<p>Generalni cilj ovog istraživanja je da se utvrdi da li postoji uticaj primenjenog<br />programa vežbanja na parametre ko&scaron;tane gustine i biohemijske markere ko&scaron;tanog<br />remodelovanja kod žena u periodu premenopauze i postmenopauze.<br />Uzorak ispitanica je činilo 26 žena starosti 45 do 55 godina, od kojih su 13 u periodu<br />premenopauze, a 13 u periodu postmenopauze. Ispitanice su učestvovale u programu vežbanja<br />u trajanju od 6 meseci, koji se realizovao u Novom Sadu, 4 puta nedeljno u trajanju od sat<br />vremena. Za utvrđivanje uticaja programa vežbanja na ko&scaron;tanu gustinu merena su 3<br />osteodenzitometrijska parametra na kičmi, vratu butne kosti i kuku i 5 parametara<br />biohemijskih markera ko&scaron;tanog remodelovanja.<br />Da bi se utvrdio uticaj vežbanja kod ispitanica, primenjena je multivarijatna analize<br />varijanse (MANOVA). Na celokupnom uzorku ispitanica nije utvrđena statistički značajna<br />razlika ni u jednom merenom parametru ko&scaron;tane gustine. U odnosu na biohemijske markere,<br />do&scaron;lo je do značajnog smanjenja nivoa ukupne alkalne fosfataze. Kod žena u periodu<br />premenopauze i kod žena u periodu postmenopauze, program vežbanja nije značajno uticao<br />na parametre ko&scaron;tane gustine merene na kičmi, vratu butne kosti i kuku (DXA, Lunar<br />Prodrigy), kao ni na parametre biohemijskih markera ko&scaron;tanog remodelovanja.<br />Primenom multivarijatne analize kovarijanse (MANCOVA) utvrđena je značajna<br />razlika u uticaju programa vežbanja između žena u pre- i postmenopauzi u mineralnoj<br />ko&scaron;tanoj gustini vrata butne kosti (BMD VF) i markera beta-crosslaps (CTX). Mineralna<br />ko&scaron;tana gustina je nakon programa vežbanja veća, a nivo beta-crosslapsa niži kod žena u<br />premenopauzi nego kod žena u periodu postmenopauze.<br />Na osnovu dobijenih rezultata, zaključujemo da je potreban duži vremenski period<br />realizacije programa vežbanja kako bi se mogla primetiti statistički značajna promena<br />merenih parametara. Ispitanicama se savetuje da nastave sa vežbanjem kako bi usporile<br />gubitak kosti</p> / <p>The genaral aim of this research is to determine is there an effects of the applied exercise<br />program on bone mineral density and and biochemical markers of bone turnover in the<br />premenopausal and postmenopausal period.<br />The sample was consisted of 26 women aged 45 to 55 years, of which 13 were in<br />premenopausal and 13 in postmenopausal period. Subjects were included (had performing) in 6-month<br />exercise program, which was implemented (maintained) in Novi Sad, 4 times a week in duration for an<br />hour. Three osteodensitometric parameters on lumbar spine, femoral neck and hip (DXA, Lunar<br />Prodrigy) and five parameters of biochemical markers of bone turnover were measured to assessed<br />(to determine) the effects of exercise program on bone density.<br />Multivariate analysis of variance (MANOVA) was used to determine the effect of exercise.<br />For the entire sample of subjects, there were no statistically significant difference in any measured<br />bone density parameter, but looking at biochemical markers, total alkaline phosphatase level were<br />significanly reduced. There were no significant changes in bone density parameters on the lumbar<br />spine, femoral neck and hip nor on the parameters of biochemical markers of bone turnover in women<br />in premenopausal and postmenopausal period.<br />Applying multivariate analyse of covariance it was found a significant difference in the<br />exercise program effect between pre- and postmenopausal women in bone mineral density of femoral<br />neck (BMD VF) and beta-crosslaps marker of turnover (CTX). Femoral neck BMD was higher, and<br />beta-crosslaps level was lower in premenopausal women than in postmenopausal women after<br />completion exercise program.<br />Based on obtained results, we conclude that is required a longer perod of exercise program<br />ralization in order to notice a statistically significant change in measured parameters. Subjects are<br />advised to continue their exercising in order to slow down the bone loss</p>

<p>In this thesis, the importance of the growth hormone (GH)/insulin-like growth factor (IGF) system and sex steroids for male bone metabolism has been investigated, and the effects of continuous low dose GH replacement in GH deficient (GHD) adults. In a population-based sample of men, positive correlations were found between bone mineral density (BMD) and IGF-I, IGF-II, IGF binding protein (IGFBP)-3 and the testosterone/sex hormone binding globulin (SHBG) ratio. Serum IGFBP-3 and testosterone levels and weight accounted for 34% to 48% of the variation in BMD at different sites. Compared to healthy age matched controls, men with idiopathic osteoporosis had lower estradiol/SHBG ratio and higher SHBG levels. There were no differences between the groups in serum levels of IGF-I, IGFBP-3, 24 hour cumulated GH secretion or peak GH secretion. In the patients, there was a positive correlation between the estradiol/SHBG ratio and BMD in femoral neck. Treatment of patients and controls with GH 0.8 mg/day for one week resulted in similar increases in serum markers for bone turnover in both groups. Several positive correlations between indices of GH secretion and markers for bone turnover were found in the patients. Men with idiopathic osteoporosis were treated with GH, continuously (0.4 mg/day) or intermittently (0.8 mg/day for two weeks every third month), for two years followed by one year of follow-up. After two years, the BMD and bone mineral content in lumbar spine and total body and serum osteocalcin levels were increased in both groups. This increase was sustained one year post treatment. Treatment of GHD adults with a low fixed dose of GH (0.17 mg/day) for three months, resulted in increases in serum IGF-I and IGFBP-3 levels and lean body mass, and a reduction in fat mass and total and low-density lipoprotein cholesterol levels. These beneficial effects were accomplished without serious side effects. These findings indicate that: i) the sex hormone and GH/IGF systems are important in male bone metabolism, ii) a combination of subtle disturbances in these two systems could contribute to the development of male idiopathic osteoporosis, iii) GH treatment could be considered as a treatment option in this condition.</p>

<p>Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. <i>Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine</i> 1037. 60 pp. Uppsala. ISBN 91-554-5021-0. </p><p>Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD. </p><p>In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (<i>p</i><0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients. </p><p>In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (<i>p</i>=0.005 and <i>p</i>=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D₃ predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D₃ may be involved in the pathophysiology of osteoporosis in CLD. </p><p>In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (<i>p</i><0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (<i>p</i>=0.003 and <i>p</i>=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (<i>p</i>=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible. </p>

<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>

Ormarsdóttir, S. 2001. Osteoporosis in Chronic Liver Disease. Acta Universitatis Upsaliensis. Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine 1037. 60 pp. Uppsala. ISBN 91-554-5021-0. Osteoporosis is a well-known and frequently reported complication of chronic liver disease (CLD) with a high fracture rate contributing to significant morbidity after liver transplantation. The pathogenesis is unknown and controversy exists about many risk factors for osteoporosis in CLD. In the present thesis, bone mineral density (BMD) was found to be significantly lower at the lumbar spine (p&lt;0.01) in a cohort of patients with CLD compared with age- and gender -matched individuals. Osteoporosis was found in 30% of the patients and 15% of the controls, respectively. Low body mass index (BMI), corticosteroid treatment, prothrombin time, age and female gender were independent risk factors for osteoporosis in the patients. In a follow-up study, 43 of 72 patients were available for a second BMD measurement 25 months (median) after the first. Bone loss at the femoral neck was 1.5 ± 2.4% in females and 2.9 ± 2.0% in males with a significant decrease in BMD Z-score over time (p=0.005 and p=0.02 for females and males, respectively), indicating increased bone loss at this site. Hyperbilirubinaemia and low circulating levels of 25-hydroxy vitamin D3 predicted increased bone loss at the femoral neck. These findings suggest that cortical bone, in addition to trabecular bone, may be affected in CLD and bilirubin and vitamin D3 may be involved in the pathophysiology of osteoporosis in CLD. In order to elucidate the suggested role of insulin-like growth factors (IGFs) and leptin in the pathophysiology of osteoporosis in CLD, we studied the relationship between these factors and BMD. Levels of IGFs were extremely low (p&lt;0.0001 compared with the controls) and related to liver function but no correlation was found between the IGFs and BMD. Serum leptin adjusted for BMI correlated negatively with BMD in female patients (p=0.003 and p=0.04 at the lumbar spine and the femoral neck, respectively) and in male patients at the femoral neck (p=0.04). Thus, the IGFs appear not to be involved in the pathophysiology of osteoporosis in CLD but a role of circulating leptin is possible.

In this thesis, the importance of the growth hormone (GH)/insulin-like growth factor (IGF) system and sex steroids for male bone metabolism has been investigated, and the effects of continuous low dose GH replacement in GH deficient (GHD) adults. In a population-based sample of men, positive correlations were found between bone mineral density (BMD) and IGF-I, IGF-II, IGF binding protein (IGFBP)-3 and the testosterone/sex hormone binding globulin (SHBG) ratio. Serum IGFBP-3 and testosterone levels and weight accounted for 34% to 48% of the variation in BMD at different sites. Compared to healthy age matched controls, men with idiopathic osteoporosis had lower estradiol/SHBG ratio and higher SHBG levels. There were no differences between the groups in serum levels of IGF-I, IGFBP-3, 24 hour cumulated GH secretion or peak GH secretion. In the patients, there was a positive correlation between the estradiol/SHBG ratio and BMD in femoral neck. Treatment of patients and controls with GH 0.8 mg/day for one week resulted in similar increases in serum markers for bone turnover in both groups. Several positive correlations between indices of GH secretion and markers for bone turnover were found in the patients. Men with idiopathic osteoporosis were treated with GH, continuously (0.4 mg/day) or intermittently (0.8 mg/day for two weeks every third month), for two years followed by one year of follow-up. After two years, the BMD and bone mineral content in lumbar spine and total body and serum osteocalcin levels were increased in both groups. This increase was sustained one year post treatment. Treatment of GHD adults with a low fixed dose of GH (0.17 mg/day) for three months, resulted in increases in serum IGF-I and IGFBP-3 levels and lean body mass, and a reduction in fat mass and total and low-density lipoprotein cholesterol levels. These beneficial effects were accomplished without serious side effects. These findings indicate that: i) the sex hormone and GH/IGF systems are important in male bone metabolism, ii) a combination of subtle disturbances in these two systems could contribute to the development of male idiopathic osteoporosis, iii) GH treatment could be considered as a treatment option in this condition.

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.

Abstract Weak and osteoporotic bones in old age are an increasing cause of mortality and painful physical impairment of the elderly, especially in the western world. Bone mineral accrual during childhood and adolescence is thought to play a vital role in preventing osteoporosis. Identifying and optimizing the factors influencing peak bone mass is thus important for the prevention of osteoporosis and related fractures. A main aim of this thesis was to investigate the potential effects of various types of weight-bearing physical activity on bone accretion in young males just out of puberty. The results from our subgroups of athletes consisting of badminton, ice hockey, and soccer players suggest that weight-bearing physical activity gives rise to regional specific bone response that is determined by the degree of impact of the activity in areas subject to mechanical loading (papers I–IV). In summary, the bone is sensitive to loading after puberty in males, and important bone mass gains can be achieved by proper amount and type of exercise. Another aim of this thesis was to studythe effect of detraining on weight-bearing and non-weight-bearing bone in a cohort of adolescent males who participated in ice hockey and soccer training. Our results indicate that exercise-induced bone mineral density benefits decline, predominantly in weight-bearing bones, after retirement from an active sports career (papers II–IV). High bone density stemming from physical loading might be at least partly preserved even by reduced physical activity at nonweight-bearing sites after about three years of reduced activity (III, IV). A final aim was to follow prospectively the development of BMD during years of reduced activity in former male athletes, and evaluate whether exercise during adolescence could be associated with fewer fractures in old age. We found fewer fragility fractures in a cohort of 400 former athletes compared to in 800 age-matched controls. Thus, high bone density stemming from previous weight-bearing physical activity may reduce the risk of sustaining fragility fractures in the elderly. Key words: physical activity, peak bone mineral density, males.

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.

With the vast array of genetically altered (knockout) mice becoming available there is a need for quantitative, repeatable, and efficient methodologies to characterize the phenotypic consequences of knocking out specific genes. Since knockout animals often have the ability to compensate for a single missing gene, it is important to examine the structural, material and morphological properties to obtain a thorough understanding of the changes occurring. For this project, femurs of knockout mice were first scanned using microcomputed tomography (micro-CT) to obtain high-resolution images of the trabecular bone in the distal femur, as well as cortical bone in the mid-diaphysis. After scanning, the femurs were tested to destruction in four-point bending at the mid-diaphysis about the medial lateral axis of the femur. These methodologies allowed quantification of (1) morphologic properties such as bone volume fraction, trabecular properties and 2nd moment of the area (2) structural properties such as stiffness, maximum load at failure, and post yield deformation and (3) material properties such as bone mineral density, elastic modulus and yield strength. As part of two independent studies, two different knockout mice, cyclooxygenase-2 (COX-2 -/-) and Apolipoprotein E (APOE -/-), were examined for structure-function relationships using these methodologies. COX-2 knockout mice were found to have decreased mineral content in their femurs, and increased post yield deformation. APOE knockout mice at 10 weeks of age had decreased bone mass and structural properties. However, by 40 weeks of age APOE deficient mice caught up to and exceeded the structural properties and bone mass of their wild type counterparts.