Osteoporosis: A "New Morbidity" for Dieting Female Adolescents?

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No. 3 September 1990

Am J Epidemiol. 1989;129:173-182

8. Measles-United States, 1988. MMWR. 1989;38:35 9. Davis RM, Whitman ED, Orenstein, WA, et al. A persistent

outbreak of measles despite appropriate prevention and control measures. Am J EpidemioL 1987;126:438-449

10. Mathias RG, Meekison WG, Arcand TA, Schechter MT.

The role of secondary vaccine failures in measles outbreaks. Am J Pub Health. 1989;74:475-478

11. Markowitz LE, Preblud SR, Orenstein WA, et al. Patterns of transmission in measles outbreaks in the United States,

1985-1986. New EngI J Med. 1989;320:75-81

12. Measles on College Campuses-United States, 1985.

MMWR. 1989;34:445-449

13. Sherrod JL, Kane R, Cherry JD, Fricker J, Maples K. Effect of timing of measles vaccination on compliance with im-munizations during the second year of life. J Pediatr.

1983;102:186-190

14. Sabin AB, Arechiga AF, DeCastro JF, et a!. Successful immunization of infants with and without maternal anti-body by aerosolized measles vaccine, II. Vaccine compari-sons and evidence for multiple antibody response. JAMA.

1983;251:2363-2371

15. Brunell PA. Measles vaccine-one or two doses? Pediatrics. 1988;81:722-724

Osteoporosis:

A “New

Morbidity”

for Dieting

Female

Adolescents?

Almost half of the adult skeletal mass is laid down during the adolescent years. The concept of

the “bone bank” reminds us that “deposits” of

calcium are normally made to the skeleton until

about 35 years of age in females. Subsequently, there are continuous “withdrawals” ofbone mineral and loss of skeletal mass, eventually resulting in osteopenia (significantly reduced bone mass) and

osteoporosis (osteopenia associated with

atrau-matic fractures) in more than 20 million

postmen-opausal women, at an annual cost of $7 to 10 billion

in the United States.’

Because there is no cure, prevention of the most common and conspicuous physical finding of adult osteoporosis, the so-called “dowager’s hump” (marked thoracic kyphosis due to vertebral compression fractures), as well as the more serious complications, such as hip fractures, must focus on optimizing the peak bone mass and maintaining the

skeletal mass. In adults, a mere 10% decrease in

bone mineral density (BMD) is associated with a two- to threefold increase in fracture risk. The report by Bachrach and colleagues2 underscores the need for clinicians to consider osteopenia and os-teoporosis as potentially significant problems not only for the elderly, but also for young females with anorexia nervosa, in particular, and those with de-creased weight for height, in general.

Reports of BMD and pathological fractures to date have focused primarily on women with long-standing anorexia nervosa. Earlier studies also used techniques, such as metacarpal cortical thickness measurements3’4 or single-photon absorptiometry,5 that are not applicable to vertebral or femoral bone. Small sample size6 and lack of appropriate control data7 limit the clinical interpretation of recent

in-vestigations of BMD in adolescents with anorexia nervosa. Thus, this study reporting vertebral and whole body bone mineral density more than 2 SD less than values for age-match controls in 12 of 18 female adolescents with anorexia nervosa (half of whom were diagnosed less than a year earlier) is an important, although worrisome, addition to the lit-erature.

The risk factors for osteopenia in anorexia ner-vosa are well known and are related to a negative net balance between bone resorption and forma-tion. Factors related to increased bone loss through resorption include hypoestrogenemia (amenorrhea) and glucocorticoid excess (chronic stress). De-creased bone formation also occurs with glucocor-ticoid excess and with inadequate calcium and pro-tein intake.

The effect of exercise on BMD in anorexia ner-vosa remains controversial. Weight-bearing activity has been reported as being protective against5 as well as unrelated to2’6 bone loss; a recent report

suggests that moderate exercise is beneficial, but

strenuous exercise is detrimental to BMD.7 This

nonlinear effect may explain the finding by

Bach-rach and colleagues of “severe osteopenia in several patients who engaged in regular vigorous exercise.” Unfortunately, there is no reliable means of ac-tually measuring the amount of weight-bearing ac-tivity through time, so that patients have been placed in one of two or three hierarchical levels of exercise. Ideally, the type, frequency, duration, and intensity of activity all need to be considered, and the combined effect could be transformed into a unit of measurement that allows for comparison among patients and studies.

Calcium intake in anorexia nervosa is generally low, but it has not been found to be related to BMD

in this or other studies of anorexia nervosa. What

is important in this regard is actual calcium (and

protein) intake through time. Like exercise, this is very difficult to determine with any degree of ac-curacy, particularly if the method used is year-long recall by telephone interview. Additionally, some of the effect of these factors on BMD may be mediated

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COMMENTARIES 479

through hormonal influences. For example, it has

been demonstrated recently that a diet low in cal-cium but high in phosphorous (typical of adolescent eating patterns) is associated with the elevation of

immunoreactive parathyroid hormone levels and

the decrease of ionized calcium levels,8 a potential

cause of osteopenia.

Unlike exercise output or nutritional intake through time, determining the duration of amen-orrhea and excess urinary cortisol excretion is rel-atively simple. Both of these factors have been shown to be related to increased bone loss in adults.57’9 Interestingly, Biller and colleagues found that adult anorexia nervosa patients with the onset

of amenorrhea before the age of 18 years had

sig-nificantly lower spinal bone density than those with later onset, despite comparable duration of

amen-orrhea between the two groups. This is in keeping

with the findings by Bachrach and colleagues who found a trend for bone density to be lower in girls

with primary amenorrhea; they propose that

estro-gen deficiency may have a more profound effect on bone mass if it begins at an earlier age. However, in contrast to other studies and difficult to explain, a correlation between the duration of secondary amenorrhea and any measure of bone density was

not found in the present study. As the authors point out, the relative contributions of estrogen defi-ciency and decreased body mass index to decreased

BMD are difficult to assess. In this regard it is

important to point out that lean body mass, as well as fat, is lost in anorexia nervosa.’#{176}

As noted, the relative contributions of increased bone resorption and decreased bone formation in determining the low BMD in Bachrach’s patient population cannot be determined from the present

study. However, there is reason to believe that

decreased bone formation is important, especially for those who have not yet completed growth. This

issue is rarely addressed in studies of adults, for

whom growth is complete and increased bone re-sorption is the primary mode of decreased BMD. Two of the subjects from Bachrach’s group at Stan-ford had height more than 2 SD less than the mean

for age, and they had been ill for 5.3 and 7 years,

respectively. Data from Rochester and Long Island

suggest that early-onset anorexia nervosa is

asso-ciated with reduced adult height.”2 In each of

these settings unrecognized dieting may have

pre-ceded the actual diagnosis of the eating disorder and resulted in slight, but measureable, changes in growth.

Concern about growth and development is par-ticularly important in light of the frequency with

which preadolescents perceive a need to diet, lose

weight, or exercise.’3 The present study emphasizes that weight for height correlates significantly with

BMD in controls as well as in patients. Thus, failure to gain weight normally during puberty, per se,

predisposes the patient to reduced skeletal mass

and an increased risk of osteoporosis later in life. Women have less skeletal mass than men, and

adolescent girls have less skeletal mass than ado-lescent boys. Therefore, any decrease in bone mass in adolescent girls makes for increased hazard later

in life. Even female athletes who are thin and

amenorrheic, although in most respects they are considered healthy, appear to be predisposed to

osteopenia and to enter midlife with a reduce bone

mass putting them at risk for osteoporosis.’4 A variety of noninvasive methods of determining BMD are currently available. Single photon ab-sorptiometry is useful in measuring appendicular

(predominantly cortical) bone, such as the distal radius. Dual photon absorptiometry, on the other

hand, is useful in measuring trabecular bone of the axial skeleton, such as the lumbar vertebrae or

femur. The fact that vertebral BMD was affected more severely than radial BMD in Bachrach’s sub-jects probably relates to the fact that trabecular bone has more rapid turnover than cortical bone and would therefore be more responsive to meta-bolic perturbations such as starvation. The use of quantitative computed tomography, involving 75 times the radiation exposure of absorptiometry, cannot be justified in females of reproductive age.’5

As in all good research, more questions are raised

by this study than are answered. Who should be screened for decreased BMD (adolescents with eat-ing disorders, female adolescents with low body

mass index, female adolescents with amenorrhea

for more than 1 year)? Should we consider certain

subgroups of adolescents with eating disorders to

be at greater risk of osteopenia than others? An-derson and LaFrance’6 have reported that patients with anorexia nervosa who also binge eat and purge have the lowest BMD among their patients with

eating disorders. What method should be used, and

what anatomic areas should be studied? Recent studies suggest that the hip may be affected more severely than the spine’7 and that the femoral tro-chanter may be affected more severely than the femoral neck.7

Although the net effect on BMD is reduction, does anorexia nervosa result in decreased bone formation, increased bone resorption, or a combi-nation? Only studies that measure bone formation and resorption rates (such as measurement of os-teocalcin and hydroxyproline) or that include bone

biopsy will be able to answer this question. More

important clinically is the issue of the reversibility of osteopenia: Can adolescents regain BMD, as infants have “catch up growth” after a prolonged illness? There is some evidence that they can.’8

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1990

Finally, who should be treated for decreased BMD, and how? Fracture risk rates related to BMD have only been determined for adults; similar thresholds need to be determined for adolescents. Weight gain is central to the treatment of anorexia

nervosa, and the evidence suggests that decreased

weight is one of the strongest determinants of low BMD. Adequate calcium intake is also prudent.

However, adolescents in general, and those with anorexia nervosa in particular, tend to avoid the

richest source of dietary calcium, dairy products,

because of the misperception that they are

“fatten-ing.” Noncompliance with recommended calcium

intake may even occur with calcium supplements. Exercise tends to be abused by patients with an-orexia nervosa, and excessive exercise may increase

the risk of fracture by placing undue structural stresses on the bony matrix. At this point, hormonal

therapy cannot be recommended without adequate research regarding its effects.

To answer these questions, researchers need to work collaboratively in longitudinal studies. The information that could be gained from such an effort would benefit not only those relatively few affected by eating disorders, but also has implica-tions for the numerous adolescents who engage in

dieting.

REFERENCES

RICHARD E. KREIPE, MD

GILBERT B. FORBES, MD

University of Rochester Medical Center Departmenbt of Pediatrics

Divisions of Adolescent Medicine and Pediatric Endocrinology

Rochester, New York 14642

1. Culliton BJ. Osteoporosis reeaxamined: complexity of bone biology is a challenge. Science. 1987;235:833-834

2. Bachrach LK, Guido D, Katzman D, Litt IF, Marcus R. Decreased bone density in adolescent girls with anorexia nervosa. Pediatrics. 1990;86:440-447

3. Ayers JWT, Gidwani GP, Schmidt HMV, et al. Osteopenia in hypoestrogenemic young women with anorexia nervosa. Fertil Steril. 1984;41:224-228

4. Crosby LO, Kaplan FS, Pertschuk MJ, et al. The effect of anorexia nervosa on bone morphometry in young women. Clin Orthop. 1985;210:271-277

5. Rigotti NA, Nussbaum SR, Herzog DB, et al. Osteoporosis

in women with anorexia nervosa. N Erzgl J Med.

1984;311:1601-1606

6. Biller BMK, Saxe V, Herzog DB, et al. Mechanisms of osteoporosis in adult and adolescent women with anorexia nervosa. J Clin Endocrinol Metab. 1989;68:548-554

7. Joyce JM, Warren DL, Humphries LL, et al. Osteoporosis in women with eating disorders: comparison of physical parameters, exercise and menstrual status with SPA and

DPA evaluation. J NucI Med. 1990;31:325-331

8. Calvo MS, Kumar R, Heath H. Persistently elevated para-thyroid hormone secretion and action in young women after four weeks of ingesting high phosphorous, low calcium diets. J Clin Endocrinol Metab. 1990;70:1334-1340

9. Newman MM, Halmi KA. Relationship of bone density to

estradiol and cortisol in anorexia nervosa and bulimia. Psy-chiatry Res. 1989;29:105-112

10. Forbes GB, Kreipe RE, Lipinski BA, Hodgman CH. Body composition changes during recovery from anorexia nervosa: comparison of two dietary regimes. Am J Clin Nutr.

1984;40:1137-1145

11. Kreipe RE, Churchill BH, Strauss J. Short stature in an-orexia nervosa. Pediatr Res. 1989;25:7A

12. Nussbaum M, Baird D, Sonnenblick M, et al. Short stature in anorexia nervosa patients. J Adolesc Health Care. 1985;6:453-455

13. Maloney MJ, McGuire J, Daniels SR, Specker B. Dieting behavior and eating attitudes in children. Pediatrics. 1989;84:482-489

14. Drinkwater BL, Bruemner MS, Chestnut CH. Menstrual history as a determinant of current bone density in young athletes. JAMA. 1990;263:545-548

15. Chestnut CH. Noninvasive techniques for measuring bone

mass: a comparative review. Clin Obstet Gynecol.

1987;30:812-819

16. Anderson AE, LaFrance N. Persisting osteoporosis in buli-mia nervosa patients with past anorexia nervosa. Presented at Fourth International Conference on Eating Disorders; April 28, 1990; New York, NY

17. Treasure J, Fogelman I, Russell GFM. Osteopaenia of the lumbar spine and femoral neck in anorexia nervosa. Scott Med J. 1986;31:206-207

18. Treasure JL, Russell GFM. Reversible bone loss in anorexia nervosa. Br Med J [Clin Res]. 1987;295:474-475

It is the customary fate of new truths to begin as heresies and to end as superstitions.

-T.H. Huxley

Submitted by Student

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1990;86;478

Pediatrics

Richard E. Kreipe and Gilbert B. Forbes