Preliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa

doi:10.1016/1054-139X(93)90181-N

Journal of Adolescent Health

Volume 14, Issue 4, June 1993, Pages 319-324

https://doi.org/10.1016/1054-139X(93)90181-N Get rights and content

Abstract

We performed tetracycline double-labeled bone biopsies and serial bone densitometry on four patients with anorexia nervosa to determine the effects of various conditions of sex hormone replacement and body weight status. We found negligible bone mineral apposition rate in two patients with anorexia nervosa who were taking estrogen and progestin pills while weighing only 79% of normal. However, bone mineral apposition rate was normal in two patients with anorexia nervosa who took no sex hormones and remained amenorrheic while weighing 87% of normal. Histomorphometric analysis revealed a decrease in intracortical trabecular area by 57% and an increase in active osteoblastic surface area by 300%, comparing the subjects who were taking hormone replacement to those who were not. There was no direct evidence of increased resorption in any subject. Six months after biopsy, the two subjects taking sex hormones decreased lumbar bone mineral density by 1.9%, while the two taking no sex hormones remained amenorrheic, but increased bone mineral density by 1.3%. Therefore, we propose that sex hormone therapy in the presence of persistently low body weight might be of limited benefit for bone mineral apposition and density.

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Osteoporosis is a common complication of anorexia nervosa (AN). Although weight recovery and resumption of menses are important goals in AN treatment, they are often achieved only after a prolonged period of recovery. Therefore, it becomes important to find therapies with the potential to prevent further decreases in bone mineral density (BMD). We conducted a non-randomized study of the effects of menatetrenone (vitamin K2) on bone loss in patients with AN. Lumbar BMD was longitudinally measured by Dual Energy X-ray Absorptiometry (DXA) in 10 patients with AN who chose to receive menatetrenone treatment (MED+ group) and 11 patients who did not (MED− group). During the mean 0.9-year follow-up period, the BMD of the lumbar vertebrae of the MED+ group decreased significantly less than that of the MED− group (−2.8% and −6.9%, respectively). Among bone metabolism markers, γ-carboxyglutamic acid osteocalcin significantly increased (128.6% and 28.3%, respectively) and urine deoxypyridinoline significantly decreased (−44.5% and −13.7%, respectively) more in the MED+ group than in the MED− group. These differences in BMD and bone metabolism markers may be attributable to menatetrenone treatment. The results suggest that menatetrenone may be beneficial in the prevention of bone loss in patients with AN. Randomized placebo-controlled studies are needed to confirm these findings.
The effect of estrogen-progestin treatment on bone mineral density in anorexia nervosa
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Design, Setting, and Participants: A prospective observational study of 50 adolescents with AN (mean age 16.8 ± 2.3 yrs) was conducted in a tertiary referral center.
Main Outcome Measures: Bone mineral density (BMD) of the lumbar spine and left hip were prospectively measured using dual-energy x-ray absorptiometry at baseline and annually.
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Results: At presentation, patients were malnourished (79.5% ± 7.6% IBW), hypoestrogenemic (estradiol 24.7 ± 10.7 pg/mL), and had reduced bone mass (lumbar spine BMD −2.01 ± 0.69 SD below the young adult reference mean). Ninety-two percent of subjects were osteopenic and 26% met WHO criteria for osteoporosis. Body weight, and no treatment group, was the major determinant of BMD. At one-year follow-up, there were no significant differences in absolute values or in net change of lumbar spine or femoral neck BMD between those who received estrogen-progestin and those who received standard Rx (80% power of finding a 3% difference in BMD at 1 yr). In those followed for 2–3 yrs, osteopenia was persistent and in some cases progressive.
Conclusion: In our study population, estrogen-progestin did not significantly increase BMD compared with standard Rx. These results question the common practice of prescribing hormone replacement therapy to increase bone mass in AN.
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Citation Excerpt :
A 1999 study of women with anorexia nervosa suggested that bone formation was reduced but bone resorption normal,122 whereas another study suggested that bone formation was decreased and bone resorption increased.20 Further analyses of bone turnover indices in women with hypothalamic amenorrhea and anorexia nervosa have also produced inconsistent results, with some data suggesting normal bone turnover and other data suggesting low bone formation that is uncoupled from bone resorption.49,68 A 1998 study of amenorrheic long-distance runners demonstrated reductions in bone turnover and, particularly, in bone formation.145
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Several environmental stressors are thought to be associated with hypothalamic amenorrhea; reproductive function may be affected by emotional stress, exercise, or weight loss. Recent research suggests that hypothalamic amenorrhea may be an adaptive response to chronic low energy intake, and that metabolic factors in response to nutritional insults might mediate reproductive adaptations. Poor nutrition or an energy deficit with an adaptation to large caloric needs is fundamentally linked with a prolonged amenorrheic state.127, 144, 145, 146
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^☆: This work was supported in part by Public Health Service Grant RR-00044 from the General Clinical Research Branch, Division of Research Resources, National Institutes of Health (R.E.K.) and NIH Grant AR28420 (J.E.P. and R.N.R.).

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Original articlePreliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa☆

Abstract

Bone

Psychiatry Res

Fertil Steril

Orthop Clin North Am

Contraception

Bone mineral density and anorexia nervosa in women

Am J Psychiatr

The clinical course of osteoporosis in anorexia nervosa: A longitudinal study of cortical bone mass

JAMA

Osteoporosis in women with anorexia nervosa

New Engl J Med

Osteoporosis in anorexia nervosa

Aust N Z J Psychiatry

Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa

J Clin Endocrinol Metab

Bone mineral density in 15- to 21-year-old eumenorrheic and amenorrheic subjects

Am J Dis Child

Investigation of osteopaenia in anorexia nervosa

Aust N Z J Psychiatry

Original article
Preliminary findings on the effects of sex hormones on bone metabolism in anorexia nervosa☆