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The Journal of Clinical Endocrinology and Metabolism logoLink to The Journal of Clinical Endocrinology and Metabolism
. 2009 Feb 17;94(5):1650–1655. doi: 10.1210/jc.2008-1654

The Effect of Bed Rest on Bone Turnover in Young Women Hospitalized for Anorexia Nervosa: A Pilot Study

Amy D DiVasta 1, Henry A Feldman 1, Ashley E Quach 1, Maria Balestrino 1, Catherine M Gordon 1
PMCID: PMC2684474  PMID: 19223524

Abstract

Context: Malnourished adolescents with anorexia nervosa (AN) requiring medical hospitalization are at high risk for skeletal insults. Even short-term bed rest may further disrupt normal patterns of bone turnover.

Objective: The objective of the study was to determine the effect of relative immobilization on bone turnover in adolescents hospitalized for AN.

Design: This was a short-term observational study.

Setting: The study was conducted at a tertiary care pediatric hospital.

Study Participants: Twenty-eight adolescents with AN, aged 13–21 yr with a mean body mass index of 15.9 ± 1.8 kg/m2, were enrolled prospectively on admission.

Intervention: As per standard care, all subjects were placed on bed rest and graded nutritional therapy.

Main Outcome Measure: Markers of bone formation (bone specific alkaline phosphatase), turnover (osteocalcin), and bone resorption (urinary N-telopeptides NTx) were measured.

Results: During the 5 d of hospitalization, serum osteocalcin increased by 0.24 ± 0.1 ng/ml · d (P = 0.02). Urine N-telopeptides reached a nadir on d 3, declining −6.9 ± 2.8 nm bone collagen equivalent per millimole creatinine (P = 0.01) but returned to baseline by d 5 (P > 0.05). Bone-specific alkaline phosphatase exhibited a decline that was strongly age dependent, being highly significant for younger subjects only [age 14 yr: −0.42 ± 0.11 (P = 0.0002); age 18 yr: −0.03 ± 0.08 (P = 0.68)]. Age had no effect on other outcome measures.

Conclusion: Limitation of physical activity during hospitalization for patients with AN is associated with suppressed bone formation and resorption and an imbalance of bone turnover. Future interventional studies involving mechanical stimulation and/or weight-bearing activity are needed to determine whether medical protocols prescribing strict bed rest are appropriate.

Limitation of physical activity during hospitalization for patients with anorexia nervosa leads to a suppression of bone formation and resorption, and an imbalance of bone turnover.

Adolescence is the critical period in a young woman’s life for bone mineral acquisition and attainment of peak bone mass. Anorexia nervosa (AN), a disorder of malnutrition, intense fear of weight gain, and amenorrhea, is becoming increasingly prevalent within this age group (1,2). Accompanying this disease are significant changes in the normal hormonal milieu, loss of lean body mass secondary to malnutrition, and frequent restrictions on the level of weight-bearing physical activity. Skeletal deficits are seen early in the course of illness in more than half of these patients (3,4). Studies have shown that this decreased bone mineral density (BMD) often does not return to preillness levels even after weight restoration (3,4,5). The skeletal health implications for this high-risk population are substantial; hence, there is a pressing need to develop better methods to prevent bone loss before it occurs.

At highest risk for skeletal insults may be those adolescents who become so malnourished that they require medical hospitalization to manage their illness and low weight. Current standards of medical care at our institution require bed rest and relative immobilization for these patients for the duration of their hospital stay, generally 5–7 d. These activity limitations are based on concerns for cardiovascular health and safety as well as a desire to maximize potential for weight gain. However, studies of healthy adults demonstrate that even short-term immobilization leads to disruptions in normal patterns of bone resorption and bone formation, also known as bone turnover (6,7,8). Even more worrisome, the abnormal bone turnover may not return to baseline within 6 wk of resumption of usual activity (6).

Under normal conditions, the body maintains a healthy balance of bone formation and bone resorption. During adolescence, bone formation should exceed bone resorption. In patients with AN, this normal balance is abnormally altered, with patients exhibiting an increase in osteoclastic activity and thus increased bone resorption. In contrast, bone formation may decrease. It is this imbalance in normal bone turnover that may lead to profound skeletal deficits over time. We hypothesized that bed rest would further exacerbate this alteration in both bone formation and resorption. The objective of the current study was to determine the effect of short-term bed rest and relative immobilization on bone turnover in adolescents and young women hospitalized for AN.

Subjects and Methods

Subjects

Twenty-eight female adolescents, aged 13–21 yr, admitted to the Adolescent Medicine Service at Children’s Hospital Boston for medical complications of AN, were prospectively enrolled on hospitalization. Eligible subjects met Diagnostic and Statistical Manual of Mental Disorders-IV criteria for AN and were at least 2 yr past menarche. All subjects had no other comorbid conditions or medication use (e.g. hormonal contraceptives, glucocorticoids, anticonvulsants) known to affect bone health. No subjects regularly consumed alcohol or used cigarettes. Study procedures were reviewed and approved by the local institutional review board. Informed consent was obtained from all subjects or their parents. Minor subjects also provided assent for participation.

Study design and treatment

Per our standardized eating disorder inpatient protocol, all subjects were placed on bed rest and graded nutritional therapy during the admission. Subjects were started on a baseline meal plan between 1250 and 1750 kcal/d and advanced at a rate of 250 kcal/d toward their goal nutritional intake. This goal was determined on an individual basis by the hospital nutritionist who was not involved with the study. Subjects were confined to their beds throughout the day, including meal times, as is the standard of care at our institution due to concerns of vital sign instability and the need for weight gain. The majority of patients were allowed in-room bathroom privileges; a few were required to use the bedside commode for the first few days of hospitalization. No exercise or walking was permitted throughout the study period.

Data collection

Height (centimeters) was measured using standardized procedure with a wall-mounted stadiometer. Weight (kilograms) was measured each morning, after voiding and in the fasting state, with subjects wearing a hospital gown. Body mass index (BMI) was calculated using the formula: BMI = weight (kilograms)/[height (meters)]2. For each subject 20 yr old or younger, percentage ideal body weight (% IBW) was determined using the 2000 Centers for Disease Control and Prevention growth charts and the formula: % IBW = 100 × [patient BMI (kilograms per square meter)/median BMI for age (kilograms per square meter)] (9). For each subject older than 20 yr, % IBW was determined by the formula: % IBW = 100 × [patient BMI (kilograms per square meter)/median BMI for adults (21.7 kg/m2)] (10). All participants responded to a semistructured interview to obtain demographic information and health history, which included information about medication use, menstrual history, smoking, and family history of osteoporosis. All subjects were asked to report their hours per week of physical activity prior to admission and detail the type of exercise (e.g. walking/running, swimming, strength training, etc.). The Youth/Adolescent Questionnaire, a comprehensive, semiquantitative food frequency questionnaire validated for use in this age group, was administered within the first 24 h of hospitalization to provide a detailed measure of outpatient calcium and vitamin D intake as well as other nutrients (11,12). To compare each subject’s reported intake to recommended nutrient values, the dietary reference intake (DRI) for adequate intake was used for vitamin D, vitamin K, and calcium intake, whereas the DRI for recommended dietary allowance was used for carbohydrate, protein, total vitamin A activity, vitamin E, vitamin C, phosphorus, magnesium, iron, zinc, and copper intake (13).

Biochemical assessments

Laboratory measurements began on the first morning that the participant awoke in the hospital and continued during d 1, 2, 3, and 5 of hospitalization. Subjects had venous blood drawn from an antecubital vein between 0830 and 1000 h after an overnight fast. Serum samples were analyzed in the Children’s Hospital Boston Core Laboratory for concentrations of calcium, phosphorus, and magnesium; these measurements were determined by Ektachem methodology (cholesterol oxidase; Vitros, Johnson & Johnson, New Brunswick, NJ). At baseline, serum 25-hydroxyvitamin D [25(OH)D] concentration was measured by chemiluminescent assay (Liason; Diasorin, Stillwater, MN), with an interassay precision of 8.6–10.0%. PTH was measured by a two-site chemoluminescence immunoassay (Nichols Institute, San Juan Capistrano, CA); interassay coefficient of variation (%CV) was 5.4–7% for PTH. Biomarkers of bone formation [serum levels of osteocalcin (OC) and bone specific alkaline phosphatase (BSAP)] were measured in a fasting state at baseline and d 1, 2, 3, and 5 of hospitalization. OC was measured by double-antibody RIA (%CV 11–13%), and immunoradiometric assay was used to measure BSAP (%CV 5.2–5.6%; Esoterix Inc. Laboratory Services, Calabasas Hills, CA). A second-morning urine specimen was obtained on the same days from each participant for measurement of highly specific biomarkers of bone resorption, degradation products of type I collagen [urinary N-telopeptides (NTx)]. Urine NTx was measured by RT-PCR (Esoterix); interassay %CV was 5.6–6.8%.

Bone density

Anteroposterior lumbar spine (L1-L4) areal BMD (aBMD; grams per square centimeter) was measured during hospitalization by dual-energy x-ray absorptiometry using the QDR-4500 Delphi scanner (Hologic, Inc., Waltham, MA). Measurements were compared with age- and gender-matched controls (14,15). For participants younger than age 20 yr, pediatric normative data were used (16).

Statistical analysis

The planned sample of 30 patients was chosen to provide 80% power to detect a relatively subtle rate of change in our primary end point measure (NTx), estimated at 2.4 mmol/mmol creatinine (Cr) per day, which accumulated over 5 d would amount to 12 mmol/mmol Cr or 15% of the mean level.

Repeated-measures ANOVA was used to determine the change in bone turnover markers over the 5 d of hospitalization. The primary independent variable in the ANOVA was a main effect for time, describing the pattern of outcome across the 5-d hospitalization. No time × subject interaction was seen, indicating that subjects shared a common time pattern within statistical limits. In the few cases of incomplete bone marker data, most of which were attributable to lost samples in the laboratory, all available measurements were included in the analysis on the assumption that missing values were unrelated to any unaccounted-for bias.

To control for mediating variables, we added the following continuous covariates to the ANOVA: age, baseline %IBW, spinal BMD, duration of amenorrhea, and indicators of regular exercise and family history of osteoporosis. One missing value for duration of amenorrhea was imputed from simple regression on age. One missing indicator of regular exercise and two missing indicators of family history of osteoporosis were replaced with the prevalence in the balance of the sample.

To estimate the linear trend in each outcome over the course of hospitalization, we constructed an alternative repeated-measures regression model, identical with the ANOVA except that time was treated as a continuous independent variable. We tested for quadratic trend by adding a time2 term to the model. To test for effect modification by age and vitamin D deficiency [25(OH)D <30 ng/ml at baseline] we added appropriate interaction terms to the model. Results are presented as adjusted linear trend ± se, derived from the regression analysis. Two implausibly high osteocalcin values (>20 ng/ml) and one extreme NTx value were omitted from ANOVA and regression to avoid undue influence.

Simple associations were assessed by Pearson correlation coefficient. Mean macro- and micronutrient intake levels were compared with established DRI thresholds for females (17) and mean macronutrient intake distributions (expressed as a percent of total calories) compared with the median values of the DRI ranges using one-sample Wilcoxon signed ranks tests. All computations were performed with SAS version 9.1 (SAS Institute, Inc., Cary, NC). Results with P < 0.05 were considered statistically significant.

Results

Demographic data

We studied 28 adolescents and young women with AN, ranging in age from 13 to 21 yr (Table 1). All but one were of Caucasian ethnicity (self-reported); one subject was African-American. The duration of amenorrhea ranged from 1 to 42 months, with median 6 months. The subjects were significantly malnourished; mean BMI was 15.9 ± 1.8 kg/m2 (mean ± sd), corresponding to ideal body weight of 77 ± 8%. Before hospitalization, 70% of subjects reported participating in regular physical exercise, of duration 9 ± 5.1 h/wk. Of those engaging in physical activity, the majority were involved in weight-bearing pursuits such as running, dancing, and strength training. There was a positive family history of osteoporosis in 27% of study subjects. Seven patients (29% of those responding) reported sustaining a previous bone fracture. All fractures involved the peripheral skeleton; no patients reported a previous fracture of the hip or spine.

Table 1.

Baseline characteristics of 28 young women hospitalized with AN

Mean ± sd or n (%) Median (minimum-maximum) Missing values
Age, yr 16.7 ± 2.3 16.1 (13.7–21.9) 0
Height, cm 161 ± 6 162 (147–171) 0
Weight, kg 41.2 ± 5.5 40.8 (31.6–54.2) 0
BMI, kg/m2 15.9 ± 1.8 15.7 (12.6–19.9) 0
Weight relative to ideal, % 77 ± 8 77 (62–95) 0
Duration of amenorrhea, months 8.3 ± 8.3 6 (1–42) 1
BSAP, ng/ml 12.4 ± 5.2 11.0 (5.8–30.0) 4
Osteocalcin, ng/ml 6.9 ± 4.5 6.0 (1.1–23.0) 2
NTx, nm BCE per mm Cr 75 ± 28 72 (22–129) 1
Regular exercise 19 (70) 1
Family history of osteoporosis 7 (27) 2
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Nutritional data

Nutritional data were collected from all participants, including information on both dietary intake and supplementation (e.g. multivitamins). On average, subjects reported consumption of 1421.5 ± 840 kcal/d before admission (range 558.2–3533.1 kcal/d). In all subjects, total fat intake was low (35.9 ± 24.9 g/d). Subjects were divided into two subgroups based on age to allow for appropriate comparison of each subject’s reported nutritional intake to the age-appropriate DRI for females. Carbohydrate and protein intake were within normal limits for younger subjects (aged 14–18 yr). In the younger age group, reported median intake of calcium (median 1047.6 vs. 1300 mg; P = 0.01) and total vitamin E (median intake 9.15 vs. 15 mg; P < 0.001) were below the DRI; all other micronutrient consumption was within the recommended range. In the group of young women older than 19 yr, median intake of only vitamins A and C met the age-specific DRI; median intake of all other measured nutritional variables (carbohydrate, protein, calcium, iron, vitamin D, vitamin E, phosphorus, magnesium, zinc, and copper) was below the DRI. However, this group was small (n = 4), and none of the nutritional deficiencies were statistically significant (P > 0.05).

Biochemical and bone density analyses

Serum biochemical data were obtained daily from all participants and compared with established normative thresholds established by our institution (18). All subjects maintained calcium levels within the normal range throughout the study (range 8.8–10.7 mg/dl). Despite routine daily oral phosphorus supplementation (phosphorus 250 mg orally twice daily to 500 mg orally thrice daily), serum phosphorus trended downward by −0.1 mg/dl · d. Baseline PTH was 32.7 ± 17.9 pg/ml (normal range 10–65 pg/ml). Although all subjects met the DRI for vitamin D based on self-reported nutritional data, vitamin D insufficiency was prevalent in this sample. Eleven subjects (39%) had 25(OH)D concentrations less than 30 ng/ml [25(OH)D range 19–27.5 ng/ml]; two subjects were vitamin D deficient [25(OH)D <20 ng/ml].

All subjects gained a clinically significant amount of weight over the course of the study. During the 5 d of hospitalization, mean weight increased at a rate of 0.33 ± 0.02 kg/d (regression trend ± se adjusted for baseline covariates), leading to an increase in both weight and BMI by the time of discharge (P < 0.001). Serum OC increased by 0.24 ± 0.1 ng/ml · d (P = 0.02). Urine NTx reached a nadir on d 3 of hospitalization (Fig. 1), declining initially at a rate of −6.9 ± 2.8 nm bone collagen equivalent (BCE) per millimole Cr (P = 0.01) but returning to baseline levels by d 5 (P > 0.05). Urine creatinine displayed a similar pattern.

Figure 1.

Figure 1

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Trends in weight and bone turnover markers in 28 young women hospitalized for AN. Estimated mean and 95% confidence interval from repeated-measures ANOVA. Solid line, Adjusted for age, baseline percentage of ideal weight, spinal aBMD, duration of amenorrhea, regular exercise, and family history of osteoporosis; dotted line, additionally adjusted for daily weight during hospitalization. See Table 2 for statistical assessment of trends.

BSAP exhibited a decline that was strongly dependent on age (interaction P < 0.005), being highly significant for the younger subjects only (Table 2). Changes in weight, OC, and NTx showed no dependence on age (P > 0.20). Vitamin D deficiency showed no influence on the level or trend in any of the bone markers.

Table 2.

Trends in weight and bone turnover markers in 28 young women hospitalized for AN

Linear trend per day ± se (P)a
Adjusted for covariatesb Adjusted for covariates + weight
Weight, kg 0.33 ± 0.02 (P < 0.001)
BSAP, ng/ml Age 14 yr:−0.42 ± 0.11 (P = 0.0002) Age 18 yr:−0.03 ± 0.08 (P = 0.68) Age 14 yr: −0.37 ± 0.13 (P = 0.005) Age 18 yr: −0.00 ± 0.10 (P = 0.96)
OC, ng/ml 0.24 ± 0.10 (P = 0.02) 0.28 ± 0.12 (P = 0.03)
NTx, nm BCE per mm Crc −6.9 ± 2.8 (P = 0.01) −6.2 ± 2.8 (P = 0.03)
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a

From repeated-measures analysis; P tests for linear trend significantly different from zero. 

b

Covariates are age, baseline % IBW, spinal aBMD, duration of amenorrhea, regular exercise, and family history of osteoporosis. Age was treated as a continuous variable in all models. For BSAP, the interaction of hospital day with age resulted in stronger, more negative coefficient at younger ages than at older ages. The linear trend over the course of hospitalization is calculated at two representative ages, 14 and 18 yr, to illustrate this phenomenon above. 

c

Initial slope of quadratic trend, reaching minimum between d 2 and 3; see Fig. 1. 

Controlling for weight gain, as well as the baseline covariates (age, percentage of ideal weight, spinal aBMD, duration of amenorrhea, regular exercise, and family history of osteoporosis), had negligible influence on the trend estimates (Table 2).

Lumbar spine aBMD was 0.89 ± 0.11 g/cm2, corresponding to a lumbar spine aBMD Z-score −0.89 ± 1.1. Baseline percentage of ideal body weight was correlated with spinal aBMD (Pearson r = −0.59, P = 0.001). Measurements of serum BSAP and urine NTx on d 2–5 were negatively associated with spinal aBMD, with Pearson r between −0.35 and −0.50 (P < 0.05).

Discussion

In this pilot study, we observed an acute suppression between baseline and hospital d 3 in markers of bone resorption (urine NTx) and bone formation (BSAP, in younger subjects only) (Fig. 1). However, by discharge (d 5), an imbalance of bone turnover was seen, with an increase in NTx concentrations from the d 3 nadir, and continued decline in BSAP levels in the younger subjects. Age had a striking effect on our BSAP results; the interaction of hospital day with age resulted in stronger, more negative coefficient at younger ages than at older ages. Age did not effect the NTx results. These highly specific bone biomarker data reflect both suppressed bone formation and initially suppressed and then increased resorption. In comparison, OC, a marker of overall bone turnover, increased from baseline to discharge, likely reflecting the high-turnover state provoked by bed rest and refeeding. There was no influence of age on osteocalcin results.

Low bone mass is a widespread, chronic source of morbidity for adolescents and young women with AN (3,4,17). These patients have numerous risk factors for skeletal deficits, including low body weight, poor nutritional intake, and hormonal deficits. In addition, activity restriction is commonly imposed on these patients, both during acute hospital admissions accompanied by bed rest and intermittently throughout their outpatient treatment course. This lack of mechanical stimulation is known to be another significant risk factor for decreased bone mass (6,8). Previous studies have examined the relationship between immobility and bone health in other populations. Skeletal unloading, such as that occurring with bed rest, leads to reductions in the mechanical forces applied to bones. It has been estimated that strict bed rest leads to bone loss of approximately 1–2% per month in healthy adults (7). Decreased mechanical usage depresses longitudinal growth and stimulates bone remodeling-dependent bone loss via decreased bone formation and a concurrent increase in the rate of bone resorption (19,20). Osteoclastic activity increases after immobilization, with a peak at 3–5 d and is likely the major contributor to the loss of trabeculae during this rapid phase (21). In healthy young adults, 20 d of bed rest led to both increased bone resorption and loss of BMD in lumbar and metacarpal bones (8).

Populations at highest risk for bone loss may be particularly vulnerable to changes induced by immobility. In a study comparing bone loss after ovariectomy with that after immobilization, the greatest loss of trabeculae occurred when the two skeletal insults were combined (ovariectomy plus immobilization) (22). This finding suggests that mechanical weight bearing provided some protection against loss of bone through hormonal influences. Given that our adolescents with AN all had hypothalamic suppression and amenorrhea, the additive effect of bed rest may be particularly deleterious. Even this type of short-term immobilization may be harmful; in healthy humans, biochemical measures of bone turnover increased after only 7–10 d of bed rest (6,23). Osteoclast activity increased quickly; by the second day of immobility, bone resorption markers profoundly increased from baseline in healthy men placed on bed rest (7). Our pilot data support a rapid disruption of the balance of bone turnover associated with 5 d of bed rest for adolescents with AN, especially for younger teens.

An additional concern is that resumption of previous mechanical loading seems insufficient to stop disuse-associated bone changes. In fact, after immobilization in rats, significant worsening of bone mechanical properties occurred during 4 wk of full remobilization without set exercise (24). In contrast, after 16 wk of forelimb immobilization, young adult dogs remobilized with exercise three times per week showed complete recovery of bone mechanical properties (25). Lack of complete resolution of deleterious changes in BMD after bed rest and reambulation has also been demonstrated in studies of young, healthy men (26,27). Exercise plus remobilization appears more efficacious compared with remobilization alone for restoring the normal bone trabecular network (28,29). Thus, to prevent ongoing skeletal aberrations, the intensity of the remobilization activity must be greater than that of normal activity. After hospitalization, exercise is prohibited for the majority of patients with AN until weight goals are reached and cardiac stability is assured; these activity restrictions are frequently long term, given the recurrent periods of relapse that are common in this population (30).

Weight-bearing and physical activity are important mechanical stimuli for bone growth and bone remodeling and reduce the prevalence of osteoporosis-related fractures (31). Currently exercise is promoted as a strategy to prevent and/or treat bone loss in postmenopausal women. Positive effects of exercise on bone geometry and strength have also been reported previously in pediatric populations (32,33,34). The positive effects of exercise on bone are explained by the mechanostat hypothesis of Frost (35), which proposes that bone strength is regulated by modeling and remodeling processes, depending on the forces acting on bone. Thereby, the skeleton adapts to tissue strain due to biomechanical forces (36). The role of physical activity in AN-related bone loss is controversial. Investigators have shown no benefit of exercise (3,37); harmful effects (38); and protective effects (39,40). The majority of the data was obtained from adult studies and is unlikely to be generalizable to young adolescents with AN. Few studies have examined the safety of a prescribed exercise regimen for patients with AN. Thien et al. (41) showed that a guided exercise program increased compliance with treatment and did not reduce the short-term gain of BMI. Unfortunately, the low-estrogen state seen in AN may impact the benefits of exercise in these patients. The mechanostat is affected by sex hormones; estrogen loss raises the remodeling threshold and may decrease the effectiveness of mechanical stress on the skeleton through inhibition of estrogen receptors (42). To date, no randomized controlled trials examining the effects of an exercise intervention on bone health in patients with AN have been carried out due to the need to prioritize weight gain and cardiac health concerns (such as orthostasis) in these patients. Further research is needed in this area.

The biochemical markers of bone turnover used in this study are molecular entities measured in serum or urine that offer a dynamic means for the assessment of bone resorption and bone formation. Whereas older markers suffered from both a lack of specificity and large intraindividual variability, the newer markers offer a much more specific, direct, and relatively precise measurement of the bone-remodeling process (43). Clinically, bone biomarkers are useful for measuring responses to antiresorptive therapy and can predict future fracture risk, independent of bone density (44). Serum BSAP is a tetrameric glycoprotein found on the cell surfaces of osteoblasts. As an indicator of osteoblastic activity, BSAP provides information on bone formation. Serum OC is a noncollagenous protein that is predominantly synthesized by mature osteoblasts during bone formation but is also released into the circulation from the matrix during resorption (45). OC is a valid marker of bone turnover when resorption and formation are coupled and is a specific marker of bone formation when uncoupling occurs (46). Therefore, OC can be considered to be a more accurate marker of bone turnover rather than a specific bone formation marker. The measured telopeptide fragments, urinary NTx, are specific to degradation of mature bone collagen, thereby accurately reflecting the bone resorption process (43). Other skeletal assessment tools would not have provided the same dynamic view of the bone turnover state captured within this pilot study.

Study limitations deserve acknowledgment and consideration. Whereas all subjects were exposed to bed rest during this study, dietary changes and large increases in nutrient intake occurred over these 5 d, leading to significant weight gain, which may have confounded the relationship between bed rest and bone turnover. However, even after controlling for weight change in our analyses, our results remained significant. Additionally, in this small pilot study, we were unable to assess potential hormonal mechanisms that may mediate the effects of bed rest and refeeding on bone turnover within these patients. All study subjects were at least 2 yr past menarche; it is noteworthy that results may not be generalizable to premenarchal girls. Information on nutrition and exercise were obtained by self-report, with inherent limitations, especially in a group of adolescents with an eating disorder. Although current bone biomarkers are more accurate and precise compared with measurements obtained using earlier assays, the precision of these markers should still be acknowledged in addition to the fact that these biomarkers represent surrogate markers of physiological processes with their inherent limitations. Histomorphometric analyses via bone biopsy would have provided the most accurate assessment of bone turnover but were not possible in this clinical protocol. Lastly, the duration of exposure to bed rest was brief; the results of this pilot study should be confirmed by a randomized, controlled trial of longer duration.

In conclusion, limitation of physical activity during medical hospitalization for patients with AN was associated with a suppression of both bone formation and resorption and a potential imbalance of bone turnover. Future interventional studies involving mechanical stimulation and/or weight-bearing activity are needed to determine whether medical protocols prescribing strict bed rest are appropriate.

Acknowledgments

We gratefully acknowledge our patients and their families, the expert nursing care of the General Clinical Research Center at Children’s Hospital Boston, contributions of the Children’s Hospital Boston Core Laboratory, and the excellent technical assistance of Katie Beth Clegg.

Footnotes

This work was sponsored by the General Clinical Research Center at Children’s Hospital Boston, the McCarthy Family Foundation, the William F. Milton Fund, and National Institutes of Health grant R01 HD 043869.

Disclosure Summary: The authors have nothing to disclose.

First Published Online February 17, 2009

Abbreviations: aBMD, Areal BMD; AN, anorexia nervosa; BCE, bone collagen equivalent; BMD, bone mineral density; BMI, body mass index; BSAP, bone-specific alkaline phosphatase; Cr, creatinine; %CV, coefficient of variation; DRI, dietary reference intake; % IBW, percentage ideal body weight; NTx, N-telopeptides; OC, osteocalcin; 25(OH)D, 25-hydroxyvitamin D.

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