RESUMEN
Although bone mineral density (BMD) is decreased and fracture risk increased in anorexia nervosa, BMD does not predict fracture history in this disorder. We assessed BMD, bone microarchitecture, and bone marrow adipose tissue (BMAT) in women with anorexia nervosa and found that only BMAT was associated with fracture history. INTRODUCTION: Anorexia nervosa (AN) is a psychiatric disorder characterized by low body weight, low BMD, and increased risk of fracture. Although BMD is reduced and fracture risk elevated, BMD as assessed by DXA does not distinguish between individuals with versus those without prior history of fracture in AN. Despite having decreased peripheral adipose tissue stores, individuals with AN have enhanced bone marrow adipose tissue (BMAT), which is inversely associated with BMD. Whether increased BMAT is associated with fracture in AN is not known. METHODS: We conducted a cross-sectional study in 62 premenopausal women, including 34 with AN and 28 normal-weight women of similar age. Fracture history was collected during patient interviews and BMD measured by DXA, BMAT by 1H-MRS, and parameters of bone microarchitecture by HR-pQCT. RESULTS: Sixteen women (47.1%) with AN reported prior history of fracture compared to 11 normal-weight women (39.3%, p = 0.54). In the entire group and also the subset of women with AN, there were no significant differences in BMD or parameters of bone microarchitecture in women with prior fracture versus those without. In contrast, women with AN with prior fracture had greater BMAT at the spine and femur compared to those without (p = 0.01 for both). CONCLUSION: In contrast to BMD and parameters of bone microarchitecture, BMAT is able to distinguish between women with AN with prior fracture compared to those without. Prospective studies will be necessary to understand BMAT's potential pathophysiologic role in the increased fracture risk in AN.
Asunto(s)
Anorexia Nerviosa , Fracturas Óseas , Femenino , Humanos , Médula Ósea , Absorciometría de Fotón , Anorexia Nerviosa/complicaciones , Estudios Transversales , Estudios Prospectivos , Densidad Ósea/fisiología , Tejido Adiposo/diagnóstico por imagenRESUMEN
IGF-1 and leptin are two nutritionally dependent hormones associated with low bone mass in women with anorexia nervosa. Using finite element analysis, we estimated bone strength in women with anorexia nervosa and found that IGF-1 but not leptin correlated significantly with estimated bone strength in both the radius and tibia. PURPOSE: Women with anorexia nervosa, a psychiatric disorder characterized by self-induced starvation and low body weight, have impaired bone formation, low bone mass, and an increased risk of fracture. IGF-1 and leptin are two nutritionally dependent hormones that have been associated with low bone mass in women with anorexia nervosa. We hypothesized that IGF-1 and leptin would also be positively associated with estimated bone strength in women with anorexia nervosa. METHODS: In this cross-sectional study of 38 women (19 with anorexia nervosa and 19 normal-weight controls), we measured serum IGF-1 and leptin and performed finite element analysis of high-resolution peripheral quantitative CT images to measure stiffness and failure load of the distal radius and tibia. RESULTS: IGF-1 was strongly correlated with estimated bone strength in the radius (R = 0.52, p = 0.02 for both stiffness and failure load) and tibia (R = 0.55, p = 0.01 for stiffness and R = 0.58, p = 0.01 for failure load) in the women with anorexia nervosa but not in normal-weight controls. In contrast, leptin was not associated with estimated bone strength in the group of women with anorexia nervosa or normal-weight controls. CONCLUSIONS: IGF-1 is strongly associated with estimated bone strength in the radius and tibia in women with anorexia nervosa. Further studies are needed to assess whether treatment with recombinant human IGF-1 will further improve bone strength and reduce fracture risk in this population.
Asunto(s)
Anorexia Nerviosa , Densidad Ósea , Factor I del Crecimiento Similar a la Insulina , Anorexia Nerviosa/metabolismo , Huesos , Estudios Transversales , Femenino , Análisis de Elementos Finitos , Humanos , Factor I del Crecimiento Similar a la Insulina/metabolismoRESUMEN
UNLABELLED: Excessive exercise can have detrimental effects on bone; however, the mechanisms leading to bone loss are not well understood. Sclerostin and preadipocyte factor (Pref)-1 are two hormones which inhibit bone formation. The present study demonstrates that these hormones may have differential effects in athletes as compared to non-athletes. INTRODUCTION: Exercise activity is common in female adolescents, however, excessive exercise can have detrimental effects on bone mineral density (BMD). Mechanisms underlying this decrease in bone mass are not well understood. We investigated the effects of sclerostin, a potent inhibitor of bone formation via WNT signaling inhibition, and Pref-1, a suppressor of osteoblast differentiation, on BMD, bone turnover markers and bone strength in adolescent athletes. METHODS: We studied 50 adolescents between 15-21 years of age: 17 amenorrheic athletes (AA), 17 eumenorrheic athletes (EA), and 16 nonathletic controls (NA). We measured spine and hip BMD by dual energy x-ray absorptiometry and estimated failure load and stiffness at the distal radius and tibia using micro-finite element analysis. We also measured fasting sclerostin, Pref-1, N-terminal propeptide of type 1 procollagen, and C-terminal collagen cross-links levels. RESULTS: Sclerostin levels were higher in AA and EA compared with NA (AA: 0.42 ± 0.15 ng/mL, EA: 0.44 ± 0.09 ng/mL, NA: 0.33 ± 0.14 ng/mL; p = 0.047). In EA, sclerostin was positively associated with lumbar spine (LS) BMD and its Z-score (R = 0.52, p = 0.03 and R = 0.55, p = 0.02, respectively) whereas in NA, sclerostin was inversely associated with LS BMD (R = -0.61, p = 0.01). Pref-1 levels were similar in all three groups and there were significant inverse associations between Pref-1, BMD, and estimated bone strength in NA. CONCLUSIONS: Sclerostin and Pref-1 may have differential effects on bone in adolescent athletes compared to non-athletes.