This twelve-month, randomized, double-blind, placebo-controlled study «Haines MS, Kimball A, Meenaghan E, ym. Denosumab i...»1 included thirty ambulatory women over 20 years of age with anorexia nervosa or atypical anorexia nervosa and areal BMD (aBMD) T-score <−1.0 at ≥1 sites. The participants were randomized to 12 months of denosumab (60 mg subcutaneously at the start of the study and repeated at 6 months (n = 20) or placebo (n = 10). Primary end point was postero-anterior (PA) lumbar spine aBMD by dual-energy x-ray absorptiometry. Secondary end points included femoral neck aBMD, tibia and radius volumetric BMD and bone microarchitecture by high-resolution peripheral quantitative CT, tibia and radius failure load by finite element analysis (FEA), and markers of bone turnover.
Baseline mean (±s.d.) age (29 ± 8 (denosumab) vs 29 ± 7 years (placebo)), BMI (19.0 ± 1.7 vs 18.0 ± 2.0 kg/m2), and aBMD (PA spine Z-score −1.6±1.1 vs −1.7±1.4) were similar between groups. PA lumbar spine aBMD increased in the denosumab vs placebo group over 12 months (P = 0.009). The mean (95 % CI) increase in PA lumbar spine aBMD was 5.5 (3.8–7.2) % in the denosumab group and 2.2 (−0.3–4.7) % in the placebo group. The change in femoral neck aBMD was similar between groups. Radial trabecular number increased, radial trabecular separation decreased, and tibial cortical porosity decreased in the denosumab vs placebo group (P ≤ 0.006). Serum C-terminal telopeptide of type
I collagen and procollagen type I N-terminal propeptide decreased in the denosumab vs placebo group (P < 0.0001). Denosumab was well tolerated. Hypocalcemia was not detected in any participant assigned to the denosumab group.
General comment:
The official indications are postmenopausal osteoporosis and glucocorticoid-induced osteoporosis, no official indication for use in premenopausal anorexic patients. Denosumab is contraindicated in treating osteoporosis in patients younger than 18 years of age. Denosumab use, as bisphosphonate use, has been associated with osteonecrosis of the jaw and atypical femoral fractures. The effect of denosumab is not permanent, and after discontinuation of the drug, bone turnover accelerates, which may increase fracture risk unless denosumab treatment is not followed by additional therapy such as bisphosphonates. The drug crosses placenta and pregnancy should be avoided during treatment and at least 5 months after treatment.