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

Maugars YM, Berthelot J-MM, Forestier R, Mammar N, Lalande S, Venisse J-L, Prost AM. Follow-up of bone mineral density in 27 cases of anorexia nervosa. Eur J Endocrinol 1996;135:591–7. ISSN 0804–4643 Cortical and trabecular bone loss can lead to osteoporosis in chronic forms of anorexia nervosa (AN). As there is some debate about the reversibility of this condition, we performed a longitudinal follow-up study of 27 cases in which clinical, biological, X-ray and lumbar and femoral neck dual photon absorptiometry examinations were conducted every 6 months for up to 30 months. Three groups were distinguished: G1, untreated amenorrheic AN (N = 14, total follow-up 126 months); G2, effectively treated AN (N = 11, total follow-up 192 months), with two subgroups: fluoride (N = 5) and estrogen (N = 6); and G3, remitting AN with normalization of the gonadic function (N = 2, total follow-up 36 months). Results were adjusted for each patient to a 6-month variation. Semestrial variations in lumbar bone mineral density (BMD) were −2.1 ± 1.3%, +2.8 ± 1.5% and −0.3 ± 1.3% (mean ± sem), respectively for G1, G2 and G3; those for femoral neck BMD semestrial variations were −5.9 ± 2.1%, −3.8 ± 1.2% and −1.0 ± 0.6%. Femoral neck and lumbar BMD variations for G1 were mainly correlated positively with bone-forming markers (serum osteocalcin, alkaline phosphatase) and negatively with initial lumbar BMD. Estrogen alone increased lumbar BMD by +1.4 ± 2.3% every 6 months but did not stabilize femoral neck BMD (−3.5 ± 1.4%). Fluoride increased lumbar BMD by 4.8 ± 1.8%. Both lumbar and femoral neck BMD were stabilized in the remission group (−0.3 ± 1.3% and −1.0 ± 0.6%), despite half of the follow-up time with amenorrhea. In conclusion, untreated AN is associated with a marked trabecular and cortical bone loss (4–10% per year), which can lead to osteoporotic fractures. In prevention of bone loss, the efficacy of estrogen is difficult to investigate in AN, even with a well-controlled trial. Our study could provide argument that, when the observance of this preventive treatment is assessed, lumbar BMD can be stabilized in chronic forms of AN. Yves Maugars, CHU de Nantes, Service de Rhumatologie, 44035 Nantes, Cédex 01, France

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Sequential Therapy With Recombinant Human IGF-1 Followed by Risedronate Increases Spine Bone Mineral Density in Women With Anorexia Nervosa

Journal of the Endocrine Society ◽

10.1210/jendso/bvab048.513 ◽

2021 ◽

Vol 5 (Supplement_1) ◽

pp. A252-A253

Author(s):

Melanie S Haines ◽

Allison Kimball ◽

Erinne Meenaghan ◽

Katherine N Bachmann ◽

Kate Santoso ◽

...

Keyword(s):

Bone Mineral Density ◽

Anorexia Nervosa ◽

Placebo Group ◽

Bone Formation ◽

Bone Mineral ◽

Sequential Therapy ◽

Controlled Study ◽

Mineral Density ◽

Quantitative Ct ◽

Lateral Spine

Abstract Anorexia nervosa is complicated by low bone mineral density (BMD) and increased fracture risk associated with low bone formation and high bone resorption. The spine, particularly its trabecular component as measured by lateral spine dual-energy x-ray absorptiometry (DXA), is most severely affected. Low BMD and bone formation are associated with relative insulin-like growth hormone-1 (IGF-1) deficiency. Our objective was to determine whether bone anabolic therapy with off-label recombinant human (rh)IGF-1 followed by antiresorptive therapy with risedronate would increase BMD more than risedronate alone 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) (Z- or T-score <-1.0). Participants were randomized to 1 of 3 groups: 6 months of rhIGF-1 (starting dose 30 mcg/kg SQ BID) followed by 6 months of risedronate (35mg PO weekly) (“rhIGF-1/Risedronate”) (n=33), 12 months of risedronate (35mg PO weekly) (“Risedronate”) (n=33), or double placebo (“Placebo”) (n=16). Participants received calcium 1200 mg and vitamin D 800 IU daily. rhIGF-1 was titrated to maintain IGF-1 levels within the age-adjusted normal range. Main outcome measures were aBMD at the spine [1° endpoint: postero-anterior (PA) spine BMD], hip, and radius by DXA, and vertebral, tibial, and radial volumetric BMD (vBMD) and estimated strength by multi-detector computed tomography (MDCT) or high-resolution peripheral quantitative CT (HR-pQCT). At baseline, mean age [28 ± 7 y (mean ± SD)], BMI (18.5 ± 1.9 kg/m2), and BMD were similar among groups. At 12 months, mean PA spine aBMD was higher in the rhIGF-1/Risedronate (p=0.03), and trended towards being higher in the Risedronate (p=0.08), group than the Placebo group. Mean lateral spine aBMD was higher in the rhIGF-1/Risedronate than either the Risedronate (p=0.002) or Placebo (p=0.04) groups. From baseline to 12 months, mean PA and lateral spine aBMD increased by 1.9 ± 0.6% and 4.2 ± 1.0% in the rhIGF-1/Risedronate (p<0.05), 1.7 ± 0.8% and 1.7 ± 1.0% in the Risedronate (p=NS), and decreased by 0.3 ± 0.8% and 1.1 ± 1.3% in the Placebo (p=NS), groups, respectively. Areal BMD Z-scores did not normalize in any group. At 12 months, vertebral vBMD by MDCT was higher (p<0.05), and vertebral strength trended towards being higher, in the rhIGF-1/Risedronate than Placebo group. Neither hip or radial BMD, nor radial or tibial estimated strength, by HR-pQCT differed among groups. rhIGF-1 was well tolerated. In conclusion, sequential therapy of 6 months of rhIGF-1 followed by 6 months of risedronate increased lateral spine aBMD, the site most severely affected in women with anorexia nervosa, more than risedronate or placebo. These data suggest that strategies that are anabolic and antiresorptive to bone may be most effective in increasing BMD in women with anorexia nervosa.

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