shown by histomorphometry. Before teriparatide treatment, ABP strongly suppressed activation frequency and bone formation rate to below levels in other treatment groups, whereas these parameters were not different from sham values for EE or Ral. Trabecular area for ABP, EE, and Ral were greater than that in Ovx controls. However, the trabecular bone effects of ABP were attributed not only to effects on the secondary spongiosa, but also to the preservation of primary spongiosa, which was prevented from remodeling. After 2 months of teriparatide treatment, lumbar vertebra showed relative bone mineral density increases of 18%, 7%, 11%, and 10% for vehicle\/teriparatide, ABP\/teriparatide, EE\/teriparatide, and Ral\/teriparatide, respectively, compared with 10 month levels. Histomorphometry showed that trabecular area was increased by 105%, 113%, 36%, and 48% for vehicle\/teriparatide, ABP\/teriparatide, EE\/teriparatide, and Ral\/teriparatide, respectively, compared with 10 month levels. Teriparatide enhanced mineralizing surface, mineral apposition rate, and bone formation rate in all groups. Compression testing of vertebra showed that teriparatide improved strength (peak load) and toughness in all groups to a proportionately similar extent compared with 10 month levels. These data showed a surprising ability of the rat skeleton to respond to teriparatide despite extensive pretreatment with ABP, EE, or Ral. Therefore, the mature skeleton of Ovx rats remains highly responsive to the appositional effects of teriparatide regardless of pretreatment status in terms of cancellous bone area or rate of bone turnover.<\/jats:p>","DOI":"10.1210\/en.2002-221061","type":"journal-article","created":{"date-parts":[[2003,4,15]],"date-time":"2003-04-15T23:43:40Z","timestamp":1050450220000},"page":"2008-2015","source":"Crossref","is-referenced-by-count":82,"title":["New Bone Formation with Teriparatide [Human Parathyroid Hormone-(1\u201334)] Is Not Retarded by Long-Term Pretreatment with Alendronate, Estrogen, or Raloxifene in Ovariectomized Rats"],"prefix":"10.1210","volume":"144","author":[{"given":"Yanfei L.","family":"Ma","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry U.","family":"Bryant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingqiang","family":"Zeng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allen","family":"Schmidt","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer","family":"Hoover","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harlan W.","family":"Cole","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Yao","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Webster S. S.","family":"Jee","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masahiko","family":"Sato","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"80","reference":[{"key":"2020071612580970700_R1","doi-asserted-by":"crossref","first-page":"957","DOI":"10.1210\/jcem.86.3.7366","article-title":"Clinical review 123: anabolic therapy for osteoporosis.","volume":"86","author":"Rosen","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612580970700_R2","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1007\/s001980200026","article-title":"The anabolic effects of parathyroid hormone [Review].","volume":"13","author":"Rubin","year":"2002","journal-title":"Osteoporosis Int"},{"key":"2020071612580970700_R3","doi-asserted-by":"crossref","first-page":"1846","DOI":"10.1359\/jbmr.2001.16.10.1846","article-title":"Effects of daily treatment with parathyroid hormone on bone microarchitecture and turnover in patients with osteoporosis: a paired biopsy study.","volume":"16","author":"Dempster","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2020071612580970700_R4","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1016\/S0140-6736(97)02342-8","article-title":"Randomised controlled study of effect of parathyroid hormone on vertebral-bone mass and fracture incidence among postmenopausal women on oestrogen with osteoporosis.","volume":"350","author":"Lindsay","year":"1997","journal-title":"Lancet"},{"key":"2020071612580970700_R5","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of parathyroid hormone (1\u201334) on fractures and bone mineral density in postmenopausal women with osteoporosis.","volume":"344","author":"Neer","year":"2001","journal-title":"N Engl J Med"},{"key":"2020071612580970700_R6","first-page":"111","article-title":"Parathyroid hormone: a cure for osteoporosis?","volume":"31","author":"Gasser","year":"1992","journal-title":"Triangle"},{"key":"2020071612580970700_R7","first-page":"690","article-title":"Anabolic actions of parathyroid hormone on bone. [Published erratum appears in Endocr Rev 1994 Apr;15(2):261.]","volume":"14","author":"Dempster","year":"1993","journal-title":"Endocr Rev"},{"key":"2020071612580970700_R8","doi-asserted-by":"crossref","first-page":"4330","DOI":"10.1210\/endo.138.10.5440","article-title":"Biosynthetic human parathyroid hormone (1\u201334) effects on bone quality in aged ovariectomized rats.","volume":"138","author":"Sato","year":"1997","journal-title":"Endocrinology"},{"key":"2020071612580970700_R9","doi-asserted-by":"crossref","first-page":"456","DOI":"10.1007\/s002230010091","article-title":"Changes in geometry and cortical porosity in adult, ovary-intact rabbits after 5 months treatment with LY333334 (hPTH 1\u201334).","volume":"66","author":"Hirano","year":"2000","journal-title":"Calcif Tissue Int"},{"key":"2020071612580970700_R10","doi-asserted-by":"crossref","first-page":"538","DOI":"10.1016\/S8756-3282(01)00433-1","article-title":"Effects of human parathyroid hormone (1\u201334), LY333334, on bone mass, remodeling, and mechanical properties of cortical bone during the first remodeling cycle in rabbits.","volume":"28","author":"Mashiba","year":"2001","journal-title":"Bone"},{"key":"2020071612580970700_R11","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/S8756-3282(99)00166-0","article-title":"Effect of treatment for 6 months with human parathyroid hormone (1\u201334) peptide in ovariectomized cynomolgus monkeys (Macaca fascicularis).","volume":"25","author":"Jerome","year":"1999","journal-title":"Bone"},{"key":"2020071612580970700_R12","doi-asserted-by":"crossref","first-page":"150","DOI":"10.1016\/S8756-3282(00)00430-0","article-title":"Treatment with human parathyroid hormone (1\u201334) for 18 months increases cancellous bone volume and improves trabecular architecture in ovariectomized cynomolgus monkeys (Macaca fascicularis).","volume":"28","author":"Jerome","year":"2001","journal-title":"Bone"},{"key":"2020071612580970700_R13","first-page":"3757","article-title":"Daily treatment with human recombinant parathyroid hormone-(1\u201334), LY333334, for 1 year increases bone mass in ovariectomized monkeys.","volume":"84","author":"Brommage","year":"1999","journal-title":"J Clin Endocrinol Metab"},{"key":"2020071612580970700_R14","doi-asserted-by":"crossref","first-page":"871","DOI":"10.1007\/s001980070047","article-title":"Three-dimensional modeling of the effects of parathyroid hormone on bone distribution in lumbar vertebrae of ovariectomized cynomolgus macaques.","volume":"11","author":"Sato","year":"2000","journal-title":"Osteop Int"},{"key":"2020071612580970700_R15","doi-asserted-by":"crossref","first-page":"157","DOI":"10.1359\/jbmr.2001.16.1.157","article-title":"Intermittently administered human parathyroid hormone(1\u201334) treatment increases intracortical bone turnover and porosity without reducing bone strength in the humerus of ovariectomized cynomolgus monkeys.","volume":"16","author":"Burr","year":"2001","journal-title":"J Bone Miner Res"},{"key":"2020071612580970700_R16","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/8756-3282(95)00445-9","article-title":"Bisphosphonates: a review of their pharmacokinetic properties.","volume":"18","author":"Lin","year":"1996","journal-title":"Bone"},{"key":"2020071612580970700_R17","first-page":"3109","article-title":"Skeletal benefits of alendronate: 7-year treatment of postmenopausal osteoporotic women. 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Report of the ASBMR Histomorphometry Nomenclature Committee.","volume":"2","author":"Parfitt","year":"1987","journal-title":"J Bone Miner Res"},{"key":"2020071612580970700_R24","doi-asserted-by":"crossref","first-page":"496","DOI":"10.1002\/jbmr.5650100322","article-title":"Human parathyroid hormone-(1\u201338) restores cancellous bone to the immobilized, osteopenic proximal tibial metaphysis in rats.","volume":"10","author":"Ma","year":"1995","journal-title":"J Bone Miner Res"},{"key":"2020071612580970700_R25","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/8756-3282(93)90081-K","article-title":"Basic biomechanical measurements of bone: a tutorial.","volume":"14","author":"Turner","year":"1993","journal-title":"Bone"},{"key":"2020071612580970700_R26","doi-asserted-by":"crossref","first-page":"2095","DOI":"10.1172\/JCI115539","article-title":"Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure.","volume":"88","author":"Sato","year":"1991","journal-title":"J Clin Invest"},{"key":"2020071612580970700_R27","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1006\/abbi.1999.1502","article-title":"Alendronate is a specific, nanomolar inhibitor of farnesyl diphosphate synthase.","volume":"373","author":"Bergstrom","year":"2000","journal-title":"Arch Biochem Biophys"},{"key":"2020071612580970700_R28","doi-asserted-by":"crossref","first-page":"339","DOI":"10.1002\/jbmr.5650060405","article-title":"The bisphosphonate alendronate (MK-217) inhibits bone loss due to ovariectomy in rats.","volume":"6","author":"Seedor","year":"1991","journal-title":"J Bone Miner Res"},{"key":"2020071612580970700_R29","first-page":"128","article-title":"Effects of continuous alendronate treatment on bone mass and mechanical properties in ovariectomized rats: comparison with pamidronate and etidronate in growing rats.","volume":"286","author":"Azuma","year":"1998","journal-title":"J Pharmacol Exp Ther"},{"key":"2020071612580970700_R30","doi-asserted-by":"crossref","first-page":"1437","DOI":"10.1056\/NEJM199511303332201","article-title":"Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group.","volume":"333","author":"Liberman","year":"1995","journal-title":"N Engl J Med"},{"key":"2020071612580970700_R31","doi-asserted-by":"crossref","first-page":"1535","DOI":"10.1016\/S0140-6736(96)07088-2","article-title":"Randomised trial of effect of alendronate on risk of fracture in women with existing vertebral fractures. Fracture Intervention Trial Research Group.","volume":"348","author":"Black","year":"1996","journal-title":"Lancet"},{"key":"2020071612580970700_R32","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1089\/15246090050118125","article-title":"Alendronate in the treatment of osteoporosis: a review of the clinical trials.","volume":"9","author":"Siris","year":"2000","journal-title":"J Womens Health Gender-Based Med"},{"key":"2020071612580970700_R33","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1007\/BF02547219","article-title":"Effect of ethane-1-hydroxy-1,1-diphosphonate (EHDP) and dichloromethylene diphosphonate (Cl 2 MDP) on the calcification and resorption of cartilage and bone in the tibial epiphysis and metaphysis of rats.","volume":"11","author":"Schenk","year":"1973","journal-title":"Calcif Tissue Res"},{"key":"2020071612580970700_R34","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1016\/8756-3282(94)00035-X","article-title":"Alendronate distributed on bone surfaces inhibits osteoclastic bone resorption in vitro and in experimental hypercalcemia models.","volume":"16","author":"Azuma","year":"1995","journal-title":"Bone"},{"key":"2020071612580970700_R35","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s002230010045","article-title":"A controlled study of the effects of alendronate in a growing mouse model of osteogenesis imperfecta.","volume":"69","author":"Camacho","year":"2001","journal-title":"Calcif Tissue Int"},{"key":"2020071612580970700_R36","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1210\/endo-123-2-681","article-title":"Estrogen treatment prevents osteopenia and depresses bone turnover in ovariectomized rats.","volume":"123","author":"Wronski","year":"1988","journal-title":"Endocrinology"},{"key":"2020071612580970700_R37","first-page":"275","article-title":"Skeletal effects of estrogen [Review].","volume":"15","author":"Turner","year":"1994","journal-title":"Endocr Rev"},{"key":"2020071612580970700_R38","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/0002-9378(79)90288-6","article-title":"Effects of long-term estrogen replacement therapy. I. Metabolic effects.","volume":"133","author":"Hammond","year":"1979","journal-title":"Am J Obstet Gynecol"},{"key":"2020071612580970700_R39","doi-asserted-by":"crossref","first-page":"1195","DOI":"10.1056\/NEJM198011203032102","article-title":"Decreased risk of fractures of the hip and lower forearm with postmenopausal use of estrogen.","volume":"303","author":"Weiss","year":"1980","journal-title":"N Engl J Med"},{"key":"2020071612580970700_R40","doi-asserted-by":"crossref","first-page":"9","DOI":"10.7326\/0003-4819-122-1-199501010-00002","article-title":"Estrogen replacement therapy and fractures in older women. Study of Osteoporotic Fractures Research Group.","volume":"122","author":"Cauley","year":"1995","journal-title":"Ann Intern Med"},{"key":"2020071612580970700_R41","doi-asserted-by":"crossref","first-page":"637","DOI":"10.1001\/jama.282.7.637","article-title":"Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. 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