Treatment of anorexia nervosa is associated with increases in bone mineral density, and recovery is a biphasic process involving both nutrition and return of menses. Am J Clin Nutr

Department of Obstetrics and Gynecology, Columbia University Medical Center, New York, NY 10032, USA.
American Journal of Clinical Nutrition (Impact Factor: 6.77). 08/2007; 86(1):92-9.
Source: PubMed


Recovery from osteoporosis in anorexia nervosa (AN) is uncertain.
The purpose of this study was to understand the changes in bone mineral density (BMD) in women with AN and the mechanisms of recovery from osteopenia.
We studied BMD and markers of bone formation and resorption, osteocalcin and N-telopeptide (NTX), in patients with AN (n=28) who were following a behavioral weight-gain protocol.
Anorexic patients experienced significant percentage increases in BMD (4.38 +/- 7.48% for spine; 3.77 +/- 8.8% for hip; P<0.05 for both) from admission until recovery of 90% ideal body weight, achieved over 2.2 mo. NTX concentrations were higher in patients with AN at admission than in healthy control subjects (n=11; 69.0 +/- 31.09 and 48.3 +/- 14.38 nmol/mmol creatinine, respectively; P<0.05) and in reference control subjects (n=30; 69.0 +/- 31.09 and 37.0+/-6.00 nmol/mmol creatinine, respectively; P<0.001). In weight-recovered subjects with AN, osteocalcin increased (from 8.0 +/- 3.05 to 11.2 +/- 6.54 ng/mL; P<0.05), whereas NTX remained elevated (from 69.0 +/- 31.09 to 66.7 +/- 45.5 nmol/mmol creatinine; NS). A decrease in NTX (from 70.7 +/- 40.84 to 45.9 +/- 22.72 nmol/mmol creatinine; NS) occurred only in the subgroup of subjects who regained menses with weight recovery.
Nutritional rehabilitation induces a powerful anabolic effect on bone. However, a fall of NTX and a shift from the dominant resorptive state, which we postulate involves full recovery, may involve a hormonal mechanism and require a return of menses. Nutritional rehabilitation appears to be critical to bone recovery and may explain the ineffectiveness of estrogen treatment alone on BMD in the cachectic state.

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    • "Persistent amenorrhea at this age may lead to reduced peak bone mass and result in an increased risk for bone fractures later in life [11]. Studies have revealed that the normalization of body weight alone does not improve bone density; rather, the optimization of body weight and the normalization of gonadal status are necessary [12-14]. Moreover, in adolescent AN, starvation-induced hormonal deficiencies may lead to impairments in the maturation of certain brain regions that result in deficits in neuropsychological functioning [15-17]. "
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    ABSTRACT: The resumption of menses is an important indicator of recovery in anorexia nervosa (AN). Patients with early-onset AN are at particularly great risk of suffering from the long-term physical and psychological consequences of persistent gonadal dysfunction. However, the clinical variables that predict the recovery of menstrual function during weight gain in AN remain poorly understood. The aim of this study was to investigate the impact of several clinical parameters on the resumption of menses in first-onset adolescent AN in a large, well-characterized, homogenous sample that was followed-up for 12 months. A total of 172 female adolescent patients with first-onset AN according to DSM-IV criteria were recruited for inclusion in a randomized, multi-center, German clinical trial. Menstrual status and clinical variables (i.e., premorbid body mass index (BMI), age at onset, duration of illness, duration of hospital treatment, achievement of target weight at discharge, and BMI) were assessed at the time of admission to or discharge from hospital treatment and at a 12-month follow-up. Based on German reference data, we calculated the percentage of expected body weight (%EBW), BMI percentile, and BMI standard deviation score (BMI-SDS) for all time points to investigate the relationship between different weight measurements and resumption of menses. Forty-seven percent of the patients spontaneously began menstruating during the follow-up period.%EBW at the 12-month follow-up was strongly correlated with the resumption of menses. The absence of menarche before admission, a higher premorbid BMI, discharge below target weight, and a longer duration of hospital treatment were the most relevant prognostic factors for continued amenorrhea. The recovery of menstrual function in adolescent patients with AN should be a major treatment goal to prevent severe long-term physical and psychological sequelae. Patients with premenarchal onset of AN are at particular risk for protracted amenorrhea despite weight rehabilitation. Reaching and maintaining a target weight between the 15th and 20th BMI percentile is favorable for the resumption of menses within 12 months. Whether patients with a higher premorbid BMI may benefit from a higher target weight needs to be investigated in further studies.
    Full-text · Article · Nov 2013 · BMC Psychiatry
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    • "Consistent with alterations in bone turnover related to short-term energy deficiency, increased caloric intake in anorexic women that results in weight gain improves markers of bone formation [9]. However, improvement in bone resorption is only observed when preceded by resumption of menses [47], indicating that an improvement in estrogen status is necessary. The degree to which improvement in energy status might also contribute to decreased resorption with the onset of menses is unclear, as these factors are difficult to tease out. "
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    ABSTRACT: Bone loss in amenorrheic athletes has been attributed to energy deficiency-related suppression of bone formation, but not increased resorption despite hypoestrogenism. To assess the independent and combined effects of energy deficiency and estrogen deficiency on bone turnover markers in exercising women. PINP, osteocalcin, U-CTX-I, TT3, leptin, and ghrelin were measured repeatedly, and bone mineral density (BMD) was measured once in 44 exercising women. Resting energy expenditure (REE) was used to determine energy status (deficient or replete) and was corroborated with measures of metabolic hormones. Daily levels of urinary estrone and pregnanediol glucuronides (E1G, PdG), were assessed to determine menstrual and estrogen status. Volunteers were then retrospectively categorized into 4 groups: 1) Energy Replete+Estrogen Replete (EnR+E2R), (n=22), 2) Energy Replete+Estrogen Deficient (EnR+E2D), (n=7), 3) Energy Deficient+Estrogen Replete (EnD+E2R), (n=7), and 4) Energy Deficient+Estrogen Deficient (EnD+E2D), (n=8). The groups were similar (p>0.05) with respect to age (24.05+/-1.75 yrs), weight (57.7+/-2.2 kg), and BMI (21.05+/-0.7 kg/m2). By design, REE/FFM (p=0.028) and REE:pREE (p<0.001) were lower in the EnD vs. EnR group, and the E2D group had a lower REE:pREE (p=0.005) compared to the E2R group. The EnD+E2D group had suppressed PINP (p=0.034), and elevated U-CTX-I (p=0.052) and ghrelin (p=0.028) levels compared to the other groups. These same women also had convincing evidence of energy conservation, including TT3 levels that were 29% lower (p=0.057) and ghrelin levels that were 44% higher (p=0.028) than that observed in the other groups. Energy deficiency was associated with suppressed osteocalcin, and TT3 (p<0.05), whereas estrogen deficiency was associated with decreased E1G (p<0.02), and lower L2-L4 BMD (p=0.033). Leptin was significant in predicting markers of bone formation, but not markers of bone resorption. When the energy status of exercising women was adequate (replete), there were no apparent perturbations of bone formation or resorption, regardless of estrogen status. Estrogen deficiency in exercising women, in the presence of an energy deficiency, was associated with bone loss and involved suppressed bone formation and increased bone resorption. These findings underscore the importance of avoiding energy deficiency, which is associated with hypoestrogenism, to avoid bone health problems.
    Full-text · Article · Jul 2008 · Bone
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    • "These dietary deficiencies, as well as hormonal changes secondary to cachexia, are responsible for the reduced BMD observed in patients with anorexia nervosa. Nutritional rehabilitation can increase the BMD of women with anorexia nervosa beyond that achieved with administration of oestrogen alone (33). Slender habitus is, however, an independent risk factor for osteoporosis with both total fat mass and total lean mass exerting a protective effect on bone in postmenopausal women (34). "
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    ABSTRACT: Osteoporotic hip fractures have a profound impact on the physical health and psychosocial wellbeing of patients. In addition, osteoporosis has considerable economic implications and is projected to become an increasing burden on developed economies over the coming decades. Nevertheless, the risk factors for both osteoporosis and hip fracture are both well understood and preventable, often with only minor lifestyle changes. This narrative review explores the pathological process underlying osteoporosis and considers how each of the major risk factors contributes to the pathology of this disease. It is hoped that a greater understanding of individual risk factors will result in renewed efforts to promote increased bone density before patients present with hip fracture.
    Full-text · Article · Jan 2008 · McGill journal of medicine: MJM: an international forum for the advancement of medical sciences by students
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