Marked increases in bone mineral density and biochemical markers of bone turnover in patients with anorexia nervosa gaining weight

doi:10.1016/j.bone.2006.11.015

Bone

Volume 40, Issue 4, April 2007, Pages 1073-1077

https://doi.org/10.1016/j.bone.2006.11.015 Get rights and content

Abstract

Anorexia nervosa (AN) is a life-threatening eating disorder characterized by an inability to maintain a normal body weight and amenorrhoea, often associated with osteoporosis and increased risk of fragility fractures.

Bone metabolism, including markers of bone turnover (serum total alkaline phosphatase, bone alkaline phosphatase [bone AP], osteocalcin [OC] and type I collagen C-telopeptide breakdown products [sCTX]) and bone mineral density (BMD) by dual energy X-ray absorptiometry (DXA) at the spine and at the hip, were evaluated in 55 consecutive women with AN undergoing a 3-month intensive nutritional rehabilitation program. The control group was constituted of 25 healthy young medical students.

In AN patients body weight increased during the 3-month nutritional program from 37.8 ± 5.1 (mean ± SD) to 51.5 ± 4.5 kg. The corresponding BMI rose to values > 17.5 kg/m² in all patients. Mean BMD significantly rose by 2.6 ± 3.5% and 1.1 ± 3.6% at the hip and at the spine, respectively. The markers of bone formation, serum bone AP and osteocalcin, significantly rose by two-folds, while sCTX decreased by 16%. The changes in hip BMD were positively related (p < 0.005) to changes in body weight and in bone AP (p < 0.02) while the changes in spine BMD were positively related to changes in serum osteocalcin (p < 0.05). In the 25 patients who attended the 12-month posttreatment control, mean body weight significantly decreased by 3.6 ± 6.0 kg and this was not associated with any significant change in BMD values. In the patients in whom BMI fell again below 17.5 kg/m² hip BMD values decreased significantly. On the contrary, in the patients who maintained BMI > 17.5 kg/m², BMD values continued to rise up to values over the 15-month observation of 4.8 ± 6.2 and 7.1 ± 12.1 at the spine and hip, respectively.

In conclusion, we have demonstrated that substantial gains in weight in women with chronic AN are associated with remarkable increases in BMD at both the hip and the spine. If weight is maintained, the overall improvement approach 1 SD within 1 year. The changes in both weight and BMD are correlated with improvements in bone formation markers and diminutions in a marker of bone resorption.

Introduction

Anorexia nervosa (AN) is a life-threatening eating disorder characterized by an overevaluation of shape and weight, with an active maintenance of an unduly low body weight, and amenorrhoea [1]. It is associated with significant excess mortality [2] and morbidity [3]. Bone loss is of special concern for its long-term consequences. Bone mineral density (BMD) values below the WHO cut-off for the diagnosis of osteoporosis have been observed in approximately 50% of the patients [4] with a three-fold increase over the expected number in fracture rate [5]. This bone loss has been ascribed to both estrogen deficiency and nutrition or nutrition-dependent factors. The best management of bone loss is not agreed on [4]. The BMD changes after recovery from AN have been investigated in limited number of patients and generally only several years after the original diagnosis [6], [7], [8], [9], [10], [11], [12], [13], [14], [15].

In this controlled study, we investigated the longitudinal changes in BMD and bone markers in a cohort of AN patients following an effective inpatient treatment.

Section snippets

Patients and controls

Seventy-one consecutive women with a diagnosis of established AN (Diagnostic Statistical Manual of Mental Diagnosis, DSM-IV) [16] admitted from all over Italy to the Department of Eating and Weight Disorder (Villa Garda Hospital, Garda, Verona, Italy) were recruited over a period of 14 months. All consecutive patients providing informed consent to participate in the study had the initial evaluation. Patient taking any drug affecting bone metabolism (calcium, vitamin D, estrogen taken also as

Results

In Table 1, listed are the main characteristics of the study population and of control subjects who attended the first follow-up DXA control. The mean age and duration of the disease were relatively high. This is related to the characteristics of our inpatient unit in Garda, where the most severe or chronic cases of AN are referred from all over Italy. In all patients BMI was < 17.5 kg/m², a value required for the diagnosis of AN. 25-OH-vitamin D serum levels were higher than 12 ng/ml (48 nM/L)

Discussion

In this cohort of patients with AN, we have shown for the first time that substantial gains in weight significantly improve within only 3 months BMD both at the hip and the spine. The magnitude of these changes (+ 3.5% at the femoral neck) are somewhat surprising for adult subjects that remains amenorrheic and usually found only in patients treated for severe osteomalacia or for localized osteoporosis. The stable BMD values observed in the control group seem to exclude any systematic shift in

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Studies of bone turnover markers in adults and adolescents with AN have reported conflicting results. Adult patients have reduced bone formation markers and increased bone resorption markers [68], whereas adolescent patients have both deceased formation and resorption markers, suggestive of suppression of bone turnover [69]. Impaired bone health in AN may also be attributed to changes in body composition due to malnutrition and multiple endocrine disruptions.
Peak bone mass is the maximum bone mass that accrues during growth and development. Consolidation of peak bone mass normally occurs during early adulthood. Low peak bone mass results from failure to achieve peak bone mass genetic potential, primarily due to bone loss caused by a variety of conditions or processes occurring at younger ages than usual. Recognized causes of low peak bone mass include genetic causes, endocrine disorders, nutritional disorders, chronic diseases of childhood or adolescence, medications, and idiopathic factors.
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In the primary intention-to-treat analysis, mean serum IGF-I levels increased during the intervention phase from 22.9 ± 1.5 to 28.6 ± 1.3 nmol/L (means ± SEM) (+20.2%) in the intervention group and from 20.2 ± 1.2 to 25.7 ± 1.5 nmol/L (+16.8%) in controls. In a preplanned analysis of covariance with repeated measures, the between-group difference was close to statistical significance (P = 0.071). In a post-hoc mixed-regression model analysis, the difference was statistically significant (4.9 nmol/l increase; P = 0.003), as was the change of the ratio IGF-I/IGF-BP3 (P = 0.004). There was no between-group difference in biochemical markers of bone turnover (osteocalcin, P1NP, CTX) or in serum parathyroid hormone level. Serum calcium levels slightly increased during the intervention phase in the higher protein group (P = 0.02). IGF-BP2 decreased significantly more in the intervention group during the follow up period at week 4 after supplements cessation (P = 0.019).
Intake of a fermented, protein-fortified, isocaloric dairy product during 4 weeks may slightly increase serum IGF-I levels in women with AN, without significant changes in bone turnover markers.
Clinical Trial Registration Number: NCT01823822 (www.clinicaltrials.gov).
Metabolomic profiling of amino acid alterations in anorexia nervosa: implications for appetite regulation and therapeutic strategies
2023, European Review for Medical and Pharmacological Sciences

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Marked increases in bone mineral density and biochemical markers of bone turnover in patients with anorexia nervosa gaining weight

Abstract

Introduction

Section snippets

Patients and controls

Results

Discussion

Lancet

Joint Bone Spine

Mayo Clin. Proc.

Behav. Res. Ther.

Am. J. Clin. Nutr.

Mortality in anorexia nervosa

Am. J. Psychiatry

Eating disorders

N. Engl. J. Med.

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

JAMA

Severity of osteopenia in oestrogen-deficient women with anorexia nervosa and hypothalamic amenorrhea

J. Clin. Endocrinol. Metab.

Recovery from osteopenia in adolescent girls with anorexia nervosa

J. Clin. Endocrinol. Metab.

Dissociation of bone turnover in anorexia nervosa

Ann. Clin. Biochem.

Anorexia nervosa: slow regain of bone mass

Osteoporosis Int.