46 research outputs found

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

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    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

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

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    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

    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

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    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

    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

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    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

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    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

    Bone trait ranking in the population is not established during antenatal growth but is robustly established in the first postnatal year

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    Efforts to understand the pathophysiology of bone fragility must focus on bone traits during growth. We hypothesized that variance in individual trait ranking in the population distribution is established by genetic factors and is reflected in foetal trait ranking in early pregnancy, but intrauterine factors modify trait ranking in late pregnancy, followed by the reinstating of this ranking during the first postnatal year. Thus, relations with paternal factors are present in early pregnancy but are then lost and subsequently reinstated postnatal. We recruited 399 healthy pregnant women aged 20–42 years from The Mercy Hospital for Woman in Melbourne, Australia. Foetal femur length (FL) and knee-heel length (KHL) were measured by ultrasound during gestation, and FL, KHL, body length and weight were measured in neonates, infants, and parents. The z-scores were calculated using Royston models. Pearson correlation was used to assess tracking and linear mixed models to test the associations. Correlations between FL and KHL z-scores of the same trait at 20 and 30 weeks gestation, at birth, and at 12 and 24 months of age (r = 0.1–0.3) and of body length and weight at birth, and 6, 12 and 24 months (r = 0.3–0.5) became more robust after 6–12 months (r = 0.4–0.8). FL and KHL z-scores at 20 weeks gestation accounted for 4–5% of total variance, while FL, KHL, body length and weight z-scores at birth accounted for 13–26% of total variance in the same traits at 24 months. Maternal FL and KHL were associated with foetal FL and KHL at 20 and 30 weeks, but there were no such associations for paternal FL and KHL with foetal traits during gestation. Both maternal and paternal traits were associated with infant traits. Tracking in traits is not established antenatal but is robustly established at 6–12 months of age

    The effect of maternal and paternal height and weight on antenatal, perinatal and postnatal morphology in sex-stratified analyses

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    Introduction - Low birthweight is associated with diseases later in life. The mechanisms for these associations are not well known. If the hypothesis concerning “maternal constraint” is correct for humans, as shown in animal experiments, we expect the maternal, not paternal, body proportions to influence antenatal growth and those of both parents to influence postnatal growth. We aimed to study the effect of maternal and paternal height and weight on fetal femur length antenatally (gestational weeks 20 and 30) and body length and weight at birth and postnatally (12 and 24 months old) in both sexes. Material and methods - In this prospective cohort study, 399 healthy pregnant women aged 20‐42 years were recruited at The Mercy Hospital for Woman, Melbourne, Australia from 2008 to 2009. Fetal femur length was measured using antenatal ultrasound (gestational weeks 20 and 30). Body length and weight were measured for parents and offspring at birth and postnatally (12 and 24 months). Results - Each standard deviation (SD) rise in maternal weight (15.5 kg) was associated with 0.24 SD (0.5 mm) and 0.18 SD (0.4 mm) longer femur length in female and male fetuses at week 20 and 0.17 SD (0.5 mm) and 0.38 SD (1.1 mm) longer femur length in female and male fetuses at week 30, respectively. In girls, each SD rise in paternal height (7.2 cm) was associated with 0.29 SD (0.6 cm) longer birth length. In boys, each SD rise in maternal height (6.7 cm) was associated with 0.23 SD (0.5 cm) longer birth length. In both sexes, parental height and weight were associated with offspring length and weight at 12 and 24 months (SD ranging from 0.20 to 0.38, length from 0.7 to 1.5 cm and weight from 0.3 to 0.6 kg). The multivariable linear regression analyses were adjusted for parental age, height and weight, maternal smoking, alcohol intake, parity, and ethnicity, all P Conclusions - Maternal, not paternal, body proportions determined fetal growth in both sexes. Paternal height predicted birth length in girls. In contrast, maternal height predicted birth length in boys. Both parents predicted postnatal body proportions at 12 and 24 months in both sexes

    Are the Relationships of Lean Mass and Fat Mass With Bone Microarchitecture Causal or Due to Familial Confounders? A Novel Study of Adult Female Twin Pairs

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    It is not known whether the relationships of lean mass (LM) and fat mass (FM) with bone microarchitecture and geometry are causal and/or are because of confounders, including familial confounders arising from genetic and environment effects shared by relatives. We tested the hypotheses that: (i) LM is associated with cortical bone traits, (ii) FM is associated with trabecular bone traits, and (iii) these relationships of LM and FM with bone microarchitecture and geometry have a causal component. Total body composition was quantified for 98 monozygotic (MZ) and 54 dizygotic (DZ) white female twin pairs aged 31 to 77 years. Microarchitecture at the distal tibia and distal radius was quantified using HRpQCT and StrAx software. We applied the Inference about Causation through Examination of FAmiliaL CONfounding (ICE FALCON) method. Within‐individuals, distal tibia total bone area, cortical area, cortical thickness, and trabecular number were positively associated with LM (standardized regression coefficient (β) = 0.13 to 0.43; all p < 0.05); porosity of the inner transitional zone (ITZ) was negatively associated with LM (β = −0.22; p < 0.01). Trabecular number was positively associated with FM (β = 0.40; p < 0.001), and trabecular thickness was negatively associated with FM (β = −0.27; p < 0.001). For porosity of ITZ and trabecular number, the cross‐pair cross‐trait association with LM was significant before and after adjustment for the within‐individual association with LM (all ps < 0.05). For trabecular number, the cross‐pair cross‐trait association with FM was significant before and after adjustment for the within‐individual association with FM (p < 0.01). There were no significant changes in these cross‐pair cross‐trait associations after adjustment for the within‐individual association (p = 0.06 to 0.99). Similar results were found for distal radius measures. We conclude that there was no evidence that the relationships of LM and FM with bone microarchitecture and geometry are causal; they must in part due to by familial confounders affecting both bone architecture and body composition. © 2020 The Authors. JBMR Plus published by Wiley Periodicals LLC. on behalf of American Society for Bone and Mineral Research

    Women with fracture, unidentied by FRAX, but identied by cortical porosity, have a set of characteristics that contribute to their increased fracture risk beyond high FRAX score and high cortical porosity

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    The Fracture Risk Assessment Tool (FRAX) is widely used to identify individuals at increased risk for fracture. However, cortical porosity is associated with risk for fracture independent of FRAX and is reported to improve the net reclassification of fracture cases. We wanted to test the hypothesis that women with fracture who are unidentified by high FRAX score, but identified by high cortical porosity, have a set of characteristics that contribute to their fracture risk beyond high FRAX score and high cortical porosity. We quantified FRAX score with femoral neck areal bone mineral density (FN aBMD), and femoral subtrochanteric architecture, in 211 postmenopausal women aged 54–94 years with non-vertebral fractures, and 232 fracture-free controls in Tromsø, Norway, using StrAx software. Of 211 fracture cases, FRAX score > 20% identified 53 women (sensitivity 25.1% and specificity 93.5%), while cortical porosity cut-off > 80th percentile identified 61 women (sensitivity 28.9% and specificity 87.9%). The 43 (20.4%) additional fracture cases identified by high cortical porosity alone, had lower FRAX score (12.3 vs. 26.2%) than those identified by FRAX alone, they were younger, had higher FN aBMD (806 vs. 738 mg/cm2), and fewer had a prior fracture (23.3 vs. 62.9%), all p 3), larger medullary and total cross-sectional areas (245 vs. 190 and 669 vs. 593 mm2), and higher cross-sectional moment of inertia (2619 vs. 2388 cm4) all p p ≤ 0.05). Thus, fracture cases, unidentified by FRAX, but identified by cortical porosity, had an architecture where the positive impact of larger bone size did not offset the negative effect of thinner cortices with increased porosity. A measurement of cortical porosity may be a marker of other characteristics that capture additional fracture risk components, not captured by FRAX
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