Rozprawy doktorskie na temat „Bone mineral density”

Bone mineral density (BMD) is a reflection of the action of osteoblasts compared to osteoclasts. An imbalance in the activity of osteoblasts or osteoclasts, results in bone disease such as osteoporosis caused by overactive osteoclasts. BMD is influenced by genetic and environmental factors as demonstrated through twin studies, association studies and linkage analysis (Ralston, 1999). Several polymorphisms involved in the determination of BMD have been identified, with Vitamin D receptor and Collagen Type 1 showing reproducible associations. To identify genes influencing BMD two distinct strategies have been employed: 1) To determine if DNA polymorphism within the runt related transcription factor (RUNX2) gene is a determinant of BMD and fracture in women. 2) The identification of RANKL target genes in osteoclastogenesis. RUNX2 is a runt domain transcription factor (Werner et al., 1999) essential for osteoblast differentiation (Lee et al., 1997). RUNX2 gene knock-out mice have no osteoblasts due to a failure in osteoblast differentiation and consequently unmineralised skeletons, (Komori et al., 1997; Otto et al., 1997). In humans, mutations in RUNX2 cause cleidocranial dysplasia (CCD), a disorder characterised by hypoplasia or aplasia of the clavicles, short stature, supernumerary teeth, patent fontanelles and other changes in skeletal patterning and growth (Mundlos et al., 1997). RUNX2 contains a poly-glutamine poly-alanine (polyQ/polyA) repeat where mutations causing cleidocranial dysplasia have been observed. BMD has not been routinely examined in CCD, two studies have identified CCD patients with lower BMD with one fracture case identified (Quack et al., 1999; Bergwitz et al., 2001). The central role of RUNX2 in determining osteoblast differentiation makes RUNX2 a prime candidate gene for regulating adult bone density. To determine if polymorphism was present in the polyQ/polyA tract the repeat was amplified within the upper and lower deciles of femoral neck (FN) BMD in the Geelong Osteoporosis study (GOS). The upper and lower deciles of FN BMD acted as a surrogate for genotyping the entire cohort. This study identified two common variants within the polyA repeat: an 18 base pair deletion (11Ala) and a synonymous alanine codon polymorphism with alleles, GCA and GCG (noted as A and G alleles, respectively). The 11Ala and SNP polymorphism are found on codon 64 and 66 respectively (RUNX2 MRIPV variant). A allele frequencies were significantly different in a comparison of the upper and lower deciles of FN BMD (p=0.019). In 495 randomly selected women of the Geelong Osteoporosis Study (GOS), the A allele was associated with higher BMD at all sites tested. The association was maximal at the ultra-distal radius (p=0.001). In a separate fracture study, the A allele was significantly protective against Colles' fracture in elderly women but not spine and hip fracture. The 11Ala polymorphism was not related to BMD in GOS. To further decipher the role of the RUNX2 A allele we genotyped 992 women from a Scottish cohort. The alleles of RUNX2 within the glutamine/alanine repeat were determined by MspA1I restriction digest. To examine the possible influence on estrogen related therapies or estrogen status on the potential genetic effect conferred by RUNX2, we divided the cohort by menopausal and hormone replacement therapy status. Within postmenopausal Scottish women the RUNX2 A allele was associated with significantly higher FN BMD (p=0.028, n=312) but not lumbar spine (LS) BMD. The A allele was associated with higher FN BMD (p=0.035) within a postmenopausal subgroup of the population (n=312). To investigate the effect of weight on the RUNX2 alleles the Scottish cohort was segregated into thin/normal (BMI ≥ 25 kg/m2) and overweight /obese (BMI > 25 kg/m2). RUNX2 A allele showed a stronger effect on FN BMD in postmenopausal women above the median BMI. The 11Ala RUNX2 deletion allele was significantly associated with decreased LS BMD (p=0.018) within overweight/obese women (n=546). The 11Ala allele was significantly associated with increased levels of pyridinoline (p=0.014) and deoxypyridinoline (p=0.038) in the HRT treated subgroup of the population (n=492). Glutamine variants and an alanine insertion were identified within the group. These data suggest that the RUNX2 11Ala and A alleles exert differing affects on BMD showing preference for different skeletal sites in a weight dependent manner. We genotyped 78 individuals from an osteoarthritic population to elucidate the role of the RUNX2 alleles on markers of bone turnover and inflammation. The RUNX2 11Ala allele was significantly associated with decreased osteocalcin (OC) serum levels (p = 0.01). The RUNX2 A allele was significantly related to reduced tumor necrosis factor alpha (TNF-alpha) serum levels (p = 0.004). RUNX2 is known to bind to the OC promoter. An OC promoter polymorphism is found 7bp upstream from a putative RUNX2 binding site. We hypothesized that OC polymorphism may effect the RUNX2 transactivation of the OC gene and thus affect OC serum levels. OC promoter polymorphism was not related to OC serum levels (n=78). These data present a novel link between RUNX2 alleles and OC and TNF serum levels, providing putative mechanisms of action for the RUNX2 alleles. Further studies in larger populations are required to confirm these findings. Ten individuals within the GOS and the Scottish cohort were found to carry rare mutations of the polyQ/polyA repeat. All polyQ variants had a normal polyA repeat (17 amino acids) and were heterozygous for a normal 23Q/17A allele. Variants observed were 15, 16, 24 and 30Q. One individual was observed with an extended polyA repeat (24A). Patient records indicated otherwise unremarkable clinical history except for fracture in 4/10 individuals from GOS (hip and spine). BMD data from the LS and the FN were expressed as T-scores, a measure that relates BMD in terms of standard deviations below the young normal value. In addition, BMD data were also expressed as Z-scores around the age-mean. Under the null hypothesis, where RUNX2 Q repeat variation has no effect on BMD, Z scores would be expected to be distributed around a mean of zero. However, when all variants were pooled the BMD was significantly lower than expected. This effect persisted when deletion variants were considered alone. The effect was stronger on FN BMD (p=0.001) rather than LS BMD (p=0.096), reflecting either difference in precision of BMD measurements at these sites or perhaps a differential genetic effect on different skeletal sites. These data suggest that polyQ and polyA variants are associated with significantly lower BMD, and may be an important determinant for fracture. Glutamine variants exist at high frequency (~0.7%): this rate of mutation could be important when considering large populations at risk of age related osteoporosis. Considering that these subjects are heterozygous for a normal allele, it suggests that a more severe phenotype might be expected in rare subjects homozygous for glutamine repeat variants. In summary, this study investigated the role of novel polymorphisms and rare variants of the RUNX2 gene in influencing BMD, fracture and markers of bone turnover. Two common polymorphisms were identified within the polyA repeat: an 18 base pair deletion and a synonymous alanine codon polymorphism with alleles, A and G. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture within a Geelong population. To verify these findings the RUNX2 alleles were genotyped in 992 women from a Scottish cohort. The magnitude and the direction of the effect of the A allele was maintained in the Scottish cohort. Interestingly, the A allele was shown to exert a menopause specific effect, with postmenopausal women showing the strongest effect. On re-analysis of the GOS data the post-menopausal women were found to drive the significance identified in the cohort. The magnitude of the effect of the A allele on BMD was greater in overweight/obese postmenopausal women indicating a gene-weight interaction for RUNX2. The RUNX2 11Ala allele showed a significant relationship with decreased LS BMD in overweight/obese Scottish women. The 11Ala allele was also associated with higher levels of urinary PYD and DPD in women treated with HRT, indicating higher levels of bone turnover in carriers of the 11Ala allele. In contrast to the Scottish cohort, no significant association with heterozygous carriers of 11Ala was observed in GOS, although a significant association was detected for homozygous carriers and LS BMAD. The 11 Ala RUNX2 allele was significantly associated with decreased serum osteocalcin levels and the A allele was significantly associated with TNF in OA patients. Glutamine variants and an alanine insertion were identified within Geelong and Scottish cohorts, which showed low Z and T scores suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis. Polymorphism of the polyQ/polyA region of RUNX2 were identified within this study were shown to associate with significant differences in BMD. The A allele showed a significant association with increased BMD in postmenopausal women from a Geelong and Scottish cohort, with a decreased frequency of the A allele observed in Colles' fracture patients from Geelong. The 11Ala deletion allele was significantly associated with decreased LS BMD and increases in markers of bone turnover in the Scottish cohort. A significant decrease in OC serum levels was observed in OA patients suggesting a direct effect of the allele on the transactivation of the RUNX2 gene. Rare variants of RUNX2 were identified which showed low BMD. These studies have provided insight into the role of RUNX2 in influencing BMD, further studies are required to verify the role of the A allele on BMD and fracture, the role of the rare variants and to identify the precise mechanisms behind the observed changes in BMD. - 2) The identification of RANKL target genes in osteoclastogenesis. Osteoclastogenesis is regulated in vivo by the action of osteoblast/stromal cells that express membrane bound, receptor activator of NF-kB ligand (RANKL). Monocytes treated in vitro with a soluble form of RANKL and macrophage colony stimulating factor (M-CSF) differentiate to osteoclasts, whereas monocytes treated with M-CSF alone differentiate to macrophage-like cells. The gene expression profile of human osteoclasts has not been extensively explored. Genes highly expressed by rabbit osteoclasts were identified through random sequencing of an osteoclast cDNA library (Sakai et al., 1995). Differential gene expression of mouse osteoclastogenesis was elucidated by array analysis (Cappellen et al., 2002). To identify genes important for human osteoclastogenesis, total RNA was isolated from monocytes treated for three weeks with either M-CSF alone or with RANKL and M-CSF. RANKL treatment for 3 weeks and 12 hours was investigated in this study, to complement previous data. Differential display was performed on RNA (12 hour treatment with RANKL) and differential gene expression profiles examined. The differential display products were pooled to generate a probe for screening a gene array system derived from a human osteoclast cDNA library. cDNA (3 week treatment with RANKL) hybridisation experiments against the array revealed additional regulated genes. Gene clones that showed significant regulation in M-CSF and RANKL treated cells compared M-CSF treated cells represent genes that are targets for RANKL-specific regulation. Osteopontin, creatine kinase and various mitochondrial genes were up regulated by the treatment of RANKL. Changes in gene expression observed in the array data were confirmed with real-time PCR using mRNA derived from in vitro induced osteoclasts. Cathepsin K gene expression was more than 300 fold greater in osteoclasts compared to macrophage-like cells after one week treatment with RANKL and M-CSF. Cystatin C expression showed a six-fold induction at two weeks of RANKL and M-CSF treatment and cystatin B showed a steady increase in expression. Some of these regulated genes may provide useful targets for influencing BMD.

In summary, this study investigated the role of novel polymorphisms and rare variants of the RUNX2 gene in influencing BMD, fracture and markers of bone turnover. Two common polymorphisms were identified within the polyA repeat: an 18 base pair deletion and a synonymous alanine codon polymorphism with alleles, A and G. The A allele was associated with increased BMD and was protective against a common form of osteoporotic fracture within a Geelong population. To verify these findings the RUNX2 alleles were genotyped in 992 women from a Scottish cohort. The magnitude and the direction of the effect of the A allele was maintained in the Scottish cohort. Interestingly, the A allele was shown to exert a menopause specific effect, with postmenopausal women showing the strongest effect. On re-analysis of the GOS data the post-menopausal women were found to drive the significance identified in the cohort. The magnitude of the effect of the A allele on BMD was greater in overweight/obese postmenopausal women indicating a gene-weight interaction for RUNX2. The RUNX2 11Ala allele showed a significant relationship with decreased LS BMD in overweight/obese Scottish women. The 11Ala allele was also associated with higher levels of urinary PYD and DPD in women treated with HRT, indicating higher levels of bone turnover in carriers of the 11Ala allele. In contrast to the Scottish cohort, no significant association with heterozygous carriers of 11Ala was observed in GOS, although a significant association was detected for homozygous carriers and LS BMAD. The 11 Ala RUNX2 allele was significantly associated with decreased serum osteocalcin levels and the A allele was significantly associated with TNF in OA patients. Glutamine variants and an alanine insertion were identified within Geelong and Scottish cohorts, which showed low Z and T scores suggesting that RUNX2 variants may be related to genetic effects on BMD and osteoporosis. Polymorphism of the polyQ/polyA region of RUNX2 were identified within this study were shown to associate with significant differences in BMD. The A allele showed a significant association with increased BMD in postmenopausal women from a Geelong and Scottish cohort, with a decreased frequency of the A allele observed in Colles’ fracture patients from Geelong. The 11Ala deletion allele was significantly associated with decreased LS BMD and increases in markers of bone turnover in the Scottish cohort. A significant decrease in OC serum levels was observed in OA patients suggesting a direct effect of the allele on the transactivation of the RUNX2 gene. Rare variants of RUNX2 were identified which showed low BMD. These studies have provided insight into the role of RUNX2 in influencing BMD, further studies are required to verify the role of the A allele on BMD and fracture, the role of the rare variants and to identify the precise mechanisms behind the observed changes in BMD.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Health Sciences
Full Text

The objective of this research was to define influence of a 6-month power training of all body (Century) from the general and regional mineral density of a bone tissue (MDBT) and the mineral maintenance of a bone (MMB) at groups of persons with different gender and century characteristics.

Thesis (M. Tech.) -- Central University of Technology, Free State, 2006
Osteoporosis is defined as a skeletal disorder characterised by low bone mass and micro-architectural deterioration of bone tissue, with the overall focus on bone quality. It affects more than 75 million people worldwide, and cause people to become bedridden with life threatening secondary complications. An estimated 10 million South Africans, out of a population of 43 million people, are at high risk of developing osteoporosis. In South Africa osteoporosis affects one in three women over 50 and one in five men. Within one year after a hip fracture, up to 20% of the people die, 15-20% needs to be institutionalised and 50% of the remainder will not be able to lead an independent life. The number of fractures is two to three times higher in women than in men due to the hormonal changes that occur after menopause. The prevalence of osteoporosis increases markedly with age and, based on the bone mineral density at the femoral neck of the hip, approximately 30% of Caucasian women, by age of 75 years will be classified as having osteoporosis. Dual-Energy X-ray Absorptiometry (DEXA) is the preferred method for measuring BMD. The results of the DEXA scan are scored in comparison with the BMD of young, healthy individuals, resulting in a measurement called a T-score. A T-score of –2.5 or lower is considered to be osteoporosis and T-scores between –0.1 and –2.5 are generally considered to show osteopenia. The aim of the study was to examine communication between referring physicians and patients who had been referred for a DEXA scan. A total of fifty patients were included in the study group. This was much smaller than was anticipated. The ideal would have been a much bigger sample group for a bigger representation of the population. Patients, who complied with the inclusion criteria and also gave their consent, were recruited between January 2004 and November 2004. Not all the patients referred for a DEXA scan had the required low BMD. Bone scans were performed on the HOLOGIC 4500 QDR, a multiple detector, fan beam, Dual Energy X-ray Densitometer. The Hologic 4500 QDR Bone Densitometer estimates the Bone Mineral Content (BMC) in grams, and the BMD in grams per cm2. The QDR 4500 uses a low level of X-rays with two different energies to estimate BMC and BMD. The radiation exposure at a distance of two metres from the equipment is less than one mR/hour. The age distribution of the study group ranged between 14 and 84 years (average age was 57,2 years). Out of the total of 50 patients, only one was male and the entire patient population was Caucasian. This may be due to the small sample size and inclusion/exclusion criteria. Concerning the references of the patient population, Universitas Academic Hospital (UAH) referred more than half of the patients (64%), while the other points of care referred only 36%. In this study, it was found that BMD results do influence the management of osteopenia/osteoporosis in the majority of patients and the test has a positive impact on the management of patients with this condition. There was however 22% of patients that did not receive feedback concerning the results of the DEXA and the necessary treatment. These findings also highlighted the fact that communication between physician and patient is a very important component in using the information provided by this test to its full potential. The ideal is to identify a low BMD early enough to stop the damaging consequences thereof, but this is not always feasible due to the high costs involved in a DEXA scan. Access to treatment and care is also not readily available to a large section of the population and, in State Hospitals; the availability of drugs to treat osteoporosis is limited due to the high costs.

Bone mineral density (BMD) is a highly heritable trait, indicating that genetic elements are partly responsible for variation in osteoporosis risk. To further understand the genetic variation underlying osteoporosis, I performed genome-wide association (GWA) studies using designs that have largely not been performed in osteoporosis literature to date. Three strategies were used: i) a selected sample of postmenopausal women with high (z ~ 1.5, n = 1,055) or low (z≥1.5, n = 900) hip BMD [as measured by Dual-energy X-ray absorptiometry (DXA)] were used for GWA, followed by replication in an unselected sample of 20,898 adults, ii) a GW A meta-analysis on unselected children from the Avon Longitudinal Study of Parents and Children [ALSPAC (n = 5,330)] and the Generation R study [GEN-R (n = 4,098)], using DXA derived total-body less head BMD (TBLH-BMD) measures, iii) refining total-body BMD measures in children by subregional analysis: i.e. quantifying the genetic and environmental correlation between paediatric BMD measures [ALSPAC (n≥5,299)] of the skull (S-BMD), lower limb (LL-BMD) and upper limb (UL-BMD) using genome-wide complex trait analysis (GCT A) and thereafter performing a GWA meta-analysis on each site using subjects from ALSPAC and GEN-R (n ~ 9,300). The role of bone resorption in bone growth and accrual was investigated via a cross-sectional analysis of 1,130 adolescents from ALSPAC using serum measures of ,β-C-telopeptides of type I collagen (CTX) and quantitative computed tomography (pQCT) measures of the mid-tibia. Two novel BMD associated loci were identified using the selective genotyping strategy: GALNTJ (rs6710518, P = 1.4x lO· 10) and RSP03 (rsI3204965, P = 3.0x lO· 10). Association studies of paediatric TBLH-BMD identified a novel variant in RlN3 (rs754388, P = 3.0x 10.9) and replicated 31 adult BMD associated loci, with six reaching the GWA threshold of association (P < 5.0x 10·R). Sub-regional GCT A analysis indicated that appendicular sites shared a greater proportion of genetic architecture (LL-/UL-BMD rg=0.78, P = 1 x 10.7) when compared to the skull [(UL-/SBMD rg = 0.58, P = 9x l0·7) and (LL-/S-BMD rg = 0.43, P = l x lO'~)]. GWA meta-analysis echoed these findings by identifying twelve known BMD-associated variants that differed in the strength of their association and magnitude of effect with each sub-region. In particular, variants at the WNTl6 and RSP03 showed considerable site-specificity as indicated by strong association with S-BMD and/or UL-BMD, but not with LL-BMD. An investigation into the role of bone resorption in adolescent bone suggested that CTX was positively related to periosteal circumference (PC) [,8 = 0.19 (0 .13, 0.24)] (coefficient = SD change per SD increase in CTX, 95% Cl)], but inversely associated with cortical BMD [,8 = -0.46 (-0.52, -0.40)] and positively related to bone strength as reflected by the strength-strain index (SSI) [,8 = 0.09 (0 .03 , 0.14)]. These relationships were replicated using genetic proxies for bone resorption . . These results suggest that the selective sampling GWA strategy represents an efficient alternative to conventional random sampling designs. However the real world feasibility of selective sampling is questionable, as it requires extensive phenotyping in order to ensure adequate sample size and study power is obtained. BMD measures of children are well suited for GW A, however the replication of adult BMD associated SNPs implies that many of the BMD associated loci identified operate throughout the life course. Whether this strategy enriches for genetic factors involved in bone modelling remains to be seen. BMD at different skeletal sites appears to be influenced by distinct genetic and environmental influences, suggesting that phenotypic refinement of BMD may represent a superior GW A strategy, when compared to using heterogeneous BMO measures (i .e TBLH-BMO). Finally, bone resorption might play an important role in paediatric bone growth, accrual and strength.

This dissertation’s three studies investigated the short and long-term relationships of bone-related nutrient intakes with bone mineral density (BMD) in postmenopausal women. This dissertation compared the equivalency of dietary intakes assessed by eight days of diet records (DR) and the Arizona Food Frequency Questionnaire (AFFQ) at one year. It also determined the association of one year (DR) and the average of four-year (AFFQ) dietary intakes with cross-sectional BMD. The dietary intake associations with BMD were further investigated by hormone therapy (HT). Participant’s BMD was measured at the lumbar spine (L2-L4), femur trochanter, femur neck, Ward's triangle and total body using dual energy X-ray absorptiometry. Separate multiple linear regression analysis (p≤0.05), controlled for various covariates, were used to examine the associations between dietary intakes and regional and total body BMD. In study number one (n=266), significant correlations (r=0.30-0.70, p≤0.05) between dietary assessment methods were found with all dietary intake variables. Iron, magnesium, zinc, dietary calcium, phosphorous, potassium, total calcium, and fiber intakes were positively associated with BMD at three or more of the same bone sites regardless of the dietary assessment method at one year. In study number two (n=266), femur trochanter, lumbar spine, and total body BMD had mostly significant inverse associations with dietary polyunsaturated fatty acid (PUFA) intake at one year. In the HT group (n=136), inverse associations with dietary PUFA intake were seen in the spine and total body BMD. In study number three (n=130), average dietary intake of selected bone-related nutrients, were significantly inversely associated with lumbar spine BMD and total body BMD at year four. In the HT group (n=92), inverse associations with dietary PUFA intake were seen in the spine and total body BMD. The DR and AFFQ are acceptable dietary tools used to determine the associations of particular nutrients and BMD sites in healthy postmenopausal women at one year. At one and four year, dietary PUFA intakes had mostly inverse associations with lumbar spine and total body BMD. When categorized by HT use the associations remained significant only in the HT groups, suggesting that HT may influence dietary intake associations with BMD.

In this thesis, bone mineral density (BMD) assessed through Quantitative Ultrasonometry (QUS) was analyzed through a dual perception: the first section is focused on anthropometry and sports science in contemporary people (o populations), whilst the second one presents a bioarchaeological perspective. An introductory chapter precedes these two parts. The first section of the thesis discusses the relationship between BMD, anthropometry, physical exercise and lifestyle. Chapter 1 is an opening chapter. Chapter 2 is an experimental study conducted from 2019 to 2022 on a cohort of 243 Italian men and women between 20 and 84 years. The aim of the study is to investigate the association between BMD, body composition, practiced sport and activity level (athletic, active and sedentary). Body composition and other somatometric characteristics were assessed by different anthropometric parameters, including Body Mass Index (BMI), Fat Mass and Fat Free Mass (Kg, %), handgrip strength, Waist to Hip Ratio (WHR), Waist to Height Ratio (WHtR), body composition of the upper limb, digit ratio, and Frame index. The main predictive factor is represented by body fat, exerting a negative effect on BMD and thus enhancing fracture risk. A positive predictive parameter is handgrip strength. The second experimental research presented in Chapter 3 proposes a new screening tool for osteopenia named QuBone. This new questionnaire was designed to evaluate an individual’s risk for developing osteopenia depending on anthropometric characteristics, sports category and lifestyle. The study was carried out on 434 Italian subjects aged between 20 and 84 years; a subgroup of 63 subjects fulfilled the questionnaire a second time in order to evaluate internal consistency and repeatability of the questionnaire, which showed substantial results. A second subgroup of 174 individuals underwent anthropometric assessment and BMD analysis to allow multiple linear regression analysis for evaluating the association between BMD, anthropometric parameters and lifestyle data. From these models, a weight score was calculated for each factor. Then, two cut-offs for osteopenia and osteoporosis risk thresholds were evaluated. The new QuBone is thus a valid, self-administrable preventive tool, aimed to provide a risk score for the whole adult population by considering a wide asset of risk factors. The second section of the thesis is focused on paleopathological and taphonomic implications of BMD in ancient skeletal remains. Chapter 1 is an introductory overview. Aim of the study in Chapter 2 is to evaluate whether QUS may be considered a more reliable technique for low BMD in skeletal remains compared to a classic methodology. Results from multivariate logistic regression analysis have shown that QUS is a more reliable method compared to radiogrammetry, and provides a quantifiable cut-off for assessing fracture risk in archaeological individuals. In chapter 3, a multi-method analysis was carried out on 17 skeletal individuals from the Bronze Age site of Castello del Tartaro (Verona). Aim of this pilot study is to design a new method to discern between pathologic and diagenetic bone loss, to avoid misdiagnosing. The skeletal sample was chosen due to its severe and particular taphonomic asset. Chosen methods were: 1) QUS analysis; 2) SEM analysis; 3) macroscopic inspection; 4) radiogrammetry and radiology.Preliminary results have shown that BMD analysis should be carefully considered when dealing with samples from alluvial contexts suffering from strong anthropic intervention. BMD appeared extremely degraded, and thus an interpretation should be considered carefully. Further analyses aim to propose new reference data in order to use QUS analysis as a quantitative method for assessing the preservation state of a skeletal assemblage. In conclusion, this thesis provides a comprehensive research concerning BMD over two different anthropological perspectives.
In questa tesi, la densità ossea (DMO) -rilevata tramite ultrasonometria ossea quantitativa (QUS)- è stata indagata sotto una doppia prospettiva: la prima parte è incentrata su studi antropometrico-sportivi su una popolazione italiana, mentre la seconda riguarda aspetti bioarcheologici. Un capitolo introduttivo precede queste due sezioni, contenti in totale 4 studi sperimentali e 2 capitoli introdottivi. La prima parte della tesi discute la relazione tra DMO, antropometria, esercizio fisico e stile di vita. Il primo studio sperimentale è stato condotto tra il 2019 e il 2022 su un campione di 243 uomini e donne italiani di età compresa tra i 20 e gli 84 anni. Lo scopo dello studio è quello di investigare l’associazione tra DMO, composizione corporea, attività sportiva praticata e livello di attività (atletici, attivi, sedentari). La composizione corporea e altri caratteri somatometrici sono stati valutati tramite diversi parametri, tra cui Body Mass Index (BMI), Massa Grassa e Massa Magra (Kg, %), forza della presa della mano, waist to hip ratio (WHR), waist to stature ratio (WHtR), aree muscolo-adipose dell’arto superiore, Digit Ratio, e Frame Index. I risultati dell’analisi di regressione lineare multipla hanno mostrato che il principale fattore predittivo per la DMO è rappresentato dal grasso corporeo, che vi esercita un’azione negativa indipendentemente da sesso ed età. Un fattore positivamente predittivo è la forza della presa della mano. Il secondo studio sperimentale propone un nuovo strumento di screening per osteopenia chiamato QuBone, progettato per valutare lo stato di rischio di insorgenza considerando l’influenza di alcune variabili antropometriche, attività sportiva e stile di vita. Lo studio è stato condotto su 434 individui italiani di età compresa tra 20 e 84 anni. Un sottoinsieme di 63 persone ha ripetuto le rilevazioni per verificare la validità e la ripetibilità del questionario, mostrando sostanziali concordanze. Un secondo sottogruppo di 174 persone è stato sottoposto anche ad indagine antropometrica e analisi QUS, per raccogliere dati utili a valutare l’associazione tra DMO, parametri antropometrici e dati del questionario. Da questi dati sono state effettuate analisi di regressione lineare multipla, in modo da assegnare uno score di rischio ad ogni variabile considerata. In seguito, sono stati calcolati due cut-offs, in modo da fornire come risultato lo stato di rischio del soggetto. La seconda parte della tesi è invece incentrata sulle implicazioni paleopatologiche e tafonomiche della DMO su campioni scheletrici antichi. Il primo studio sperimentale della seconda parte compara differenti tecniche di indagine, con scopo di valutare se il QUS sia una metodologia più attendibile su resti antichi rispetto alla radiogrammetria. 104 resti scheletrici da siti medievali sono stati sottoposti a varie analisi (osteometria, QUS e radiogrammetria), in relazione alla presenza di fratture osteoporotiche. I risultati dall’analisi statistica logistica multivariata hanno mostrato che il QUS rappresenta un metodo più efficace rispetto alla radiogrammetria e quantifica l’effettivo rischio di frattura in popolazioni antiche. Nel terzo studio sperimentale (preliminare) è stata condotta un’analisi tafonomica attraverso varie tecniche (QUS, SEM, microscopia, radiologia) su 17 resti scheletrici dal sito di Castello del Tartaro (Verona), per individuare un metodo per discernere tra perdita di massa ossea patologica e diagenetica. I risultati preliminari hanno mostrato che in contesti di conservazione precari (sito alluvionale e fortemente antropizzato) la DMO è fortemente degradata, ed occorre particolare cautela in fase di analisi paleopatologica. In conclusione, questa tesi fornisce una ricerca diversificata riguardo la DMO sotto una duplice prospettiva antropologica.

In this thesis, bone mineral density (BMD) assessed through Quantitative Ultrasonometry (QUS) was analyzed through a dual perception: the first section is focused on anthropometry and sports science in contemporary people (o populations), whilst the second one presents a bioarchaeological perspective. An introductory chapter precedes these two parts. The first section of the thesis discusses the relationship between BMD, anthropometry, physical exercise and lifestyle. Chapter 1 is an opening chapter. Chapter 2 is an experimental study conducted from 2019 to 2022 on a cohort of 243 Italian men and women between 20 and 84 years. The aim of the study is to investigate the association between BMD, body composition, practiced sport and activity level (athletic, active and sedentary). Body composition and other somatometric characteristics were assessed by different anthropometric parameters, including Body Mass Index (BMI), Fat Mass and Fat Free Mass (Kg, %), handgrip strength, Waist to Hip Ratio (WHR), Waist to Height Ratio (WHtR), body composition of the upper limb, digit ratio, and Frame index. The main predictive factor is represented by body fat, exerting a negative effect on BMD and thus enhancing fracture risk. A positive predictive parameter is handgrip strength. The second experimental research presented in Chapter 3 proposes a new screening tool for osteopenia named QuBone. This new questionnaire was designed to evaluate an individual’s risk for developing osteopenia depending on anthropometric characteristics, sports category and lifestyle. The study was carried out on 434 Italian subjects aged between 20 and 84 years; a subgroup of 63 subjects fulfilled the questionnaire a second time in order to evaluate internal consistency and repeatability of the questionnaire, which showed substantial results. A second subgroup of 174 individuals underwent anthropometric assessment and BMD analysis to allow multiple linear regression analysis for evaluating the association between BMD, anthropometric parameters and lifestyle data. From these models, a weight score was calculated for each factor. Then, two cut-offs for osteopenia and osteoporosis risk thresholds were evaluated. The new QuBone is thus a valid, self-administrable preventive tool, aimed to provide a risk score for the whole adult population by considering a wide asset of risk factors. The second section of the thesis is focused on paleopathological and taphonomic implications of BMD in ancient skeletal remains. Chapter 1 is an introductory overview. Aim of the study in Chapter 2 is to evaluate whether QUS may be considered a more reliable technique for low BMD in skeletal remains compared to a classic methodology. Results from multivariate logistic regression analysis have shown that QUS is a more reliable method compared to radiogrammetry, and provides a quantifiable cut-off for assessing fracture risk in archaeological individuals. In chapter 3, a multi-method analysis was carried out on 17 skeletal individuals from the Bronze Age site of Castello del Tartaro (Verona). Aim of this pilot study is to design a new method to discern between pathologic and diagenetic bone loss, to avoid misdiagnosing. The skeletal sample was chosen due to its severe and particular taphonomic asset. Chosen methods were: 1) QUS analysis; 2) SEM analysis; 3) macroscopic inspection; 4) radiogrammetry and radiology.Preliminary results have shown that BMD analysis should be carefully considered when dealing with samples from alluvial contexts suffering from strong anthropic intervention. BMD appeared extremely degraded, and thus an interpretation should be considered carefully. Further analyses aim to propose new reference data in order to use QUS analysis as a quantitative method for assessing the preservation state of a skeletal assemblage. In conclusion, this thesis provides a comprehensive research concerning BMD over two different anthropological perspectives.
In questa tesi, la densità ossea (DMO) -rilevata tramite ultrasonometria ossea quantitativa (QUS)- è stata indagata sotto una doppia prospettiva: la prima parte è incentrata su studi antropometrico-sportivi su una popolazione italiana, mentre la seconda riguarda aspetti bioarcheologici. Un capitolo introduttivo precede queste due sezioni, contenti in totale 4 studi sperimentali e 2 capitoli introdottivi. La prima parte della tesi discute la relazione tra DMO, antropometria, esercizio fisico e stile di vita. Il primo studio sperimentale è stato condotto tra il 2019 e il 2022 su un campione di 243 uomini e donne italiani di età compresa tra i 20 e gli 84 anni. Lo scopo dello studio è quello di investigare l’associazione tra DMO, composizione corporea, attività sportiva praticata e livello di attività (atletici, attivi, sedentari). La composizione corporea e altri caratteri somatometrici sono stati valutati tramite diversi parametri, tra cui Body Mass Index (BMI), Massa Grassa e Massa Magra (Kg, %), forza della presa della mano, waist to hip ratio (WHR), waist to stature ratio (WHtR), aree muscolo-adipose dell’arto superiore, Digit Ratio, e Frame Index. I risultati dell’analisi di regressione lineare multipla hanno mostrato che il principale fattore predittivo per la DMO è rappresentato dal grasso corporeo, che vi esercita un’azione negativa indipendentemente da sesso ed età. Un fattore positivamente predittivo è la forza della presa della mano. Il secondo studio sperimentale propone un nuovo strumento di screening per osteopenia chiamato QuBone, progettato per valutare lo stato di rischio di insorgenza considerando l’influenza di alcune variabili antropometriche, attività sportiva e stile di vita. Lo studio è stato condotto su 434 individui italiani di età compresa tra 20 e 84 anni. Un sottoinsieme di 63 persone ha ripetuto le rilevazioni per verificare la validità e la ripetibilità del questionario, mostrando sostanziali concordanze. Un secondo sottogruppo di 174 persone è stato sottoposto anche ad indagine antropometrica e analisi QUS, per raccogliere dati utili a valutare l’associazione tra DMO, parametri antropometrici e dati del questionario. Da questi dati sono state effettuate analisi di regressione lineare multipla, in modo da assegnare uno score di rischio ad ogni variabile considerata. In seguito, sono stati calcolati due cut-offs, in modo da fornire come risultato lo stato di rischio del soggetto. La seconda parte della tesi è invece incentrata sulle implicazioni paleopatologiche e tafonomiche della DMO su campioni scheletrici antichi. Il primo studio sperimentale della seconda parte compara differenti tecniche di indagine, con scopo di valutare se il QUS sia una metodologia più attendibile su resti antichi rispetto alla radiogrammetria. 104 resti scheletrici da siti medievali sono stati sottoposti a varie analisi (osteometria, QUS e radiogrammetria), in relazione alla presenza di fratture osteoporotiche. I risultati dall’analisi statistica logistica multivariata hanno mostrato che il QUS rappresenta un metodo più efficace rispetto alla radiogrammetria e quantifica l’effettivo rischio di frattura in popolazioni antiche. Nel terzo studio sperimentale (preliminare) è stata condotta un’analisi tafonomica attraverso varie tecniche (QUS, SEM, microscopia, radiologia) su 17 resti scheletrici dal sito di Castello del Tartaro (Verona), per individuare un metodo per discernere tra perdita di massa ossea patologica e diagenetica. I risultati preliminari hanno mostrato che in contesti di conservazione precari (sito alluvionale e fortemente antropizzato) la DMO è fortemente degradata, ed occorre particolare cautela in fase di analisi paleopatologica. In conclusione, questa tesi fornisce una ricerca diversificata riguardo la DMO sotto una duplice prospettiva antropologica.

In this thesis, bone mineral density (BMD) assessed through Quantitative Ultrasonometry (QUS) was analyzed through a dual perception: the first section is focused on anthropometry and sports science in contemporary people (o populations), whilst the second one presents a bioarchaeological perspective. An introductory chapter precedes these two parts. The first section of the thesis discusses the relationship between BMD, anthropometry, physical exercise and lifestyle. Chapter 1 is an opening chapter. Chapter 2 is an experimental study conducted from 2019 to 2022 on a cohort of 243 Italian men and women between 20 and 84 years. The aim of the study is to investigate the association between BMD, body composition, practiced sport and activity level (athletic, active and sedentary). Body composition and other somatometric characteristics were assessed by different anthropometric parameters, including Body Mass Index (BMI), Fat Mass and Fat Free Mass (Kg, %), handgrip strength, Waist to Hip Ratio (WHR), Waist to Height Ratio (WHtR), body composition of the upper limb, digit ratio, and Frame index. The main predictive factor is represented by body fat, exerting a negative effect on BMD and thus enhancing fracture risk. A positive predictive parameter is handgrip strength. The second experimental research presented in Chapter 3 proposes a new screening tool for osteopenia named QuBone. This new questionnaire was designed to evaluate an individual’s risk for developing osteopenia depending on anthropometric characteristics, sports category and lifestyle. The study was carried out on 434 Italian subjects aged between 20 and 84 years; a subgroup of 63 subjects fulfilled the questionnaire a second time in order to evaluate internal consistency and repeatability of the questionnaire, which showed substantial results. A second subgroup of 174 individuals underwent anthropometric assessment and BMD analysis to allow multiple linear regression analysis for evaluating the association between BMD, anthropometric parameters and lifestyle data. From these models, a weight score was calculated for each factor. Then, two cut-offs for osteopenia and osteoporosis risk thresholds were evaluated. The new QuBone is thus a valid, self-administrable preventive tool, aimed to provide a risk score for the whole adult population by considering a wide asset of risk factors. The second section of the thesis is focused on paleopathological and taphonomic implications of BMD in ancient skeletal remains. Chapter 1 is an introductory overview. Aim of the study in Chapter 2 is to evaluate whether QUS may be considered a more reliable technique for low BMD in skeletal remains compared to a classic methodology. Results from multivariate logistic regression analysis have shown that QUS is a more reliable method compared to radiogrammetry, and provides a quantifiable cut-off for assessing fracture risk in archaeological individuals. In chapter 3, a multi-method analysis was carried out on 17 skeletal individuals from the Bronze Age site of Castello del Tartaro (Verona). Aim of this pilot study is to design a new method to discern between pathologic and diagenetic bone loss, to avoid misdiagnosing. The skeletal sample was chosen due to its severe and particular taphonomic asset. Chosen methods were: 1) QUS analysis; 2) SEM analysis; 3) macroscopic inspection; 4) radiogrammetry and radiology.Preliminary results have shown that BMD analysis should be carefully considered when dealing with samples from alluvial contexts suffering from strong anthropic intervention. BMD appeared extremely degraded, and thus an interpretation should be considered carefully. Further analyses aim to propose new reference data in order to use QUS analysis as a quantitative method for assessing the preservation state of a skeletal assemblage. In conclusion, this thesis provides a comprehensive research concerning BMD over two different anthropological perspectives.
In questa tesi, la densità ossea (DMO) -rilevata tramite ultrasonometria ossea quantitativa (QUS)- è stata indagata sotto una doppia prospettiva: la prima parte è incentrata su studi antropometrico-sportivi su una popolazione italiana, mentre la seconda riguarda aspetti bioarcheologici. Un capitolo introduttivo precede queste due sezioni, contenti in totale 4 studi sperimentali e 2 capitoli introdottivi. La prima parte della tesi discute la relazione tra DMO, antropometria, esercizio fisico e stile di vita. Il primo studio sperimentale è stato condotto tra il 2019 e il 2022 su un campione di 243 uomini e donne italiani di età compresa tra i 20 e gli 84 anni. Lo scopo dello studio è quello di investigare l’associazione tra DMO, composizione corporea, attività sportiva praticata e livello di attività (atletici, attivi, sedentari). La composizione corporea e altri caratteri somatometrici sono stati valutati tramite diversi parametri, tra cui Body Mass Index (BMI), Massa Grassa e Massa Magra (Kg, %), forza della presa della mano, waist to hip ratio (WHR), waist to stature ratio (WHtR), aree muscolo-adipose dell’arto superiore, Digit Ratio, e Frame Index. I risultati dell’analisi di regressione lineare multipla hanno mostrato che il principale fattore predittivo per la DMO è rappresentato dal grasso corporeo, che vi esercita un’azione negativa indipendentemente da sesso ed età. Un fattore positivamente predittivo è la forza della presa della mano. Il secondo studio sperimentale propone un nuovo strumento di screening per osteopenia chiamato QuBone, progettato per valutare lo stato di rischio di insorgenza considerando l’influenza di alcune variabili antropometriche, attività sportiva e stile di vita. Lo studio è stato condotto su 434 individui italiani di età compresa tra 20 e 84 anni. Un sottoinsieme di 63 persone ha ripetuto le rilevazioni per verificare la validità e la ripetibilità del questionario, mostrando sostanziali concordanze. Un secondo sottogruppo di 174 persone è stato sottoposto anche ad indagine antropometrica e analisi QUS, per raccogliere dati utili a valutare l’associazione tra DMO, parametri antropometrici e dati del questionario. Da questi dati sono state effettuate analisi di regressione lineare multipla, in modo da assegnare uno score di rischio ad ogni variabile considerata. In seguito, sono stati calcolati due cut-offs, in modo da fornire come risultato lo stato di rischio del soggetto. La seconda parte della tesi è invece incentrata sulle implicazioni paleopatologiche e tafonomiche della DMO su campioni scheletrici antichi. Il primo studio sperimentale della seconda parte compara differenti tecniche di indagine, con scopo di valutare se il QUS sia una metodologia più attendibile su resti antichi rispetto alla radiogrammetria. 104 resti scheletrici da siti medievali sono stati sottoposti a varie analisi (osteometria, QUS e radiogrammetria), in relazione alla presenza di fratture osteoporotiche. I risultati dall’analisi statistica logistica multivariata hanno mostrato che il QUS rappresenta un metodo più efficace rispetto alla radiogrammetria e quantifica l’effettivo rischio di frattura in popolazioni antiche. Nel terzo studio sperimentale (preliminare) è stata condotta un’analisi tafonomica attraverso varie tecniche (QUS, SEM, microscopia, radiologia) su 17 resti scheletrici dal sito di Castello del Tartaro (Verona), per individuare un metodo per discernere tra perdita di massa ossea patologica e diagenetica. I risultati preliminari hanno mostrato che in contesti di conservazione precari (sito alluvionale e fortemente antropizzato) la DMO è fortemente degradata, ed occorre particolare cautela in fase di analisi paleopatologica. In conclusione, questa tesi fornisce una ricerca diversificata riguardo la DMO sotto una duplice prospettiva antropologica.

INTRODUCTION: Osteoporosis and osteoporotic fractures represent an enormous health burden and economic cost for most societies in the world, and future projections forecast their steady increase over the next few decades. Strategies to detect and treat those individuals with high risk of fracture have proved to be cost-effective, but still an important lack of awareness exists among health professionals and institutions. Low bone mineral density (BMD) is one of the factors better correlated with fracture risk. The Global Burden of Disease Study 2010 estimated the worldwide health burden of 291 diseases and injuries and 67 risk factors. The main metrics for the burden measurements were the Disability-Adjusted Life Years (DALYs), the Years lived with disability (YLDs), the Years of Life Lost due to premature mortality (YLLs) and Deaths. For the first time, BMD was analysed as a risk factor for fractures, which formed part of the health burden due to falls. Risk analysis followed the Comparative Risk Assessment (CRA) methodology to determine which proportion of the falls burden was attributable to low BMD. OBJECTIVES: To calculate the global distribution of BMD, its population attributable fraction (PAF) for falls, and the number of DALYs, YLDs, YLLs and deaths due to low BMD, with estimates for each region, age group, sex and time period (1990 and 2010). METHODS: Systematic review was performed seeking population-based studies with BMD measured by Dual-X-Ray-Absorptiometry at femoral neck in people 50 years and over. Age- and sex- specific levels of mean BMD+/-SD (g/cm2) were extracted from eligible studies. For the CRA methodology to calculate PAFs of BMD for fractures, the theoretical minimum risk factor exposure distribution was estimated as the age and sex-specific 90th percentile from NHANES III. Relative risks for fractures were obtained from a previous meta-analysis. Hospital data with double coding (cause and nature of injury) was used to calculate the fraction of the health burden of falls due to fractures. RESULTS: Global deaths and DALYs attributable to low BMD increased from 103,000 and 3,125,000 in 1990 to 188,000 and 5,216,000 in 2010 respectively. The contribution to the total DALYs was slightly superior for YLLs compared to YLDs. The percentage of low BMD in the total global burden almost doubled from 1990 (0.12%) to 2010 (0.21%). In population 70 years old and over these percentages increased from 0.64% in 1990 to 0.79% in 2010. Around one third of all falls-related deaths were attributable to low BMD, with slight increase between 1990 and 2010. Low BMD was responsible for 12.1% and 14.8% of all global DALYs due to falls in 1990 and 2010, respectively. Males showed more contribution to the global deaths and DALYs, with a higher increase over time, compared to females. Asia South and Asia East were the world regions contributing the most in the increase of the global burden attributable to low BMD over time. The greatest proportion of DALYs within the regional burden was found in Europe Western, Europe Central and Asia Pacific-High Income. Low BMD was the eight risk factor with the highest number of global YLDs in population 80 years and over. CONCLUSION: Results showed an increase of the burden attributable to low BMD worldwide from 1990 to 2010, greatly influenced by the ageing of the population. A significant fraction of all falls-related deaths and health burden in the world was attributable to low BMD and, therefore, preventable. Data systems should improve in the detection of injuries potentially related to low BMD and osteoporosis in general. This information can be used by health institutions and authorities to identify priorities and allocate resources.
INTRODUCCIÓN: En la iniciativa The Global Burden of Disease Study 2010, la densidad mineral ósea (DMO) ha sido analizada como un factor de riesgo de fracturas, las cuales son analizadas como parte de la carga en salud atribuida a las caídas. Las medidas métricas principales para determinar la carga en salud de dicha iniciativa son los Disability-Adjusted Life Years (DALYs), los Years lived with disability (YLDs), los Years of Life Lost due to premature mortality (YLLs), y las Muertes. OBJETIVOS: Calcular la distribución mundial de los valores de DMO; calcular el número de DALYs, YLDs, YLLs y muertes debidos a la baja DMO. MÉTODOS: Se realizó una revisión sistémica de estudios poblacionales con valores de DMO medidos con Dual-X-Ray-Absorptiometry en cuello femoral en población a partir de 50 años. Se utilizó análisis de riesgo comparativo para determinar la fracción poblacional atribuible de la DMO para caídas. El percentil 90 por grupo de edad y género del estudio americano NHANESIII se adquirió como la distribución de mínimo riesgo posible del factor de exposición. Los riesgos relativos DMO-fractura se obtuvieron de una meta-análisis previa. Datos hospitalarios con doble codificación (causa y tipo de lesión) se utilizaron para calcular la fracción de la carga en salud de las caídas debido a las fracturas. RESULTADOS: Las muertes y los DALYs mundiales atribuibles a la baja DMO incrementaron de 103.000 y 3.125.000 en 1990 a 188.000 y 5.216.000 en 2010, respectivamente. Un tercio de todas las muertes relacionadas con caídas fueron atribuibles a la baja DMO. La DMO fue responsable de un 12.1% y un 14.8% de todos los DALYs por caídas en 1990 y 2010, respectivamente. El Asia Sur y Asia Este fueron las regiones del mundo que más contribuyeron al aumento de la carga mundial en salud atribuible a la baja DMO. CONCLUSIÓN: Los resultados muestran un aumento de la carga en salud mundial debido a la bajo DMO entre 1990 y 2010. Una séptima parte de los DALYs y un tercio de las muertes en el mundo debido a caídas fueron atribuibles a la baja DMO, y por lo tanto, prevenibles.

Introduction: The benefits of regular exercise on skeletal health have been well-documented in terms of stimulation of bone accrual and bone maintenance. Medium-impact sports activities such as running have been demonstrated to exert site-specific enhancement of bone mass in the lower appendicular skeleton. However, elite female runners engaged in high intensity training and sports activity may also be at risk of amenorrhea and low bone mineral density (BMD) resulting from inadequate caloric intake. Purpose: To investigate the effect of intensive exercise and maintenance of adequate caloric intake on BMD in a group of elite female runners. Methods: This study represents a secondary assessment of existing data that were obtained between 1994 and 2009. Using dual-energy X-ray absorptiometry, a group of elite runners (n=11) in this study was screened in the Laboratory for Elite Athlete Performance at Georgia State University. This was a longitudinal study in which three sequential measurements of BMD, as well as fat and lean tissue body composition of each athlete took place. The average interval between measurements was 1.1 years and 2.6 years respectively. Regional BMD measurements for head, arms, legs, trunk, ribs, pelvis, and spine were assessed, as well as the value for total body BMD. The study participants also received dietary counseling emphasizing daily caloric balance and adequate calcium intake. Results: The average age of the runners increased from 24.59 (±4.41) to 28.14 (±5.94) years over the study. This was accompanied by an increase in body mass (54.98±3.54 to 56.11±4.07 kg), while height remained constant. The average body mass index (BMI) of the subjects increased from 19.34 to 19.71 kg/m2, largely due to an increase in total per cent body fat (13.97±2.96% to 16.01±4.28%). Average regional and total BMD values increased over the study period and increases were between 2 and 4%. A majority of subjects (n=7) had a BMI>19 kg/m2, while a sub-group of runners (n=4) had a BMI˂19 kg/m2. Mean trunk, pelvis and spine BMD parameters for the two BMI groups were significantly different (p˂0.05), with reduced BMD values in the lower BMI sub-group. The average T-scores associated with arm BMD were considerably lower than T-scores associated with leg BMD values in the runners. The average T-scores for leg BMD values were almost two standard deviations higher than leg BMD values for a reference population at peak bone mass. Two subjects were osteopenic, resulting in an 18% prevalence rate of osteopenia in the group of runners. Conclusions: The majority of elite runners in this study exhibited a positive trend in BMD parameters. This was reflected as increased total as well as regional BMD values. Increased body mass in addition to the activity of running positively contributed to bone mass via a weight-bearing effect. Increased adipose tissue may also have been a source of endocrine hormones such as estrogen and leptin, which exert a positive effect on bone accrual.

The purpose of this study was to determine the effect of oral contraceptives (OC) on bone health in active women during early adulthood. Thirty-eight women between the ages of 18 and 35 years participated in this study. Participants were placed into two groups: 1) those who had taken OCs (Ortho Tri-Cyclen for a minimum of two years (n=22) and 2) those who had never taken OCs (n=16). The two groups were matched based on age, nutritional habits, percent body fat, and activity level. Participants completed a health history questionnaire, food frequency questionnaire, and received a full body scan via dual energy x-ray absorptiometry (DEXA). An independent t-test revealed no significant difference (p < 0.05) between the bone mineral density of the women taking OCs (1.188 g/cm2 ± 0.09) and those women who never consumed OCs (1.207 g/cm2 ± 0.09). The effect of taking OCs in a young healthy population of women appears to have no osteogenic influence on bone health.
School of Physical Education

Final publication is avilable at http://www.sciencedirect.com/science/article/pii/S0954611115300172
Kyoto University (京都大学)
0048
新制・課程博士
博士(医学)
甲第19577号
医博第4084号
新制||医||1013(附属図書館)
32613
京都大学大学院医学研究科医学専攻
(主査)教授 伊達 洋至, 教授 平家 俊男, 教授 松田 秀一
学位規則第4条第1項該当

The main hypotheses tested within this research focussed on the identification of polymorphisms within Runx2, and the classification of these with respect to bone mineral density (BMD). A separate set of hypotheses focussed upon the effects of calcium treatment in an elderly population, to identify any differences in BMD, bone mineral content (BMC) and bone area between the specific genotypes identified. The initial research strategy included taking subjects’ from the extremes of a population to identify alleles specifically related to the bone mineral density trait. The idea was tested using Runx2, the well known osteoblast transcription factor. From a population of 1300 subjects (from the Geelong Osteoporosis Study: the GOS) the age-weight adjusted femoral neck BMD was ranked and the upper and lower deciles taken to represent the adjusted extremes. After adjusting and ranking, the two groups (n=130 each) were not significantly different for age or weight. In these 260 subjects, we identified 16 allelic variations within the Runx2 gene and gene promoters (P1 and P2), and characterized these novel variations with respect to BMD strata by genotype using DHPLC.
Thesis (PhD Doctorate)
Doctor of Philosophy (PhD)
School of Medical Science
Griffith Health
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Background: Lithium is the most effective long-term treatment for bipolar disease. It has, however,been associated with hypercalcemia and hyperparathyroidism. The aim of the study is to research howlithium associated hyperparathyroidism(LHPT)affects bone mineral density. Method: A sub-analysis was performed on an ongoing randomized prospective study evaluating the operation results from parathyroidectomy versus watchful waiting in 22patients with LHPT. The patients were followed-up for 2 years and their blood samples, bone mineral density (BMD) and FRAX assessment were analysed. The data from LHPT patients was also compared to a separate group of patients with primary hyperparathyroidism (PHPT) corresponding in age.Results: In comparing LHPT patients with PHPT apparent differences in the biochemical profile were detected, including elevated values of ionized Ca in PHPT (p=0.001), lower excretion of 24h urinary calcium in LHPT (p=0.003) and significantly higher values of PTH excretion in PHPT. LHPT showed tendencies to having better BMD (p=0.176). At 2-year follow-up of 8 LHPT patients, biochemicalvalues improved, suggesting cure, including lower risks of skeletal fractures. Discussion: The biochemical features in LHPT are distinctive from PHPT. However, each case is unique, and thebiochemicalvariety issimilar to PHPT. Confounding factors include age, sex, renal function and stability of the bipolar condition. Conclusions:The present study illustratesthat LHPT differs biochemically from PHPT. In comparison to PHPT, LHPT patients tend to have reduced BMD and the present study could not confirm the previous postulation that lithium could be protective of the skeleton. In conclusion, casesof LHPT should be assessed individually, since the clinical course is diverse. In patients risking fracture, parathyroidectomy should be considered.

Results: Age of gymnasts was positively associated with BMD at all measured sites (p <0.001; r=0.62-0.68). Weight was positively associated with BMD at all measured sites (p <0.001; r=0.82-0.90). Lean body mass was positively associated with BMD at all measured sites (p <0.001; r=0.74-0.87). Body fat percentage was positively associated with BMD at all measured sites (p <0.001-p=0.01; r=0.39-0.54). However, calcium intake was not significantly associated with any of the BMD sites. Sunlight exposure and indirect estimates of vitamin D were not significantly associated with any of the BMD sites; all r-values indicated a weak positive association with BMD. Of the gymnasts who had experienced menses (n=15), those with regular menstrual periods (n=8) had significantly higher BMD values at the arm, leg, trunk, rib, and spine, and total body than those who did not have regular menstrual periods (n=7). There was no significant difference in BMD for gymnasts who had regular periods at the pelvis. A regression analysis was performed. The predictors total BMD values from the regression equation were the following: regular menses, height, weight, percent kilocalorie requirement consumed from predicted kilocalorie needs, calcium intake with supplements, lean body mass, hourly deficits >300 kilocalories from predicted kilocalorie needs, and hourly surpluses >300 kilocalories from predicted kilocalorie needs.

Objective. The use of cyclooxygenase-2 (COX-2) inhibitors may impair load-induced bone formation but also prevent menopause-associated bone loss. We hypothesized that COX-2 inhibitor use would be associated with an increased bone mineral density (BMD) in postmenopausal women not using estrogen therapy and conversely, a decreased BMD in men.
Methods. We used data from the Canadian Multicenter Osteoporosis Study, a longitudinal, randomly selected, population-based community cohort study. The outcome measure was percent difference in bone mineral density (g/cm2). Using linear regression, we estimated the effect of COX-2 inhibitors on this outcome, while adjusting for important potential confounders.
Results. There were 4780 subjects available for study, of which 394 subjects reported daily COX-2 inhibitor use. In males, daily use of COX-2 inhibitors was associated with a lower BMD at all hip sites (percent difference between users and non-users at total hip: -3.1% [95% confidence interval (CI), -6.0, -0.3]. In post-menopausal women not using estrogen replacement therapy, daily COX-2 inhibitor use was associated with higher BMD at most sites (percent difference at total hip: +3.0% [95% Cl, 0.3, 5.8]).
Conclusions. COX-2 inhibitor use was associated with a lower BMD in men and, on the other hand, a higher BMD in post-menopausal women not using estrogen replacement therapy. Men who have used COX-2 inhibitors may wish to seek a BMD measurement to assess their fracture risk. However, COX-2 inhibitors may have utility in post-menopausal women if bone-selective analogues can be developed.

The late second and early third decades of life are critical periods for bone health due to the attainment of peak bone mass during this time, yet little is known about relationships between lifestyle factors and bone health among young-adult females. Therefore, anthropometric, body composition, and nutritional variables were examined in relation to bone mineral density (BMD) and biochemical markers of bone turnover in a group of 60 healthy, young-adult females aged 18 to 25 years. Body weight, body mass index (BMI), fat-free soft tissue mass (FFST), and fat mass had statistically significant and positive associations with BMD. Mean daily dietary protein, magnesium, and iron intakes had statistically significant and negative associations with BMD. A second study compared dietary intake, BMD, and biochemical markers of bone turnover in young-adult females with chronic dieting habits to nondieters. Anthropometric and body composition variables between chronic dieters and nondieters were not statistically different; however, chronic dieters had statistically significantly lower average daily dietary intakes of energy, macronutrients, and selected micronutrients compared to nondieters. Chronic dieters had statistically significantly higher whole body (WB) BMD compared to nondieters. Moderate effects were observed for WB, lumbar spine, trochanter, and total proximal femur BMD such that chronic dieters possessed greater BMD compared to nondieters. It appears that among young-adult females, total body weight, particularly FFST mass, has an important association with BMD. Although nutritional inadequacies among young-adult females raise concerns, overconsumption of nutrients may increase the likelihood of nutrient-nutrient interactions that may have a less than optimal impact on BMD. Future investigations of dietary intake and BMD among young-adult females are warranted.
Master of Science

"October, 2003" Bibliography: leaves 204-223. Patients with respiratory disease have decreased mean bone mineral density (BMD) and thereby increased risk of fractures compared to people without respiratory disease. A clinical screening tool was developed to identify patients unlikely to have low BMD who do not require bone densitometry, and estimated number needed to screen (NNS) and number needed to treat to prevent one hip fracture in this patient group. The screening tool was found to have a high negative predictive value, and therefore may assist clinicians to identify those who would benefit most from densitometry. Using this screening tool together with NNS may enable the development of a cost-effective screening programme for low BMD in respiratory patients.

Osteoporosis is a condition involving decreased bone mineral density (BMD) and increased fragility of the skeletal system. Osteoporosis affects ~75 million individuals in the United States, Europe, and Japan. In the United States alone, hip fractures affect 500,000 individuals per year, and annual healthcare costs for osteoporotic fractures are approximately $14 billion. A high peak BMD can prevent or delay the onset of osteoporosis and its complications. Exercise and diet may affect peak BMD by as much as 20 to 40% each and have been identified as the two most important controllable factors determining BMD. The current study investigated the effect of a calcium, vitamin D, and vitamin K supplement combination during initial military cadet exercise training on: BMD, stress fracture occurrence, hormones associated with BMD, and biochemical markers of bone turnover. Significant changes in BMD, either between the supplemented group or the unsupplemented group or across time for both groups were not found. The majority of participants (n = 22) had unexpectedly high levels of physical activity prior to enrollment, and the initial military exercise training program included only moderate levels of activity. Therefore, the exercise stimulus to bone was likely insufficient to promote gains in BMD, regardless of the nutrient supplement status. Serum insulin-like growth factor-1 and osteocalcin significantly increased over time (p < 0.05 and p < 0.001, respectively), irrespective of treatment group. Significant decreases were found in dietary intake of calories (p < 0.01), carbohydrate (p < 0.05), protein (p < 0.0001), and fat (p < 0.01) over time. Decreases in reported dietary intake were likely due to less variety of foods eaten, and diminished compliance with food records. Significant differences were not found between groups or across time in dietary intakes of calcium, vitamin D, or vitamin K. Low dose supplementation with a calcium, vitamin D, vitamin K supplement during initial military training in young-adult cadets did not change BMD or alter stress fracture occurrence.
Master of Science

A food frequency questionnaire (FFQ) was developed for a study investigating dietary influences on bone mineral density (BMD) and bone metabolism (BM). The percentage contribution of food groups to nutrients of interest were identified from 20 7d weighed records (WR) and incorporated to form a 98 food item FFQ. The FFQ was validated against a further 20 7d WR, and the short (6 weeks) and long-term (1 year) reproducibility tested. Mean nutrient intakes by 7d WR and FFQ, and initial and repeat FFQ were similar and cross-classification showed few women to be grossly misclassified. Information was also collected on past intakes of milk and fruit, weight, height, smoking, social class and physical activity. The effect of dietary intake on BMD was investigated in 994 healthy premenopausal women aged 45-49 years. BMD was measured using dual energy X-ray absorptiometry at the lumbar spine (LS) and hip (femoral neck [FN], trochanter [FT], Wards [FW]). Nutrient intakes were adjusted for energy intake by calculating the residual from regression analysis. Positive relationships were found between BMD and intakes of Mg, K, Zn and vitamin C, remaining significant after adjustment for confounding variables. LS BMD was lower in women who reported a low intake of milk and fruit in their childhood and early adulthood. The influence of dietary intake on BM was assessed in 62 healthy peri-menopausal women aged 45-55 years. Bone resorption was determined by urinary excretion of pyridinoline (Pyd) and deoxypyridinoline (Dpd) using reversed-phase HPLC, and bone formation by serum osteocalcin (OC) using an ELISA. Energy adjusted intakes of K, Mg, carotene and vitamin C were negatively associated with Pyd and Dpd concentrations, remaining significant after appropriate adjustment including menopausal status. OC was positively associated with energy intake and weight. Twenty-six women were measured after one year, but no relationships were found between changes in bone mass and baseline bone metabolism markers or dietary intake. Results suggest there is a higher bone mass and lower bone resorption in women with high intakes of K, Mg, carotene and vitamin C, independent of confounding factors. Positive effects on acid-base balance, Mg deficiency or the role of vitamin C in collagen liydroxylation may provide some explanations for these findings.

Studies have demonstrated the effect of dominance on bone mineral density (BMD) of both weight bearing and non-weight bearing limbs and the effect of physical activity and specific sports, such as tennis, gymnastics, and volleyball on bmd of the predominantly used limb(s) versus non-used limb(s). Like tennis and volleyball, the Wichita State University (WSU) bowling team performs a high volume of repetitive use of their bowling arm on a regular basis. This is the first study to investigate the effect of ten-pin bowling at an elite collegiate level on BMD of the bowling arm compared to the non-bowling arm. Dual Energy X-ray Absorptiometry Unit (Hologic QDR 4500W Elite) was used to assess BMD of bilateral arms (whole body scan) and bilateral forearms (forearm scan) of 25 (N=13 males, N=12 females) collegiate bowlers (20.72 ± 1.46 yrs). In this study, the forearm scans showed significantly greater (p<0.05) BMD in the bowling arm (0.635 ± .05 g·cm-2) compared to the non-bowling arm (0.618 ± .06 g·cm-2) of both male and female bowlers. However, when separated by gender, the female bowling arm showed a significantly greater difference between arms (4.1 ± 3.1% difference, p<0.05) and compared to the males (1.5 ± 2.6% difference, p<0.05). Whole body scans of the left and right arms were also assessed and similar results were observed in the bowling arm compared to the non-bowling arms of males (3.81 ± 5.19%, p<0.05) and females (4.15 ± 2.54%, p<0.05). In conclusion, the female elite level collegiate ten-pin bowlers demonstrate an increased BMD in the bowling forearm when compared to the non-bowling forearm.
Thesis (M.Ed.)--Wichita State University, College of Education, Dept. of Human Performance Studies

Bone density and body composition among the average population has been extensively researched; little research has been reported on the effects of Severe Mental Illness (SMI). Recent studies have suggested that individuals with SMI are at greater risk of osteoporosis, but the study groups have been primarily patients that required chronic institutionalized care. Purpose: To assess bone mineral density (BMD) and body composition in individuals with SMI. Methods: BMD of the forearm and femoral neck and body composition was measured by a DXA unit (Hologic QDR 4500). 28 individuals (15 male; 13 female) with Severe Mental Illness (bipolar (N=13), schizophrenia (N=4), schizoaffective (N=4), major depression/depression (N=2), and other (N=5)) volunteered for this study. Results: Total group (N=28) body fat percentage (35.5±9.4) and BMI (31.7±6.24) is significantly greater (<0.05) than the national and state averages. Forearm BMD results showed t-score values of 0.0±1.1 and femoral neck t-scores of -0.4±0.8. By groups, results showed bipolar (N=14) to have the highest body fat % (39.1±8.1 vs. 30.7±9.4 %, p<0.05) and greatest risk of CVD (DXA forearm t-score and femoral neck were normal). The schizophrenia group (N=5), (body fat % = 26.38±8.0; forearm t-score -0.6±1.43; femoral neck t-score -1.0±1.08), schizoaffective group (N=4), (body fat % = 27.33±3.8; forearm t-score -0.4+1.56; femoral neck t-score -0.4+0.51), major depression/depression group (N=2), body fat % = 32.8±8.13; forearm t-score 0.8±0.42 femoral neck t-score -0.4±0.42), and other (N=5), (body fat % = 34.7±8.33; forearm t-score -0.7±0.91; femoral neck t-score -0.9±0.70) were within normal range. Conclusion: People with SMI that are stabilized on a medication regime and integrated into the community do not appear to be at a greater risk of low BMD. Body composition findings agree with recent studies indicating that a higher incidence of obesity exists in individuals with SMI. Supported by WSU U-Link Award.
Thesis (M.Ed.)--Wichita State University, College of Education, Dept. of Human Performance Studies.

Physical activity is critical to bone health. However, not all physical activity has optimum effect on bone health and metabolism. The purpose of this study was to determine the effects of a short term progressive jumping protocol on bone mineral density in college age Asian females. Sixteen participants aged18-28 years enrolled in the study. Participants were assigned to exercise (n=9) and control (n=8) groups. The exercise group completed a two-legged depth jump from an approximate 20cm stepbench followed immediately by a maximum vertical jump using arm swings for five days per week for two weeks. Each depth jump and vertical jump was performed ten times during each session. The exercise intervention progressed from one session per day to three sessions per day in ten days. The bone mineral density (BMD) by dualenergy x-ray absorptiometry (DXA), ground reaction force (GRF), bone specific physical activity questionnaire (BPAQ), and dietary log were administered to the participants pre- and post-intervention. The data were analysed using a dependent t-test and one-way repeated measures. There were no significant changes noted in BMD value in the study. The past BPAQ showed significant correlation to BMD change of left hip (p<0.01) in exercise group. The vertical GRF showed significant increase (p<0.05) in exercise group. It can be concluded from the study that intensity of the progressive jumping was intense enough to stimulate some changes in the bone metabolism.

Bone mineral density (BMD) is a strong indicator of bone strength, which is used to discern between individuals with healthy bones and those with metabolic bone diseases such as osteoporosis. The use of DXA is largely centred around measuring key skeletal sites such as the femoral neck and lumbar spine, however some research has used it to measure BMD in the mandible in older edentulous or osteoporotic sample groups. Within craniofacial research, there is little understanding about the mechanisms used to maintain bone mineral density in the craniofacial skeleton as it only experiences small loads. These loads may be generated through mastication or movement of the head and neck. There is a body of research that uses DXA to measure the BMD of facial bones; however, the studies focus on older, edentulous or osteoporotic individuals and do not include comparisons between sexs, age groups or ethnicities in healthy, dentate sample groups. There is a large body of research that has investigated the differences in bite force and muscle activity between sample groups, however little research has been conducted into ethnic differences in these areas. Furthermore, there is very little research that has explored the force-muscle-bone relationship in the craniofacial skeleton. This study aimed to explore that relationship, and investigate how it is affected by differences in sex, age and ethnicity. In particular, the study measured bilateral bite force, jaw elevator muscle activity and mandibular BMD at the ramus and mandibular body. The present study developed a novel bite force device using existing technologies, it also used a new technique of measuring bite force and muscle activity through computer software, which facilitated synchronisation of the data. Furthermore, this study used a new approach to normalising muscle activity data to a submaximal bite force level, a technique used in other disciplines that measure muscle activity but is not often used in bite force studies. The study also developed a different approach to analysing mandibular BMD from DXA scans, building on the work of previous research. Finally, the study used a new technique for measuring facial dimensions from later photographs rather than radiographs. The present findings indicate no significant differences between males and females in a cohort of young adult Caucasians. The findings indicate a significant effect of age in a cohort of females aged <25yrs compared to >50yrs, but similar differences were not found in males. Significant differences between Caucasian males and African Caribbean males were identified, with particular reference to BMD. Finally, the study reported the significant effect of facial dimensions on the outcome variables bite force, jaw elevator muscle activity and mandibular BMD. The findings are largely concurrent with existing research but also provide new evidence for under investigated areas of research. Overall, this study highlights the use of new techniques for measuring bite force and muscle activity and for analysing BMD from DXA measurements. It has also identified relationships in bite force, muscle activity and mandibular BMD between or within sample groups that have not been reported in previous literature.

Reports of lumbar spine (IS) skeletal deficits in female athletes with menstrual disorders are common, although it is not clear whether the deficits are confined to this group. The main factor presumed to be responsible is oestrogen deficiency characterised by amenorrhoea, however emerging evidence indicates that energy deficiency can also disturb bone turnover. This thesis aimed to determine whether male distance runners are at a comparable risk for bone loss and whether there was a relationship between reported energy balance and BMD. Methods: 109 distance runners (18-50 years) participated (65 females, 44 males). A questionnaire assessed menstrual status, performance level and training characteristics. 7-day dietary and exercise records were used to quantify energy balance. LS, dual femur (DF) and total body (TB) BMD were measured using dual-energy X-ray absorptiometry. Bone size was accounted for: bone mineral apparent density (BMAD) = BMD / √Bone area. Results: Male and female IS T-scores were similar (-0.8, -0.8). 41.6% of female and 36.4% of male runners were osteopenic (LS). Age, BMI and body fat- adjusted LS T-scores were lower in male than female runners (p<0.05). Adjusted LS T-scores were lower in male compared to eumenorrhoeic runners (p<0.01). Female runners who used the oral contraceptive pill had similar BMD to amen/oligo-menorrhoeic runners, which were significantly lower than eumenorrhoeic runners (p<0.01). These runners were also more energy deficient (p<0.01). Elite runners had greater energy deficits, lower IS T-scores, BMAD and a smaller bone area than club runners (p<0.001). DF and TB T-scores were normal, did not correlate with weekly mileage and after adjustment for calcium intake, did not correlate with energy balance. IS T-score negatively correlated with stress fracture incidence (p