Sequential therapy beefs up bone density in women with anorexia

Administering recombinant human insulin-like growth hormone-1 (rhIGF-1) for 6 months followed by risedronate for another 6 months helps improve bone mineral density (BMD) at the spine in women with anorexia nervosa, according to a study.

The women who received sequential therapy had greater increases in spine BMD than those on risedronate alone or placebo, said study co-author Dr Melanie Haines of the Massachusetts General Hospital/Harvard Medical School in Boston, MA, USA, during the Endocrine Society meeting (ENDO 2021).

“These data suggest that strategies that are anabolic and antiresorptive to bone may be most effective in increasing BMD in women with anorexia nervosa,” she said.

Anorexia is complicated by low BMD, and patients with the psychiatric disorder exhibit low bone formation as well as high bone resorption rates, Haines pointed out. This puts the patients at risk of developing fractures. “The spine, particularly its trabecular component as measured by lateral spine dual-energy x-ray absorptiometry, is most severely affected.”

Based on the premise that low BMD and bone formation are associated with relative IGF-1 deficiency, Haines and colleagues tested whether anabolic therapy with off-label rhIGF-1 followed by antiresorptive treatment with risedronate would provide huge gains in spine BMD. They randomized 90 ambulatory women (mean age 28 years, mean body mass index 18.5 kg/m²) with anorexia nervosa and low areal BMD (aBMD; Z- or T-score ≤1.0).

Of the patients, 33 received 6 months of rhIGF-1 (administered subcutaneously twice daily at a starting dose of 30 mcg/kg, then titrated to maintain IGF-1 levels within the age-adjusted normal range) followed by 6 months of risedronate (given at 35 mg orally weekly), 33 were treated with 12 months of risedronate (35 mg orally weekly), and 16 were given double placebo. In addition, all of them received daily calcium 1,200 mg and vitamin D 800 IU supplements.

In her presentation, Haines noted that mean postero-anterior (PA) spine at month 12 showed the biggest gain with sequential therapy (p=0.03), with a trend toward being higher with risedronate alone (p=0.08), when compared with placebo. On the other hand, mean lateral spine aBMD was higher in the sequential therapy group than in either groups (p=0.002 and p=0.04, respectively). [ENDO 2021, abstract OR06-1]

From baseline to 12 months, mean PA and lateral spine aBMD increased markedly by 1.9 percent and 4.2 percent on sequential therapy (p<0.05), both by 1.7 percent on risedronate (not significant), and dropped by 0.3 percent and 1.1 percent on placebo, respectively.

Nevertheless, areal BMD Z-scores did not normalize in any group, Haines said.

The changes induced by sequential therapy in vertebral volumetric BMD (measured using multi-detector computed tomography) were more favourable than placebo (p<0.05), while that in vertebral strength trended toward being higher. There were no between-group differences noted in hip or radial BMD and in radial or tibial estimated strength (evaluated using high-resolution peripheral quantitative CT).

RhIGF-1 was well tolerated.

Taken together, the findings highlight the beneficial effect of sequential therapy with rhIGF-1 and risedronate on “lateral spine aBMD, the site most severely affected in women with anorexia nervosa,” according to Haines.