Citations

ABSTRACT Distal forearm fractures are among the most common fractures during childhood, but it remains unclear whether they predict an increased fracture risk later in life. We studied a population-based cohort of 1776 children ≤18 years of age, from Olmsted County, MN, USA, who had a distal forearm fracture in 1935–1992. Incident fractures occurring at age ≥35 years were identified through review of complete medical records using the linkage system of the Rochester Epidemiology Project. Observed nonpathologic fractures resulting from no more than moderate trauma (fragility fractures) were compared with expected numbers estimated from fracture site–specific incidence rates, based on age, sex, and calendar year, for Olmsted County (standardized incidence ratios [SIR]). In 1086 boys (mean ± SD age; 11 ± 4 years) and 690 girls (10 ± 4 years) followed for 27,292 person-years after the age of 35 years, subsequent fragility fractures were observed in 144 (13%) men and 74 (11%) women. There was an increased risk for future fragility fractures in boys who had a distal forearm fracture (SIR, 1.9; 95% CI, 1.6–2.3) but not girls (SIR, 1.0; 95% CI, 0.8–1.2). Fragility fractures at both major osteoporotic (hip, spine, wrist, and shoulder) sites (SIR, 2.6; 95% CI, 2.1–3.3) and remaining sites (SIR, 1.7; 95% CI, 1.3–2.0) were increased in men, irrespective of age at distal forearm fracture as boys. A distal forearm fracture in boys, but not girls, is associated with an increased risk for fragility fractures as older adults. It is necessary to determine whether the increased fractures observed in men is due to persistent deficits of bone strength, continued high fracture risk activity, or both. Until then, men should be asked about a childhood distal forearm fracture and, if so, warrant further screening and counseling on measures to optimize bone health and prevent fractures.

Abstract Hip fracture risk rises exponentially with age, but there is little knowledge about how fracture-related alterations in hip structure differ from those of aging. We employed computed tomography (CT) imaging to visualize the three-dimensional (3D) spatial distribution of bone mineral density (BMD) in the hip in relation to age and incident hip fracture. We used intersubject image registration to integrate 3D hip CT images into a statistical atlas comprising women aged 21 to 97 years (n = 349) and a group of women with (n = 74) and without (n = 148) incident hip fracture 4 to 7 years after their imaging session. Voxel-based morphometry was used to generate Student's t test statistical maps from the atlas, which indicated regions that were significantly associated with age or with incident hip fracture. Scaling factors derived from intersubject image registration were employed as measures of bone size. BMD comparisons of young, middle-aged, and older American women showed preservation of load-bearing cortical and trabecular structures with aging, whereas extensive bone loss was observed in other trabecular and cortical regions. In contrast, comparisons of older Icelandic fracture women with age-matched controls showed that hip fracture was associated with a global cortical bone deficit, including both the superior cortical margin and the load-bearing inferior cortex. Bone size comparisons showed larger dimensions in older compared to younger American women and in older Icelandic fracture women compared to controls. The results indicate that older Icelandic women who sustain incident hip fracture have a structural phenotype that cannot be described as an accelerated pattern of normal age-related loss. The fracture-related cortical deficit noted in this study may provide a biomarker of increased hip fracture risk that may be translatable to dual-energy X-ray absorptiometry (DXA) and other clinical images. © 2013 American Society for Bone and Mineral Research.

To determine if the revised US FRAX can identify those at high risk for fractures at any skeletal site, we studied 250 women and 249 men ≥ 40 years old from an age-stratified random sample of Rochester, MN residents. At baseline, femoral neck (FN) bone density was assessed, as were the clinical risk factors included in FRAX, along with additional fracture risk factors such as bone turnover markers and fall history. Fracture ascertainment through periodic interviews and comprehensive medical record review was performed over 10 years of followup. In both women and men, a higher FRAX probability at baseline was associated with greater subsequent likelihood of a major osteoporotic fracture. However, a relative 10% increase in the FRAX 10-year fracture probability was also associated with a 1.4-fold increase (95% confidence interval (CI) 1.1–1.7) in other fractures in women and a 1.7-fold increase (95% CI 0.8–3.1) in men. Furthermore, FRAX predicted asymptomatic vertebral fractures and fractures generally in both sexes. The addition of risk factors not currently included in FRAX did not appear to improve the accuracy of fracture risk prediction. FRAX may provide a conservative estimate of risk for major osteoporotic fractures, but it also predicts fractures generally.

Background: It is unclear if all patients with relapsing–remitting multiple sclerosis (RRMS) ultimately develop progressive MS. Onset of progressive disease course seems to be age- rather than disease duration-dependent. Some forms of progressive MS (e.g. primary progressive MS (PPMS)) are uncommon in population-based studies. Ascertainment of patients with PPMS from clinic-based populations can facilitate a powerful comparison of age at progression onset between secondary progressive MS (SPMS) and PPMS but may introduce unclear biases. Objective: Our aim is to confirm that onset of progressive disease course is more relevant to the patient’s age than the presence or duration of a pre-progression relapsing disease course in MS. Methods: We studied a population-based MS cohort ( n =210, RRMS n =109, progressive MS n =101) and a clinic-based progressive MS cohort ( n =754). Progressive course was classified as primary (PPMS; n =322), single attack (SAPMS; n =112) and secondary progressive (SPMS; n =421). We studied demographics (chi 2 or t -test), age-of-progression-onset ( t -test) and time to Expanded Disability Status Scale of 6 (EDSS6) (Kaplan–Meier analyses). Results: Sex ratio ( p =0.58), age at progression onset ( p =0.37) and time to EDSS6 ( p =0.16) did not differ between the cohorts. Progression had developed before age 75 in 99% of patients with known progressive disease course; 38% with RRMS did not develop progression by age 75. Age at progression onset did not differ between SPMS (44.9±9.6), SAPMS (45.5±9.6) and PPMS (45.7±10.8). In either cohort, only 2% of patients had reached EDSS6 before onset of progression. Conclusions: Patients with RRMS do not inevitably develop a progressive disease course. Onset of progression is more dependent on age than the presence or duration of a pre-progression symptomatic disease course. Moderate disability is sustained predominantly after the onset of a progressive disease course in MS.

BACKGROUND Atrial natriuretic factor (ANF) is produced by myocardial tissue, and the plasma ANF concentration is known to be elevated in congestive heart failure (CHF). Data from animal models indicate that myocardial concentrations of ANF are depleted in CHF, and this has given rise to the hypothesis that CHF is characterized by depletion of stored ANF. To date, the molecular forms of ANF and their concentrations in atrial and ventricular myocardium remain poorly characterized in the normal and the failing human heart. METHODS AND RESULTS We measured ANF concentrations in fresh tissue from failing human hearts explanted at the time of cardiac transplantation and from organ donors whose normal hearts could not be used for transplantation. We determined total ANF and alpha, beta, and gamma ANF concentrations in the right and left atrial appendages, atrial free walls, and ventricles. In normal hearts, ANF concentration in the atrial appendages was 40-fold higher than ANF in the rest of the atrial free wall and in the ventricles. In the failing hearts, atrial appendage ANF concentrations increased 5- to 10-fold, and atrial free wall ANF concentrations increased 200-fold. Analysis of molecular forms of ANF demonstrated significant increases in the gamma and beta forms in the left atrial appendage of failing hearts. alpha, beta, and gamma ANF forms were also significantly increased in right and left atrial free wall tissue from failing hearts. In addition, failing hearts were characterized by absolute and relative increases in the precursor form gamma ANF. CONCLUSIONS These data from fresh tissues suggest that cardiac ANF stores are not decreased in severe CHF in humans; rather, chronic CHF is characterized by marked increases in atrial ANF tissue concentrations, particularly the beta and gamma ANF forms. These findings are consistent with intracellular accumulation of precursor ANF forms in severe chronic human CHF.