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

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

Forearm fractures–are we counting them all? An attempt to identify and include the missing fractures treated in primary care

Objective: Norway has a high incidence of forearm fractures, however, the incidence rates based on secondary care registers can be underestimated, as some fractures are treated exclusively in primary care. We estimated the proportion of forearm fracture diagnoses registered exclusively in primary care and assessed the agreement between diagnosis for forearm fractures in primary and secondary care. Design: Quality assurance study combining nationwide data from 2008 to 2019 on forearm fractures registered in primary care (Norwegian Control and Payment of Health Reimbursement) and secondary care (the Norwegian Patient Registry). Setting and patients: Forearm fracture diagnoses in patients aged ≥20 treated in primary care (n = 83,357) were combined with injury diagnoses for in- and outpatients in secondary care (n = 3,294,336). Main outcome measures: Proportion of forearm fractures registered exclusively in primary care, and corresponding injury diagnoses for those registered in both primary and secondary care. Results: Of 189,105 forearm fracture registrations in primary and secondary care, 13,948 (7.4%) were registered exclusively in primary care. The proportion ranged from 4.9% to 13.5% on average between counties, but was higher in some municipalities (>30%). Of 66,747 primary care forearm fractures registered with a diagnosis in secondary care, 62% were incident forearm fractures, 28% follow-up controls, and 10% other fractures or non-fracture injuries. Conclusion: An overall small proportion of forearm fractures were registered only in primary care, but it was larger in some areas of Norway. Failing to include fractures exclusively treated in primary care could underestimate the incidence rates in these areas

Betydning av tilbakemelding gitt ved avvikende CRP-verdi fra Tromsø 7. Kvalitetssikring av tilbakemeldingsprosedyrer ved Tromsøundersøkelsen

Formål: Denne oppgaven er en del av en større undersøkelse der formålet er å bidra til kvalitetssikring av tilbakemeldingsrutinene til Tromsøundersøkelsen. Dette ved å undersøke hvilken betydning det har for deltakere i Tromsøundersøkelsen å få tilbakemelding om patologisk forhøyet CRP. Metode: Mixed-methods. Data fra spørreskjema ble analysert i den kvantitative delen av oppgaven. For kvalitativ analyse ble det gjennomført seks semistrukturerte intervju. Resultater: Majoriteten av deltakerne (83 %) rapporterte at tilbakemeldingen fra Tromsø 7 var nyttig, og 71 % hadde kontrollert CRP-verdien hos fastlege. To av 31 deltakere fikk nye diagnoser (Bechterews sykdom og temporalisarteritt). Det var ingen signifikant sammenheng mellom grad av avvikende CRP-verdi og opplevd nytte. Den kvalitative analysen viste at deltakerne syntes det var viktig å få informasjon om egen helsetilstand, uavhengig av eventuelle helsemessige konsekvenser. Alle svarte benektende på spørsmål om tilbakemeldingen førte til bekymring. Konklusjon: Funnene viser at de aller fleste fant tilbakemeldingen fra Tromsø 7 nyttig og at informasjonen kan være viktig for å oppdage udiagnostiserte sykdommer. Alle deltakerne i den kvalitative analysen mente at tilbakemeldingen ikke førte til bekymring, blant annet fordi de så en sammenheng mellom den forhøyede CRP-verdien og en kroppslig plage. Implikasjoner for tilbakemeldingsrutinene ved Tromsøundersøkelsen handler i hovedsak om å forbedre og tydeliggjøre informasjonen i brevet med tilbakemelding om forhøyet CRP. Hvorvidt grenseverdien på 25 mg/L bør endres er usikkert fordi resultatene gir dårlig grunnlag til å vurdere dette

Cortical bone structure of the proximal femur and incident fractures

Purpose: Fracture risk is most frequently assessed using Dual X-ray absorptiometry to measure areal bone mineral density (aBMD) and using the Fracture Risk Assessment Tool (FRAX). However, these approaches have limitations and additional bone measurements may enhance the predictive ability of these existing tools. Increased cortical porosity has been associated with incident fracture in some studies, but not in others. In this prospective study, we examined whether cortical bone structure of the proximal femur predicts incident fractures independent of aBMD and FRAX score. Methods: We pooled 211 postmenopausal women with fractures aged 54–94 years at baseline and 232 fracturefree age-matched controls based on a prior nested case-control study from the Tromsø Study in Norway. We assessed baseline femoral neck (FN) aBMD, calculated FRAX 10-year probability of major osteoporotic fracture (MOF), and quantified femoral subtrochanteric cortical parameters: porosity, area, thickness, and volumetric BMD (vBMD) from CT images using the StrAx1.0 software. Associations between bone parameters and any incident fracture, MOF and hip fracture were determined using Cox's proportional hazard models to calculate hazard ratio (HR) with 95% confidence interval. Results: During a median follow-up of 7.2 years, 114 (25.7%) of 443 women suffered one or more incident fracture. Cortical bone structure did not predict any incident fracture or MOF after adjustment for age, BMI, and previous fracture. Each SD higher total cortical porosity, thinner cortices, and lower cortical vBMD predicted hip fracture with increased risk of 46–62% (HRs ranging from 1.46 (1.01–2.11) to 1.62 (1.02–2.57)). After adjustment for FN aBMD or FRAX score no association remained significant. Both lower FN aBMD and higher FRAX score predicted any incident fracture, MOF and hip fractures with HRs ranging from 1.45–2.56. Conclusions: This study showed that cortical bone measurements using clinical CT did not add substantial insight into fracture risk beyond FN aBMD and FRAX. We infer from these results that fracture risk related to the deteriorated bone structure seems to be largely captured by a measurement of FN aBMD and the FRAX tool

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

Funder: The Northern Norway Regional Health Authority funded the study (HNF 1471‐19).Funder: JLH is supported by an NHMRC Fellowship (GMT1137349).Funder: SL is supported by a Victorian Cancer Agency Early Career Research Fellowship (ECRF19020).Funder: VFCE is supported by an Australian Government Research Training Program (RTP) Scholarship.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 cross-trait 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 cross-trait 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. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)

Epidemiology of forearm fractures in women and men in Norway 2008–2019

Summary The purpose of this paper is to describe rates of forearm fractures in adults in Norway 2008–2019. Incidence rate of distal forearm fractures declined over time in both sexes. Forearm fracture constitute a significant health burden and prevention strategies are needed. Purpose To assess age- and sex-specific incidence rates, and time trends for forearm fractures in Norway, and compare these with incidence rates in other Nordic countries. Methods Data on all patients aged 20–107 years with forearm fractures treated in Norwegian hospitals from 2008 to 2019 was retrieved from the Norwegian Patient Registry. Fractures were identified based on International Classification of Disease 10th revision code S52. Age- and sex-specific incidence rates and changes in incidence rates were calculated. Results We identified 181,784 forearm fractures in 45,628,418 person-years. Mean annual forearm fracture incidence rates per 100,000 person-years were 398 (95% CI 390–407) for all, 565 (95% CI 550–580) for women, and 231 (95% CI 228–234) for men above 20 years. Mean annual number of forearm fractures was 15,148 (95% CI 14,575–15,722). From 2008 to 2019, age-adjusted total incidence rates of forearm fractures S52 diagnoses declined by 3.5% (incidence rate ratio (IRR) of 0.997 (95% CI 0.994–0.999)) in men. The corresponding decline in women was not significant (IRR: 0.999 (95% CI 0.997–1.002)). In the same period, the age-adjusted incidence rates of distal forearm fractures declined by 7.0% in men (IRR = 0.930; 95% CI 0.886–0.965) and 4.7% in women (IRR = 0.953; 95% CI 0.919–0.976). The incidence rates of distal forearm fractures were similar to rates in Sweden and Finland. Conclusion Age-adjusted incidence rates of distal forearm fractures in both sexes declined over time.publishedVersio

Validation of forearm fracture diagnoses in administrative patient registers

Summary The validity of forearm fracture diagnoses recorded in fve Norwegian hospitals was investigated using image reports and medical records as gold standard. A relatively high completeness and correctness of the diagnoses was found. Algorithms used to defne forearm fractures in administrative data should depend on study purpose. Purpose In Norway, forearm fractures are routinely recorded in the Norwegian Patient Registry (NPR). However, these data have not been validated. Data from patient administrative systems (PAS) at hospitals are sent unabridged to NPR. By using data from PAS, we aimed to examine (1) the validity of the forearm fracture diagnoses and (2) the usefulness of washout periods, follow-up codes, and procedure codes to defne incident forearm fracture cases. Methods This hospital-based validation study included women and men aged≥19 years referred to fve hospitals for treatment of a forearm fracture during selected periods in 2015. Administrative data for the ICD-10 forearm fracture code S52 (with all subgroups) in PAS and the medical records were reviewed. X-ray and computed tomography (CT) reports from examinations of forearms were reviewed independently and linked to the data from PAS. Sensitivity and positive predictive values (PPVs) were calculated using image reports and/or review of medical records as gold standard. Results Among the 8482 reviewed image reports and medical records, 624 patients were identifed with an incident forearm fracture during the study period. The sensitivity of PAS registrations was 90.4% (95% CI: 87.8–92.6). The PPV increased from 73.9% (95% CI: 70.6–77.0) in crude data to 90.5% (95% CI: 88.0–92.7) when using a washout period of 6 months. Using procedure codes and follow-up codes in addition to 6-months washout increased the PPV to 94.0%, but the sensitivity fell to 69.0%. Conclusion A relatively high sensitivity of forearm fracture diagnoses was found in PAS. PPV varied depending on the algorithms used to defne cases. Choice of algorithm should therefore depend on study purposes. The results give useful measures of forearm fracture diagnoses from administrative patient registers. Depending on local coding practices and treatment pathways, we infer that the fndings are relevant to other fracture diagnoses and registers