Abnormal Bone Mineral Accrual in Adolescent Girls with Anorexia Nervosa

Abstract

Anorexia nervosa (AN) is increasingly common in adolescent girls and occurs at a time of peak bone mass formation. Osteopenia is common in adolescent girls with AN, and in a cross-sectional study, we have reported low bone formation markers in such girls. To determine the impact of chronic undernutrition on bone mineral accrual in contrast to healthy controls, we prospectively measured bone mineral density (BMD) and body composition by dual energy x-ray absorptiometry, bone metabolism markers, and nutritional and hormonal status at baseline, 6 months, and 12 months in 19 adolescent girls with AN (mean +/- SEM, 15.4 +/- 0.4 yr) and 19 controls of comparable chronological and skeletal age. Overall, nutritional status in subjects with AN improved (mean percentage increase in body mass index from baseline, 9.2 +/- 1.9% and 15.2 +/- 2.6% at 6 and 12 months, respectively), with 11 subjects having recovered weight at 12 months. However, lumbar BMD at 12 months (AN, 0.88 +/- 0.02 g/cm(2), vs. control, 0.98 +/- 0.03 g/cm(2); P = 0.008) remained significantly reduced in AN compared with controls, even in recovered subjects. This was due to significant increases in lumbar BMD in controls vs. no change in AN subjects over the year (0.003 +/- 0.001 g/cm(2).month vs. 0.000 +/- 0.001 g/cm(2).month, respectively; P = 0.04). The most significant determinant of change in lumbar BMD at 12 months was change in lean body mass in both AN (r = 0.62; P = 0.008) and control (r = 0.80; P = 0.0006) groups. There were significant increases in surrogate markers of bone turnover in subjects with AN compared with controls as assessed by osteocalcin (AN, 0.9 +/- 0.4 micro g/liter.month, vs. control, -1.1 +/- 0.4 micro g/liter.month; P = 0.0007), bone-specific alkaline phosphatase (AN, 0.6 +/- 0.5 U/liter.month, vs. control, -1.5 +/- 0.4 U/liter.month; P = 0.002), deoxypyridinoline [AN, 0.1 +/- 0.1 nmol/mmol creatinine (cr).month, vs. control, -0.4 +/- 0.1 nmol/mmol cr.month; P = 0.005], and N-telopeptide (AN, 4 +/- 4 nmol BCE/mmol cr/month, vs. control, -9 +/- 4 nmol BCE/mmol cr/month; P = 0.01). Changes in IGF-I levels over the year were highly correlated with changes in bone turnover over the same period in AN (osteocalcin, r = 0.77; P = 0.001; deoxypyridinoline, r = 0.66; P = 0.01). A rise in N-telopeptide over the year was correlated with an increase in all bone mineral measures, including lumbar bone mineral content (r = 0.58; P = 0.03) and BMD (r = 0.53; P = 0.05) and total bone mineral content (r = 0.69; P = 0.006) and BMD (r = 0.69; P = 0.006) in the AN group. Therefore, despite recovery over 1 yr, poor bone mineral accrual persists in adolescent girls with AN in contrast to rapid bone accrual in healthy girls. Normalization of bone turnover markers occurs in association with nutritional recovery and an increase in the nutritionally dependent bone trophic factor IGF-I. A rise in bone turnover markers may be an early indicator of increase in BMD in recovering girls with AN.

Optimizing Bone Health in Children and Adolescents

“…Mechanical loading during weight-bearing activities stimulates bone formation, and multiple studies in healthy adolescents 8,[71][72][73] and in those with anorexia nervosa [74][75][76][77] have demonstrated that BMD is directly correlated with BMI. Lean body mass is most strongly associated with BMD, 78 but increased adiposity can also be associated with increased fracture risk.…”

“…84 Eating disorders are prevalent in adolescents. 85 Anorexia nervosa is associated with reduced BMD and increased fracture risk, [74][75][76][86][87][88][89] and the reduction in bone mass occurs after a relatively short duration of illness. 74,90 Etiologic factors include poor nutrition, low body weight, estrogen deficiency, and hypercortisolism.…”

Osteoporosis in paediatric patients with spina bifida

“…36 Low BMD among children may not indicate accelerated bone loss 41 but rather a failure to achieve the expected peak bone mass, bone loss or a combination of the two. 78,79 It is important to acknowledge that the use of antiresorptive drugs, such as bisphosphonates, may not be the optimal approach. Therefore, an understanding of the pathogenesis of low bone mass in paediatric patients with SB is needed.…”

Low bone mass in children and adolescents

“…Anorexia nervosa (7,8) Athletic amenorrhea (9) Celiac disease (10) Cystic fibrosis (11) Diabetes (type I) (12) Hematologic thalassemia, sickle-cell anemia (13) Inflammatory bowel disease (14) Malignancy (15)(16)(17) Post transplantation (18) Renal failure (19) Rheumatologic disorders (20) …”

“…in a child can result from inadequate gains of bone mineral, bone loss, or a combination of the two (8,58,59). Understanding this is critical, because most drugs used to treat osteoporosis in adults are anticatabolic agents that reduce bone loss.…”