Sex steroids, bone loss and non-vertebral fractures in women and men : the Tromsø study

When this thesis was planned in 2000-2001 it was well known that bone loss accelerates after menopause, and is prevented by using hormone replacement therapy (HRT). Case reports of young men with estrogen receptor dysfunction or aromatase deficiency showed that estrogen was important for normal growth and maturation of the male skeleton. However, there were few prospective studies examining the contribution of endogenous sex steroids on bone loss and fracture risk in women, and no prospective study in men. We wanted to know if levels of sex steroids were relevant as predictors of bone loss and fractures and whether this knowledge could be useful for developing future treatment by low dose of HRT. During the work on this thesis results from a large randomized controlled trial assessed the risks and benefits of estrogen plus progestin treatment in 16,608 healthy postmenopausal women. The investigators concluded that the overall health risks exceeded benefits from the use of estrogen plus progestin in this group. They estimated hazard ratios with 95% confidence interval as follows: coronary heart disease 1.29 (1.02- 1.63); breast cancer 1.26 (1.00-1.59); stroke 1.41 (1.07-1.85); pulmonary embolism 2.13 (1.39-3.25); colorectal cancer 0.63 (0.43-0.92); endometrial cancer 0.83 (0.47-1.47) and hip fracture 0.66 (0.45-0.98). This publication led to a reassessment of the role of HRT, which was no longer recommended in women for fracture risk reduction alone. Left unresolved was the question whether women and men with low levels of circulating sex steroids have higher risk of bone loss or fractures. This was still relevant for our understanding of the contribution of sex steroids on bone fragility. From a clinical point of view it was interesting to know, if sex steroids are relevant predictors of bone loss or fractures, if these measurements could be useful in signalling the need for further investigation or treatment

En komparativ case studie av elevers muntlig og skriftlig uttrykte matematiske kompetanse

I dette forskningsprosjektet ble ungdomsskoleelevers (9. og 10. trinn) uttrykte matematiske kompetanse innenfor emnet funksjonslære undersøkt. Studien sammenlignet skriftlig og muntlig uttrykt matematisk kompetanse blant 12 elever i forbindelse med et undersøkende undervisningsforløp. Vurdering av deltakernes muntlig uttrykt matematiske kompetanse var basert på muntlige innspill som kom til uttrykk i undervisningsforløpet, imens skriftlig uttrykt matematisk kompetanse ble vurdert på bakgrunn av en skriftlig individuell prøve gjennomført etter undervisningsforløpet. Det ble i tillegg undersøkt uttrykte holdninger hos deltakerne som kunne være til hinder for å utvikle og uttrykke deres matematiske kompetanse. Det ble benyttet kvalitative metoder, i form av observasjon, videoopptak og en skriftlig test. Datamaterialet ble transkribert, kodet og kategorisert gjennom bruk av tematisk analyse. Det ble utviklet en rubric for å kategorisere kvaliteten av deltakernes uttrykte matematiske kompetanse. Uttrykte holdninger ble gjennom en kombinasjon av empirinær og tematisk koding kategorisert. Studiens hovedfunn var at 10 av de 12 deltakernes muntlige uttrykte matematiske kompetanse ble vurdert til å være av høyere kvalitet sammenlignet med vurderingen av deres skriftlige uttrykte matematiske kompetanse. Ytterligere funn indikerte at ensidig vurdering var spesielt utfordrende for elever vurdert som lavtpresterende (av deres egen lærer). Uttrykt lav selvtillit og negative holdninger til matematikkfaget ble identifisert hos en deltaker som et mulig hinder for fremtidig mestring. To deltakere ga uttrykk for å være stille og beskjedne, og hadde få muntlige bidrag og innspill i undervisningen. Dette ble identifisert som et hinder for deres mulighet til å utvikle og uttrykke relevante matematiske kompetanser. I avhandlingen diskuteres det hvorvidt ensidig vurdering ikke fange opp deltakernes helhetlige matematiske kompetanse. Dette i kombinasjon med at deltakerne viste bedre muntlige prestasjoner, anbefales det derfor ikke bruk av skriftlige indidivuelle prøver som ensidig vurderingsform. The data-gathering paradigm trekkes frem som en fremtidsrettet løsning for å danne et mer rettferdig vurderingsgrunnlag, samt fremme elevdeltakelse, motivasjon og prestasjoner

Physical activity, unrest and school performance : about the students behind the numbers and diagnosis ADHD

Masteroppgave i kroppsøvings- og idrettsvitenskap - Nord universitet, 201

Is There a Causal Relationship between Physical Activity and Bone Microarchitecture? A Study of Adult Female Twin Pairs

The reasons for the association between physical activity (PA) and bone microarchitecture traits are unclear. We examined whether these associations were consistent with causation and/or with shared familial factors using a cross-sectional study of 47 dizygotic and 93 monozygotic female twin pairs aged 31–77 years. Images of the nondominant distal tibia were obtained using high-resolutionperipheral quantitative computed tomography. The bone microarchitecture was assessed using StrAx1.0 software. Based on a self-completed questionnaire, a PA index was calculated as a weighted sum of weekly hours of light (walking, light gardening), moderate (social tennis, golf, hiking), and vigorous activity (competitive active sports) = light + 2 * moderate + 3 * vigorous. We applied Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) to test whether cross-pair cross-trait associations changed after adjustment for within-individual associations. Within-individual distal tibia cortical cross-sectional area (CSA) and cortical thickness were positively associated with PA (regression coefficients [β] = 0.20 and 0.22), while the porosity of the inner transitional zone was negatively associated with PA (β = 0.17), all p < 0.05. Trabecular volumetric bone mineral density (vBMD) and trabecular thickness were positively associated with PA (β = 0.13 and 0.14), and medullary CSA was negatively associated with PA (β = 0.22), all p ≤ 0.01. Cross-pair crosstrait associations of cortical thickness, cortical CSA, and medullary CSA with PA attenuated after adjustment for the within-individual association (p = 0.048, p = 0.062, and p = 0.028 for changes). In conclusion, increasing PA was associated with thicker cortices, larger cortical area, lower porosity of the inner transitional zone, thicker trabeculae, and smaller medullary cavities. The attenuation of cross-pair crosstrait associations after accounting for the within-individual associations was consistent with PA having a causal effect on the improved cortical and trabecular microarchitecture of adult females, in addition to shared familial factors

Target Values and Daytime Variation of Bone Turnover Markers in Monitoring Osteoporosis Treatment After Fractures

The serum bone turnover markers (BTM) procollagen type 1 N-terminal propeptide (P1NP) and C-terminal cross-linking telopeptide of type 1 collagen (CTX) are recommended for monitoring adherence and response of antiresorptive drugs (ARD). BTM are elevated about 1 year after fracture and therefore BTM target values are most convenient in ARD treatment follow-up of fracture patients. In this prospective cohort study, we explored the cut-off values of P1NP and CTX showing the best discriminating ability with respect to adherence and treatment effects, reflected in bone mineral density (BMD) changes. Furthermore, we explored the ability of BTM to predict subsequent fractures and BTM variation during daytime in patients using ARD or not. After a fragility fracture, 228 consenting patients (82.2% women) were evaluated for ARD indication and followed for a mean of 4.6 years (SD 0.5 years). BMD was measured at baseline and after 2 years. Serum BTM were measured after 1 or 2 years. The largest area under the curve (AUC) for discrimination of patients taking ARD or not was shown for P1NP 2% gain in BMD (lumbar spine and total hip) was largest at cut-off values for P1NP <30 μg/L and CTX <0.25 μg/L. Higher P1NP was associated with increased fracture risk in patients using ARD (hazard ratio [HR]logP1NP = 15.0; 95% confidence interval [CI] 2.7–83.3), p = 0.002. P1NP and CTX were stable during daytime, except in those patients not taking ARD, where CTX decreased by 21% per hour during daytime. In conclusion, P1NP <30 μg/L and CTX <0.25 μg/L yield the best discrimination between patients taking and not taking ARD and the best prediction of BMD gains after 2 years. Furthermore, higher P1NP is associated with increased fracture risk in patients on ARD. BTM can be measured at any time during the day in patients on ARD.publishedVersio

Estimated Glomerular Filtration Rate (eGFR) based on cystatin C was associated with increased risk of hip and proximal humerus fractures in women and decreased risk of hip fracture in men, whereas eGFR based on creatinine was not associated with fracture risk in both sexes: The Tromsø Study

Purpose - Patients with end-stage kidney disease have an increased fracture risk. Whether mild to moderate reductions in kidney function is associated with increased fracture risk is uncertain. Results from previous studies may be confounded by muscle mass because of the use of creatinine-based estimates of the glomerular filtration rate (eGFRcre). We tested the hypothesis that lower eGFR within the normal range of kidney function based on serum cystatin C (eGFRcys) or both cystatin C and creatinine (eGFRcrecys) predict fractures better than eGFR based on creatinine (eGFRcre). Methods - In the Tromsø Study 1994–95, a cohort of 3016 women and 2836 men aged 50–84 years had eGFRcre, eGFRcys and eGFRcrecys estimated using the Chronic Kidney Disease Epidemiology Collaboration equations. Hazard ratios (HRs) (95% confidence intervals) for fracture were calculated in Cox's proportional hazards models and adjusted for age, height, body mass index, bone mineral density, diastolic blood pressure, smoking, physical activity, previous fracture, diabetes and cardiovascular disease. Results - During a median of 14.6 years follow-up, 232, 135 and 394 women and 118, 35 and 65 men suffered incident hip, proximal humerus and wrist fractures. In women, lower eGFRcre did not predict fracture, but the risk for hip and proximal humerus fracture increased per standard deviation (SD) lower eGFRcys (HRs 1.36 (1.16–1.60) and 1.33 (1.08–1.63)) and per SD lower eGFRcrecys (HRs 1.25 (1.08–1.45) and 1.30 (1.07–1.57)). In men, none of the eGFR estimates were related to increased fracture risk. In contrast, eGFRcys and eGFRcrecys were inversely associated with hip fracture risk (HRs 0.85 (0.73–0.99) and 0.82 (0.68–0.98)). Conclusions - In women, each SD lower eGFRcys and eGFRcrecys increased the risk of hip and proximal humerus fracture by 25–36%, whereas eGFRcre did not. In men, none of the estimates of eGFR were related to increased fracture risk, and each SD lower eGFRcys and eGFRcrecys decreased the risk of hip fracture by 15–18%. The findings particularly apply to a cohort of generally healthy individuals with a normal kidney function. In future studies, the association of measured GFR using the gold standard method of iohexol clearance with fractures risk should be examined for causal inference. More clinical research is needed before robust clinical inferences can be made

Grip strength in men and women aged 50–79 years is associated with non-vertebral osteoporotic fracture during 15 years follow-up: The Tromsø Study 1994–1995

Under embargo until: 2020-10-25Summary In 50–79-year-olds who participated in the Tromsø Study (1994–1995), the risk of non-vertebral osteoporotic fractures during 15 years follow-up increased by 22% in men and 9% in women per 1 SD lower grip strength. The strongest association was observed in men aged 50–64 years. Introduction We aimed to explore whether low grip strength was associated with increased risk of non-vertebral osteoporotic fracture in the population-based Tromsø Study 1994–1995. Methods Grip strength (bar) was measured by a Martin Vigorimeter and fractures were retrieved from the X-ray archives at the University Hospital of North Norway between 1994 and 2010. At baseline, weight and height were measured, whereas information on the other covariates were obtained through self-reported questionnaires. Cox regression was used to estimate the hazard ratio (HR) of fracture in age- and gender-specific quintiles of grip-strength, and per 1 SD lower grip strength. Similar analyses were done solely for hip fractures. Adjustments were made for age, height, body mass index (BMI), marital status, education, smoking, physical activity, use of alcohol, self-perceived health, and self-reported diseases. Results In 2891 men and 4002 women aged 50–79 years, 1099 non-vertebral osteoporotic fractures—including 393 hip fractures—were sustained during the median 15 years follow-up. Risk of non-vertebral osteoporotic fracture increased with declining grip strength: hazard ratios per SD decline was 1.22 (95% CI 1.05–1.43) in men and 1.09 (95% CI 1.01–1.18) in women. HR for fracture in lower vs. upper quintile was 1.58 (95% CI 1.02–2.45) in men and 1.28 (95% CI 1.03–1.59) in women. The association was most pronounced in men aged 50–64 years with HR = 3.39 (95% CI 1.76–6.53) in the lower compared to the upper quintile. Conclusions The risk of non-vertebral osteoporotic fracture increased with declining grip-strength in both genders, particularly in men aged 50–64 years.acceptedVersio