{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T19:12:23Z","timestamp":1790881943528,"version":"4.1.0"},"reference-count":44,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2010,9,2]],"date-time":"2010-09-02T00:00:00Z","timestamp":1283385600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2011,3,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Clinical data suggest concomitant therapy with bisphosphonates and parathyroid hormone (PTH) may blunt the anabolic effect of PTH; rodent models suggest that infrequently administered bisphosphonates may interact differently. To evaluate the effects of combination therapy with an intravenous infusion of zoledronic acid 5\u2009mg and daily subcutaneous recombinant human (rh)PTH(1\u201334) (teriparatide) 20\u2009\u00b5g versus either agent alone on bone mineral density (BMD) and bone turnover markers, we conducted a 1-year multicenter, multinational, randomized, partial double-blinded, controlled trial. 412 postmenopausal women with osteoporosis (mean age 65\u2009\u00b1\u20099 years) were randomized to a single infusion of zoledronic acid 5\u2009mg plus daily subcutaneous teriparatide 20\u2009\u00b5g (n\u2009=\u2009137), zoledronic acid alone (n\u2009=\u2009137), or teriparatide alone (n\u2009=\u2009138). The primary endpoint was percentage increase in lumbar spine BMD (assessed by dual-energy X-ray absorptiometry [DXA]) at 52 weeks versus baseline. Secondary endpoints included change in BMD at the spine at earlier time points and at the total hip, trochanter, and femoral neck at all time points. At week 52, lumbar spine BMD had increased 7.5%, 7.0%, and 4.4% in the combination, teriparatide, and zoledronic acid groups, respectively (p\u2009&amp;lt;\u2009.001 for combination and teriparatide versus zoledronic acid). In the combination group, spine BMD increased more rapidly than with either agent alone (p\u2009&amp;lt;\u2009.001 versus both teriparatide and zoledronic acid at 13 and 26 weeks). Combination therapy increased total-hip BMD more than teriparatide alone at all times (all p\u2009&amp;lt;\u2009.01) and more than zoledronic acid at 13 weeks (p\u2009&amp;lt;\u2009.05), with final 52-week increments of 2.3%, 1.1%, and 2.2% in the combination, teriparatide, and zoledronic acid groups, respectively. With combination therapy, bone formation (assessed by serum N-terminal propeptide of type I collagen [PINP]) increased from 0 to 4 weeks, declined minimally from 4 to 8 weeks, and then rose throughout the trial, with levels above baseline from 6 to 12 months. Bone resorption (assessed by serum \u03b2-C-telopeptide of type I collagen [\u03b2-CTX]) was markedly reduced with combination therapy from 0 to 8 weeks (a reduction of similar magnitude to that seen with zoledronic acid alone), followed by a gradual increase after week 8, with levels remaining above baseline for the latter half of the year. Levels for both markers were significantly lower with combination therapy versus teriparatide alone (p\u2009&amp;lt;\u2009.002). Limitations of the study included its short duration, lack of endpoints beyond DXA-based BMD (e.g., quantitative computed tomography and finite-element modeling for bone strength), lack of teriparatide placebo, and insufficient power for fracture outcomes. We conclude that while teriparatide increases spine BMD more than zoledronic acid and zoledronic acid increases hip BMD more than teriparatide, combination therapy provides the largest, most rapid increments when both spine and hip sites are considered. \u00a9 2011 American Society for Bone and Mineral Research.<\/jats:p>","DOI":"10.1002\/jbmr.238","type":"journal-article","created":{"date-parts":[[2010,9,3]],"date-time":"2010-09-03T15:56:22Z","timestamp":1283529382000},"page":"503-511","source":"Crossref","is-referenced-by-count":319,"title":["Effects of intravenous zoledronic acid plus subcutaneous teriparatide [rhPTH(1\u201334)] in postmenopausal osteoporosis"],"prefix":"10.1093","volume":"26","author":[{"given":"Felicia","family":"Cosman","sequence":"first","affiliation":[{"name":"Department of Medicine, Columbia University, New York, NY, USA"},{"name":"Clinical Research Center, Helen Hayes Hospital, West Haverstraw, NY, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik Fink","family":"Eriksen","sequence":"additional","affiliation":[{"name":"Faculty Division, Aker University Hospital, Oslo, Norway"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chris","family":"Recknor","sequence":"additional","affiliation":[{"name":"United Osteoporosis Centers, Gainesville, GA, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D","family":"Miller","sequence":"additional","affiliation":[{"name":"Colorado Center for Bone Research, Lakewood, CO, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"N\u00faria","family":"Gua\u00f1abens","sequence":"additional","affiliation":[{"name":"Department of Rheumatology, University of Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian","family":"Kasperk","sequence":"additional","affiliation":[{"name":"Department of Medicine and Clinical Chemistry, University of Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philemon","family":"Papanastasiou","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aimee","family":"Readie","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corp., East Hanover, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanumantha","family":"Rao","sequence":"additional","affiliation":[{"name":"Novartis Healthcare Private, Ltd., Hyderabad, India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrg A","family":"Gasser","sequence":"additional","affiliation":[{"name":"Novartis Pharma AG, Basel, Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Bucci-Rechtweg","sequence":"additional","affiliation":[{"name":"Novartis Pharmaceuticals Corp., East Hanover, NJ, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Steven","family":"Boonen","sequence":"additional","affiliation":[{"name":"Division of Gerontology and Geriatrics, University of Leuven, Leuven, Belgium"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2010,9,2]]},"reference":[{"key":"2024020318055050500_bib1"},{"key":"2024020318055050500_bib2","doi-asserted-by":"crossref","first-page":"483","DOI":"10.4158\/EP08306.ORR1","article-title":"Treatment of osteoporosis and prevention of new fractures: role of intravenously administered bisphosphonates","volume":"15","author":"Cosman","year":"2009","journal-title":"Endocr Pract."},{"key":"2024020318055050500_bib3","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1056\/NEJM200105103441904","article-title":"Effect of parathyroid hormone (1-34) on fractures and bone mineral density in postmenopausal women with osteoporosis","volume":"344","author":"Neer","year":"2001","journal-title":"N Engl J Med."},{"key":"2024020318055050500_bib4","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1097\/MED.0b013e32831a46d6","article-title":"Parathyroid hormone treatment for osteoporosis","volume":"15","author":"Cosman","year":"2008","journal-title":"Curr Opin Endocrinol Diabetes Obes."},{"key":"2024020318055050500_bib5","doi-asserted-by":"crossref","first-page":"1932","DOI":"10.1359\/jbmr.2003.18.11.1932","article-title":"Recombinant human parathyroid hormone (1-34) [teriparatide] improves both cortical and cancellous bone structure","volume":"18","author":"Jiang","year":"2003","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib6","doi-asserted-by":"crossref","first-page":"855","DOI":"10.1359\/jbmr.060314","article-title":"Teriparatide increases bone formation in modeling and remodeling osteons and enhances IGF-II immunoreactivity in postmenopausal women with osteoporosis","volume":"21","author":"Ma","year":"2006","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib7","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":"2024020318055050500_bib8","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1359\/jbmr.061011","article-title":"Effects of teriparatide and alendronate on vertebral strength as assessed by finite element modeling of QCT scans in women with osteoporosis","volume":"22","author":"Keaveny","year":"2007","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib9","author":"Keaveny"},{"key":"2024020318055050500_bib10","doi-asserted-by":"crossref","first-page":"2028","DOI":"10.1056\/NEJMoa071408","article-title":"Teriparatide or alendronate in glucocorticoid-induced osteoporosis","volume":"357","author":"Saag","year":"2007","journal-title":"N Engl J Med."},{"key":"2024020318055050500_bib11","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1359\/jbmr.090820","article-title":"Quantitative computed tomography assessment of the effects of 24 months of teriparatide treatment on 3-D femoral neck bone distribution, geometry and bone strength: Results from the EUROFORS study","volume":"25","author":"Borggrefe","year":"2010","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib12","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bone.2005.03.003","article-title":"Effects of teriparatide [rhPTH(1-34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women","volume":"36","author":"Uusi-Rasi","year":"2005","journal-title":"Bone."},{"key":"2024020318055050500_bib13","doi-asserted-by":"crossref","first-page":"1762","DOI":"10.1001\/archinte.165.15.1762","article-title":"Opposite bone remodeling effects of teriparatide and alendronate in increasing bone mass","volume":"165","author":"McClung","year":"2005","journal-title":"Arch Intern Med."},{"key":"2024020318055050500_bib14","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1056\/NEJMoa031975","article-title":"PaTH Study Investigators 2003 The effects of parathyroid hormone and alendronate alone or in combination in postmenopausal osteoporosis","volume":"349","author":"Black","journal-title":"N Engl J Med."},{"key":"2024020318055050500_bib15","doi-asserted-by":"crossref","first-page":"1809","DOI":"10.1056\/NEJMoa067312","article-title":"HORIZON Pivotal Fracture Trial 2007 Once-yearly zoledronic acid for treatment of postmenopausal osteoporosis","volume":"356","author":"Black","journal-title":"N Engl J Med."},{"key":"2024020318055050500_bib16","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":"2024020318055050500_bib17","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1359\/jbmr.2001.16.5.925","article-title":"Parathyroid hormone added to established hormone therapy: effects on vertebral fracture and maintenance of bone mass after parathyroid hormone withdrawal","volume":"16","author":"Cosman","year":"2001","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib18","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1007\/s00198-007-0475-0","article-title":"Effect of prior and ongoing raloxifene therapy on response to PTH and maintenance of BMD after PTH therapy","volume":"19","author":"Cosman","year":"2008","journal-title":"Osteoporos Int."},{"key":"2024020318055050500_bib19","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1359\/jbmr.040117","article-title":"Differential effects of teriparatide on BMD after treatment with raloxifene or alendronate","volume":"19","author":"Ettinger","year":"2004","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib20","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1056\/NEJMoa050157","article-title":"Daily and cyclic parathyroid hormone in women receiving alendronate","volume":"353","author":"Cosman","year":"2005","journal-title":"N Engl J Med."},{"key":"2024020318055050500_bib21","doi-asserted-by":"crossref","first-page":"852","DOI":"10.1210\/jc.2007-0711","article-title":"EUROFORS Investigators 2008 Effects of previous antiresorptive therapy on the bone mineral density response to 2 years of teriparatide treatment in postmenopausal women with osteoporosis","volume":"93","author":"Boonen","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318055050500_bib22","doi-asserted-by":"crossref","first-page":"3785","DOI":"10.1210\/jc.2008-0353","article-title":"Open-label Study to Determine How Prior Therapy with Alendronate or Risedronate in Postmenopausal Women with Osteoporosis Influences the Clinical Effectiveness of Teriparatide Investigators 2008 Early responsiveness of women with osteoporosis to teriparatide after therapy with alendronate or risedronate","volume":"93","author":"Miller","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318055050500_bib23","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1056\/NEJMoa035725","article-title":"The effects of parathyroid hormone, alendronate, or both in men with osteoporosis","volume":"349","author":"Finkelstein","year":"2003","journal-title":"N Engl J Med."},{"key":"2024020318055050500_bib24","doi-asserted-by":"crossref","first-page":"3772","DOI":"10.1210\/jc.2008-2719","article-title":"Effects of teriparatide in postmenopausal women with osteoporosis on prior alendronate or raloxifene: differences between stopping and continuing the antiresorptive agent","volume":"94","author":"Cosman","year":"2009","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318055050500_bib25","first-page":"53","article-title":"PTH and interactions with bisphosphonates","volume":"1","author":"Gasser","year":"2000","journal-title":"J Musculoskel Neuron Interact."},{"key":"2024020318055050500_bib26","author":"Gasser"},{"key":"2024020318055050500_bib27","doi-asserted-by":"crossref","first-page":"3632","DOI":"10.1210\/endo.136.8.7628403","article-title":"Evidence that intermittent treatment with parathyroid hormone increases bone formation in adult rats by activation of bone lining cells","volume":"136","author":"Dobnig","year":"1995","journal-title":"Endocrinology."},{"key":"2024020318055050500_bib28","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1359\/JBMR.040920","article-title":"Fosamax Actonel Comparison Trial Investigators 2005 Treatment with once-weekly alendronate 70mg compared with once-weekly risedronate 35mg in women with postmenopausal osteoporosis: a randomized double-blind study","volume":"20","author":"Rosen","year":"2005","journal-title":"J Bone Miner Res."},{"issue":"(suppl 6)","key":"2024020318055050500_bib29","first-page":"S2","article-title":"Committee of Scientific Advisors of the International Osteoporosis Foundation 2000 The use of biochemical markers of bone turnover in osteoporosis. Committee of Scientific Advisors of the International Osteoporosis Foundation","volume":"11","author":"Delmas","journal-title":"Osteoporos Int."},{"key":"2024020318055050500_bib30","doi-asserted-by":"crossref","first-page":"330","DOI":"10.1359\/JBMR.0301228","article-title":"Relationship between changes in bone mineral density and fracture risk reduction with antiresorptive drugs: some issues with meta-analyses","volume":"19","author":"Delmas","year":"2004","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib31","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1210\/jcem.85.1.6267","article-title":"Antifracture efficacy of antiresorptive agents are related to changes in bone density","volume":"85","author":"Wasnich","year":"2000","journal-title":"J Clin Endocrinol Metab."},{"key":"2024020318055050500_bib32","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1177\/009286150103500212","article-title":"Statistical methods for comparison to placebo in active-control trials","volume":"35","author":"Hasselblad","year":"2001","journal-title":"Drug Info J."},{"key":"2024020318055050500_bib33","doi-asserted-by":"crossref","first-page":"389","DOI":"10.1359\/jbmr.080703","article-title":"Establishing a reference interval for bone turnover markers in 637 healthy, young, premenopausal women from the United Kingdom, France, Belgium and the United States","volume":"24","author":"Glover","year":"2009","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib34","doi-asserted-by":"crossref","first-page":"495","DOI":"10.1359\/jbmr.070104","article-title":"Effects of a one-month treatment with PTH(1-34) on bone formation on cancellous, endocortical, and periosteal surfaces of the human ilium","volume":"22","author":"Lindsay","year":"2007","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib35","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1359\/JBMR.051109","article-title":"A novel tetracycline labeling schedule for longitudinal evaluation of the short-term effects of anabolic therapy with a single iliac crest bone biopsy: early actions of teriparatide","volume":"21","author":"Lindsay","year":"2006","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib36","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1007\/s11914-005-0023-9","article-title":"Does early PTH treatment compromise bone strength? The balance between remodeling, porosity, bone mineral, and bone size","volume":"3","author":"Burr","year":"2005","journal-title":"Curr Osteoporos Rep."},{"key":"2024020318055050500_bib37","doi-asserted-by":"crossref","first-page":"948","DOI":"10.1016\/j.bone.2005.03.003","article-title":"Effects of teriparatide [rhPTH (1-34)] treatment on structural geometry of the proximal femur in elderly osteoporotic women","volume":"36","author":"Uusi-Rasi","year":"2005","journal-title":"Bone."},{"key":"2024020318055050500_bib38","doi-asserted-by":"crossref","first-page":"623","DOI":"10.1359\/JBMR.040112","article-title":"Teriparatide [PTH(1-34)] strengthens the proximal femur of ovariectomized nonhuman primates despite increasing porosity","volume":"19","author":"Sato","year":"2004","journal-title":"J Bone Miner Res."},{"key":"2024020318055050500_bib39","doi-asserted-by":"crossref","first-page":"185","DOI":"10.1016\/S8756-3282(01)00485-9","article-title":"Alendronate increases degree and uniformity of mineralization in cancellous bone and decreases the porosity in cortical bone of osteoporotic women","volume":"29","author":"Roschger","year":"2001","journal-title":"Bone."},{"key":"2024020318055050500_bib40","first-page":"992","article-title":"Effect of h-PTH on bone and bone marrow tissue in experimental osteopenia in rat","volume":"69","author":"Ishigaki","year":"1995","journal-title":"Nippon Seikeigeka Gakkai Zasshi."},{"key":"2024020318055050500_bib41","first-page":"886","article-title":"Influence of bone marrow fat on the determination of bone mineral content by QCT","volume":"54","author":"Ikeda","year":"1994","journal-title":"Nippon Igaku Hoshasen Gakkai Zasshi."},{"key":"2024020318055050500_bib42","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1007\/BF01626534","article-title":"Accuracy and the influence of marrow fat on quantitative CT and dual-energy X-ray absorptiometry measurements of the femoral neck in vitro","volume":"6","author":"Kuiper","year":"1996","journal-title":"Osteoporos Int."},{"key":"2024020318055050500_bib43","doi-asserted-by":"crossref","first-page":"e130","DOI":"10.1016\/j.archger.2008.11.004","article-title":"PTH-analogs: Comparable or different?","volume":"49","author":"Verhaar","year":"2009","journal-title":"Arch Gerontol Geriatr."},{"key":"2024020318055050500_bib44","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1196\/annals.1402.089","article-title":"Bisphosphonates: an update on mechanisms of action and how these relate to clinical efficacy","volume":"1117","author":"Russell","year":"2007","journal-title":"Ann N Y Acad Sci."}],"container-title":["Journal of Bone and Mineral Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fjbmr.238","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/3\/503\/56558947\/238_ftp.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jbmr\/article-pdf\/26\/3\/503\/56558947\/238_ftp.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,3,13]],"date-time":"2024-03-13T10:53:05Z","timestamp":1710327185000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jbmr\/article\/26\/3\/503-511\/7598101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2010,9,2]]},"references-count":44,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2010,9,2]]},"published-print":{"date-parts":[[2011,3,1]]}},"URL":"https:\/\/doi.org\/10.1002\/jbmr.238","relation":{},"ISSN":["0884-0431","1523-4681"],"issn-type":[{"value":"0884-0431","type":"print"},{"value":"1523-4681","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2011,3,1]]},"published":{"date-parts":[[2010,9,2]]}}}