Madhusmita Misra
Research interests
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InterestsPediatric Endocrinology, Pediatric
Publications
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4.40Impact points
Higher Ghrelin and Lower Leptin Secretion is Associated with Lower LH Secretion in Young Amenorrheic Athletes Compared with Eumenorrheic Athletes and Controls.
American journal of physiology. Endocrinology and metabolism. 01/2012;
CONTEXT: Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increase... [more] CONTEXT: Amenorrhea is common in young athletes and is associated with low fat mass. However, hormonal factors that link decreased fat mass with altered gonadotropin pulsatility and amenorrhea are unclear. Low levels of leptin (an adipokine) and increased ghrelin (an orexigenic hormone that increases as fat mass decreases) impact gonadotropin pulsatility. Studies have not examined luteinizing hormone (LH) secretory dynamics in relation with leptin and ghrelin secretory dynamics in adolescent and young adult athletes. OBJECTIVE: We hypothesized that (i) young amenorrheic athletes (AA) would have lower LH and leptin and higher ghrelin secretion than eumenorrheic athletes (EA) and non-athletes, and (ii) higher ghrelin and lower leptin would be associated with lower LH secretion. DESIGN: This was a cross-sectional study SETTING: Clinical Research Center SUBJECTS AND OUTCOME MEASURES: We examined ghrelin and leptin secretory patterns (over 8-hours from 11 p.m.-7 a.m.) in relation to LH secretory patterns in AA, EA and non-athletes 14-21 years old. Ghrelin and leptin were assessed every 20 minutes, and LH every 10 minutes. RESULTS: Groups did not differ for age, bone age or BMI. However, fat mass was lower in AA than EA and non-athletes. AA had lower LH and higher ghrelin pulsatile secretion and area under the curve (AUC) than non-athletes, and lower leptin pulsatile secretion and AUC than EA and non-athletes. Percent body fat was associated positively with LH and leptin secretion and inversely with ghrelin. In a regression model, ghrelin and leptin secretory parameters were associated independently with LH secretory parameters. CONCLUSION: Higher ghrelin and lower leptin secretion in AA related to lower fat mass may contribute to altered LH pulsatility and amenorrhea.
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Recombinant human IGF-1 (insulin-like growth factor) therapy: where do we stand today?
Indian journal of pediatrics. 11/2011; 79(2):244-9.
Recombinant human (rh) IGF-1 has been available for therapy since the 1980s and has been commercially available for over 5 y, yet the role of rhIGF-1 in treating children with short stature remains ambiguous. This is consequent to the inherent difficulty in defining criteria for IGF-1 deficiency, an... [more] Recombinant human (rh) IGF-1 has been available for therapy since the 1980s and has been commercially available for over 5 y, yet the role of rhIGF-1 in treating children with short stature remains ambiguous. This is consequent to the inherent difficulty in defining criteria for IGF-1 deficiency, and in determining the outcome of rhIGF-1 therapy in terms of growth rate and adult height. The rationale for its efficacy compared with rhGH (recombinant human growth hormone) for treatment of short stature is still widely debated. Additionally, adverse events such as increased intracranial pressure and hypoglycemia are of therapeutic concern. The goal of this article is to review published data that describes the impact of IGF-1 therapy in treatment of short stature and other growth disorders.
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3.07Impact points
Adipokines and Cardiovascular Risk in Cushing's Syndrome.
Neuroendocrinology. 11/2011;
Cushing's syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered productio... [more] Cushing's syndrome (CS) is associated with increased cardiovascular morbidity and mortality. Recent evidence also suggests that increased cardiovascular risk may persist even after long-term remission of CS. Increased central obesity, a typical feature of CS, is associated with altered production of adipokines, which contributes to the pathogenesis of several metabolic and cardiovascular complications observed in this condition. In vitro and in vivo studies have shown a relationship between cortisol and adipokines in several experimental settings. In patients with either active or 'cured' CS, an increase in leptin and resistin levels as well as the release of pro-inflammatory cytokines, such as tumor necrosis factor-α and interleukin-6, may be associated with increased cardiovascular risk. For other adipokines, including adiponectin, results are inconclusive. Studies are needed to further elucidate the interactions between clinical and subclinical increases in cortisol production and altered adipokine release in CS.
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4.02Impact points
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3.20Impact points
Estradiol levels predict bone mineral density in male collegiate athletes: a pilot study.
Clinical endocrinology. 09/2011; 76(3):339-45.
Objective Strenuous training commonly results in amenorrhoea, which contributes to bone loss in some female collegiate athletes. However, the impact of athletic training on endocrine function and bone mineral density (BMD) in male collegiate athletes is less well understood. The objective of the st... [more] Objective Strenuous training commonly results in amenorrhoea, which contributes to bone loss in some female collegiate athletes. However, the impact of athletic training on endocrine function and bone mineral density (BMD) in male collegiate athletes is less well understood. The objective of the study was to investigate the specific endocrine determinants of BMD in male collegiate runners and wrestlers, including the potential impact of gonadal steroid levels. Design Cross-sectional study. Patients Twenty-six division I collegiate male athletes (wrestlers, runners and golfers). Measurements Main outcome measures included (i) BMD endpoints measured by dual energy x-ray absorptiometry (DXA); (ii) endocrine end-points: total and free oestradiol, total and free testosterone; (iii) body composition end-points: lean and fat mass, measured by DXA; and (iv) exercise end-points: maximal oxygen uptake (VO(2) max), number of miles run weekly and grip strength. Results Free and total oestradiol levels were important positive determinants of BMD. In contrast, total and free testosterone levels were not significant predictors of BMD at any skeletal site (except for free testosterone at the radius). In addition, lean body mass, % ideal body weight, total body weight, body mass index (BMI) and hours per week of resistance training were positive predictors of BMD. VO(2) max was a negative predictor of BMD. Mean BMD was higher at all skeletal sites in the wrestlers compared with the runners and a comparison group (golfers). Conclusions Our data suggest that oestradiol levels, BMI, and resistance training are more important determinants of BMD in male collegiate athletes than testosterone.
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Bone health in anorexia nervosa.
Current opinion in endocrinology, diabetes, and obesity. 09/2011; 18(6):376-82.
Anorexia nervosa is associated with low bone mineral density (BMD), concerning for an increased risk of fractures, and decreased bone accrual in adolescents, concerning for suboptimal peak bone mass. This review discusses causes of impaired bone health in anorexia nervosa and potential therapeutic s... [more] Anorexia nervosa is associated with low bone mineral density (BMD), concerning for an increased risk of fractures, and decreased bone accrual in adolescents, concerning for suboptimal peak bone mass. This review discusses causes of impaired bone health in anorexia nervosa and potential therapeutic strategies. Low BMD in anorexia nervosa is consequent to decreased lean mass, hypogonadism, low insulin-like growth factor-1 (IGF-1), relative hypercortisolemia and alterations in hormones impacted by energy availability. Weight gain causes some improvement in bone accrual, but not to the extent observed in controls, and vitamin D supplementation does not increase BMD. Oral estrogen is not effective in increasing BMD, likely from IGF-1 suppressive effects. In contrast, transdermal estrogen replacement is effective in increasing bone accrual in adolescents with anorexia nervosa, although not to the extent seen in controls. Recombinant human IGF-1 increases bone formation in adolescents, and with oral estrogen increases BMD in adults with anorexia nervosa. Bisphosphonates increase BMD in adults, but not in adolescents, and should be used cautiously given their long half-life. Further investigation is necessary to explore therapies for low BMD in anorexia nervosa. Weight gain is to be encouraged. Transdermal estrogen in adolescents, and bisphosphonates in adults, have a potential therapeutic role.
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5.22Impact points
Decreased nocturnal oxytocin levels in anorexia nervosa are associated with low bone mineral density and fat mass.
The Journal of clinical psychiatry. 08/2011; 72(11):1546-51.
Anorexia nervosa is characterized by self-induced starvation and associated with severe bone and fat loss. Oxytocin is a peptide hormone involved in appetite and energy homeostasis. Recent data show that oxytocin has an anabolic effect on bone and stimulates osteoblast function. There is limited inf... [more] Anorexia nervosa is characterized by self-induced starvation and associated with severe bone and fat loss. Oxytocin is a peptide hormone involved in appetite and energy homeostasis. Recent data show that oxytocin has an anabolic effect on bone and stimulates osteoblast function. There is limited information about oxytocin levels or their relationship to decreased bone mineral density in anorexia nervosa. Our objective was to investigate the relationship between oxytocin levels, bone mineral density, and body composition in women with anorexia nervosa. We studied 36 women, mean ± SEM age 27.6 ± 1.3 years: 17 with DSM-IV anorexia nervosa and 19 healthy controls in a cross-sectional study. Oxytocin levels were determined from pooled serum samples obtained every 20 minutes from 8 pm to 8 am during an inpatient overnight visit. Fasting leptin levels were measured. Bone mineral density at the anterior-posterior and lateral spine and hip and body composition were assessed by dual energy x-ray absorptiometry. The study was conducted from September 2004 to June 2008. Subjects with anorexia nervosa versus healthy controls had lower mean ± SEM oxytocin levels (14.3 ± 1.5 vs 31.8 ± 5.1 pg/mL, P = .003), leptin levels (2.7 ± 0.5 vs 11.4 ± 1.1 ng/mL, P < .0001), bone mineral density (anterior-posterior spine: 0.83 ± 0.02 vs 1.04 ± 0.03; lateral spine: 0.63 ± 0.02 vs 0.81 ± 0.02; total hip: 0.79 ± 0.03 vs 0.97 ± 0.03 g/cm², P < .0001), and fat mass (8.8 ± 0.6 vs 19.7 ± 0.9 kg, P < .0001). Oxytocin levels were associated with bone mineral density at the anterior-posterior (r = 0.40, P = .02) and lateral (r = 0.36, P = .04) spine, fat mass (r = 0.42, P = .01), and leptin levels (r = 0.55, P = .001). Overnight secretion of oxytocin in women with anorexia nervosa is decreased compared with healthy women. Low oxytocin levels are associated with decreased bone mineral density and body fat and may contribute to anorexia nervosa-induced bone loss.
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6.20Impact points
Bone microarchitecture is impaired in adolescent amenorrheic athletes compared with eumenorrheic athletes and nonathletic controls.
The Journal of clinical endocrinology and metabolism. 08/2011; 96(10):3123-33.
Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has no... [more] Bone mineral density (BMD) is lower in young amenorrheic athletes (AA) compared to eumenorrheic athletes (EA) and nonathletic controls and may contribute to fracture risk during a critical time of bone accrual. Abnormal bone microarchitecture is an independent determinant of fracture risk and has not been assessed in young athletes and nonathletes. We hypothesized that bone microarchitecture is impaired in AA compared to EA and nonathletes despite weight-bearing exercise. We conducted this cross-sectional study at the Clinical Research Center of Massachusetts General Hospital. SUBJECTS AND OUTCOME MEASURES: We assessed BMD and bone microarchitecture in 50 subjects [16 AA, 18 EA, and 16 nonathletes (15-21 yr old)] using dual-energy x-ray absorptiometry and high-resolution peripheral quantitative computed tomography. Groups did not differ for chronological age, bone age, body mass index, or vitamin D levels. Lumbar BMD Z-scores were lower in AA vs. EA and nonathletes; hip and femoral neck BMD Z-scores were highest in EA. At the weight-bearing tibia, athletes had greater total area, trabecular area, and cortical perimeter than nonathletes, whereas cortical area and thickness trended lower in AA. Trabecular number was lower and trabecular separation higher in AA vs. EA and nonathletes. At the non-weight-bearing radius, trabecular density was lower in AA vs. EA and nonathletes. Later menarchal age was an important determinant of impaired microarchitecture. After controlling for covariates, subject grouping accounted for 18-24% of the variability in tibial trabecular number and separation. In addition to low BMD, AA have impaired bone microarchitecture compared with EA and nonathletes. These are the first data to show abnormal bone microarchitecture in AA.
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3.20Impact points
Leptin levels are associated with decreased depressive symptoms in women across the weight spectrum, independent of body fat.
Clinical endocrinology. 07/2011; 76(4):520-5.
Objective Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and st... [more] Objective Leptin is anorexigenic, and levels are markedly decreased in women with low body weight and high in women with obesity. Ghrelin opposes leptin effects on appetite and is negatively associated with body mass index. These appetite-regulating hormones may have opposing effects on mood and stress pathways. Women with anorexia nervosa (AN), hypothalamic amenorrhoea (HA) and obesity are at increased risk of depression and anxiety. It is unknown whether dysregulation of leptin or ghrelin contributes to the development of depression and/or anxiety in these disorders. We investigated the relationship between leptin and ghrelin levels and symptoms of depression, anxiety and perceived stress in women across the weight spectrum. Design Cross-sectional. Patients 64 women: 15 with AN, 12 normal-weight with HA, 17 overweight or obese (OB) and 20 normal-weight in good health (HC). Measurements Fasting serum leptin and plasma ghrelin levels were measured. Hamilton Rating Scales for Depression (HAM-D) and Anxiety (HAM-A) and the Perceived Stress Scale were administered. Results Leptin levels were inversely associated with HAM-D, HAM-A and Perceived Stress scores. The negative relationships between leptin and severity of symptoms of both depression and anxiety remained significant after controlling for body fat or weight. There was no relationship between ghrelin and symptoms of depression or anxiety. Although ghrelin levels were positively associated with the degree of perceived stress, this relationship was not significant after controlling for body fat or weight. Conclusions Leptin may mediate depressive symptoms across the weight spectrum. Further investigation of the role of leptin in modulating mood will be important.
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3.05Impact points
Bone health in primary ovarian insufficiency.
Seminars in reproductive medicine. 07/2011; 29(4):317-27.
The etiology of primary ovarian insufficiency (POI) may be genetic, autoimmune, or iatrogenic. Genetic conditions include 45,X, 46,XX and 46,XY POI, and POI associated with galactosemia and FMR premutations. Women with autoimmune polyglandular syndromes 1 and 2 may develop autoimmune POI, as may tho... [more] The etiology of primary ovarian insufficiency (POI) may be genetic, autoimmune, or iatrogenic. Genetic conditions include 45,X, 46,XX and 46,XY POI, and POI associated with galactosemia and FMR premutations. Women with autoimmune polyglandular syndromes 1 and 2 may develop autoimmune POI, as may those who receive chemotherapy or radiotherapy. Hypogonadism in POI can result in reduced rates of bone mass accrual in adolescents and young women, and low bone density for age in older women. Measures to optimize bone density in women with POI include attention to lifestyle measures and hormone replacement. Resistance training and adequate calcium and vitamin D supplementation are essential, as is replacement of estrogen/progestin. Estrogen/progestin replacement may be problematic in women with estrogen-sensitive breast cancer who developed POI in the course of therapy for cancer. In these instances, bisphosphonates are an option. In particular, zoledronic acid has been used successfully in conjunction with chemotherapy, tamoxifen, and aromatase inhibitors.
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6.04Impact points
Physiologic estrogen replacement increases bone density in adolescent girls with anorexia nervosa.
Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research. 06/2011; 26(10):2430-8.
Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low BMD in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategi... [more] Anorexia nervosa (AN) is prevalent in adolescents and is associated with decreased bone mineral accrual at a time critical for optimizing bone mass. Low BMD in AN is a consequence of nutritional and hormonal alterations, including hypogonadism and low estradiol levels. Effective therapeutic strategies to improve BMD in adolescents with AN have not been identified. Specifically, high estrogen doses given as an oral contraceptive do not improve BMD. The impact of physiologic estrogen doses that mimic puberty on BMD has not been examined. We enrolled 110 girls with AN and 40 normal-weight controls 12 to 18 years of age of similar maturity. Subjects were studied for 18 months. Mature girls with AN (bone age [BA] ≥15 years, n = 96) were randomized to 100 µg of 17β-estradiol (with cyclic progesterone) or placebo transdermally for 18 months. Immature girls with AN (BA < 15 years, n = 14) were randomized to incremental low-dose oral ethinyl-estradiol (3.75 µg daily from 0 to 6 months, 7.5 µg from 6 to 12 months, 11.25 µg from 12 to 18 months) to mimic pubertal estrogen increases or placebo for 18 months. All BMD measures assessed by dual-energy X-ray absorptiometry (DXA) were lower in girls with AN than in control girls. At baseline, girls with AN randomized to estrogen (AN E + ) did not differ from those randomized to placebo (AN E-) for age, maturity, height, BMI, amenorrhea duration, and BMD parameters. Spine and hip BMD Z-scores increased over time in the AN E+ compared with the AN E- group, even after controlling for baseline age and weight. It is concluded that physiologic estradiol replacement increases spine and hip BMD in girls with AN.
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3.20Impact points
Growth hormone is positively associated with surrogate markers of bone turnover during puberty.
Clinical endocrinology. 04/2011; 75(4):482-8.
Puberty is characterized by increases in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) and the pubertal growth spurt. Bone formation and resorption also increase, consistent with increased bone metabolism. To determine the relationship between pubertal bone metabolism, GH and IGF-1. W... [more] Puberty is characterized by increases in growth hormone (GH) and insulin-like growth factor-1 (IGF-1) and the pubertal growth spurt. Bone formation and resorption also increase, consistent with increased bone metabolism. To determine the relationship between pubertal bone metabolism, GH and IGF-1. We hypothesized that bone turnover peaks at the time of greatest pubertal GH secretion. Design and Subjects included 86 girls and boys, 9-17 years-old (BMI 10th-90th percentiles). Because higher endogenous GH secretion is associated with a higher nadir following oral glucose, we used the GH nadir following a 2-h OGTT as indicative of GH status. Fasting serum IGF-1, aminoterminal propeptide of type 1 procollagen (P1NP) and carboxy-terminal collagen crosslinks (CTX) were obtained. Subjects were grouped per expected timing of peak growth. Group 1: Tanner 1 girls and Tanner 1-2 boys (period preceding peak growth), Group 2: Tanner 2-3 girls and Tanner 3-4 boys (period of peak growth) and Group 3: Tanner 4-5 girls and Tanner 5 boys (period following peak growth). GH peaked at mid-puberty (Group 2) and IGF-1 in late puberty (Group 3). P1NP and CTX were highest in mid-puberty compared with early and late puberty (P = 0·0009 and 0·006 in girls and P = 0·005 and 0·04 in boys). GH, but not IGF-1, correlated with P1NP (r = 0·46 in both genders, P ≤ 0·008) and CTX (r = 0·37 and 0·38, P = 0·04 and 0·02 in girls and boys, respectively). Similarly, on regression modelling, GH (but not IGF-1) predicted both bone turnover markers in both genders. GH is strongly associated with pubertal bone metabolism, independent of systemic IGF-1 in girls and boys.
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6.20Impact points
Effects of risedronate and low-dose transdermal testosterone on bone mineral density in women with anorexia nervosa: a randomized, placebo-controlled study.
The Journal of clinical endocrinology and metabolism. 04/2011; 96(7):2081-8.
Anorexia nervosa is complicated by severe bone loss and clinical fractures. Mechanisms underlying bone loss in adults with anorexia nervosa include increased bone resorption and decreased formation. Estrogen administration has not been shown to prevent bone loss in this population, and to date, ther... [more] Anorexia nervosa is complicated by severe bone loss and clinical fractures. Mechanisms underlying bone loss in adults with anorexia nervosa include increased bone resorption and decreased formation. Estrogen administration has not been shown to prevent bone loss in this population, and to date, there are no approved, effective therapies for this comorbidity. To determine whether antiresorptive therapy with a bisphosphonate alone or in combination with low-dose transdermal testosterone replacement would increase bone mineral density (BMD) in women with anorexia nervosa. We conducted a12-month, randomized, placebo-controlled study at a clinical research center. Participants included 77 ambulatory women with anorexia nervosa. Subjects were randomized to risedronate 35 mg weekly, low-dose transdermal testosterone replacement therapy, combination therapy or double placebo. BMD at the spine (primary endpoint), hip, and radius and body composition were measured by dual-energy x-ray absorptiometry. Risedronate increased posteroanterior spine BMD 3%, lateral spine BMD 4%, and hip BMD 2% in women with anorexia nervosa compared with placebo in a 12-month clinical trial. Testosterone administration did not improve BMD but increased lean body mass. There were few side effects associated with either therapy. Risedronate administration for 1 yr increased spinal BMD, the primary site of bone loss in women with anorexia nervosa. Low-dose testosterone did not change BMD but increased lean body mass.
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3.54Impact points
Appetite-regulating hormones cortisol and peptide YY are associated with disordered eating psychopathology, independent of body mass index.
European journal of endocrinology / European Federation of Endocrine Societies. 02/2011; 164(2):253-61.
Disordered eating occurs in women at both weight extremes of anorexia nervosa (AN) and obesity. Cortisol, peptide YY (PYY), leptin, and ghrelin are hormones involved in appetite and feeding behavior that vary with weight and body fat. Abnormal levels of these hormones have been reported in women wit... [more] Disordered eating occurs in women at both weight extremes of anorexia nervosa (AN) and obesity. Cortisol, peptide YY (PYY), leptin, and ghrelin are hormones involved in appetite and feeding behavior that vary with weight and body fat. Abnormal levels of these hormones have been reported in women with AN, functional hypothalamic amenorrhea (HA), and obesity. The relationship between appetite-regulating hormones and disordered eating psychopathology is unknown. We therefore studied the relationship between orexigenic and anorexigenic hormones and disordered eating psychopathology in women across a range of weights. A cross-sectional study of 65 women, 18-45 years: 16 with AN, 12 normal-weight with HA, 17 overweight or obese, and 20 normal-weight in good health. Two validated measures of disordered eating psychopathology, the Eating Disorders Examination-Questionnaire (EDE-Q) and Eating Disorders Inventory-2 (EDI-2), were administered. Fasting PYY, leptin, and ghrelin levels were measured; cortisol levels were pooled from serum samples obtained every 20 min from 2000 to 0800 h. Cortisol and PYY levels were positively associated with disordered eating psychopathology including restraint, eating concerns, and body image disturbance, independent of body mass index (BMI). Although leptin levels were negatively associated with disordered eating psychopathology, these relationships were not significant after controlling for BMI. Ghrelin levels were generally not associated with EDE-Q or EDI-2 scores. Higher levels of cortisol and PYY are associated with disordered eating psychopathology independent of BMI in women across the weight spectrum, suggesting that abnormalities in appetite regulation may be associated with specific eating disorder pathologies.
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1.35Impact points
Bone metabolism in adolescents with anorexia nervosa.
Journal of endocrinological investigation. 02/2011; 34(4):324-32.
Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years... [more] Adolescents with anorexia nervosa (AN) are at risk for low bone mass at multiple sites, associated with decreased bone turnover. Bone microarchitecture is also affected, with a decrease in bone trabecular volume and trabecular thickness, and an increase in trabecular separation. The adolescent years are typically the time when marked increases occur in bone mass accrual towards the attainment of peak bone mass, an important determinant of bone health and fracture risk in later life. AN often begins in the adolescent years, and decreased rates of bone mass accrual at this critical time are therefore also concerning for deficits in peak bone mass. Factors contributing to low bone density and decreased rates of bone accrual include alterations in body composition such as low body mass index and lean body mass, and hormonal alterations such as hypogonadism, a nutritionally acquired resistance to GH and low levels of IGF-I, relative hypercortisolemia, low levels of leptin, and increased adiponectin (for fat mass) and peptide YY. Therapeutic strategies include optimizing weight and menstrual recovery, and adequate calcium and vitamin D replacement. Oral estrogen-progesterone combination pills are not effective in increasing bone density in adolescents with AN. Recombinant human IGF-I increases levels of bone formation markers in the short term, while long-term effects remain to be determined. Bisphosphonates act by decreasing bone resorption, and are not optimal for use in adolescents with AN, in whom the primary defect is low bone formation.
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0.20Impact points
Bone health and the female athlete triad in adolescent athletes.
The Physician and sportsmedicine. 02/2011; 39(1):131-41.
Peak bone mass (PBM) is a negative predictor of osteoporosis and lifelong fracture risk. Because osteoporosis is such a prevalent disease with life-threatening consequences, it is important to try to maximize PBM. Adolescence is a critical period for bone acquisition. This article discusses some of ... [more] Peak bone mass (PBM) is a negative predictor of osteoporosis and lifelong fracture risk. Because osteoporosis is such a prevalent disease with life-threatening consequences, it is important to try to maximize PBM. Adolescence is a critical period for bone acquisition. This article discusses some of the differences in male and female skeletal development and modifiable factors that enhance bone accrual in this age group, particularly in athletes. Hormonal influences, effects of physical activity, and nutritional contributions are included, with a focus on the adolescent athlete. Emphasis is placed on the importance of appropriate energy availability in this age group. We also review prevention and treatment strategies for the female athlete triad (ie, the inter-relationship of decreased energy availability, menstrual irregularity, and low bone density) in adolescents and athletic women. Recommendations for maximizing bone density in both male and female adolescents are discussed.
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0.74Impact points
DXA surrogates for visceral fat are inversely associated with bone density measures in adolescent athletes with menstrual dysfunction.
Journal of pediatric endocrinology & metabolism : JPEM. 01/2011; 24(7-8):497-504.
Lean mass is associated with bone mineral density (BMD) in athletes, attributable to the anabolic pull of muscle on bone. Fat mass is also important, and subcutaneous fat positively and visceral fat negatively correlates with BMD in obese adolescents. The contribution of regional body composition to... [more] Lean mass is associated with bone mineral density (BMD) in athletes, attributable to the anabolic pull of muscle on bone. Fat mass is also important, and subcutaneous fat positively and visceral fat negatively correlates with BMD in obese adolescents. The contribution of regional body composition to low BMD in amenorrheic athletes (AA) has not been elucidated. We hypothesized that in adolescent athletes (runners), BMD is associated positively with total fat (surrogate for subcutaneous fat) and lean mass, and inversely with percent trunk fat and trunk-to-extremity fat ratio (surrogates for visceral fat). Cross-sectional study. We examined BMD and body composition using dual energy X-ray absorptiometry (DXA) in 21 AA and 19 eumenorrheic athletes (EA) (12-18 years) (runners). We report total hip and height-adjusted BMD [lumbar bone mineral apparent density (LBMAD) and whole body bone mineral content/height (WBBMC/Ht)]. AA had lower BMD than EA. Lean mass was less strongly associated with hip BMD in AA than EA; fat mass was positively associated with LBMAD in EA. Percent trunk fat and trunk-to-extremity fat ratio were inversely associated with lumbar and WB measures in AA. In a regression model, lean and fat mass were positively, and percent trunk fat and trunk-to-extremity fat ratio negatively associated with LBMAD and WBBMC/Ht for all athletes, even after controlling for serum estradiol. DXA surrogates for visceral fat are inversely associated with bone density in athletes.
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3.07Impact points
The neuroendocrine basis of anorexia nervosa and its impact on bone metabolism.
Neuroendocrinology. 01/2011; 93(2):65-73.
Anorexia nervosa (AN) is a condition of profound undernutrition associated with alterations in various neuroendocrine axes, many of which contribute to a marked impairment in bone accrual and low bone mineral density. This review focuses on changes in the hypothalamo-pituitary-gonadal axis, the grow... [more] Anorexia nervosa (AN) is a condition of profound undernutrition associated with alterations in various neuroendocrine axes, many of which contribute to a marked impairment in bone accrual and low bone mineral density. This review focuses on changes in the hypothalamo-pituitary-gonadal axis, the growth hormone insulin-like growth factor-1 axis, and the hypothalamo-pituitary-adrenal axis in AN, as well as alterations in various appetite-regulating hormones. In addition, the review discusses low bone mineral density and altered bone microarchitecture in AN, the pathophysiology underlying impaired bone metabolism, and possible therapeutic strategies to optimize bone health.
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47.05Impact points
Case records of the Massachusetts General Hospital: Case 38-2010: a 13-year-old girl with an enlarging neck mass.
The New England journal of medicine. 12/2010; 363(25):2445-54.
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4.02Impact points
Clinical monitoring guidelines for congenital hypothyroidism: laboratory outcome data in the first year of life.
The Journal of pediatrics. 11/2010; 158(4):532-7.
To examine whether current recommendations for thyroid status monitoring in children with congenital hypothyroidism (CH) (monthly in the first 6 months and every 3-4 months subsequently) are adequate, or whether monthly monitoring is necessary throughout the first year. We reviewed charts of 70 chil... [more] To examine whether current recommendations for thyroid status monitoring in children with congenital hypothyroidism (CH) (monthly in the first 6 months and every 3-4 months subsequently) are adequate, or whether monthly monitoring is necessary throughout the first year. We reviewed charts of 70 children with CH for initial thyroid-stimulating hormone (TSH), frequency of follow-up, dose changes, and thyroxine (T(4)) and TSH levels in the first year. Need for monthly monitoring was determined on the basis of guidelines to maintain T(4)/free T(4) in the upper half of the normal range and rapidly normalize TSH. Monthly monitoring was justified in 75% in the first 6 months and 36% in the next 6 months. Children requiring monthly monitoring in the second 6 months had higher baseline TSH (P = .02) and lower T(4) (P = .01) than those not requiring monthly monitoring. Thyroid dysgenesis, starting levothyroxine dose, sex, and ethnicity did not predict requirement for monthly monitoring. Thirty percent of children in the first and second 6 months had ≥1 high TSH level, with a T(4)/free T(4) not in the upper half of the normal range. More than a third of children with CH require monthly monitoring between 6 to 12 months on the basis of study criteria. Current monitoring guidelines may need to be reexamined.
Following (7)
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Sunday Eric
de skyric nigeria limited -
David Schoenfeld
Massachusetts General Hospital -
Miriam Bredella
Harvard Medical School -
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Ijad Madisch
Massachusetts General Hospital
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