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formation and high bone resorption. The lumbar spine is most severely affected. Low bone formation is associated with relative insulin-like growth factor 1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with recombinant human (rh) IGF-1 used off-label followed by antiresorptive therapy with risedronate would increase BMD more than risedronate or placebo in women with anorexia nervosa. We conducted a 12-month, randomized, placebo-controlled study of 90 ambulatory women with anorexia nervosa and low areal BMD (aBMD). Participants were randomized to three groups: 6\u2009months of rhIGF-1 followed by 6\u2009months of risedronate (\u201crhIGF-1\/Risedronate\u201d) (n\u00a0=\u200933), 12\u2009months of risedronate (\u201cRisedronate\u201d) (n\u00a0=\u200933), or double placebo (\u201cPlacebo\u201d) (n\u00a0=\u200916). Outcome measures were lumbar spine (1\u00b0 endpoint: postero-anterior [PA] spine), hip, and radius aBMD by dual-energy X-ray absorptiometry (DXA), and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by high-resolution peripheral quantitative computed tomography (HR-pCT) (for extremity measurements) and multi-detector computed tomography (for vertebral measurements). At baseline, mean age, body mass index (BMI), aBMD, and vBMD were similar among groups. At 12\u2009months, mean PA lumbar spine aBMD was higher in the rhIGF-1\/Risedronate (p\u00a0=\u20090.03) group and trended toward being higher in the Risedronate group than Placebo. Mean lateral lumbar spine aBMD was higher, in the rhIGF-1\/Risedronate than the Risedronate or Placebo groups (p\u00a0&amp;lt;\u20090.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1\/Risedronate than Placebo group (p\u00a0&amp;lt;\u20090.05). Neither hip or radial aBMD or vBMD, nor radial or tibial estimated strength, differed among groups. rhIGF-1 was well tolerated. Therefore, sequential therapy with rhIGF-1 followed by risedronate increased lateral lumbar spine aBMD more than risedronate or placebo. Strategies that are anabolic and antiresorptive to bone may be effective at increasing BMD in women with anorexia nervosa. \u00a9 2021 American Society for Bone and Mineral Research (ASBMR).<\/jats:p>","DOI":"10.1002\/jbmr.4420","type":"journal-article","created":{"date-parts":[[2021,8,6]],"date-time":"2021-08-06T07:31:10Z","timestamp":1628235070000},"page":"2116-2126","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa: A Randomized, Placebo-Controlled Trial"],"prefix":"10.1093","volume":"36","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1002-4754","authenticated-orcid":false,"given":"Melanie Schorr","family":"Haines","sequence":"first","affiliation":[{"name":"Harvard Medical School Boston MA USA"},{"name":"Neuroendocrine Unit Massachusetts General Hospital Boston MA 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