Thesis (M.Sc. (Animal Production)) -- University of Limpopo, 2023 / Two experiments were conducted to determine the effect of citric acid inclusion level in the diet on growth performance, carcass weight, tibia bone breaking strength and ash content of male Ross 308 broiler chickens aged one to 35 days. The first experiment determined the effect of citric acid inclusion level in the diet on growth performance traits of male Ross 308 broiler chickens aged one to 21 days. The experiment commenced with 200 male day-old Ross 308 broiler chickens with an initial average live weight of 40±1.6g per chick. The chicks were assigned to five treatment groups in a completely randomized design, each replicated five times, and each replicate having ten chicks. The citric acid inclusion levels were at 0, 12.5, 25 or 50g per kg DM of feed. The second experiment determined the effect of citric acid inclusion level in the diet on growth performance, carcass weight, tibia bone breaking strength and ash content traits of male Ross 308 broiler chickens aged 22 to 35 days. The experiment commenced with 180 male Ross 308 broiler chickens aged 22 days. The chickens were assigned to four treatment groups, each having three replicate pens of eight chickens per replicate in a completely randomized design. Data was analysed using the General Linear model (GLM) procedures of the Statistical Analysis of System, version 9.3.1 software program. Where there were significant differences (P<0.05) between the treatment means, Tukey Multiple Comparison Test was used for mean separation. Citric acid inclusion in the starter diets improved (P<0.05) live weight and growth rate of male Ross 308 broiler chickens aged one to 21 days. Citric acid inclusion in the starter diets did not affect (P>0.05) daily feed intake, body weight gain and feed conversion ratio of male Ross 308 broiler chickens aged one to 21 days. The inclusion of citric acid did affect (P<0.05) live weight, body weight gain, feed conversion ratio and growth rate of chickens aged 22 to 35 days. Citric acid inclusion levels used in the present study influenced (P<0.05) DM and CP digestibility, ME intake and N-retention of male broiler chickens aged 22 to 35 days. The results of the current study showed that citric acid inclusion in a diet improved (P<0.05) chicken bone morphology. Thus, positive relationships were observed between citric acid inclusion level and right tibia bone weight, diameter, calcium, phosphorous and Magnesium contents of chicken bones aged 35 days. There were positive relationships between citric acid inclusion level and breast weight of male Ross 308 broiler chickens aged 35 days. Further studies are recommended to ascertain these findings. / National Research Foundation (NRF)

The main focus of this thesis is the study of the burned bones from Uppgarde, Vallstena, on the island of Gotland. Vallstena is a place where artifacts, graves and other activities are dated from the Stone Age to the Late Iron Age. This indicates that Vallstena was a place humans frequently used for a long period of time and a prominent remain is a Stone Ship Setting that once was placed here but when excavations were carried out in the 1970s only the depressions of the stones became visible. The purpose of this study is toco-analyse osteological and archaeological material found, to obtain a clearer image of the place and contribute to the existing research of this area. The goal study is to determine the nature of the activities seen in relationship to the analysis of the cremated bones found here and how they were connected to the surrounding landscape. The basis for this analysis is a combination of thorough examinations of the osteological material, archaeological features as well as relevant literature.

Thesis (MScMedSc (Medical Imaging and Clinical Oncology. Nuclear Medicine))--University of Stellenbosch, 2007. / Introduction: Whole body bone scintigraphy with Tc-99m MDP is able to provide a survey of the entire skeleton. The question arises if it is mandatory to perform a whole body bone scan in all patients, irrespective of the clinical indication. The aim of this study is to determine the implications of performing limited imaging in patients who had whole body bone scan for various clinical patholgy with Tc-99m MDP, in order to determine if limited imaging would be acceptable in selected pathologies. This may enable gamma camera time to be optimally utilized in units with limited facilities. Materials and Methods: Reports of 3015 patients with various clinical pathologies who had whole body bone scans with Tc-99m MDP in our department from January 2002 to December 2004 were retrospectively reviewed. The presence of pathologic radiotracer uptake was analyzed in order to establish the pattern of distribution. Clinically significant skeletal lesions were classified according to the anatomical regions where they were located viz; skull (including the neck), axial skeleton (including the pelvis and shoulders) and limbs. Results: Our results showed that in patients with lung cancer, soft tissue sarcoma, and myeloma, there was an error in more than 25% of patients when limited imaging was performed. In patients with cancer of the breast, prostate, kidney, gastrointestinal system, and reproductive system and lymphoma there is an error in less than 5% of patients when limited imaging is employed. For iv patients with more localized musculoskeletal disorders such as suspected stress fractures, complicated joint prosthesis and avascular necrosis of the femur head, regional imaging of the area of pathology showed a percentage error of less than 6%.

Thesis (MSc)--University of Stellenbosch, 2002. / ENGLISH ABSTRACT: Insulin is a mitogen for many cells and commonly signals through the classical, mitogenic Raf- MEK-ERK or metabolic PB-kinase pathways. Insulin deficiency or type I diabetes causes severe osteopenia. Obese patients with type II diabetes or insulin resistance, a disease associated with defective insulin signaling pathways and high levels of circulating insulin, have increased or normal bone mineral density. The question of whether hyperinsul inemia preserves bone mass is frequently raised. However, there is still a lot of controversy on the role of insulin as an osteoanabolic agent and this question still remains unanswered. A critical role for insulin signaling in bone building osteoblasts has recently been demonstrated with IRS-l knock-out mice. These mice developed low-turnover osteopenia due to impaired proliferation and differentiation, stressing the importance of osteoblastic IRS-l for maintaining normal bone formation. In the present study it was found that insulin does function in vitro as an osteoblast mitogen. This was illustrated in three relatively immature osteoblast (MBA-15.4, -15.6 mouse and MG- 63 human) cell lines, which responded to insulin with significant increases in proliferation. In the MBA -15.4 preosteoblasts insulin stimulation of proliferation was comparable to the welldescribed mitogen, TPA. The UMR-I06 cell line expresses markers of differentiated osteoblasts, and was much less responsive to insulin treatment. The difference in proliferative potential may be due to differences between spontaneously transformed cell lines, or the stage of cell differentiation. UOI26, a MEKI/2 inhibitor and wortmannin, a PB-kinase inhibitor, were used to investigate the pathway used by insulin to signal and activate ERK and osteoblast proliferation. In MBA-15.4 mouse preosteoblasts, GF-containing FCS was completely dependent on MEK for DNA synthesis. In contrast, in both MBA-15.4 and more mature MBA-15.6 osteoblasts, insulininduced proliferation was resistant to the inhibitors alone or in combination. Higher MEKinhibitor concentrations had no effect, and proliferation was also increased by the inhibitors in several experiments. This indicated that the classical, insulin mitogenic pathway was not involved in MBA-15.4 proliferation. Wortmannin had no effect on either insulin- or 20% FCSstimulated proliferation, but inhibited activation of Akt/PKB, the metabolic downstream target of PI3-kinase. Insul in signal ing to ERK was both MEK-and PI3-kinase- dependent, but this had no effect on proliferation. In contrast, FCS-stimulated ERK activation and proliferation was almost completely dependent on MEK-ERK activation. Proliferative signaling in the MG-63 human osteoblastic cell line in response to insulin was partially dependent on MEK and partially dependent on PB-kinase. In contrast, signaling in response to the phorbol ester, TPA, was partially dependent on PI3K but totally dependent on MEK-ERK. This indicates that the signal converges on ERK, suggesting the involvement of a PB-kinase upstream of a dominant MEK-ERK pathway. The differences found here between mouse and human insulin mitogenic signaling pathways indicate that there may be species differences between osteoblast signaling pathways, with mouse cells being independent and human cells being dependent on MEK for DNA synthesis in response to insulin. The effects of glucocorticoids on insulin mitogenic signaling in osteoblasts were also investigated, because chronic long-term steroid use results in excessive bone loss. The PTP inhibitor, sodium orthovanadate, reversed GC-impaired TPA- and FCS- induced proliferation in MBA-1SA and MG-63 preosteoblasts. PTPs, such as SHP-l and PTP-IB, dephosphorylate and inactivate phosphorylated kinases. Both SHP-l and PTPlB associated with kinases in the mitogenic signaling cascade of MBA-lS.4 preosteoblasts growing rapidly in 10% FCS. Further, SHP-I co-irnmunoprecipitated with active, tyrosine phosphorylated ERK, which may indicate that it can dephosphorylate and inactivate ERK. However, since the MEK-ERK or PB-kinase pathways are not important in insulin-induced proliferation in mouse osteoblasts, the PTPs are unlikely to be role players in the negative regulation of this signaling pathway. This was confirmed by the finding that vanadate was unable to reverse GC-induced decreases in insulinstimulated DNA synthesis. This suggests that vanadate-sensitive PTPs may not be important in the negative regulation of insulin-induced mouse osteoblast proliferation, and provides further evidence of a novel insulin mitogenic pathway in the MBA-lSA but not MG-63 osteoblastic cell line. / AFRIKAANSE OPSOMMING: Insulien is 'n mitogeen vir baie selle en gelei na binding aan die insulien reseptor, intrasellulêre seine via die klassieke, mitogeniese Raf-MEK-ERK of die metaboliese PB-kinase seintransduksie pad. 'n Insulien gebrek of tipe I diabetes veroorsaak osteopenie. Vetsugtige pasiënte met insulien weestandigheid of tipe II diabetes, 'n siekte wat geassosieer word met foutiewe insulien seintransduksie en hoë vlakke van sirkuierende insulien, het verhoogde of normale been mineraal digtheid (BMD). Die vraag of hiper insulin ernie 'n verlies aan beenmassa teëwerk word dikwels gevra. Teenstrydigheid oor die rol van insulien as 'n osteo-anaboliese stof bestaan egter steeds en hierdie vraag bly dus onbeantwoord. Dat insulien seintransduksie wel 'n kritiese rol speel in beenvormende osteoblaste is onlangs bevestig in studies met muise waarvan die geen vir IRS-l uitgeslaan is. Hierdie muise ontwikkel 'n lae omset osteopenie weens verswakte proliferasie en differensiasie. fn hierdie studie is gevind dat insulien wel in vitro as 'n osteoblast mitogeen kan funksioneer. Dit is in drie relatief onvolwasse (MBA-15.4, -15.6 muis en MG-63 mens) sellyne geillistreer, deur betekenisvolle verhogings in insulien-geaktiveerde proliferasie. In MBA-15.4 preosteoblaste is die persentasie verhoging in insulien-gestimuleerde proliferasie vergelykbaar met dié van die bekende mitogeniese forbolester, TPA. Die UMR-I06 sellyn het kenmerke van gedifferensieerde osteoblaste, en was baie minder responsief op insulien behandeling. Die verskil in die proliferasie vermoë van die verskillende sellyne kan die gevolg wees van verskille wat bestaan tussen spontaan getransformeerde sellyne of die stadium van sel differensiasie. 'n MEK 1/2 inhibitor, UO126 en 'n PB-kinase inhibitor, wortmannin, is gebruik om die insulien seintransduksie pad noodsaaklik vir die aktivering van ERK en osteoblast proliferasie te bepaal. In MBA-1S.4 muis pre-osteoblaste, was fetale kalf SenlTI1(FKS)-geinduseerde DNA sintese totaal afhanklik van MEK. Beide die MBA-15.4 en die meer volwasse MBA-15.6 muis osteoblaste was weerstandig teen die inhibitors op hulle eie, of in kombinasie. Verhoogde MEK-inhibitor konsentrasies het geen verdere effek gehad nie en in verskeie eksperimente is 'n verhoging in preliferasie selfs waargeneem met MEK-inhibisie. Hierdie resultate dui aan dat die klassieke insulien mitogeniese pad nie betrokke is in MBA-I5.4 gestimuleerde selproliferasie nie. Wortmannin het geen effek gehad op insulien- of20% FKS-gestimuleerde DNA sintese nie, maar het wel die aktivering van PB-kinase se metaboliese teiken, AktJPKB geinhibeer. Insulien seintransduksie aktiveer dus ERK deur beide MEK en PB-kinase, maar het geen effek op proliferasie gehad nie. FKS-gestimuleerde ERK aktivering en proliferasie was totaal afhanlik van MEK-ERK aktivering. Insulien-geaktiveerde DNA sintese in die mens MG-63 osteoblaste was gedeeltelik afhanklik van beide MEK en PB-kinase. Alhoewel IPA ook PB-kinase kon aktiveer, was dit totaal afhanklik van MEK vir DNA sintese. Dit dui aan dat daar 'n PB-kinase stroom-op van 'n dominante MEK-ERK seintransduksie pad voorkom. Die verskille wat ons dus waargeneem het in insulien mitogeniese seintransduksie tussen muis en mens, kan aandui dat insuliengestimuleerde seintranduksie paaie kan verskil van spesie tot spesie. Dit is bevestig met die muisselle wat onafhanklik is en mens selle wat afhanklik is van MEK aktivering vir insuliengeaktiveerde DNA sintese. Kroniese, langtermyn steroied behandeling kan beenverlies veroorsaak en die effek van glukokortikoide (GK) op die insulien mitogeniese pad in osteoblaste is dus ook ondersoek. Natrium-ortovanadaat, 'n proteien tirosien fosfatase (PIP) inhibitor het GK-verlaagde proliferasie in repons tot beide IPA- en FKS behandeling herstel in MBA-lSA en MG-63 preosteoblaste. PIPs soos SHP-l en PIP-l B funksioneer deur gefosforileerde kinases te defosforileer en dus te inaktiveer. Beide SHP-l and PIP-lB kon assosieer met kinases in die mitogeniese insulien seintransduksie pad van vinnig groeiende MBA-IS A preosteoblaste in 10% FKS. Verder het SHP-I ook geko-immunopresipiteer met aktiewe, tirosien-gefosforileerde ERK, wat aandui dat SHP-I met ERK assosieer om dit te defosforileer en inaktiveer. Die MEKERK of PB-kinase paaie is nie belangrik vir insulien-geaktiveerde seintransduksie in muis osteoblaste nie. Dit is dus onwaarskynlik dat die PIPs 'n rol sal speel in die negatiewe regulering van hierdie seintransduksie paaie. Die ontdekking dat vanadaat nie glukokortikoiedverlaagde insulien-geaktiveerde DNA sintese kan herstel nie, toon dat vanadaat-sensitiewe PIPs nie 'n rol speel in insulien-geaktiveerde proliferasie in muisselle nie. Hierdie bevinding het verder bevestig dat 'n nuwe insulien mitogeniese pad in die MBA-ISA, maar nie die MG-63 selle moontlik bestaan.

ENGLISH ABSTRACT: Background: The detection of bone infection can be very difficult especially in bone with altered structure due to prior trauma or surgical procedures. Complicated osteomyelitis (COM) is becoming a public health problem especially with the difficult choice between, high cost surgery and prolonged courses of intravenous or oral antibiotic therapy, as well as the social and psychological effect of longterm disease and disability of the patient. The correct localisation of especially bone infection is still a challenge for the clinician. The single photon emission computed tomography/low dose computed tomography (SPECT/CT), by fusing the functional information with the anatomical parts, is a wellestablished tool used in many nuclear medicine studies. This improves the overall quality of the study with more clear answers. The aim of the study was to determine the added value of SPECT/CT in the management of complicated osteomyelitis (COM) in patients with endo-prosthesis, post traumatic osteomyelitis with and without metal implants and diabetic foot. Methods: This was a prospective study, between February 2010 and February 2012. Patients with suspected COM who fulfilled the selection and inclusion criteria were included. All had abnormal three phase bone scan followed by infection imaging with 99mTc labelled white blood cells and 99mTc -colloid if the99mTc labelled white blood cell study was abnormal. 67Ga citrate was used in vertebral involvement. Planar and SPECT/CT images were reviewed for presence of abnormal uptake and for its localization in bone and soft tissue. Scan results were defined as positive or negative. Both planar and SPECT/CT images were compared regarding diagnosis and precise localization of infection. The final diagnosis was obtained from surgical specimen or microbiological culture as well as clinical follow-up of all patients. Results: There were 72 patients, 29 male and 43 female with mean age of 57 yrs [range 27-88].There were 24 patients with prosthesis, 16 with hip prosthesis (PH=16), and 8 with knee prosthesis (PK=8). There were 44 patients with post traumatic osteomyelitis, 26 with metal implants (TOM=26) and 18 without metal implants (TOWM= 18). Four patients had diabetic foot (DF= 4). Infection was diagnosed in 19/72 patients on planar images and in 21/72 on SPECT/CT. Infection was diagnosed in 4 patients with prosthesis, 16 patients with post traumatic injury and one diabetic foot patient. The four patients with prosthesis, SPECT /CT added diagnostic value by excluding osteomyelitis in 3 patients and by defining the exact extent and localizing soft tissue and bone infection (STI/OM) in one patient. In 16 patients with post traumatic OM on planar images, SPECT /CT added diagnostic value, by excluding OM in 4 patients and confirming only STI, better localisation of the uptake in bone and soft tissue in 5 patients, of them 2 patient was negative on planar, and in 7 patients, confirmed and defined the exact extent of both OM and STI. One diabetic foot was positive for STI on the planar, the SPECT/CT added diagnostic value by defining the extent of the infection. In summary the added value of SPECT/CT was: a. Overall infection: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (10%) 2. Better localization in bone and soft tissue: 6 patients (8%) 3. Better delineation of extent of infection: 9 patients (12%) 4. None: 50 patients (70%) b. In positive cases only: 1. Exclusion of osteomyelitis by confirming only soft tissue involvement: 7 patients (33%) 2. Better localization in bone and soft tissue: 5 patients (24%) 3. Better delineation of extent of infection: 9 patients (43%) 4. None: 0 patients The overall sensitivity, specificity, positive predictive value, negative predictive value and accuracy for infection, on planar was 90%, 100%, 100%, 97%, 97%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. For OM on planar, the sensitivity, specificity , positive predictive value, negative predictive value and accuracy was 100%, 89%, 53%, 100%, 90%, respectively and for SPECT/CT 100%, 100%, 100%, 100%, 100%. Conclusion: In complicated osteomyelitis, SPECT/CT is useful in localizing, defining the exact extent of infection where the planar images are abnormal, with no added value if the planar images are negative. We recommend in clinical practice the routine use of hybrid SPECT/CT imaging in complicated osteomyelitis when planar images are abnormal. / AFRIKAANSE OPSOMMING: Agtergrond: Die opspoor van beeninfeksie is veral moeilik in been wat as gevolg van vorige trauma of chirurgiese prosedures misvorm is. Gekompliseerde osteomiëlitis word ‘n gesondheidsprobleem veral as gevolg van die moeilike keuse tussen hoë koste chirurgie en langdurige kursusse binneaarse of orale antibiotika, asook die sosiale en sielkundige gevolge van langstaande siekte en die gestremdheid van die pasiënt. Die korrekte lokalisering van veral beeninfeksie is steeds ‘n uitdaging vir die geneesheer. Enkel foton emissie rekenaartomografie / lae dosis rekenaartomografie (SPECT/CT), die kombinasie van funksionele en anatomiese inligting, is ‘n goed gevestigde metode in baie kerngeneeskunde ondersoeke. Dit verbeter die algemene kwaliteit van die studie met ‘n meer spesifieke antwoord. Die doel van hierdie studie was om die bykomende waarde van SPECT/CT in die hantering van gekompliseerde osteomiëlitis in pasiënte met endo-protese, post traumatise osteomiëlitis met en sonder metaal prosteses asook diabetiese voet te bepaal. Metode: ‘n Prospektiewe studie is tussen Februarie 2010 en Februarie 2012 gedoen. Pasiënte met vermoedelik gekompliseerde osteomiëlitis wat aan die keuse en insluitingskriteria voldoen het, is ingesluit. Almal het abnormale drie-fase beenflikkergramme gehad, gevolg deur infeksiebeelding met 99mTc gemerkte witselle en 99mTc kolloïed indien die 99mTc gemerkte witselstudie abnormaal was. 67Ga sitraat is gebruik wanneer daar werwelaantasting teenwoordig was. Die planare en SPECT/CT beelde is vergelyk ten opsigte van diagnose en presiese lokalisering van die infeksie. Die finale diagnose is met behulp van chirurgiese monsters en mikrobiologiese kweking asook die kliniese opvolg van alle pasiënte bepaal. Resultate: Die studie het 72 pasiënte, 29 mans en 43 vroue, met gemiddelde ouderdom van 57 jaar [27 – 88 ingesluit]. Daar was 24 pasiënte met prosteses, waarvan 16 met heupprosteses (PH= 16) en 8 met knieprosteses (PK= 8). Van die 44 pasiënte met post traumatiese osteomiëlitis, het 26 metaal prosteses (TOM= 26) en 18 geen metaalprosteses gehad nie (TOWM= 18). Vier pasiënte het diabetiese voet gehad (DF= 4). By 19/72 van die pasiënte is infeksie op die planare beelde gediagnoseer en in 21/72 op die SPECT/CT beelde. Die bykomende twee gevalle was 1 met TOM en 1 met TOWM. Infeksie is by 4 pasiënte met prosteses, 16 pasiënte met post traumatiese besering en 1 met diabetiese voet gediagnoseer. In die vier pasiënte met prosteses, het SPECT/CT ‘n diagnostiese bydrae gelewer om osteomiëlitis by 3 van die pasiënte uit te skakel en die presiese omvang en lokalisering van sagte weefsel en beeninfeksie (STI/OM) in een pasiënt te bepaal. In 16 pasiënte met post traumatise osteomiëlitis op die planare beelde, was SPECT/CT van diagnostiese waarde, waar osteomiëlitis in 4 pasiënte uitgesluit is, en slegs STI bevestig is. Beter lokalisering van die opname in been en sagte weefsel was in 5 pasiënte moontlik, van wie 2 op die planare beelde negatief was, en in 7 pasiënte bevestig en die presiese omvang met beide OM en STI gedefinieer is. Een diabetiese voet was positief vir STI op die planare beelde, maar die SPECT/CT het diagnostiese waarde verbeter deur die omvang van die infeksie beter te toon. Ter opsomming, was die waarde van die SPECT/CT: 1. Uitsluiting van osteomiëlitis deur slegs van sagte weefsel aantasting te bevestig: 7 pasiënte 10% 2. Beter lokalisering in been en sagte weefsel: 5 pasiënte 7% 3. Beter definisie van omvang van infeksie: 9 pasiënte 12% 4. Geen bykomende waarde: 51 pasiënte 71% Die algehele sensitiwiteit, spesifisiteit, positiewe voorspellingswaarde, negatiewe voorspellingswaarde en akkuraatheid vir die opspoor van infeksie vir die planare beelde was 90%, 100%, 100%, 97%, 97%, onderskeidelik en vir die SPECT/CT 100%, 100%, 100%, 100% en 100%. Vir osteomiëlitis was sensitiwiteit, spesifisiteit, positiewe voorspellingswaarde, negatiewe voorspellingswaarde en akkuraatheid van planare beelde 100%, 89%, 53%, 100%, 90%, onderskeidelik en die van SPECT/CT 100%, 100%, 100%, 100% , 100%. Gevolgtrekking: SPECT/CT is nuttig in die lokalisering en definiëring van die presiese omvang van die infeksie in gekompliseerde osteomiëlitis in gevalle waar die planare beelde abnormaal is, met geen bykomende waarde wanneer planare beelde negatief is nie. Ons beveel SPECT/CT beelding as roetine in kliniese praktyk aan wanneer planare beelde in gekompliseerde osteomiëlitis abnormaal is.

Dissertation (PhD)--University of Stellenbosch, 2003. / ENGLISH ABSTRACT: The Effect of Statins on Bone and Mineral Metabolism Both statins and amino-bisphosphonates reduce the prenylation of proteins which are involved in cytoskeletal organization and activation of polarized and motile cells. Consequently statins have been postulated to affect bone metabolism. We investigated the effects of different doses of simvastatin (1,5,10 and 20mg/Kg/day), administered orally over 12 weeks to intact female Sprague-Dawley rats, and the effect of simvastatin 20mg/Kg/day in sham and ovariectomised rats, on femoral bone mineral density (BMD) and quantitative bone histomorphometry (QBH), compared to controls. Similarly, the affect of atorvastatin (2,5mg/Kg/day) and pravastatin (10mg/Kg/day) on BMD was investigated and compared to controls. BMD was decreased by simvastatin 1mg/Kg/day (p = 0.042), atorvastatin (p = 0,0002) and pravastatin (p = 0.002). The effect on QBH parameters differed with different doses of simvastatin (ANOVA; p = 0.00012). QBH parameters of both bone formation and resorption were equivalently and markedly increased by simvastatin 20mg/Kg/day in two independent groups of intact rats, and reflected by a relatively unchanged BMD. At lower doses, simvastatin 1mg/Kg/day decreased bone formation while increasing bone resorption as reflected by a marked decrease in BMD. Ovariectomised animals receiving simvastatin 20mg/Kg/day showed no change in BMD relative to the untreated ovariectomised controls, their increase in bone formation was smaller than in sham-operated rats receiving simvastatin and there was no change in bone resorption. The dose response curves of simvastatin for bone formation and resorption differed from each other. From these studies it is concluded that:- a) low-dose simvastatin (1mg/Kg/day), atorvastatin 2.5mg/Kg/day) and pravastatin 10mg/Kg/day) decrease BMD in rodents;b) 1mg/Kg/day simvastatin decreases bone formation and increases bone resorption and is reflected by a reduced BMD; c) 20mg/Kg/day simvastatin increases bone formation and resorption and results in an unchanged BMD; d) the effects of simvastatin on QBH differ at different dosages; e) the dose-response curves for QBH parameters of bone resorption and bone formation differ from each other; f) the effects of simvastatin seen in intact rats are not observed in ovariectomised rats; g) simvastatin is unable to prevent the bone loss caused by ovariectomy. / AFRIKAANSE OPSOMMING: Die Effek van Statiene op Been en Mineraal Metabolisme Beide statiene en aminobisfosfonate verminder die prenelasie van proteïene wat betrokke is in die sitoskeletale organisasie en aktivering van gepolariseerde en beweeglike selle. Gevolglik is dit gepostuleer dat statiene ‘n invloed sal hê op been metabolisme. Ons het die effekte van verskillende dossisse van simvastatien (1, 5, 10 en 20mg/Kg/dag), mondelings toegedien oor 12 weke aan intakte vroulike Sprague-Dawley rotte, en die effek van simvastatien 20mg/Kg/dag op skyn- en ge-ovariektomeerde rotte, op femorale been mineral digtheid (BMD) en kwantitatiewe been histomorfometrie (KBH), vergeleke met kontroles, ondersoek. Op ‘n soortgelyke manier is die effek van atorvastatien (2,5mg/Kg/day) en pravastatien (10mgKg/dag) op BMD ondersoek en vergelyk met kontroles. BMD is verminder deur simvastatien 1mg/Kg/dag (p = 0.042), atorvastatien (p = 0.0002) en pravastatien (p = 0.002). Die effekte op KBH parameters het verskil met verskillende dossisse van simvastatien (ANOVA; p = 0.00012). KBH parameters van beide been vormasie en resorpsie is vergelykend en merkbaar verhoog deur simvastatien 20mg/Kg/dag in twee onafhanklike groepe van intakte rotte en is vergesel deur ‘n relatiewe onveranderde BMD. Met laer dossisse het simvastatien 1mg/Kg/dag been vormasie verminder terwyl been resorpsie verhoog is en is weerspieël deur ‘n merkbaar verminderde BMD. Ge-ovariektomeerde diere wat simvastatien 20mg/Kg/dag ontvang het, het geen verandering in BMD relatief tot die onbehandelde geovariektomeerde kontroles getoon nie, en die toename in been vormasie was kleiner as in die skyngeopereerde rotte wat simvastatien ontvang het en daar was geen verandering in been resorpsie nie. Die dosis-respons kurwes vir simvastatien vir been vormasie en resorpsie het van mekaar verskil. Uit hierdie studies word die volgende gevolgtrekkings gea) lae-dosis simvastatien (1mg/Kg/dag), atorvastatien 2.5mg/Kg/dag en pravastatien 10mg/Kg/dag verminder BMD in knaagdiere; b) 1mg/Kg/dag simvastatien verminder been vormasie en verhoog been resorpsie en veroorsaak gevolglik ‘n velaging in die BMD; c) 20mg/Kg/dag simvastatien verhoog been vormasie en resorpsie met ‘n gevolglike onveranderde BMD; d) die effekte van simvastatien op KBH verskil met verskillende dossisse; e) die dosis-repons kurwes van been resorpsie en been vormasie veskil van mekaar f) die effekte van simvastatien wat waargeneem in intakte rotte word nie gesien in ge-ovariektomeerde rotte nie; g) simvastatien kannie die verlies van been wat veroorsaak word deur ovariektomie voorkom nie.

published_or_final_version / Dentistry / Doctoral / Doctor of Philosophy

published_or_final_version / Orthopaedic Surgery / Master / Master of Philosophy

published_or_final_version / Computer Science and Information Systems / Master / Master of Philosophy

Bone age assessment is a method of assigning a level of biological maturity to a child. It is usually performed either by comparing an x-ray of a child's left hand and wrist with an atlas of known bones, or by analysing specific features of bones such as ratios of width to height, or the degree of overlap with other bones. Both methods of assessment are labour intensive and prone to both inter- and intra-observer variability. This is motivation for developing a computerised method of bone age assessment. The majority of research and development on computerised bone age assessment has focussed on analysing the bones of the hand. The wrist bones, especially the carpal bones, have received far less attention and have only been analysed in young children in which there is clear separation of the bones. An argument is presented that the evidence for excluding the carpal bones from computerised bone age assessment is weak and that research is required to identify the role of carpal bones in the computerised assessment of bone age for children over eight years of age. Computerised analysis of the carpal bones in older children is a difficult computer vision problem plagued by radiographic noise, poor image contrast, and especially poor definition of bone contours. Traditional image processing methods such as region growing fail and even the very successful Canny linear edge detector can only find the simplest of bone edges in these images. The field of partial differential equation-based image processing provides some possible solutions to this problem, such as the use of active contour models to impose constraints upon the contour continuity. However, many of these methods require regularisation to achieve unique and stable solutions. An important part of this regularisation is image denoising. Image denoising was approached through development of a noise model for the Kodak computed radiography system, estimation of noise parameters using a robust estimator of noise per pixel intensity bin, and incorporation of the noise model into a denoising method based on oriented Laplacians. The results for this approach only showed a marginal improvement when using the signal-dependent noise model, although this likely reflects how the noise characteristics were incorporated into the anisotropic diffusion method, rather than the principle of this approach. Even without the signal-dependent noise term the oriented Laplacians denoising of the hand-wrist radiographs was very effective at removing noise and preserving edges.