Anorexia nervosa is complicated by
low bone mineral density (BMD) and increased fracture risk associated with low bone 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 months of rhIGF-1 followed by 6 months of
risedronate ("rhIGF-1/
Risedronate") (n = 33), 12 months of
risedronate ("
Risedronate") (n = 33), or double placebo ("Placebo") (n = 16). Outcome measures were lumbar spine (1° 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 months, mean PA lumbar spine aBMD was higher in the rhIGF-1/
Risedronate (p = 0.03) 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 < 0.05). Vertebral vBMD was higher, and estimated strength trended toward being higher, in the rhIGF-1/
Risedronate than Placebo group (p < 0.05). 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. © 2021 American Society for Bone and
Mineral Research (ASBMR).