Bone metabolism in adolescent girls

J.J. Amy

Emeritus Professor, Vrije Universiteit Brussel, Brussels, Belgium

Bone mineral density (BMD) reflects the balance between the continuous processes of bone formation and resorption. These are controlled by intricate mechanisms wherein exercise, as well as nutritional and endocrine factors, plays a very important role.

Moderate exercise helps to prevent bone loss, whereas strenuous exercise may promote it. Body weight is a major determinant of BMD accrual in postpubertal girls. Leptin, which is secreted by adipocytes, binds to its receptors in the GnRH pulse generator located in the arcuate nucleus of the hypothalamus. The pulsatile release of GnRH in turn elicits the production of gonadotrophins that stimulate ovarian folliculogenesis and steroid production.

Normally, at least 40 % of bone mass is formed during adolescence and early adulthood. During this phase of life, the dietary requirement of calcium increases from about 900 mg/day to about 1500 mg/day. Unfortunately, the calcium intake in that age group is often insufficient, which adversely affects skeletal development. Women attain their peak bone mass around 25 years of age; bone loss starts normally after the age of 40, and accelerates after menopause, unless this latter is treated.

Oestrogens, in particular oestradiol, inhibit the activity of osteoclasts. Oral, vaginal and transdermal oestrogen/progestogen contraceptives used by adolescents and young women presumably enhance the acquisition of a satisfactory bone mass. Long-term users of depot-medroxyprogesterone acetate on the contrary show a decrease in their bone density, which is reversible after cessation of therapy. Hypooestrogenism as seen in hypothalamic amenorrhoea (e.g., GnRH deficiency) or ovarian failure (e.g., Turner's syndrome) is associated with a negative skeletal mineral balance, which can be corrected by hormone replacement therapy (HRT).

This treatment is of limited benefit in anorexia nervosa. Indeed, multiple interacting factors contribute to the development of osteoporosis in anorectic patients : beside the decreased body fat and body weight, and the deficient oestrogen production, one notes an inadequate dietary calcium intake, vitamin D deficiency, elevated cortisol levels, and excessive strenuous physical exercise. The only proven treatment for osteoporosis in anorexia nervosa consists of regaining sufficient body weight and body fat, leading to the resumption of menstrual cycles. Yet, HRT should be contemplated if amenorrhoea has lasted for more than one year, and the patient is still underweight. Bisphosphonates and recombinant insulin-like growth factor-1 (IGF-1) are presently being investigated but show little promise in terms of clinical application in this entity.

BMD is decreased and stress fractures are more frequent in athletes with exercise-associated amenorrhoea; this is due to delayed skeletal maturation, accelerated bone loss, or both. These subjects often began endurance training at an early age, and this interfered with their development of an adequate bone mass. The bone loss is worsened by the nutritional disturbances so common in amenorrhoeic athletes. Treatment consisting of a modification of the exercise programme, an adjustment of diet and, possibly, the cyclic administration of an oestrogen/progestogen preparation will partially or completely reverse the observed skeletal anomalies.

Patients with a complete androgen insensitivity syndrome have BMDs lower than those of unaffected women. The anomaly precedes gonadectomy; it may be worsened by an inadequate oestrogen replacement following the procedure.