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We have reported that sequential treatment with teriparatide and denosumab improves central skeletal bone mineral density (BMD) by dual-energy X-ray absorptiometry and central QCT in PreMenIOP. We conducted preplanned analyses of high-resolution peripheral quantitative computed tomography (HR-pQCT) scans from teriparatide and denosumab extension studies to measure effects on volumetric BMD (vBMD), microarchitecture, and estimated strength at the distal radius and tibia. Of 41 women enrolled in the parent teriparatide study (20 mcg daily), 34 enrolled in the HR-pQCT study. HR-pQCT participants initially received teriparatide (N\u00a0=\u200924) or placebo (N\u00a0=\u200910) for 6\u2009months; all then received teriparatide for 24\u2009months. After teriparatide, 26 enrolled in the phase 2B denosumab extension (60\u2009mg q6M) for 24\u2009months. Primary outcomes were percentage change in vBMD, microstructure, and stiffness after teriparatide and after denosumab. Changes after sequential teriparatide and denosumab were secondary outcomes. After teriparatide, significant improvements were seen in tibial trabecular number (3.3%, p\u00a0=\u20090.01), cortical area and thickness (both 2.7%, p\u00a0&amp;lt;\u20090.001), and radial trabecular microarchitecture (number: 6.8%, thickness: 2.2%, separation: \u22125.1%, all p\u00a0&amp;lt;\u20090.02). Despite increases in cortical porosity and decreases in cortical density, whole-bone stiffness and failure load increased at both sites. After denosumab, increases in total (3.5%, p\u00a0&amp;lt;\u20090.001 and 3.3%, p\u00a0=\u20090.02) and cortical vBMD (1.7% and 3.2%; both p\u00a0&amp;lt;\u20090.01), and failure load (1.1% and 3.6%; both p\u00a0&amp;lt;\u20090.05) were seen at tibia and radius, respectively. Trabecular density (3.5%, p\u00a0&amp;lt;\u20090.001) and number (2.4%, p\u00a0=\u20090.03) increased at the tibia, while thickness (3.0%, p\u00a0=\u20090.02) increased at the radius. After 48\u2009months of sequential treatment, significant increases in total vBMD (tibia: p\u00a0&amp;lt;\u20090.001; radius: p\u00a0=\u20090.01), trabecular microstructure (p\u00a0&amp;lt;\u20090.05), cortical thickness (tibia: p\u00a0&amp;lt;\u20090.001; radius: p\u00a0=\u20090.02), and whole bone strength (p\u00a0&amp;lt;\u20090.02) were seen at both sites. Significant increases in total vBMD and bone strength parameters after sequential treatment with teriparatide followed by denosumab support the use of this regimen in PreMenIOP. \u00a9 2022 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4739","type":"journal-article","created":{"date-parts":[[2022,11,6]],"date-time":"2022-11-06T16:20:10Z","timestamp":1667751610000},"page":"35-47","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":23,"title":["Teriparatide Followed by Denosumab in Premenopausal Idiopathic Osteoporosis: Bone Microstructure and Strength by HR-pQCT"],"prefix":"10.1093","volume":"38","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4978-0717","authenticated-orcid":false,"given":"Sanchita","family":"Agarwal","sequence":"first","affiliation":[{"name":"Department of Medicine Columbia University Vagelos College of Physicians & Surgeons New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephanie","family":"Shiau","sequence":"additional","affiliation":[{"name":"Department of Biostatistics & Epidemiology Rutgers School of Public Health Piscataway NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mafo","family":"Kamanda-Kosseh","sequence":"additional","affiliation":[{"name":"Department of Medicine Columbia University Vagelos College of Physicians & Surgeons New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariana","family":"Bucovsky","sequence":"additional","affiliation":[{"name":"Department of Medicine Columbia University Vagelos College of Physicians & Surgeons New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nayoung","family":"Kil","sequence":"additional","affiliation":[{"name":"Department of Medicine Columbia University Vagelos College of Physicians & Surgeons New York NY USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joan M.","family":"Lappe","sequence":"additional","affiliation":[{"name":"Department of Medicine Creighton University Medical Center Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Julie","family":"Stubby","sequence":"additional","affiliation":[{"name":"Department of Medicine Creighton University Medical Center Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert R.","family":"Recker","sequence":"additional","affiliation":[{"name":"Department of Medicine Creighton University Medical Center Omaha NE USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"X. 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