Early life factors such as birth weight have been associated with the risk of disease in adulthood, including osteoporosis. In the United States, an estimated eight million women have osteoporosis, a disease characterized by low bone mass and associated with increased risk of fracture. Peak bone mass, achieved during early adulthood, is a key determinant of risk of subsequent osteoporosis. Prior studies have suggested that an individual's birth weight is positively associated with bone mineral content (BMC) and bone mineral density (BMD) but results have differed depending on site of bone measurement and other factors considered. We assessed the relationship between birth weight and BMC and BMD using data from the University of Massachusetts Vitamin D Status Study, a cross-sectional study of 186 US women aged 18 to 30 years. Birth weight was assessed via self report and BMC and BMD were measured by dual energy x-ray absorptiometry (DXA). Multivariable linear regression and multivariable logistic regression were used to model the association between birth weight and BMC and BMD, adjusting for established risk factors for low bone density. After controlling for important factors, birth weight was positively associated with BMC and BMD, in large part due to the strong relationship between birth weight and body size. A better understanding of the physiology of the association between birth weight and adult body size and peak bone mass is needed to determine if birth weight is independently associated with peak bone mass.

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Bone mineral content (BMC) and bone mineral density (BMD), measured by dual x-ray absorptiometry are used clinically to diagnose osteoporosis and estimate risk for fragility fractures. Bone mineral explains up to 70% of bone strength; however, it does not take into account bone geometry. Mechanical Response Tissue Analysis is a method of non-invasively measuring the bending stiffness (EI) of bone which is determined by the product of Young's modulus of elasticity (E) and the areal cross sectional moment of inertia (I). The aim of the current study was to determine if high intensity strength training will increase ulnar bending stiffness in young women. Forty-nine women aged 19.9 ± 1.7 yrs, trained their nondominant arm either concentrically or eccentrically in the Isokinetic modality on the Biodex® system III 3d/wk for 32 wks. The dominant arm served as the control limb (untrained). Analysis of all subjects regardless of training mode demonstrated a significant increase in ulnar EI (22% ↑, P=0.01) with no significant difference in the untrained arm. When EI results were assessed by training mode, subjects who trained eccentrically showed a significant increase for ulnar EI in the trained limb (40% ↑, P=0.01) with no significant effect on the untrained limb while concentric training demonstrated no significant gain in either the trained or untrained arm. There was no effect of time x mode of training interaction for either the trained or untrained limb. Bone mineral density and bone mineral content of the ulna increased significantly in the trained arm in both concentric and eccentric training modes (P<0.05). These findings suggest support for the hypothesis that a critical threshold of mechanical bending loads may be necessary to effect an adaptation in bone strength and thus, eccentric training may be a novel approach to increase ulnar EI in young women. / Master of Science

High body weight seems protective of bone mass, specifically bone mineral content (BMC) and bone mineral density (BMD), thereby reducing the risk of osteoporosis. Cognitive eating restraint (CER), diet composition, and the satiety hormone, leptin, produced by adipocytes, are associated with body mass and may also influence bone mass. Few studies have examined these relationships. To investigate the relationship between leptin and CER score, 36 premenopausal, healthy weight women, as defined by body mass index (BMI) of 18-25 kg/m², aged 18-25 years were studied. Women were categorized by baseline Eating Inventory questionnaire scores into either the high CER group (score > 9, n = 20) or low CER group (score < 9, n = 16). Serum leptin concentration was significantly lower in the low CER group versus high CER group at baseline. A positive relationship between serum leptin concentration and body fat mass and body fat % in normal weight women despite differences in CER scores was observed. In a separate study, overweight and obese women, (BMI > 25 to < 43 kg/m²), aged 32-45 years, were randomly assigned to either a low-carbohydrate, high-protein (LCHP) or low-fat, high-carbohydrate (LFHC) diet for 12 weeks. Serum leptin concentration was significantly greater in the LCHP versus the LFHC diet group at 12 weeks (p < 0.05). Over time, significant decreases in serum leptin concentration, BMI, body weight, total lean mass, total fat mass, and body fat % were observed in both diet groups. Serum leptin concentration was positively associated with body weight, fat mass, and body fat % regardless of diet consumed. Both studies are novel in their respective populations and show no direct link between leptin and bone mass when considered in the context of CER or diet composition. / Master of Science

Selective Serotonin Reuptake Inhibitors and Bone mineral Density in a Population of U.S. Premenopausal Women May 2011 M.S., UNIVERSITY of Massachusetts Amherst Directed by: Professor Elizabeth R. Bertone-Johnson Low bone mineral density (BMD) in post-menopausal women is a risk factor for bone fractures and osteoporosis development. Prior studies in post-menopausal women have shown the use of antidepressant medications, specifically selective serotonin reuptake inhibitors (SSRIs) to be inversely related to BMD. However, the association has not been studied in pre-menopausal women. Current SSRI use is widespread with 8% of U.S. women age 18-44 reporting use. We evaluated the association between SSRIs and BMD and bone mineral content (BMC) cross-sectionally using data from the University of Massachusetts Vitamin D Status Study. SSRI use, diet, and lifestyle factors were assessed by questionnaire. BMD and BMC were measured using dual-energy x-ray absorptiometry (DEXA). The study included 256 women aged 18-30 (mean=21.6 years, SD=4.3 years). In this population, SSRI use was 5%, BMD values ranged from 0.97-1.38 g/cm2 (mean 1.16, SD 0.08), and BMC values ranged from 1833g to 3682g (mean 2541.5, SD=349.2). After adjustment for age, body mass index, and physical activity, mean BMD in the 13 users of SSRIs was 1.15g/cm2 (SD=0.06) compared to 1.16g/cm2 (SD=0.77) in the 243 non-users (p =0.66). After the same adjustments, mean BMC in the 13 users was 2467.1g (SD=285.0) compared to 2547.6g (SD=352.6) in the 243 non-users (p=0.94). Our findings do not support an inverse association between SSRI use and BMD or BMC. However, given the prevalence of SSRI use in young women and the potential for adverse effects on bone health, further study of this association is warranted.

Obesity is a worldwide epidemic increasing at an alarming rate among youth who are facing similar health problems as adults. Sleep Apnea Syndrome (SAS) is an underdiagnosed comorbidity of obesity, characterized by repetitive nocturnal interruptions in breathing. Obesity is associated with delayed skeletal maturation in overweight youth, but mechanisms contributing to this problem are unclear. Obesity and SAS both have been shown to disrupt regulatory hormones and cytokines that influence bone accretion during adolescence. PURPOSE: The purpose of this study was to assess the combined effects of excess body weight and SAS on bone mineral density (BMD) and content (BMC), bone turnover, and on the regulatory hormones leptin and IGF-1 known to potentially influence bone accretion during adolescence. METHODS: Men aged 18-28 years were assigned to groups as follows: normal weight controls (CON: AHI <3, n=8); overweight without SAS (OWT: BMI < 26 kg/m2 and AHI <3, n=9); and overweight with SAS (SAS: BMI >26 kg/m2 and AHI >5, n=8). The apnea/hypopnea index (AHI) expresses the score for disrupted nighttime breathing events/hr and was obtained in this study with results from a home sleep screening test. Health history and Epworth Sleepiness Scale (ESS) questionnaires also were administered. Bone mineral parameters and body composition variables were measured with dual-energy X-ray absorptiometry. Serum osteocalcin, leptin, IGF-1, and NTx-1 were measured, respectively, by radioimmunoassay and enzyme-linked immunoabsorbent assay. RESULTS: Fat-free mass, intra-abdominal fat, and fat mass were higher in the SAS and OWT groups (p<0.03). ESS scores revealed that SAS individuals were sleepier than CON and OWT groups (p<0.009). Total body and site-specific BMD and BMC values (lumbar spine, hip, and forearm) were similar between groups and did not relate to the estimated AHI score. Serum OC and NTx-1 did not differ between groups. Leptin levels were 30% higher in OWT and SAS than in the CON group (p<0.02), but did not correlate with the AHI score. Across all subjects (n=25), only lumbar spine BMC (p<0.005) was correlated to AHI (r=-.52; p<0.01). The preponderance of this relationship between AHI and lumbar spine BMC was attributable to the close inverse association of these two variables within the SAS group (r = -.81; p<0.001). CONCLUSION: The effects of SAS were not influenced by the amount of whole-body, intra-abdominal adiposity or lean body mass. Neither leptin nor IGF-1 predicted bone status across all groups. Daytime fatigue and sleepiness, a cardinal symptom of SAS, combined with overweight may contribute to lower lumbar BMC by chronically reducing weight-bearing physical activity and thereby reduce exposure time for mechanical loading of the spine in affected individuals. Further research is needed to explore the biochemical, physiological, and apparently the physical activity implications of SAS on skeletal status and turnover. / Master of Science

A obesidade encontra-se associada a uma série de alterações metabólicas que podem elevar o risco de doenças crônicas não-transmissíveis. Em contraste, o excesso de peso apresenta-se como um fator protetor para a ocorrência de fraturas e baixa densidade óssea. Considerando que a adolescência é um período crucial para aquisição da massa óssea e minimização do risco de osteoporose na maturidade e os efeitos da perda de peso sobre a massa óssea, neste estágio de vida, não são completamente elucidados, o presente estudo foi desenvolvido. Objetivou-se investigar os efeitos da perda de peso sobre a massa óssea e as alterações metabólicas em adolescentes obesos pós-púberes. Realizou-se a revisão bibliográfica sobre o tema e um estudo longitudinal contemplando um período de 9 meses de intervenção baseada em dieta hipocalórica e orientações nutricionais. Foram incluídos 55 adolescentes pós-púberes, 43 meninas, com média de idade de 16,6 (1,4) anos, com índice de massa corporal por idade superior ao percentil 95. Os participantes foram monitorados a cada três semanas por meio de avaliação antropométrica (aferição do peso, estatura e circunferência) e do consumo alimentar (recordatório alimentar de 24 horas). Realizaram-se avaliações da composição corporal e da densidade mineral óssea de corpo total por meio da DXA (dual energy X-ray absorptiometry), do consumo alimentar (registro alimentar de 3 dias) e de parâmetros metabólicos (colesterol total e frações, tricilgliceróis, glicemia de jejum, insulina, leptina e grelina) no início do estudo, após 3 meses e ao fim da intervenção. Verificou-se que 44,4 por cento dos participantes não apresentavam redução do peso. O grupo que respondeu à intervenção apresentou média de perda de peso de 6,2 (4,6) por cento ao fim do estudo. Neste grupo, houve significativa redução do consumo energético, de 2105,4 (537,6) Kcal/dia na primeira avaliação para 1738,8 (608,4) Kcal/dia ao fim do estudo. Observou-se incremento da atividade física entre os participantes e melhora dos parâmetros metabólicos entre adolescentes que perderam peso. / Obesity is associated with several metabolic changes that may increase the risk of chronic diseases. Body weight is recognized as a protective factor against fractures and lower bone density. Considering that adolescence is a crucial period for bone mass acquisition and osteoporosis risk reduction in maturity and the effects of weight loss on bone mass in this life stage are not completely elucidated, the present study was performed. The objective was to investigate the effects of weight loss as well the metabolic changes related to bone mass in post-puberal adolescents. Bibliographic review and a longitudinal study, with adolescents submitted to nutritional intervention based on hipocaloric diet and nutritional advice during 9 months, were realized. Fifty-five subjects, 43 girls, mean age of 16.6 (1.4) years, with body mass index by age superior than 95 percentile, were recruited. Subjects were monitored every three weeks with anthropometric (weight, height and circumferences) and dietary intake (24h food intake recall) evaluation. Body composition and total-body bone mineral density. (assessed by dual-energy X-ray absorptiometry), metabolic parameters (plasma lipids, glucose, insulin, leptin and ghrelin concentrations) and dietary intake (3-day food records) were evaluated at the baseline, after 3-months and at the end of the study. Sixteen participants thatcompleted the study did not lost weight. The group that adhered to intervention nutritional had mean weight loss of 6.2 (4.6) %. In this group, there was a significant decrease in energy intake, from 2105.4 (537.6) Kcal/day to 1738.8 (608.4) Kcal/day. Physical activity pratice increased between participants and there were metabolic parameters improvement in adolescents who lose weight. In these subjects, hypercholesterolemia and insulin resistance decreased, 7,9% and 27.2% (p<0.05) respectively, after 3 months of intervention. There was a significant increase of total bone mineral density and bone mineral content (BMC) in adolescents did not lost weight. Increased BMC and bone area was verified in participants that adhered to intervention nutritional. Bone parameters changes were associated with body fat alterations. The increment in bone mineral density even under weight loss showed no negative effect of bone mass. Dietary intake change and weight control contributed to metabolic parameters improvement of obese adolescents.

<p>Osteoporosis is a major health care problem, by reason of its devastating consequences, in particular hip fractures. Worldwide it has been estimated that the incidence of hip fracture will increase to more than 6 million per year by 2050 compared to 1.7 million per year in 1990. Osteoporosis can be caused by various factors namely, genetic, lifestyle and environmental factors, and since the rising incidence of its consequences is not fully explained by the growing age of the population, there is an urgent need to identify individual causal factors of this condition. </p><p>The present research has focused on aluminium, one potential environmental factor of importance for bone disease, and its possible relation to osteoporosis, since it is known to cause osteoporosis-like bone disease and has been associated with induction of progressive central nervous system diseases.</p><p>Aluminium is the third most common element in the earth’s crust and the most abundant metal (8%). It is widely utilized industrially and it is also naturally present in many foods. Although aluminium is ubiquitous in the human environment, evolution has not given it an essential biological function.</p><p>The aluminium content of bone was measured by inductively coupled mass spectrometry in a large group of patients suffering from hip fractures, high energy fractures and osteoarthrosis. An exponential increase in aluminium content of bone with age was found (p=0.0004). However, no significant association of aluminium in bone with occurrence of hip fracture or dementia could be found, and no indirect evidence was obtained, e.g. through bone mineral density or biomechanical properties, that aluminium is involved in the pathogenesis of osteoporosis. Although we accumulate aluminium in bone throughout our lives, and there are experimental suggestions that aluminium induces premature cell death, the body content of this metal does not seem to influence the overall mortality risk. </p>

Osteoporosis is a major health care problem, by reason of its devastating consequences, in particular hip fractures. Worldwide it has been estimated that the incidence of hip fracture will increase to more than 6 million per year by 2050 compared to 1.7 million per year in 1990. Osteoporosis can be caused by various factors namely, genetic, lifestyle and environmental factors, and since the rising incidence of its consequences is not fully explained by the growing age of the population, there is an urgent need to identify individual causal factors of this condition. The present research has focused on aluminium, one potential environmental factor of importance for bone disease, and its possible relation to osteoporosis, since it is known to cause osteoporosis-like bone disease and has been associated with induction of progressive central nervous system diseases. Aluminium is the third most common element in the earth’s crust and the most abundant metal (8%). It is widely utilized industrially and it is also naturally present in many foods. Although aluminium is ubiquitous in the human environment, evolution has not given it an essential biological function. The aluminium content of bone was measured by inductively coupled mass spectrometry in a large group of patients suffering from hip fractures, high energy fractures and osteoarthrosis. An exponential increase in aluminium content of bone with age was found (p=0.0004). However, no significant association of aluminium in bone with occurrence of hip fracture or dementia could be found, and no indirect evidence was obtained, e.g. through bone mineral density or biomechanical properties, that aluminium is involved in the pathogenesis of osteoporosis. Although we accumulate aluminium in bone throughout our lives, and there are experimental suggestions that aluminium induces premature cell death, the body content of this metal does not seem to influence the overall mortality risk.

Die Dualenergie-Röntgenabsorptiometrie (DEXA, Dual Energy X-Ray Absorptiometry) ist ein in der Humanmedizin und Teilen der Veterinärmedizin etabliertes Verfahren zur Untersuchung der Knochenmineraldichte, des Knochenmineralgehaltes und der Körperzusammensetzung. Für das Pferd existieren bisher lediglich vereinzelte Studien zur Untersuchung des Knochens mittels der DEXA-Methode, welche allesamt auf nur sehr geringen Versuchstierzahlen beruhen. Ziel dieser Arbeit war es daher die DEXA-Methode für die Untersuchung am Pferd zu validieren. Hierfür wurden die Röhrbeine von 103 Schlachtpferden mittels des Densitometers PIXI LUNAR®, welches aus der Humanmedizin stammt und dort zur Untersuchung des Unterarmes dient, untersucht und die densitometrische Knochenmineraldichte (BMD) und der densitometrische Knochenmineralstoffgehalt (BMC) ermittelt. Als Messpunkt wurde standar-disiert die Mitte zwischen der Basis und dem Caput des Os metacarpale tertium bzw. des Os metatarsale tertium gewählt. Im Anschluss an die densitometrische Messung wurde als Referenzverfahren eine chemische Analyse durchgeführt, in welcher der Rohasche- sowie der Calcium- Phosphor- und Magnesiumgehalt der Röhrbeine bestimmt wurden. Die Angabe der Ergebnisse erfolgt als Median und 25-/75-Perzentil. Der Rohaschegehalt lag im Mittel über alle Röhrbeine bei 698 (69,1 - 70,3) g/kg TS. Für die Mineralstoffe konnten folgende Gehalte ermittelt werden: Calcium 265 (259 - 272) g/kg TS, Phosphor 123 (121 - 126) g/kg TS und Magnesium 2,40 (2,19 - 2,66) g/kg TS. Das Calcium-Phosphor-Verhältnis lag in einem Bereich von 2,14 - 2,18. Die Resultate der DEXA-Methode werden neben dem Mineralstoffgehalt auch vom Knochenumfang beeinflusst, so dass die folgenden Ergebnisse für die Vorder- und Hintergliedmaße (VGM, HGM) separat dargestellt werden: BMD: VGM 3,22 (2,80 - 3,65) g/cm², HGM 4,21 (3,76 - 4,65) g/cm²; BMC: VGM 26,5 (22,8 - 30,1) g, HGM 32,9 (29,0 - 36,3) g. Im Rahmen dieser Arbeit wurden Reproduzierbarkeitsstudien durchgeführt, bei denen für die BMD bei der Reproduzierbarkeit ohne Reposition Abweichungen in einem Bereich von 1,06 - 1,85 % und mit Reposition in einem Bereich von 3,51 - 4,48 % gefunden wurden. Für die BMC lag die Abweichung für die Reproduzierbarkeit ohne Reposition in einem Bereich von 1,28 - 2,79 % und mit Reposition schwankte sie zwischen 3,38 und 3,94 %. Um für den Einsatz der DEXA-Methode bei Verlaufsuntersuchungen den Einfluss der exakten Messlokalisation zu eruieren, wurden Messungen in einem Abstand von ein, zwei und drei Zentimetern proximal und distal des ursprünglichen Messpunktes vorgenommen. Die Ergeb-nisse dieser Studie wichen für die BMD um 3,53 - 9,16 % und für den BMC um 4,21 - 12,5 % von den Ergebnissen des zentralen Messpunktes in der Mitte der Diaphyse ab. Diese Abweichung liegt innerhalb der 25-/75-Perzentile der Messergebnisse des zentralen Messpunktes. Die Ergebnisse der vorliegenden Studie führen zu dem Schluss, dass es möglich ist die Knochenmineraldichte und den Knochenmineralgehalt des Röhrbeines des Pferdes mittels der DEXA-Methode zu ermitteln. Die guten Ergebnisse der Reproduzierbarkeitsstudien und der Abstandsmessungen vom zentralen Messpunkt legen die Durchführbarkeit am stehenden, sedierten Pferd nahe. Bei der DEXA-Methode wird ein Knochenabschnitt mit einem sehr hohen Kortikalisanteil erfasst, welcher auf Einflüsse, wie beispielsweise Training oder Ruhigstellung mit einer Veränderung des Knochenumfanges bei gleichbleibenden Mineralstoffkonzentrationen reagiert. Diese Eigenschaft führt zu einem geringen Zusammenhang zwischen der DEXA-Methode und der chemischen Analyse, so dass sich die Ergebnisse der beiden Messverfahren zwar gut in den Kontext anderer Studien einfügen, der direkte Vergleich der beiden Methoden jedoch nicht möglich ist. / DXA (dual energy X-ray absorptiometry) is an established method for the measurement of bone mineral density (BMD), bone mineral content (BMC) and whole body composition in human and partly in veterinary medicine. However, there are only a small number of studies that examine the bone in horses using DXA. All these studies are based on small samples. Therefore, the objective of this study was to validate the use of DXA for the measurement of BMD and BMC in the horse. In total the cannons of 103 horses were scanned ex vivo, using the PIXI LUNAR® densitometer. In human medicine this densitometer is used for the exami-nation of the forearm. The measuring point was the exact middle between basis and caput of the third metacarpal/metatarsal bone. In a second step the DXA measurements were complemented with a chemical analysis, analyzing the ash content, calcium, phosphorus and magnesium content of the bones. The results are presented as median and 25-/75-percentile. The average ash content of the cannon bones was 698 (691 - 703) g/kg DM. The average mineral content was measured in the following order: calcium 265 (259 - 272) g/kg DM, phosphorus 123 (121 - 126) g/kg DM und magnesium 2.44 (2.19 - 2.66) g/kg DM. The ratio of calcium to phosphorus ranged from 2.14 to 2.18. The DXA results are influenced not only by the bone´s mineral content, but also by its diameter. Because of this the results are separated into the results of the forelimb (fl) and the hindlimb (hl) which generates the following results: BMD: fl 3.22 (2.80 - 3.65) g/cm², hl 4.21 (3.76 - 4.65) g/cm²; BMC: fl 26.5 (22.8 - 30.1) g, hl 32.9 (29.0 - 36.3) g. Several robustness checks of the measurements were conducted. For the BMD measurements, the range of measurements diverged by 3.51-4.48 % for measurements with limb repositioning, and by 1.06-1.85 % for measurements without limb repositioning. For the BMC measurements, the range of measurements diverged by 3.38-3.94 % for measurements with limb repositioning, and by 1.28-2.79 for measurements without limb repositioning. To determine the importance of the exact bone position for follow-up investigations, measurements in a distance of one, two and three centimeters proximal and distal of the original measuring point were performed. The results of these measurements deviated from the result of the central measuring point at the centre of the diaphysis in a range of 3.53 – 9.16 % for BMD and a range of 4.21 – 12.5 % for BMC. This variation falls within the percentiles of the central measuring point. Overall, the results of this study indicate that DXA is useable for determining BMD and BMC at the third metacarpal/metatarsal bone of the horse. The high reproducibility of the results and the distance measurements suggest that DXA is suitable for measurements at the standing, tranquilized horse. However, the cannon bone is a bone with a high content of cortical bone. This means that the diameter of the bone changes as a result of training or immobilization, while the BMD and BMC remain unchanged by such influence. This leads to a weak correlation between the results from the DXA and chemical analyses. Thus, while these two types of analysis fit well into the context of prior studies, a direct comparison between these measurements is not possible.