Abstract
One of the most serious and potentially permanently disabling medical complications of anorexia nervosa is osteoporosis, which greatly increases the long-term risk of bone fractures. The decreased bone density in patients with anorexia nervosa (AN) is due to the many effects on bone metabolism of amenorrhea, reduced levels of insulin growth factor-1 (IGF-1), high cortisol levels and weight loss. Although estrogen replacement therapy is clearly efficacious in preventing postmenopausal osteoporosis, its efficacy in AN is uncertain. Clinicians caring for patients with AN need to be aware of this because, despite such therapy, there may be an inexorable decline in bone mineral density in what is a relatively young group of patients. AN frequently has its onset during adolescence, when peak bone mass is normally reached, and an anorectic episode in youth may permanently impair skeletal integrity and lead to debilitating fractures and pain. It is important to recognise this formidable risk, counsel AN patients about the longterm and possibly permanent sequelae of low body weight, use densitometry to screen for bone loss and treat it accordingly. The most effective treatment is still early weight restoration and the resumption of menses.
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Shisslak C.M., Crago M., Estes L.S.: The spectrum of eating disorders. Int. J. Eat. Disord., 18, 208–219, 1995.
Engles J., Honnston M., Hunter D.: Increasing incidence of AN. Am. J. Psychiatry, 18, 1266–1271, 1995.
White C.M., Hergenroeder A.C., Klish W.J.: Bone mineral density in amenorrheic 15–21 year old females. Am. J. Dis. Child., 146, 31–35, 1992.
Lucas A.R., Melton L.J., Crowson C.S., O’Fallon W.M.: Long-term fracture risk among women with AN: a population-based cohort study. Mayo Clin. Proc., 74, 972–977, 1999.
Lucas A.R., Beard C.M., O’Fallon W.M., Kurland L.T.: 50 year trends in the incidence of AN. Am. J. Psychiatry, 148, 917–922, 1991.
Brotman A.W., Stern T.A.: Osteoporosis and pathologic fractures in AN. Am. J. Psychiatry, 142, 495–496, 1985.
Soyka L.A., Grinspoon S., Levitsky L.L., Herzog D.B., Klibanski A.: The effects of AN on bone metabolism in female adolescents. J. Clin. Endocrinol. Metab., 84, 4489–4496, 1999.
Grinspoon S., Miller K., Coyle C., Krempin J., Armstrong C., Pitts S., Herzog D., Klibanski A.: Severity of osteopenia in estrogen-deficient women with AN and hypothalamic amenorrhea. J. Clin. Endocrinol. Metab., 84, 2049–2055, 1999.
Biller B.M., Saxe V., Herzog D.G., Rosenthal D.I., Holzman S., Klibanski A.: Mechanisms of osteoporosis in adult and adolescent women with AN. J. Clin. Endocrinol. Metab., 68, 548–554, 1989.
Grinspoon S., Thomas E., Pitts S., Gross E., Mickley D., Miller K., Herzog D., Klibanski A.: Prevalence and predictive factors for regional osteopenia in women with AN. Ann. Intern. Med., 133, 790–794, 2000.
Hay P.J., Hall A., Delahunt J.W., Harper G., Mitchell A.W., Salmond C.: Investigation of osteopenia in AN. Aust. N. Z. J. Psychiatry, 23, 261–268, 1989.
Rigotti N.A., Nussbaum S.R., Herzog D.B., Neer R.M.: Osteoporosis in women with AN. N. Engl. J. Med., 311, 1601–1606, 1984.
Bachrach L.K., Guido D., Katzman D., Litt I.F., Marcus R.: Decreased bone density in adolescent girls with AN. Pediatrics, 86, 440–447, 1990.
Powers P.S.: Osteoporosis and eating disorders. J. Pediatr. Adolesc. Gynecol., 12, 51–57, 1999.
Anderson A.E., Watson T., Schlechte J.: Osteoporosis and osteopenia in men with eating disorders. Lancet, 355, 1967–1968, 2000.
Lennkh C., de Zwaan M., Bailer U., Strnad A., Nagy C., el-Giamal N., Wiesnagrotzki S., Vytiska E., Huber J., Kasper S.: Osteopenia in AN: specific mechanisms of bone loss. J. Psychiatr. Res., 33, 349–356, 1999.
Kulak C.A., Bilezikian J.P.: Bone mass measurement in identification of women at risk for osteoporosis. Int. J. Fertil. Womens Med., 44, 269–278, 1999.
Jilka R.L., Hangoc G., Girasole G.: Increased osteoclast development estrogen loss; mediation by interleukin-1. Science, 257, 88–97, 1992.
Bonjour J.P., Theintz G., Buchs B., Slosman D., Rizzoli R.: Critical years and stages of puberty for spinal and femoral bone mass accumulation during adolescence. J. Clin. Endocrinol. Metab., 73, 555–563, 1991.
Grinspoon S., Gulick T., Askari H., Landt M., Lee K., Anderson E., Ma Z., Vignati L., Bowsher R., Herzog D., Klibanski A.: Serum leptin levels in women with AN. J. Clin. Endocrinol. Metab., 81, 3861–3863, 1996.
Counts B., Gwirtsman H., Carlsson L.: The effect of AN on growth hormone-binding protein and insulin-like growth factor’s (IGFs) and binding proteins. J. Clin. Endocrinol. Metab., 75, 762–767, 1992.
Mehler P.S., Donahue T., Eckel R.: Leptin levels in AN. Int. J. Eat. Disord., 26, 189–194, 1999.
Mundy G.R. Secondary osteoporosis: the potential relevance of leptin and low body weight. Ann. Intern. Med., 133, 828–830, 2000.
Boyar R., Hellman L., Roffuarg G.: Cortisol se cretion in AN. N. Engl. J. Med., 296, 190–194, 1997.
Newman M.M., Halmi K.A.: Relationship of bone density to estradiol and cortisol in AN. Psychiatry Res., 29, 105–112, 1989.
Gold P.W., Guirstman H., Augerinus C.: Abnormal hypothalamic-pituitary function in AN. N. Engl. J. Med., 314, 1335–1341, 1986.
Delany A.M., Dong Y., Canalis E.: Mechanisms of glucocorticoid action in bone cells. J. Cell. Biochem., 56, 295–302, 1994.
Golden N., Shenker I.: Amenorrhea in AN; neuroendocrine control of hypothalamic dysfunction. Int. J. Eat. Disord., 16, 53–59, 1994.
Warren M.P.: Amenorrhea in endurance runners. J. Clin. Endocrinol. Metab., 75, 1393–1398, 1992.
Frish R.E., Revelle R., Cook S.: Components of weight at menarche: estimated total water, lean body weight and fat. Hum. Biol., 45, 469–483, 1973.
Katz M.G., Vollenhoven B.: The reproductive endocrine consequences of AN. Br. J. Obstet. Gynaecol., 107, 707–713, 2000.
Swerdloff R.S., Wang C.: Androgens, estrogens and bone in men. Ann. Intern. Med., 133, 1002–1004, 2000.
Rigotti N.A., Neer R.M., Skates S.J., Herzog D.B., Nussbaum S.R.: The clinical course of osteoporosis in AN. A longitudinal study of cortical bone mass. JAMA, 265, 1133–1138, 1991.
Anderson A.E., Woodward P.J., LaFrance N.: Bone mineral density of eating disorder subgroups. Int. J. Eat. Disord., 18, 335–342, 1995.
Iketani T., Kiriike N., Nakanishi S., Nakasuji T.: Effects of weight gain and resumption of menses on reduced bone density in patients with AN. Biol. Psychiatry, 37, 521–527, 1995.
Ward A., Brown N., Treasure J.: Persistent osteopenia after recovery from AN. Int. J. Eat. Disord., 22, 71–75, 1997.
Prior J.C., Vigna Y.M., Schechter M.T., Burgess A.E.: Spinal bone loss and ovulatory disturbances. N. Engl. J. Med., 323, 1221–1227, 1990.
Hergenroeder A.C.: Bone mineralization hypothalamic amenorrhea and sex steroid therapy in female adolescents. J. Pediatr., 126, 683–689, 1995.
Cauley J.A., Gutni J.P., Kuller L.H.: Differences in serum sex hormones and bone mineral density. Am. J. Epidemiol., 139, 1035–1046, 1994.
Goebel G., Schweiger U., Kruger R., Fichter M.M.: Predictors of bone mineral density in patients with eating disorders. Int. J. Eat. Disord., 25, 143–150, 1999.
Grinspoon S., Baum H., Lee K., Anderson E., Herzog D., Klibaski A.: Effect of shortterm insulin-like growth factor administration on bone turnover in AN. J. Clin. Endocrinol. Metab., 81, 3864–3870, 1996.
Hotta M., Fukuda I., Sato K., Hizuka N., Takano K.: The relationship between boneturnover and body weight, serum insulinlike growth factor and serum IGF-binding protein levels in patient with AN. J Clin. Endocrinol. Metab., 85, 200–206, 2000.
De Cree C.: Sex steroid metabolism and menstrual irregularities in the exercising female. Sports Med., 25, 369–406, 1998.
National osteoporosis foundation.: Physicians guide to prevention and treatment of osteoporosis. Bell Mead, NJ, Excerpta Media, 1998.
Cummings S.R., Black D.M., Nevitt M.C.: Bone density at various sites for prediction of hip fracture. Lancet, 341, 72–75, 1993.
Bauer D.C., Gluer C.C., Cauley J.A., Vogt T.M., Ensrud K.E., Genant H.K., Black D.M.: Broad band ultrasound attenuation predicts fractures strongly and in dependently of densitometry in older wo men. A prospective study. Study of osteoporotic fractures Research Group. Arch. Intern. Med., 157, 629–634, 1997.
Kanis J.A., and the WHO Study Group: Assessment of fracture risk and its application for screening post-menopausal osteoporosis. Osteoporos. Int., 4, 368–381, 1994.
Mehler P.S., Andersen A.E.: Eating Disorders: A guide to medical care and complications, The Johns Hopkins University Press, Baltimore, 2000.
Maugars Y.M., Berthelot J.M., Forrestier R., Mammar N., Lalande S., Venisse J.L., Prost A.M.: Follow-up of bone mineral density in 27 cases of AN. Eur. J. Endocrinol., 135, 591–597, 1996.
Cummings S.R., Palermo L., Browner W., Marcus R., Wallace R., Pearson J., Blackwell T., Eckert S., Black D.: Monitoring osteoporosis therapy with bone densitometry: misleading changes and regression to the mean. JAMA 283, 1318–1321, 2000.
Zipfel S., Lowe B., Peter H.C., Herzog W.: Long-term prognosis in AN, lessons from a 21-year follow up study. Lancet, 283, 1318–1321, 2000.
Sullivan P.F., Bulik C.M., Fear J.L., Pickering A.: AN: a 12-year follow up study. Am. J. Psychiatry, 155, 934–946, 1998.
Wong J.C.H., Lewindon P., Mortinsen R.: Bone mineral density in adolescents with recently diagnosed AN. Int. J. Eat. Disord., 29, 11–16, 2001.
Heaney R.P.: Pathophysiology of osteoporosis. Endocrinol. Metab. Clin. North Am., 27, 255–265, 1998.
Klibanski A., Biller B.M., Schoenfeld D.A., Herzog D.B., Saxe V.C.: The effects of estrogen administration on trabecular bone loss in young women with AN. J. Clin. Endocrinol. Metab., 80, 898–904, 1995.
Bachrach L.K., Katzman D.K., Litt I.F., Guido D., Marcus R.: Recovery from osteopenia in adolescent girls with AN. J. Clin. Endocrinol. Metab., 72, 602–606, 1991.
Baker D., Roberts R., Towell T.: Factors predictive of bone mineral density in eating-disordered women: a longitudinal study. Int. J. Eat. Disord., 27, 29–35, 2000.
Siemers B., Chakmakjian Z., Gench B.: Bone density patterns in women with AN. Int. J. Eat. Disord., 19, 179–186, 1996.
Sieman E., Wahner H.W., Offord K.P., Johnson W.J., Riggs B.L.: Differential effects of appendicular skeleton. J. Clin. Invest., 102, 1302–1313, 1982.
Davies K.M., Pearson P.H., Huseman C.A., Greger N.G., Kimmel D.K., Recker R.R.: Reduced bone mineral in patients with eating disorders. Bone, 11, 143–147, 1990.
Kotler L., Katz L., Anyan W., Comite F.: Case study of the effects of prolonged and severe AN on bone mineral density. Int. J. Eat. Disord., 15, 395–399, 1994.
Golden N.H., Jacobson M.S., Schebendach J., Solanto M.V., Hertz S.M., Shenker I.R.: Resumption of menses in AN. Arch. Pediatr. Adolesc. Med., 151, 16–21, 1997.
Bone H.G., Greenspan S.L., Bell N., Miller S.S., Yates A.J., Lombardi A.: Alendronate and estrogen effect in postmenopausal women with low bone density. J. Clin. Endocrinol. Metab., 85, 720–726, 2000.
Hergenroeder A.C., Smith E.O., Shypailo R., Jones L.A., Klish W.J., Ellis K.: Bone mineral changes in young women with hypothalamic amenorrhea treated with oral contraceptives, medroxyprogesterone, or placebo over 12 months. Am. J. Obstet. Gynecol., 176, 1017–1025, 1997.
Cumming D.C.: Exercise-associated amenorrhea, low bone density, and estrogen replacement therapy. Arch. Intern. Med., 156, 2193–2195, 1996.
Iketani T., Kiriike N., Nakanishi S., Nakasuji T.: Effect of weight gain and resumption of menses on reduced bone density in AN. Biol. Psychiatry, 37, 521–527, 1998.
Karlsson M.K., Weigall S.J., Duan Y., Seeman E.: Bone size and volumetric density in women with AN receiving estrogen replacement therapy and in women recovered from AN. J. Clin. Endocrinol. Metab., 85, 3177–3182, 2000.
Carmicheal K.A., Carmicheal D.H.: Bone metabolism and osteopenia in eating disorders. Medicine, 74, 254–267, 1995.
Naganathan V., Jones G., Nicholson G., Eisman J., Sambrook P.N.: Vertebral fracture risk with long-term corticosteroid therapy. Arch. Intern. Med., 160, 2917–2922, 2000.
Buckley L., Leib E.S., Cartularo K.S., Vacek P.M., Cooper S.M.: Calcium and vitamin D supplementation prevents bone loss in the spine secondary to corticosteroids in patients with rheumatoid arthritis. Ann. Intern. Med., 125, 961–968, 1996.
Adachi J.D., Bensen W.G., Brown J., Hanley D., Hodsman D., Josse R., Kendler D.L., Lentle B., Olszynski W., Ste-Marie L.G., Tenenhouse A., Chines A.A.: Intermittent etidronate therapy to prevent corticosteroid-induced osteoporosis. N. Engl. J. Med., 337, 382–387, 1997.
Sundgot-Borgen J., Bahr R., Falch J.A., Schneider L.S.: Normal bone mass in bulimic women. J. Clin. Endocrinol. Metab., 83, 3144–3149, 1998.
Greenspan S.L.: A 73-year-old women with osteoporosis. JAMA, 281, 1531–1540, 1999.
Recker R.R., Hinders S., Davies K.M., Heaney R.P., Stegman M.R., Lappe J.M., Kimmel D.B.: Correcting calcium nutritional deficiency prevents spine fractures in elderly women. J. Bone Miner. Res., 11, 1961–1966, 1996.
Chapuy M., Arlot M.E., Delmas P., Meunier P.J.: Effect of calcium and cholecalciferol treatment for three years on hip fractures in elderly women. B. Med. J., 308, 1081–1082, 1994.
Deal C.: Can calcium and vitamin D supplementation adequately treat patients with osteoporosis? Cleve. Clin. J. Med., 10, 696–698, 2000.
Lloyd T.: Oral contraceptive use by teenage women does not affect peak bone mass. Fertil. Steril., 74, 734–738, 2000.
Ettinger B., Black D.M., Mitlak B.H.: Reduction of vertebral risk-factor in postmenopausal women with osteoporosis treated with raloxifene. JAMA, 282, 637–645, 1999.
Johnston C.C., Bjarnason W.H., Cohen F.J., Shah A., Lindsay R., Mitlak B.H., Huster W., Draper M.W., Harper K.D., Heath H. 3rd, Gennari C., Christiansen C., Arnaud C.D., Delmas P.D.: Long-term effects of raloxifene on bone mineral density, bone turnover, and serum lipid levels in early postmenopausal women. Arch. Intern. Med., 160, 3444–3450, 2000.
Riggs B.L., Melton L.J., O’Fallon W.M.: Drug therapy for vertebral fractures in osteoporosis. Bone, 18, 197–201, 1996.
Bone H.G., Greenspan S.L., McKeever C., Bell N., Davidson M., Downs R.W., Emkey R., Meunier P.J., Miller S.S., Mulloy A.L., Recker R.R., Weiss S.R., Heyden N., Musliner T., Suryawanshi S., Yates A.J., Lombardi A.: Alendronate and estrogen effects in postmenopausal women with low bone mineral density. Alendronate/Estrogen study group. J. Clin. Endocrinol. Metab., 85, 720–726, 2000.
Schnitzer T., Bone H.G., Kiel D, Levine M.A., Yates J., Orloff J.J.: Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Aging Clin. Exp. Res., 12, 1–12, 2000.
Mehler P.S.: Diagnosing and caring for patients with AN in primary care settings. Ann. Intern. Med., 134, 1048–1059, 2001.
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Wolfert, A., Mehler, P.S. Osteoporosis: Prevention and treatment in anorexia nervosa. Eat Weight Disord 7, 72–81 (2002). https://doi.org/10.1007/BF03354433
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DOI: https://doi.org/10.1007/BF03354433