Osteoporosis in underweight women with amenorrhoea

Osteoporosis is common and important problem in women with anorexia nervosa. It is associated with a serious risk of fracture. The mechanisms underlying its development are complex and in addition to oestrogen deficiency (as seen in postmenopausal women) there are other metabolic and hormonal abnormalities all contributing to poor bone health. Leptin, an appetite regulating hormone produced in fat cells, is not surprisingly very low in women with anorexia nervosa or weight related amenorrhoea. It has been documented that, in addition to regulating appetite this hormone has important roles in controlling reproduction and bone cells differentiation and function. Raised cortisol levels often seen in women with anorexia have an important negative impact on bone health. Nutritional deficiency itself may be critical, either because of lack of specific nutrients or because of the consequent low circulating IGF-1 concentrations. Other factors are dietary deficiencies of calcium and vitamin D. Lean body mass is the major determinant of low BMD and this is independent of oestrogen status. Most women with anorexia nervosa have low BMD and over 50% have a BMD that is more than 2 standard deviations below that of their peers. Low BMD is seen after a brief duration of illness and may persist after recovery leading to a permanently low BMD.

Long term follow up study of over 200 women diagnosed with anorexia nervosa, revealed that their risk of fracture was increased 3 fold. Fractures occurred at all three sites (hip, radius and vertebrae) and, most worryingly, their peak incidence occurred some 30 years after diagnosis.

Unfortunately current regimens of treatment, other than weight gain, are not at all successful. While bone mineral density generally improves when patients regain sufficient weight and resume menstrual cycles, little or no improvement was observed in persistently underweight women treated over an 18 month period with oestrogen based hormone replacement. Reports on catch up in BMD with recovery of weight and resumption of regular periods are somewhat controversial. It is apparently observed that women with a history of anorexia tend to have low BMD at the hip for the rest of their life.

At the present time, management of osteoporosis in women with anorexia nervosa is focused on restoration of body weight and ovarian function together with calcium supplementation.