Peptide YY (PYY) levels and bone mineral density (BMD) in women with anorexia nervosa

Neuroendocrine Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Bone (Impact Factor: 3.97). 08/2008; 43(1):135-9. DOI: 10.1016/j.bone.2008.03.007
Source: PubMed


Anorexia nervosa (AN) is a psychiatric illness that results in significant bone loss. Studies examining the neuroendocrine dysregulation that occurs in AN may increase understanding of endocrine systems that regulate bone mass. Peptide YY (PYY) is an anorexigenic peptide derived primarily from the intestine, with actions mediated via activation of Y receptors. We have previously shown that PYY levels are elevated in adolescents with AN. Y2 receptor knockout mice have increased bone mineral density (BMD) and thus PYY may play a role in regulating bone mass. We hypothesized that PYY levels would be inversely associated with BMD in women with AN.
This was a cross-sectional study performed in a General Clinical Research Center of 12 adult women with AN, (mean+/-SEM) mean age 30.9+/-1.8 years, BMI 17.1+/-0.4 kg/m2, and % ideal body weight 77.5+/-1.7%. PYY concentrations were measured hourly from 20:00 h to 08:00 h. BMD was measured using dual X-ray absorptiometry (DXA).
In women with AN, mean overnight PYY levels strongly inversely correlated with BMD at the PA spine (r=-0.77, p=0.003), lateral spine (r=-0.82, p=0.002), total hip (r=-0.75, p=0.005), femoral neck (r=-0.72, p=0.009), total radius (r=-0.72, p=0.009) and 1/3 distal radius (r=-0.81, p=0.002). Body mass index was inversely correlated with PYY level (r=-0.64, p=0.03). Multivariate stepwise regression analysis was performed to determine the contribution of age, duration of AN, BMI, fat-free mass, and PYY to BMD. For PA and lateral spine, PYY was the primary determinant of BMD, accounting for 59% and 67% of the variability, respectively. Fat-free mass and duration of anorexia nervosa were the primary determinants of BMD at other skeletal sites.
In women with anorexia nervosa, an elevated PYY level is strongly associated with diminished BMD, particularly at the spine. Therefore further investigation of the hypothesis that PYY may contribute to the prevalent bone pathology in this disorder is merited.

Download full-text


Available from: Elizabeth A Lawson
  • Source
    • "Previous studies evaluated the association between PYY and bone density in metabolic diseases that affect PYY such as anorexia nervosa or in special groups such as athletes. In two studies on anorexia nervosa patients, PYY was negatively associated with bone density [19,36]. However, these studies were done in patients that had lower body weight and usually lower BMD because of the anorexia nervosa [37]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Ghrelin and peptide YY (PYY) are appetite regulating hormones secreted from the gastrointestinal tract (gut). Aside from their known effect on energy homeostasis, accumulating data indicates that these gut hormones also affect bone metabolism. However, data regarding the influence of ghrelin and PYY on bone density in humans is very limited, and the results are inconclusive. Therefore, this study was designed to investigate the potential association between circulating ghrelin and PYY with bone density indices in the general population. A total of 2257 adult subjects from the CODING (Complex Diseases in the Newfoundland Population: Environment and Genetics) study participated in this investigation. Acylated ghrelin and total PYY were measured in serum after a 12-hour fasting, with the Enzyme- Linked Immunosorbent Assay (ELISA) method. Bone mineral density was measured by dual-energy X-ray absorptiometry at the spine, femoral neck, and total hip. Multiple regression analyses adjusting for age, BMI, physical activity, smoking, and alcohol consumption were employed to analyze the association between serum ghrelin and PYY with bone mineral density parameters. Significant positive associations of ghrelin concentration with L2-L4 BMD, L2-L4 Z-score, femoral neck BMD, femoral neck Z-score, total hip BMD, and total hip Z-score were found in women. No significant correlations between ghrelin and bone density indices were present in men. After dividing the female group into pre-menopausal and post-menopausal, ghrelin was positively correlated with femoral neck Z-score, and total hip Z-score in pre-menopausal women and L2-L4 BMD, and Z-score in post-menopausal group. Moreover, no significant association was discovered between serum PYY and bone density at any site. Our results suggest a beneficial association of circulating ghrelin concentration with bone density in women at the population level. This association is independent of major confounding factors including BMI, physical activity, age, alcohol consumption, and smoking. Effect of menopause on this association seemed to be site specific. However, PYY does not seem to be associated with bone density parameters.
    Full-text · Article · Sep 2013 · BMC Endocrine Disorders
  • Source
    • "The majority of environmental factors affecting bone mineralization are associated with lifestyle – diet, supply of calcium, smoking, alcohol consumption and physical activity (Ebeling, 1998; Orwoll and Klein, 1995). Improper diet and/or lack of physical activity may accelerate bone mass reduction; on the other hand, low body mass is a risk factor for osteoporosis and bone fractures (Utz et al., 2008), while higher body mass may be protective against the decline in bone mineral with age. The relationship between bone mass and body mass has been addressed by numerous researchers (Coin et al., 2000; Kardinaal et al., 2000; Ribot et al., 1988). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The aim of this work was to estimate the body mass index (BMI) at which risk of hypertension is lowest in men and women, while concurrently considering the protective role of adipose tissue in osteoporosis. Healthy, occupationally active inhabitants of the city of Wrocław, Poland, 1218 women and 434 men were studied. BMI, systolic and diastolic blood pressures, bone mineral density (BMD) of the trabecular compartment and distal radius of the non-dominant hand were recorded. Overweight in young women (≤45years) was associated with increased risk of hypertension, whereas the risk of low bone mineral was decreased for the same BMI. In older women (>45years), a BMI>27 was the threshold for increased risk of hypertension. In this age group, extremely slim women (BMI<21) had the highest risk of low bone mineral density. In younger males (≤45years), risk of hypertension was lowest among the thinnest subjects (BMI<21). Increase in BMI over 21kg/m(2) increased the risk of hypertension. The probability of low bone mineral density was the same in all BMI categories of men. In older men (>45years), the thinnest (BMI<21) had higher risk of hypertension. To begin from BMI=25kg/m(2), there was a monotonous increase in risk of hypertension in men. Higher risk for low bone mineral density was observed in older men with the BMI<23. Among younger adults, risk of hypertension and low bone mineral density increase at BMI≥21kg/m(2) in men and BMI≥23kg/m(2) in women. Among older men and women, the BMI threshold was 27kg/m(2).
    Full-text · Article · Aug 2012 · Homo: internationale Zeitschrift fur die vergleichende Forschung am Menschen
  • Source
    • "These findings provide a possible mechanism for the clinical observation of bone loss in situations associated with elevated circulating PYY. PYY is considered as a potential contributor to the low bone mass of anorexia nervosa, where PYY levels are reported to be increased [14]. Several techniques of bariatric surgery (gastric sleeve and Roux en Y bypass) may also produce a marked elevation in PYY responses [19], [20], and with it a potential for exaggerated bone loss in addition to that associated with weight reduction. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Gastrointestinal peptides are increasingly being linked to processes controlling the maintenance of bone mass. Peptide YY (PYY), a gut-derived satiety peptide of the neuropeptide Y family, is upregulated in some states that also display low bone mass. Importantly, PYY has high affinity for Y-receptors, particularly Y1R and Y2R, which are known to regulate bone mass. Anorexic conditions and bariatric surgery for obesity influence circulating levels of PYY and have a negative impact on bone mass, but the precise mechanism behind this is unclear. We thus examined whether alterations in PYY expression affect bone mass. Bone microstructure and cellular activity were analyzed in germline PYY knockout and conditional adult-onset PYY over-expressing mice at lumbar and femoral sites using histomorphometry and micro-computed tomography. PYY displayed a negative relationship with osteoblast activity. Male and female PYY knockout mice showed enhanced osteoblast activity, with greater cancellous bone mass. Conversely, PYY over-expression lowered osteoblast activity in vivo, via a direct Y1 receptor mediated mechanism involving MAPK stimulation evident in vitro. In contrast to PYY knockout mice, PYY over expression also altered bone resorption, as indicated by greater osteoclast surface, despite the lack of Y-receptor expression in osteoclastic cells. While evident in both sexes, cellular changes were generally more pronounced in females. These data demonstrate that the gut peptide PYY is critical for the control of bone remodeling. This regulatory axis from the intestine to bone has the potential to contribute to the marked bone loss observed in situations of extreme weight loss and higher circulating PYY levels, such as anorexia and bariatric obesity surgery, and may be important in the maintenance of bone mass in the general population.
    Full-text · Article · Jul 2012 · PLoS ONE
Show more