Abstract

Anorexia nervosa, a psychiatric disorder predominantly affecting women, is characterized by self-induced starvation, low body weight, low subcutaneous and visceral fat depots, and low bone mass. More than 85% of women with anorexia nervosa have bone mineral density (BMD) values more than one standard deviation below the mean of women of comparable age. Although there is a significantly increased risk of fracture in women with anorexia nervosa, low BMD has not been shown to consistently predict the increased fracture rate in this population. Despite low subcutaneous and visceral adipose tissue stores, women with anorexia nervosa have increased bone marrow adiposity, which is inversely associated with BMD. We hypothesized that increased bone marrow adipose tissue would be associated with the increased fracture rate in women with anorexia nervosa. We studied sixty-two women: 34 with anorexia nervosa (mean age + SEM: 28.3 + 0.9 years) and 28 normal-weight controls of similar age (28.3 + 1.1 years; p=0.72). We examined associations between lifetime self-reported fracture history and 1) BMD of the lumbar spine (L1-L4), lateral spine (L2-L4), total hip, and femoral neck measured by dual energy X-ray absorptiometry and 2) bone marrow adipose tissue at the spine (L4 vertebra) and hip (femoral metaphysis, diaphysis and epiphysis) measured by 1H-magnetic resonance spectroscopy. Women with anorexia nervosa had significantly lower BMD at the spine and hip (p<0.0001 at all sites) and significantly higher bone marrow adipose tissue at the L4 vertebra (p<0.0001) and femoral metaphysis (p=0.001) as compared to normal-weight controls. Forty-seven percent (n=16) of women with anorexia nervosa versus 39% (n=11) of normal-weight controls reported a lifetime history of fracture (p=0.54). In women with anorexia nervosa, there was no significant association between fracture history and BMD at the spine or hip (p=0.27-0.98). In the group as a whole, bone marrow adipose tissue was greater in the L4 vertebra in individuals with a history of fracture compared to those without a fracture history (p=0.02). In subjects with anorexia nervosa, those with a history of fracture had greater bone marrow adipose tissue at the L4 vertebra (p=0.01) and femoral diaphysis (p=0.01) compared to those without a history of fracture; these differences in bone marrow adipose tissue remained significant after controlling for BMI (p=0.01-0.03) and also after controlling for BMD (p<0.01 for both). Higher bone marrow adipose tissue is associated with increased fracture prevalence and may be a better predictor of fracture risk than BMD in women with anorexia nervosa. Future prospective studies will be necessary to better understand the association between bone marrow adiposity and fracture risk in this population.

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