Femoral Neck Areal Bone Mineral Research Articles

Restrictive Eating and Prior Low-Energy Fractures Are Associated With History of Multiple Bone Stress Injuries.

Bone stress injuries (BSIs) are common among athletes and have high rates of recurrence. However, risk factors for multiple or recurrent BSIs remain understudied. Thus, we aimed to explore whether energy availability, menstrual function, measures of bone health, and a modified Female Athlete Triad Cumulative Risk Assessment (CRA) tool are associated with a history of multiple BSIs. We enrolled 51 female runners (ages 18-36years) with history of ≤1 BSI (controls; n = 31) or ≥3 BSIs (multiBSI; n = 20) in this cross-sectional study. We measured lumbar spine, total hip, and femoral neck areal bone mineral density by dual-energy X-ray absorptiometry, bone material strength index using impact microindentation, and volumetric bone mineral density, microarchitecture, and estimated strength by high-resolution peripheral quantitative computed tomography. Participants completed questionnaires regarding medical history, low-energy fracture history, and disordered eating attitudes. Compared with controls, multiBSI had greater incidence of prior low-energy fractures (55% vs. 16%, p = .005) and higher modified Triad CRA scores (2.90 ± 2.05 vs. 1.84 ± 1.59, p = .04). Those with multiBSI had higher Eating Disorder Examination Questionnaire (0.92 ± 1.03 vs. 0.46 ± 0.49, p = .04) scores and a greater percentage difference between lowest and highest body mass at their current height (15.5% ± 6.5% vs. 11.5% ± 4.9% p = .02). These preliminary findings indicate that women with a history of multiple BSIs suffered more prior low-energy fractures and have greater historical and current estimates of energy deficit compared with controls. Our results provide strong rationale for future studies to examine whether subclinical indicators of energy deficit contribute to risk for multiple BSIs in female runners.

Cross-sectional associations between adipose tissue depots and areal bone mineral density in the UK Biobank imaging study.

Assess the relationship between direct measures of adiposity (total body fat mass, visceral adipose tissue, and abdominal subcutaneous adipose tissue) with the whole body and clinically relevant bone sites of the lumbar spine, and femoral neck areal bone mineral density (aBMD) in men and women. This cross-sectional analysis was conducted utilizing de-identified data from the UK Biobank on participants (n = 3674) with available dual-energy X-ray absorptiometry (DXA) and magnetic resonance imaging (MRI) data. Sex-stratified multiple linear regression was used to assess the relationship between adiposity measures and aBMD outcomes, controlling for age, race, total body lean mass (DXA), height, BMI class, physical activity, smoking, menopausal status (women), and hormone use (women). In men, significant interactions were observed between measures of adiposity and BMI on aBMD for the whole body and lumbar spine. Interactions indicated a positive relationship between adiposity and aBMD in men classified as normal weight, but an inverse relationship in men with elevated BMI. In women, significant interactions between adiposity measures and menopausal status were observed primarily for the whole body and femoral neck aBMD bone outcomes which indicated a negative relationship between adiposity and aBMD in premenopausal women, but a positive relationship in postmenopausal women. Total body adiposity, abdominal subcutaneous adipose tissue, and visceral adipose tissue were all significantly associated with aBMD in both men and women. The strength and direction of association were dependent on sex, BMI classification, and menopausal status (women).

Falls, fractures, and areal bone mineral density in older adults with sarcopenic obesity: A systematic review and meta-analysis.

Sarcopenia and obesity are common conditions in older adults that may have differing effects on falls and fracture risk. This systematic review and meta-analysis aimed to determine whether older adults with sarcopenic obesity have increased risk of falls and fractures or lower bone mass compared with older adults with sarcopenia, obesity, or neither condition. Twenty-six studies (n = 37,124) were included in the systematic review and 17 (n = 31,540) were included in the meta-analysis. Older adults with sarcopenic obesity had lower femoral neck areal bone mineral density (aBMD) compared with those with obesity alone but had higher femoral neck aBMD compared with counterparts with sarcopenia alone (both P < 0.05). Older adults with sarcopenic obesity had higher nonvertebral fracture rates (incidence rate ratio: 1.88; 95% confidence intervals: 1.09, 3.23; based on two studies), compared with those with sarcopenia alone, and also had higher falls risk compared with controls (risk ratio: 1.30; 95% confidence intervals: 1.10, 1.54) and obesity alone (risk ratio: 1.17; 95% confidence intervals: 1.01, 1.36). In conclusion, this systematic review and meta-analysis has demonstrated that older adults with sarcopenic obesity are at increased risk of adverse musculoskeletal outcomes compared with individuals with obesity, sarcopenia, or neither condition. These data support the need for developing interventions to improve bone health and physical function in this population.

Simulated effects of early menopausal bone mineral density preservation on long-term fracture risk: a feasibility study.

Preventing early menopausal bone loss may substantially reduce the future burden of osteoporosis. We modelled the effects of infrequent zoledronic acid infusions on long-term fracture risk. Data from the Canadian Multicentre Osteoporosis Study (CaMos) were used to determine the expected natural history of femoral neck areal bone mineral density (BMD) and fracture risk (using FRAX®) from ages 50-80 for women with no antiresorptive drug exposures. We modelled the effects of three infusions of zoledronic acid (at ages 50, 55, 60) on long-term fracture risk, assuming this intervention would preserve BMD until age 65 years, followed by losses mirroring early menopausal BMD loss. At age 65, untreated women and zoledronic acid recipients had expected mean (SD) femoral neck T-scores of - 1.5(1.0) and - 0.8(1.0), 10-year major osteoporotic fracture (MOF) risks of 9.8%(5.0) and 8.0%(3.7) and hip fracture risks of 1.7%(2.4) and 0.8%(1.2), respectively. At age 80, untreated women and zoledronic acid recipients had expected femoral neck T-scores of - 1.9(0.9) and - 1.4(0.9), MOF risks of 17.9%(8.2) and 14.9%(6.4) and hip fracture risks of 6.3%(6.2) and 4.4%(4.5), respectively. The expected proportion of women with femoral neck T-score ≤ - 2.5 was 14.9% for untreated women and 3.8% for zoledronic acid recipients at age 65, increasing to 28.1% and 12.0%, respectively, at age 80. Numbers-needed-to-treat to prevent one case of densitometric osteoporosis were 9 at age 65 and 5 at age 80. Infrequent infusions of zoledronic acid, initiated early in menopause, are expected to reduce long-term fracture risk and result in a substantial reduction in the proportion of women with densitometric osteoporosis after age 65.

Hip Fractures in Older Adults Are Associated With the Low Density Bone Phenotype and Heterogeneous Deterioration of Bone Microarchitecture.

Femoral neck areal bone mineral density (FN aBMD) is a key determinant of fracture risk in older adults; however, the majority of individuals who have a hip fracture are not considered osteoporotic according to their FN aBMD. This study uses novel tools to investigate the characteristics of bone microarchitecture that underpin bone fragility. Recent hip fracture patients (n= 108, 77% female) were compared with sex- and age-matched controls (n= 216) using high-resolution peripheral quantitative computed tomography (HR-pQCT) imaging of the distal radius and tibia. Standard morphological analysis of bone microarchitecture, micro-finite element analysis, and recently developed techniques to identify void spaces in bone microarchitecture were performed to evaluate differences between hip fracture patients and controls. In addition, a new approach for phenotyping bone microarchitecture was implemented to evaluate whether hip fractures in males and females occur more often in certain bone phenotypes. Overall, hip fracture patients had notable deterioration of bone microarchitecture and reduced bone mineral density compared with controls, especially at weight-bearing sites (tibia and femoral neck). Hip fracture patients were more likely to have void spaces present at either site and had void spaces that were two to four times larger on average when compared with non-fractured controls (p< 0.01). Finally, bone phenotyping revealed that hip fractures were significantly associated with the low density phenotype (p< 0.01), with the majority of patients classified in this phenotype (69%). However, female and male hip fracture populations were distributed differently across the bone phenotype continuum. These findings highlight how HR-pQCT can provide insight into the underlying mechanisms of bone fragility by using information about bone phenotypes and identification of microarchitectural defects (void spaces). The added information suggests that HR-pQCT can have a beneficial role in assessing the severity of structural deterioration in bone that is associated with osteoporotic hip fractures. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Women with fracture, unidentified by FRAX, but identified by cortical porosity, have a set of characteristics that contribute to their increased fracture risk beyond high FRAX score and high cortical porosity.

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 < 0.05. They had higher cortical porosity (48.7 vs. 42.1%), thinner cortices (3.75 vs. 4.12 mm), lower cortical and total volumetric BMD (942 vs. 1053 and 586 vs. 699 mg HA/cm3), 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 < 0.001. When the fracture cases and controls with high cortical porosity were compared, cases had higher cortical porosity, lower cortical vBMD, lower total vBMD, smaller cortical CSA/Total CSA, larger medullary CSA and larger total CSA than controls (all 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.

Factors associated with proximal femur fracture determined in a large cadaveric cohort.

Many researchers have used cadaveric fracture tests to determine the relationship between proximal femur (hip) fracture strength and a multitude of possible explanatory variables, typically considered one or two at a time. These variables include subject-specific proximal femur variables such as femoral neck areal bone mineral density (aBMD), sex, age, and geometry, as well as physiological hip fracture event variables such as fall speed and angle of impact. However, to our knowledge, no study has included all of these variables simultaneously in the same experimental dataset. To address this gap, the present study simultaneously included all of these subject-specific and fracture event variables in multivariate models to understand their contributions to femoral strength and fracture type. The primary aim of this study was to determine not only whether each of these variables contributed to the prediction of femoral strength, but also to determine the relative importance of each variable in strength prediction. A secondary aim was to similarly characterize the importance of these variables for the prediction of fracture type. To accomplish these aims, we characterized 197 proximal femurs (covering a wide range of subject-specific variables) with DXA and CT scans, and then tested the femurs to fracture in a sideways fall on the hip configuration. Each femur was tested using one of three fall speed conditions and one of four angles of impact (bone orientations). During each test, we acquired measurements of relevant force and displacement data. We then reduced the test data to determine femoral strength, and we used post-fracture CT scans to classify the fracture type (e.g., trochanteric, cervical). Using these results, the explanatory variables were analyzed with mixed statistical models to explain variations in hip fracture strength and fracture type, respectively. Five explanatory variables were statistically significant in explaining the variability in femoral strength: aBMD, sex, age, fall speed, and neck-shaft angle (P ≤ 0.0135). These five variables, including significant interactions, explained 80% of the variability in hip fracture strength. Additionally, when only aBMD, sex, and age (P < 0.0001) were considered in the model, again including significant interactions, these three variables alone explained 79% of the variability in hip fracture strength. So while fall speed (P = 0.0135) and neck-shaft angle (P = 0.0041) were statistically significant, the inclusion of these variables did not appreciably improve the prediction of hip fracture strength compared to the model that considered only aBMD, sex and age. For the variables we included in this study, in the ranges we considered, our findings indicate that the clinically-available information of patient age, sex and aBMD are sufficient for femoral strength assessment. These findings also suggest that there is little value in the extra effort required to characterize the effect of femoral geometry on strength, or to account for the probabilistic nature of fall-related factors such as fall speed and angle of impact. For fracture type, the only explanatory variable found to be significant was aBMD (P ≤ 0.0099). We found that the odds of having intertrochanteric fractures increased by 47% when aBMD decreased by one standard deviation (0.2 g/cm2).

Serum parathyroid hormone is associated with increased cortical porosity of the inner transitional zone at the proximal femur in postmenopausal women: the Tromsø Study.

Vitamin D deficiency leads to secondary hyperparathyroidism and increased risk for fractures, whereas its association with cortical porosity is less clear. We tested (i) whether serum 25-hydroxyvitamin D (25(OH)D) and PTH were associated with cortical porosity and (ii) whether the associations of 25(OH)D) and PTH with fracture risk are dependent on cortical porosity. This case-control study included 211 postmenopausal women, 54-94years old, with prevalent fractures and 232 controls from the Tromsø Study. Serum 25(OH)D, PTH, and bone turnover markers (procollagen type I N-terminal propeptide [PINP] and C-terminal cross-linking telopeptide of type I collagen [CTX]) were measured. Femoral subtrochanteric cortical and trabecular parameters were quantified using computed tomography, and femoral neck areal bone mineral density (FN aBMD) was quantified using dual-energy X-ray absorptiometry. Compared with controls, fracture cases exhibited reduced serum 25(OH)D and increased PTH, PINP, and CTX, increased femoral subtrochanteric cortical porosity, and reduced cortical thickness and FN aBMD (all, p < 0.05). Serum 25(OH)D was not associated with cortical parameters (all, p > 0.10). PTH was associated with increased PINP, CTX, and cortical porosity of the inner transitional zone and reduced trabecular bone volume/tissue volume and FN aBMD (p ranging from 0.003 to 0.054). Decreasing 25(OH)D and increasing PTH were associated with increased odds for fractures, independent of age, height, weight, calcium supplementation, serum calcium, cortical porosity, and thickness. These data suggest that serum PTH, not 25(OH)D, is associated with increased intracortical bone turnover resulting in trabecularisation of the inner cortical bone; nevertheless, decreasing 25(OH)D) and increasing PTH are associated with fracture risk, independent of cortical porosity and thickness.

The Relationship of Disordered Eating Attitudes with Stress Level, Bone Turnover Markers, and Bone Mineral Density in Obese Adolescents.

Objective:To investigate the effect of stress caused by disordered eating attitudes on bone health in obese adolescents.Methods:A cross-sectional study comprising 80 obese adolescents was performed from November 2013 to September 2014. Twenty-four-hour urinary free cortisol levels were measured as a biological marker of stress. Bone turnover was evaluated using bone-specific alkaline phosphatase, serum osteocalcin, and urinary N-telopeptide concentrations. Bone mineral density was measured using dual-energy X-ray absorptiometry. The Eating Disorder Examination Questionnaire, Dutch Eating Behavior Questionnaire, Children’s Depression Inventory, and the State-Trait Anxiety Inventory for Children were used to assess eating disorders, depression, and anxiety. Psychiatric examinations were performed for binge eating disorders.Results:In the Pearson’s correlation test, a positive correlation was found between the 24-hour urinary cortisol level and Dutch Eating Behavior Questionnaire total and restrained eating subscale scores (p<0.05 for both). In linear regression analyses, the Dutch Eating Behavior Questionnaire total and restrained eating subscale scores were found to be significant contributors for urinary cortisol level (β=1.008, p=0.035; β=2.296, p=0.014, respectively). The femoral neck areal bone mineral density was found to be significantly higher in subjects who had binge eating disorder compared with those without binge eating disorder (p=0.049).Conclusion:Despite the lack of apparent effects on bone turnover and bone mineral density in our obese adolescents at the time of the study, our results suggest that disordered eating attitudes, and especially restrained eating attitudes, might be a source of stress. Therefore, studies in this area should continue.

The LIFTMOR-M (Lifting Intervention For Training Muscle and Osteoporosis Rehabilitation for Men) trial: protocol for a semirandomised controlled trial of supervised targeted exercise to reduce risk of osteoporotic fracture in older men with low bone mass

IntroductionThe primary aim of the proposed study is to examine the efficacy of an 8-month supervised, high-intensity progressive resistance training and impact loading programme in comparison with a supervised machine-based...

Bone turnover markers are associated with higher cortical porosity, thinner cortices, and larger size of the proximal femur and non-vertebral fractures

Bone turnover markers (BTM) predict bone loss and fragility fracture. Although cortical porosity and cortical thinning are important determinants of bone strength, the relationship between BTM and cortical porosity has, however, remained elusive. We therefore wanted to examine the relationship of BTM with cortical porosity and risk of non-vertebral fracture.In 211 postmenopausal women aged 54–94 years with non-vertebral fractures and 232 age-matched fracture-free controls from the Tromsø Study, Norway, we quantified femoral neck areal bone mineral density (FN aBMD), femoral subtrochanteric bone architecture, and assessed serum levels of procollagen type I N-terminal propeptide (PINP) and C-terminal cross-linking telopeptide of type I collagen (CTX).Fracture cases exhibited higher PINP and CTX levels, lower FN aBMD, larger total and medullary cross-sectional area (CSA), thinner cortices, and higher cortical porosity of the femoral subtrochanter than controls (p≤0.01). Each SD increment in PINP and CTX was associated with 0.21–0.26 SD lower total volumetric BMD, 0.10–0.14 SD larger total CSA, 0.14–0.18 SD larger medullary CSA, 0.13–0.18 SD thinner cortices, and 0.27–0.33 SD higher porosity of the total cortex, compact cortex, and transitional zone (all p≤0.01). Moreover, each SD of higher PINP and CTX was associated with increased odds for fracture after adjustment for age, height, and weight (ORs 1.49; 95% CI, 1.20–1.85 and OR 1.22; 95% CI, 1.00–1.49, both p<0.05). PINP, but not CTX, remained associated with fracture after accounting for FN aBMD, cortical porosity or cortical thickness (OR ranging from 1.31 to 1.39, p ranging from 0.005 to 0.028).In summary, increased BTM levels are associated with higher cortical porosity, thinner cortices, larger bone size and higher odds for fracture. We infer that this is produced by increased periosteal apposition, intracortical and endocortical remodeling; and that these changes in bone architecture are predisposing to fracture.

Serum 25(OH) vitamin d level is associated with treatment outcome of whole-body vibration (WBV) for osteopenia in girls with adolescent idiopathic scoliosis (AIS)

Objectives AIS was associated with low bone mass which, apart from being an important health issue that could persist into adulthood, was also a significant prognostic factor for curve progression in AIS. We have performed a randomized controlled trial on WBV and reported its effect on increasing femoral neck areal bone mineral density (aBMD) mainly at the dominant leg but less obviously at the non-dominant side. The objective of this study was to evaluate the role of Vit-D in affecting the anabolic bone effect of WBV.

Relationship of femoral neck areal bone mineral density to volumetric bone mineral density, bone size, and femoral strength in men and women

Relationship of femoral neck areal bone mineral density to volumetric bone mineral density, bone size, and femoral strength in men and women

Diabetes and Femoral Neck Strength: Findings from The Hip Strength Across the Menopausal Transition Study

Diabetes mellitus is associated with increased hip fracture risk, despite being associated with higher bone mineral density in the femoral neck. The objective of the study was to test the hypothesis that composite indices of femoral neck strength, which integrate dual-energy x-ray absorptiometry derived femoral neck size, femoral neck areal bone mineral density, and body size and are inversely associated with hip fracture risk, would be lower in diabetics than in nondiabetics and be inversely related to insulin resistance, the primary pathology in type 2 diabetes. This was a cross-sectional analysis. The study consisted of a multisite, multiethnic, community-dwelling sample of 1887 women in pre- or early perimenopause. Composite indices for femoral neck strength in different failure modes (axial compression, bending, and impact) were measured. Adjusted for age, race/ethnicity, menopausal stage, body mass index, smoking, physical activity, calcium and vitamin D supplementation, and study site, diabetic women had higher femoral neck areal bone mineral density [+0.25 sd, 95% confidence interval (CI) (+0.06, +0.44) sd] but lower composite strength indices [-0.20 sd, 95% CI (-0.38, -0.03) sd for compression, -0.19 sd, 95% CI (-0.38, -0.003) sd for bending, -0.19 sd, 95% CI (-0.37, -0.02) sd for impact] than nondiabetic women. There were graded inverse relationships between homeostasis model-assessed insulin resistance and all three strength indices, adjusted for the same covariates. Despite having higher bone density, diabetic women have lower indices of femoral neck strength relative to load, consistent with their documented higher fracture risk. Insulin resistance appears to play an important role in bone strength reduction in diabetes.

Relationship of femoral neck areal bone mineral density to volumetric bone mineral density, bone size, and femoral strength in men and women

Using combined dual-energy X-ray absorptiometry (DXA) and quantitative computed tomography, we demonstrate that men matched with women for femoral neck (FN) areal bone mineral density (aBMD) have lower volumetric BMD (vBMD), higher bone cross-sectional area, and relatively similar values for finite element (FE)-derived bone strength. aBMD by DXA is widely used to identify patients at risk for osteoporotic fractures. aBMD is influenced by bone size (i.e., matched for vBMD, larger bones have higher aBMD), and increasing evidence indicates that absolute aBMD predicts a similar risk of fracture in men and women. Thus, we sought to define the relationships between FN aBMD (assessed by DXA) and vBMD, bone size, and FE-derived femoral strength obtained from quantitative computed tomography scans in men versus women. We studied men and women aged 40 to 90 years and not on osteoporosis medications. In 114 men and 114 women matched for FN aBMD, FN total cross-sectional area was 38% higher (P < 0.0001) and vBMD was 16% lower (P < 0.0001) in the men. FE models constructed in a subset of 28 women and 28 men matched for FN aBMD showed relatively similar values for bone strength and the load-to-strength ratio in the two groups. In this cohort of young and old men and women from Rochester, MN, USA who are matched by FN aBMD, because of the offsetting effects of bone size and vBMD, femoral strength and the load-to-strength ratio tended to be relatively similar across the sexes.

Dietary protein deficiency induces osteoporosis in aged male rats.

Low dietary intake is common in elderly males with low femoral neck areal bone mineral density (BMD). To evaluate the selective influence of a low-protein diet in the pathogenesis of osteoporosis in males and to uncover early and late adaptation of bone cells to protein deficiency, 8-month-old male rats were pair-fed a control (15% casein) or isocaloric low-protein (2.5% casein) diet for 1 or 7 months. BMD, bone ultimate strength, stiffness, and absorbed energy were measured in tibia proximal metaphysis and diaphysis. After double-labeling, histomorphometric analysis was performed at the same sites. Serum osteocalcin, insulin-like growth factor I (IGF-I), and urinary deoxypyridinoline excretion were measured. In proximal tibia, isocaloric low-protein diet significantly decreases BMD (12%), cancellous bone mass (71%), and trabecular thickness (Tb.Th; 30%), resulting in a significant reduction in ultimate strength (27%). In cortical middiaphysis, a low-protein diet decreases BMD (9%) and enlarges the medullary cavity (36%), leading to cortical thinning and lower mechanical strength (20%). In cancellous bone, protein deficiency transiently depresses the bone formation rate (BFR; 60%), osteoid seam thickness (15%), and mineral apposition rate (MAR; 20%), indicating a decrease in osteoblast recruitment and activity. Cortical loss (15%) results from an imbalance between endosteal modeling drifts with impaired BFR (70%). From the first week of protein deficiency, osteocalcin and IGF-I levels drop significantly. Bone resorption activity and urinary deoxypyridinoline remain unchanged throughout the experiment. Protein deficiency in aged male rats induces cortical and trabecular thinning, and decreases bone strength, in association with a remodeling imbalance with a bone formation impairment and a decrease in IGF-I levels.