Bone metabolism in adolescent girls
Emeritus Professor, Vrije Universiteit Brussel, Brussels,
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.