Abstract Genetic factors and their resulting phenotypes were evaluated in three different bone disorders: osteogenesis imperfecta (OI), juvenile idiopathic osteoporosis (JIO), and stress fractures. The spectrum of the OI phenotypes caused by mutations in the COL1A1 and COL1A2 genes is well defined, but the mechanisms by which the variations affect the hearing phenotype are not well-known. A total of 54 Finnish OI patients with previously diagnosed hearing loss, or aged 35 or more years, were analyzed here for mutations in COL1A1, or COL1A2. Altogether, 49 mutations were identified, of which 41 were novel. No correlation was observed between the mutated gene, or the mutation type, and the hearing pattern. This indicates that the basis of hearing loss in OI is complex, and is a result of multifactorial, still unknown genetic effects, or of variable expressions of the COL1A1 and COL1A2 genes. JIO presents peri-pubertally as an acute symptomatic osteoporosis (bone pain and fractures) in otherwise healthy children, and no underlying cause has yet been identified for this disorder. Here, the analysis of the low-density lipoprotein receptor-related protein 5 gene (LRP5) in 20 patients with JIO revealed two missense mutations (A29T and R1036Q) and one frameshift mutation (C913fs) in 3 of the patients. The LRP5 gene has recently been shown to be also involved in osteoporosis-pseudoglioma syndrome and a high-bone-mass phenotype. Stress fractures are a significant problem among athletes and soldiers. Genetic factors may increase the fracture risk, but no susceptibility genes have yet been identified. Seven genes involved in bone metabolism, or pathology, were studied in terms of their roles in stress fracture. No disease-causing, or predisposing variations were found in the candidate gene, or association analyses, but a highly significant association was found between the phenotype and a vitamin D receptor (VDR) haplotype, TGT, which is composed of three polymorphic sites, FokI, BsmI and TaqI. We showed that femoral neck stress fractures are associated with a certain VDR haplotype, accounting for a five-fold increase in the risk of developing stress fractures, with an associated attributable risk of 12%. The results of this study show that genetic factors play a role in different pathological bone phenotypes. These findings provide new information on the pathogenesis of the disorders and for the development of genetic testing and targeted treatment for the disorders.

Stress fractures represent one of the most common and serious overuse injuries in the military environment. The aim of this prospective study was to determine the incidence of stress fractures during 12 weeks of Basic Training (BT) by comparing the results of the intrinsic risk indicators obtained from a group of participants who suffered stress fractures, with the rest of the original group (controls) who did not suffer from any stress fractures, and to assess any changes in physical markers whilst following a progressive, scientifically designed, Physical Training (PT) Programme during the BT. The intrinsic risk factors investigated included sex, age, race (measured via questionnaire), foot morphology (wet test), Q angle, leg length discrepancy, bone density (dual-energy X-ray absorptiometry(DEXA), physical fitness (standardized military fitness test, isokinetic upper and lower leg strength, handgrip strength), flexibility (ankle plantarflexion and dorsiflexion, hip internal and external rotation), anthropometry (skinfold method and DEXA), female menstrual disturbances and lifestyle behaviours including smoking, female contraception use and medical history of previous injury (questionnaire). The cohort (n=183), also refered to as the Experimental Group (EG), was measured at the beginning and at the end of the BT period. The standardized physical fitness test was also completed in the fifth week of training. The latter’s results were compared to the results obtained by a Control Group (CG), who had undergone BT the year prior to this cohort. The size of the cohort, the intrinsic risk factor profile and the control of certain extrinsic risk factors may have contributed to zero incidences of stress fractures found. Within the intrinsic risk factor profile, sex, age, race, foot morphology, Q angle, hip external rotation and bone density were normal whilst the measured leg discrepancy and limited ankle dorsiflexion appeared to not have a sufficient risk for stress fracture development. The small sample of the cohort that reported having menstrual irregularities, smoked and had a history of previous fractures, did not place this cohort at risk for stress fracture development. The cohort did, however have lower isotonic, isokinetic and isometric strengths than the other cohorts who reported a relatively high stress fracture incidence. The BT period found statistically significant changes in bone density, flexibility, body composition, muscle strength and endurance. Female participants showed an increase in the T- and Z-scores of the left femur area, a deterioration in left ankle dorsiflexion and hip external rotation, whilst their plantarflexion increased. Their mesomorph component increased, and decreases in % body fat (BF) as well as in the ectomorph and endomorph component were also found. Male participants’ plantarflexion and hip external rotation decreased whilst their dorsiflexion increased. Lean body mass and mesomorph component increased whilst %BF, ectomorph and endomorph component decreased. The new cyclic-progressive PT programme controlled for risk of injury by allowing sufficient periods of recovery, by gradually increasing the duration, frequency, and intensity of training, by reducing repetitive weight-bearing activities and by including a variation of exercises. Running shoes, rather than combat boots, were also worn during PT. Marching on concrete was eliminated. Significant improvements were shown by both male and female participants in aerobic fitness and muscular endurance and muscular strength. Future research should include a larger size cohort, who developed stress fractures utilising BT groups from different corps and units in the South African Military environment. Other potential extrinsic risk factors, such as surface and equipment, should also be investigated. / Thesis (DPhil)--University of Pretoria, 2009. / Biokinetics, Sport and Leisure Sciences / unrestricted

Tibial stress fractures are common in runners. However, it is unclear what factors are associated with tibial stress fractures. This study aimed to investigate 1) magnitudes of bone contact forces occurring while running 2) whether or not repeated application of running loads is sufficient to explain tibial stress fractures and 3) whether or not muscle fatigue alters the potential of tibial stress fractures. Tibial stress fractures were predicted through an estimation of the minimum number of cycles to failure (Nfail) using an integrated experimental and mathematical modeling approach. Short running trials within a speed range of 3.5-4 m/s of ten male runners were evaluated with a coupled force plate and 3 dimensional motion analysis system. The collected data were used to estimate joint reaction forces (JRF) and joint moments. Using these JRF and muscle forces predicted from optimization, 2-D bone contact forces at the distal end of the tibia were determined. Next, tibial stresses were estimated by applying these bone contact forces to a tibial model, which were then used to predict the Nfail. All procedures were repeated after plantarflexors fatigued from prolonged running. This study found that peaks of compressive and posterior shear forces occurred during mid stance, and these peaks equaled 8.91 ± 1.14 BW and -0.53 ± 0.16 BW, respectively. These bone contact forces led to a backward bending of the tibia during most of the stance phase and resulted in the maximum stresses of - 43.4 ± 10.3 MPa on the posterior face of the tibia. These maximum stresses predicted the group mean of Nfail as being 5.28*10⁶ cycles. However, 2.5% to 56% of population of runners have a chance of getting tibial stress fractures within 1 million cycles of a repeated foot impact. Within the context of muscle force and stress estimation procedures used in this study, Nfail appeared to increase after fatigue, not decrease as we hypothesized. / Graduation date: 2005

Investigation of activated remodelling in the healing of experimental stress fractures and the influence of anti-inflammatory treatments Lisa Jane Kidd Abstract Targeted and focal remodelling are important processes in bone homeostasis and pathology. However, the factors that initiate and direct remodelling to repair microcracks, or respond to excess loading are still poorly understood. The rat ulna-loading (RUL) model has been widely used to examine modelling and remodelling responses to axial cyclic loading. However the model has not yet been fully characterised. Stress fractures are common amongst athletes, dancers and military recruits, but there is almost no information available on the mechanism of healing of these fractures. Although cyclooxygenase-2 (COX-2) is a key mediator of bone resorption and bone formation, very little information is available on the effect of non-steroidal antiinflammatories (NSAIDs) on stress fracture healing. Remodelling may play a role in the pathogenesis of stress fractures, and there is growing interest in the potential use of bisphosphonates to prevent them. Nonetheless, the effect of bisphosphonates on stress fracture healing is not known. PMX53 is a C5a receptor antagonist developed as a novel anti-inflammatory agent. It is effective against inflammatory arthritis, but has not been tested in any fracture models. The aims of this study were to undertake a detailed examination of the histology, histomorphometry and gene expression of the healing and remodelling process initiated by RUL, and to use this model to determine the effects of selective and non-selective NSAIDs, a bisphosphonate and PMX53 on stress fracture healing. To characterise the RUL model, fatigue fractures were created by loading ulnae until displacement was observed to increase by between 4% and 50%. Ulnae were bulk-stained in basic fuchsin and processed for undecalcified histology. For all remaining experiments, loading was stopped when the displacement had increased by 10%. For detailed histology and histomorphometry, ulnae were decalcified, paraffin embedded and stained with toluidine blue, saffranin-O or for tartrate resistant acid phosphatase (TRAP). Ulnae were examined at 1, 2, 4, 6, 8, and 10 weeks after loading. The effects of DFU (a selective COX-2 inhibitor, 2 mg/kg po), ibuprofen (a non-selective NSAID, 30 mg/kg po) and PMX53 (10 mg/kg po) were examined at 2, 4 and 6 weeks after loading. Effects of risedronate (a bisphosphonate) were examined at a high (1.0 mg/kg po) and low dose (0.1 mg/kg po) at 2, 6 and 10 weeks after loading. RUL did not create isolated intracortical microcracks, but curvilinear fatigue fractures that occurred at a standard position in the medial cortex of the distal ulna diaphysis. These stress fractures induced rapid periosteal woven bone formation and direct intracortical remodelling along the fracture line that originated at the periosteum and progressed towards the medullary cavity. Basic multicellular units (BMUs) could be followed through serial sections extending along the fracture line towards the centre of the bone. Quantitative, real-time PCR was performed at 4 hours, 24 hours, 4 days, 7 days and 14 days after fatigue fracture. Following each period, bones were dissected and mRNA was extracted using standard protocols. Gene expression was compared between loaded and unloaded ulnae and to an unloaded control group. Four hours after loading, there was a marked, 220-fold increase (P<0.0001) in expression of Interleukin-6 (IL-6). There were also prominent peak increases in mRNA expression for Osteoprotegerin (OPG), cyclooxygenase-2 (COX-2), and vascular endothelial growth factor (VEGF) (all P<0.0001). At 24 hours there was a peak increase in mRNA expression for IL-11 (73-fold increase, P<0.0001). At 4 days there was a significant increase in mRNA expression for Bcl-2, COX-1, bone morphogenic protein (BMP)-2, insulin-like growth factor (IGF)-1, osteopontin (OPN), and stromal cell derived factor SDF-1. At 7 days there was a significant increase in mRNA expression of Receptor activator of nuclear factor kappa β ligand (RANKL) and OPN. The dramatic, early up-regulation of IL-6 and IL-11 suggests they play a central role in initiating signalling events for stress fracture healing. Treatment with PMX53 did not affect any measures of woven bone formation or stress fracture remodelling. There were no treatment effects of Ibuprofen or DFU on the area of woven bone. DFU treatment resulted in a significant reduction in the area of porosity (resorption) and BMU area along the fracture line at 2 weeks after fracture. Ibuprofen treatment resulted in a significant reduction in length and area of BMUs and new bone formation along the fracture line at 6 weeks (p < 0.05). This is the first report to demonstrate a negative effect on stress fracture healing of both a selective COX-2 inhibitor and a non-selective NSAID. These data confirm the importance of cyclooxygenase in bone resorption and formation during remodelling. Bisphosphonates are potent inhibitors of osteoclastic bone resorption Two, 6 and 10 weeks after loading, measures of resorption and new bone formation were significantly reduced along the fracture line by high dose risedronate treatment, but not by the low dose. Only the porosity along the fracture line 2 weeks after loading was significantly reduced by the low dose risedronate. The low dose more closely resembles the clinical dose used to treat patients. Woven bone formation and consolidation were not affected by the low or high doses of risedronate. In conclusion, fatigue fractures in the rat ulna are highly reproducible, induce exuberant periosteal woven bone formation, and heal by direct remodelling along the fracture line. Remodelling is associated with gene expression for molecules typically associated with bone resorption and formation, angiogenesis and cell signalling. Remodelling of the stress fracture line was adversely affected by treatment with selective and non-selective COX inhibitors, by high dose treatment with risedronate, but not by PMX53, a C5a antagonist.

Thesis PlanB (M.S.)--University of Wisconsin--Stout, 2007. / Includes bibliographical references.

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No. of bitstreams: 1 lynch_kr_me_prud.pdf: 832983 bytes, checksum: 06433c144b0dda4669f10d1027f1f123 (MD5) Previous issue date: 2018-06-21 / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / Objetivo: Analisar o risco de fraturas traumáticas de acordo com o engajamento em esportes com diferentes níveis de impacto, assim como identificar o potencial impacto da participação esportiva nos gastos entre adolescentes. Métodos: Estudo longitudinal com 24 meses de seguimento. A amostra foi composta por 285 adolescentes de ambos os sexos (202 meninos e 83 meninas) que foram contatados pelos pesquisadores em escolas (n= 104) e clubes esportivos (n= 181) localizados na região metropolitana de Presidente Prudente, SP, Brasil. Todos os adolescentes foram convidados considerando os seguintes critérios de inclusão: a) idade entre 10-19 anos, 2) assinatura dos pais no termo de consentimento, 3) se contatados em clubes esportivos, pelo menos um ano de treino; se contatados na escola, pelo menos um ano sem prática esportiva ou exercícios. Os grupos foram classificados em: Controle (n= 104), Natação (n= 34), e Esportes de Impacto (n= 147). A ocorrência de fraturas e gastos em saúde foram avaliadas mensalmente durante 12 meses antes da linha de base e 12 meses após linha de base. Sexo, idade, composição corporal, participação esportiva, maturação biológica e proteína CReativa (PCR) foram avaliados durante os 12 meses após a linha de base. Análise estatística foi composta por teste Mann-Whitney, qui-quadrado, Regressão de Cox, Kruskal-Wallis, Analise de Covariância e medidas de tamanho de efeito. A significância estatística foi fixada em p<0.05 e todas as análises foram realizadas no software BioEstat (versão 5,2 [BioEstat, Teffe, Brasil]). Resultados: A incidência de novas fraturas foi de 2,1% (n= 6). A ocorrência de fraturas traumáticas durante o período de 24 meses (12 meses de seguimento + 12 meses prévios) foi de 6,0% ([IC95%: 3,2% a 8,7%]; n= 17). Os gastos totais acumulados durante o período de 12 meses de seguimento foram de U$ 2.991,96. Quando comparados os adolescentes de acordo com a incidência de novas fraturas, não houveram diferenças por sexo, idade, densidade óssea, gordura corporal, esportes, maturação biológica e PCR. Gastos totais também não apresentaram diferença de acordo com a ocorrência de qualquer fratura durante o período de 24 meses. Participação esportiva não mostrou qualquer associação ou risco para a ocorrência de fraturas traumáticas. Quando desmembrados os grupos por esportes, atletismo [US$ 4,13 (27,67)], ginástica [US$ 10,77 (23,90)], judô [US$ 4,24 (6,96)] e natação [US$ 24,67 (46,50)] apresentaram maiores gastos quando comparados ao grupo controle. Caratê, kung-Fu, tênis, basquete e baseball não apresentaram diferenças significativas quando comparados ao grupo controle. Nadadores apresentaram maiores gastos com medicação (p-valor= 0,001), consultas (p-valor= 0,001) e exames (p-valor= 0,005) quando comparados ao grupo controle e esportes de impacto. Mesmo após ajustes por fatores de confusão, nadadores (Média: US$ log10 1,172 [IC95%: 0.925 a 1.420]) tiveram maiores gastos do que o grupo controle (Média: US$ log10 0,280 [IC95%: 0,101 a 0,459]) e esportes de impacto (Média: US$ log10 0,404 [IC95%: 0,290 a 0,519]) (p-valor = 0,001). Participação esportiva explicou 13,2% de toda variância em gastos com saúde, enquanto sexo (2,6% da variância) e fraturas (3,5% da variância) também foram covariáveis relacionadas aos gastos nesse modelo. Conclusão: Os achados desse estudo indicaram que participação esportiva (incluindo esportes de impacto) não aumentou o risco de fraturas entre adolescentes, enquanto fraturas traumáticas foram o principal determinante de gastos com saúde entre adolescentes. Além disso, alguns esportes pareceram estar mais relacionados a maiores gastos com saúde entre adolescentes, independente do impacto econômico de fraturas e sexo. / Objective: To analyze the risk of traumatic fractures according to the engagement in sports with different levels of physical impact, as well as to identify the potential impact of sports participation on health care costs among adolescents. Methods: Longitudinal study with 24 months of follow-up. The sample was composed of 285 adolescents of both sexes (202 boys and 83 girls) who were contacted by the researchers in schools (n= 104) and sports clubs (n= 181) located in the metropolitan region of Presidente Prudente, Sao Paulo, Brazil. All adolescents were invited, considering the inclusion criteria: 1) 10-19 years-old, 2) parents' consent form signed, 3) if contacted in any sports club, at least one year of training experience; if contacted in any school unit, at least one year without regular practice of sport or exercise. The groups were classified as: Control (n= 104), Swimming (n= 34), and Impact Sports (n= 147). The occurrence of fractures and health care costs were assessed monthly during the 12 months before baseline, as well as 12 months after baseline. Sex, age, body composition, sports participation, peak height velocity (PHV) and C-reactive protein (CRP) were assessed during the 12 months of follow-up. Statistical analyses were composed of Mann-Whitney test, chisquare test, Cox Regression, Kruskal-Wallis test, Analysis of Covariance and measures of effect size. Statistical significance was set at p<0.05 and all analyzes were performed using BioEstat software (version 5.2 [BioEstat, Teffe, Brazil]). Results: The incidence of new fractures was 2.1% (n= 6). The occurrence of traumatic fractures during the 24-month period (12-month follow-up plus previous 12 months) was 6.0% ([95%CI: 3.2% to 8.7%]; n= 17). The overall costs accounted during the 12-month follow-up were U$ 2,991.96. When comparing the adolescents according to the incidence of new fractures, there were no differences regarding age, BMD, BF, sports, PHV, and CRP. Overall health care costs were also not different according to subjects with any fracture during the 24-month period. Sports participation did not show any significant association or risk with the occurrence of traumatic fractures. When breaking the groups down by sport, track and field [US$ 4.13 (27.67)], gymnastics [US$ 10.77 (23.90)], judo [US$ 4.24 (6.96)], and swimming [US$ 24.67 (46.50)] presented higher costs when compared to the control group. Karate, kung-Fu, tennis, basketball and baseball did not show significant differences when compared to the control group. Concerning health care costs, swimmers presented higher costs with medicine (p-value= 0.001), appointments (p-value= 0.001), and tests (p-value= 0.005) when compared to control and impact sports groups. Even after adjustment by confounders, swimmers (Mean: US$ log10 1.172 [95%CI: 0.925 to 1.420]) had higher health care costs than control (Mean: US$ log10 0.280 [95%CI: 0.101 to 0.459]) and impact sports (Mean: US$ log10 0.404 [95%CI: 0.290 to 0.519]) (p-value = 0.001). Sports participation explained 13.2% of all variance in health care costs, while sex (2.6% of the variance) and fractures (3.5% of the variance) were also covariates related to health care costs in this model. Conclusion: The findings from this study indicate that sports participation (including impact sports) did not increase the risk of fracture among adolescents, while traumatic fracture was the main determinant of health care costs among these adolescents. Moreover, some sports seem to be related to higher health care costs among adolescents, independently of the significant economic burden of fractures and sex. / 2016/20377-0

The identification of risk factors associated with overuse injuries, specifically Medial Tibial Stress Syndrome (MTSS) and Tibial Stress Fractures (TSF), may help professionals with management and prevention of these injuries. The purpose of this study was to identify risk factors associated with MTSS and TSF in female intercollegiate athletes. This study used a mulitifactorial, prospective design for 13-26 weeks. Thirty-nine Division I intercollegiate female student-athletes in volleyball, soccer, and track were examined. Anatomical, physiological (eating disorder and menstrual history), and training (duration and recovery time) characteristics were examined as possible risk factors. Only two injuries were reported during the study; therefore, analysis for risk factors was not possible. Descriptive statistics for the dependent variables were calculated, and comparisons across sport were performed. Differences in leg length values and dorsiflexion ROM were observed across sports. No conclusions could be drawn regarding possible risk factors for MTSS and TSF in this population.

Abstract Osteoporosis is a bone disorder that leads to a reduction in bone volume, deterioration of bone microarchitecture and therefore increased fracture risk. Bone disorders such as osteoporosis commonly have both genetic and environmental components. Family and twin studies have shown the importance of genetics in bone formation and health, but most of the genetic factors contributing to bone formation are still largely unknown. The aim of this thesis was to search for and identify genetic factors that predispose to two different bone disorders manifesting in fractures, namely femoral neck stress fractures and childhood primary osteoporosis without features of OI (i.e. non-OI primary osteoporosis). Furthermore, in vitro studies were performed to elucidate the importance and mechanism of action of identified genetic factors in non-OI primary osteoporosis. By using candidate gene analyses we identified predisposing alleles, haplotypes and their interactions that increased the risk for femoral neck stress fractures in young male military conscripts. The conscripts lacking the CTR C allele and/or VDR C-A haplotype had a three-fold increased risk for femoral neck stress fractures compared to the carriers of both. Furthermore, conscripts carrying the LRP5 A-G-G-C haplotype had a three-fold increased risk for femoral neck stress fractures and in combination with VDR C-A haplotype a four-fold increased risk for stress fractures. These associations were mediated by low body weight and BMI. In the search for genetic factors of non-OI primary osteoporosis in children and adolescent, two novel mutations in LRP5 and two more variants in WNT3A and DKK1 were found in patients. The variants were also observed in the affected family members, but not in the control group. The effects of these variants were examined in in vitro studies and the results showed that some LRP5 mutations and the WNT3A variant might reduce bone formation by decreasing the canonical Wnt signalling activity. / Tiivistelmä Osteoporoosi on luustosairaus, joka alentaa luuntiheyttä ja heikentää luun rakennetta ja siten lisää murtumien riskiä. Osteoporoosin kaltaiset luusairaudet ovat usein monitekijäisiä tauteja, joiden syntyyn vaikuttavat sekä perinnölliset että ympäristölliset tekijät. Perhe- ja kaksostutkimukset ovat osoittaneet perinnöllisten tekijöiden olevan tärkeitä luun muodostuksessa ja terveydessä, mutta nämä tekijät ovat kuitenkin vielä suurelta osin tuntemattomia. Tutkimustyön tavoitteena oli etsiä ja tunnistaa perinnöllisiä tekijöitä, jotka altistavat kahdelle luunmurtumina ilmenevälle sairaudelle: reisiluunkaulan rasitusmurtumille ja lasten primaariselle osteoporoosille. Lisäksi primaariselle osteoporoosille altistavien perinnöllisten tekijöiden merkitystä ja vaikutusmekanismeja tutkittiin in vitro- kokeilla. Reisiluunkaulan rasitusmurtumille altistavien alleelien, haplotyyppien ja näiden vuorovaikutusten tunnistamiseen käytettiin ehdokasgeenianalyysiä nuorten alokkaiden aineistossa. Potilailla, joilta CTR-geenin C-alleeli ja/tai VDR-geenin C-A haplotyyppi puuttuivat, oli kolminkertainen riski rasitusmurtumien syntyyn molempien geenimuotojen kantajiin verrattuna. Myös LRP5-geenin A-G-G-C haplotyypin kantajilla oli kolminkertainen riski rasitusmurtumiin ja VDR-geenin C-A haplotyyppi ja A-G-G-C yhdessä lähes nelinkertaistivat rasitusmurtumien riskin alokkailla. Näiden assosiaatioiden todettiin välittyvän alhaisen painon ja painoindeksin välityksellä. Lapsuudessa tai varhaisnuoruudessa puhkeavan primaarisen osteoporoosin perinnöllisten tekijöiden etsinnässä löydettiin kaksi uutta mutaatiota LRP5-geenistä ja yhteensä kaksi uutta muutosta WNT3A- ja DKK1-geeneistä. Uusien ehdokasgeenilöydösten osuutta primaarisen osteoporoosin syntyyn tukee se, että muutokset löydettiin potilaiden lisäksi heidän sairailta sukulaisiltaan eikä muutoksia havaittu kontrolliaineistoissa. Uusien mutaatioiden mahdollisia vaikutuksia tutkittiin in vitro-kokein, jotka osoittivat, että eräät LRP5-geenin mutaatiot ja WNT3A-geenin muutos alentavat kanonisen Wnt-signalointireitin aktiivisuutta ja voivat siten vähentää luunmuodostusta.

Problem: Track and field athletes, along with cross-country athletes have multiple and back to back seasons, creating overuse injuries. Stress fractures or stress reactions to the bone are the overuse injuries focused on in this study and literature review. There is a lack of information in the literature regarding stress reactions. Purpose: The goal of the study is to understand more information about stress reactions to bone and possibly increase the knowledge of health care professionals. Methods: Three case studies were examined through pre-existing medical chart notes and athletic trainer's notes regarding the stress reactions. A literature review was also performed to provide further information about stress fractures and stress reactions. Conclusions: There are multiple risk factors for stress injuries. All three of the athletes in the case studies are female, which is found to be a risk factor. Many risk factors need more studies to provide support. Magnetic Resonance Imaging (MRI) was obtained in all three case studies where there was found to be a stress reaction. These three females also had a recent increase in activity level and had similar symptoms to each other and what is found in the literature.

The humerus of a racing horse Thoroughbred is highly susceptible to stress fractures at a characteristic location as a result of cyclic loading. The propensity of a Thoroughbred to exhibit humeral fracture has made equines useful models in the epidemiology of stress fractures. In this study, a racing Thoroughbred humerus was simulated during training using a 3D finite element model in conjunction with a bone remodeling algorithm. Nine muscle forces and two contact forces were applied to the 3-dimensional finite element model, which contains four separate load cases representing fore-stance, mid-stance, aft-stance, and standing. Four different training programs were incorporated into the model, which represent Baseline Layup and Long Layup training programs along with two newly implemented programs for racing, which have an absence of a layup period, last a period of 24 weeks, and a race once every four weeks. Muscle and contact forces were rescaled for all load cases to simulate dirt, turf, and synthetic track surfaces. Bone porosity, damage, and BMU activation frequency were examined at the stress fracture site and compared with a control location called the caudal diaphysis. It was found that race programs exhibited similar remodeling patterns between each other. Damage at the stress fracture site and caudal diaphysis was reduced during all training programs for the turf and synthetic track surfaces with respect to the dirt track surface. Key findings also included changes in bone remodeling at the stress fracture site and caudal diaphysis as a result of turf and synthetic track surfaces. This model can serve as a framework for further studies in human or equine athletes who are susceptible to stress fractures.