Browsing by Subject "Bone mineral density"
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Item A Comprehensive Set of Ultrashort Echo Time Magnetic Resonance Imaging Biomarkers to Assess Cortical Bone Health: A Feasibility Study at Clinical Field Strength(Elsevier, 2024) Jacobson, Andrea M.; Zhao, Xuandong; Sommer, Stefan; Sadik, Farhan; Warden, Stuart J.; Newman, Christopher; Siegmund, Thomas; Allen, Matthew R.; Surowiec, Rachel K.; Radiology and Imaging Sciences, School of MedicineIntroduction: Conventional bone imaging methods primarily use X-ray techniques to assess bone mineral density (BMD), focusing exclusively on the mineral phase. This approach lacks information about the organic phase and bone water content, resulting in an incomplete evaluation of bone health. Recent research highlights the potential of ultrashort echo time magnetic resonance imaging (UTE MRI) to measure cortical porosity and estimate BMD based on signal intensity. UTE MRI also provides insights into bone water distribution and matrix organization, enabling a comprehensive bone assessment with a single imaging technique. Our study aimed to establish quantifiable UTE MRI-based biomarkers at clinical field strength to estimate BMD and microarchitecture while quantifying bound water content and matrix organization. Methods: Femoral bones from 11 cadaveric specimens (n = 4 males 67-92 yrs of age, n = 7 females 70-95 yrs of age) underwent dual-echo UTE MRI (3.0 T, 0.45 mm resolution) with different echo times and high resolution peripheral quantitative computed tomography (HR-pQCT) imaging (60.7 μm voxel size). Following registration, a 4.5 mm HR-pQCT region of interest was divided into four quadrants and used across the multi-modal images. Statistical analysis involved Pearson correlation between UTE MRI porosity index and a signal-intensity technique used to estimate BMD with corresponding HR-pQCT measures. UTE MRI was used to calculate T1 relaxation time and a novel bound water index (BWI), compared across subregions using repeated measures ANOVA. Results: The UTE MRI-derived porosity index and signal-intensity-based estimated BMD correlated with the HR-pQCT variables (porosity: r = 0.73, p = 0.006; BMD: r = 0.79, p = 0.002). However, these correlations varied in strength when we examined each of the four quadrants (subregions, r = 0.11-0.71). T1 relaxometry and the BWI exhibited variations across the four subregions, though these differences were not statistically significant. Notably, we observed a strong negative correlation between T1 relaxation time and the BWI (r = -0.87, p = 0.0006). Conclusion: UTE MRI shows promise for being an innocuous method for estimating cortical porosity and BMD parameters while also giving insight into bone hydration and matrix organization. This method offers the potential to equip clinicians with a more comprehensive array of imaging biomarkers to assess bone health without the need for invasive or ionizing procedures.Item Alterations to maternal cortical and trabecular bone in multiparous middle-aged mice(Hylonome, 2017-12-01) Gu, A.; Sellamuthu, R.; Himes, E.; Childress, P.J.; Pelus, L.M.; Orschell, C.M.; Kacena, Melissa A.; Orthopaedic Surgery, School of MedicineOBJECTIVES: During the reproductive cycle, altered calcium homeostasis is observed due to variable demand for mineral requirements. This results in increased bone resorption during the time period leading up to parturition and subsequent lactation. During lactation, women will lose 1-3% of bone mineral density per month, which is comparable to the loss experienced on an annual basis post-menopausal. The purpose of this study was to determine the effect of parity on bone formation in middle-aged mice. METHODS: Mice were mated and grouped by number of parity and compared with age matched nulliparous controls. Measurements were taken of femoral trabecular and cortical bone. Calcium, protein and alkaline phosphatase levels were also measured. RESULTS: An increase in trabecular bone mineral density was observed when comparing mice that had undergone parity once to the nulliparous control. An overall decrease in trabecular bone mineral density was observed as parity increased from 1 to 5 pregnancies. No alteration was seen in cortical bone formation. No difference was observed when calcium, protein and alkaline phosphatase levels were assessed. CONCLUSIONS: This study demonstrates that number of parity has an impact on trabecular bone formation in middle-aged mice, with substantial changes in bone density seen among the parous groups.Item Association of Circulating Renin and Aldosterone With Osteocalcin and Bone Mineral Density in African Ancestry Families(American Heart Association, 2016-05) Kuipers, Allison L.; Kammerer, Candace M.; Pratt, J. Howard; Bunker, Clareann H.; Wheeler, Victor W.; Patrick, Alan L.; Zmuda, Joseph M.; Medicine, School of MedicineHypertension is associated with accelerated bone loss, and the renin-angiotensin-aldosterone system is a key regulator of blood pressure. Although components of this system are expressed in human bone cells, studies in humans are sparse. Thus, we studied the association of circulating renin and aldosterone with osteocalcin and bone mineral density. We recruited 373 African ancestry family members without regard to health status from 6 probands (mean family size: 62 and relative pairs: 1687). Participants underwent a clinical examination, dual-energy x-ray absorptiometry, and quantitative computed tomographic scans. Renin activity, aldosterone concentration, and osteocalcin were measured in fasting blood samples. Aldosterone/renin ratio was calculated as aldosterone concentration/renin activity. All models were analyzed using pedigree-based variance components methods. Full models included adjustment for age, sex, body composition, comorbidities, lifestyle factors, blood pressure, and antihypertensive medication. Higher renin activity was significantly associated with lower total osteocalcin and with higher trabecular bone mineral density (both P<0.01). There were also significant genetic correlations between renin activity and whole-body bone mineral density. There were no associations with aldosterone concentration in any model and results for aldosterone/renin ratio were similar to those for renin activity. This is the first study to report a significant association between renin activity and a marker of bone turnover and bone mineral density in generally healthy individuals. Also, there is evidence for significant genetic pleiotropy and, thus, there may be a shared biological mechanism underlying both the renin-angiotensin-aldosterone system and bone metabolism that is independent of hypertension.Item Associations of Low Vitamin D and Elevated Parathyroid Hormone Concentrations With Bone Mineral Density in Perinatally HIV-Infected Children(Wolters Kluwer, 2017-09-01) Jacobson, Denise L.; Stephensen, Charles B.; Miller, Tracie L.; Patel, Kunjal; Chen, Janet S.; Van Dyke, Russell B.; Mirza, Ayesha; Schuster, Gertrud U.; Hazra, Rohan; Ellis, Angela; Brummel, Sean S.; Geffner, Mitchell E.; Silio, Margarita; Spector, Stephen A.; DiMeglio, Linda A.; Pediatrics, School of MedicineBACKGROUND: Perinatally HIV-infected (PHIV) children have, on average, lower bone mineral density (BMD) than perinatally HIV-exposed uninfected (PHEU) and healthy children. Low 25-hydroxy vitamin D [25(OH)D] and elevated parathyroid hormone (PTH) concentrations may lead to suboptimal bone accrual. METHODS: PHIV and PHEU children in the Pediatric HIV/AIDS Cohort Study had total body (TB) and lumbar spine (LS) BMD and bone mineral content (BMC) measured by dual-energy x-ray absorptiometry; BMD z-scores (BMDz) were calculated for age and sex. Low 25(OH)D was defined as ≤20 ng/mL and high PTH as >65 pg/mL. We fit linear regression models to estimate the average adjusted differences in BMD/BMC by 25(OH)D and PTH status and log binomial models to determine adjusted prevalence ratios of low 25(OH)D and high PTH in PHIV relative to PHEU children. RESULTS: PHIV children (n = 412) were older (13.0 vs. 10.8 years) and more often black (76% vs. 64%) than PHEU (n = 207). Among PHIV, children with low 25(OH)D had lower TB-BMDz [SD, -0.38; 95% confidence interval (CI), -0.60 to -0.16] and TB-BMC (SD, -59.1 g; 95% CI, -108.3 to -9.8); high PTH accompanied by low 25(OH)D was associated with lower TB-BMDz. Among PHEU, children with low 25(OH)D had lower TB-BMDz (SD, -0.34; 95% CI, -0.64 to -0.03). Prevalence of low 25(OH)D was similar by HIV status (adjusted prevalence ratio, 1.00; 95% CI, 0.81 to 1.24). High PTH was 3.17 (95% CI, 1.25 to 8.06) times more likely in PHIV children. CONCLUSIONS: PHIV and PHEU children with low 25(OH)D may have lower BMD. Vitamin D supplementation trials during critical periods of bone accrual are needed.Item Bone Density in Children with Single Ventricle Physiology(Springer, 2015-04) Bendaly, Edgard A.; DiMeglio, Linda A.; Fadel, William F.; Hurwitz, Roger A.; Department of Pediatrics, Indiana University School of MedicineBackground Children with chronic diseases are at risk for low bone mineral density (BMD). There are no studies of BMD in children with congenital heart disease and particularly SV. Children with this defect are often treated with warfarin, suspected to negatively impact BMD in adults. We assessed BMD in patients with single ventricle (SV) physiology and compared the BMD of subjects taking warfarin to those who were not. Methods Subjects 5-12 years with SV were included. BMD z-scores by dual-energy X-ray absorptiometry (DXA) of the spine and total body less head (TBLH) were obtained. Calcium intake, activity level, height, and Tanner stage were assessed. Linear regression models and t-tests were used to investigate differences between participants and normative data as well as between subjects' subgroups. Results Twenty six subjects were included; 16 took warfarin. Mean BMD z-score at the spine was significantly lower than expected at -1.0±0.2 (p<0.0001), as was the BMD z-score for TBLH at - 0.8±0.2 (p<0.0001). Those results remained significant after adjusting for height. Subjects who were on warfarin tended to have lower BMD at both the spine and TBLH than those who were not, with a z-score difference of 0.6±0.46 at the spine (p=0.106) and a difference of 0.4±0.34 at TBLH (p=0.132). Conclusions BMD is significantly reduced in children with SV. Warfarin appears to lower BMD but the effect is less conclusive. Continued evaluation is recommended for these patients at risk for reduced bone density. Evaluation of other cardiac patients on warfarin therapy should also be considered.Item Bone Quality in Chronic Kidney Disease: Definitions and Diagnostics(Springer, 2017-06) McNerny, Erin M.B.; Nickolas, Thomas L.; Medicine, School of MedicinePURPOSE OF REVIEW: In this paper, we review the epidemiology, diagnosis, and pathogenesis of fractures and renal osteodystrophy. RECENT FINDINGS: The role of bone quality in the pathogenesis of fracture susceptibility in chronic kidney disease (CKD) is beginning to be elucidated. Bone quality refers to bone material properties, such as cortical and trabecular microarchitecture, mineralization, turnover, microdamage, and collagen content and structure. Recent data has added to our understanding of the effects of CKD on alterations to bone quality, emerging data on the role of abnormal collagen structure on bone strength, the potential of non-invasive methods to inform our knowledge of bone quality, and how we can use these methods to inform strategies that protect against bone loss and fractures. However, more prospective data is required. CKD is associated with abnormal bone quality and strength which results in high fracture incidence.Item Current Analysis of Skeletal Phenotypes in Down Syndrome(Springer, 2021) Thomas, Jared R.; Roper, Randall J.; Biology, School of SciencePurpose: Down syndrome (DS) is caused by trisomy 21 (Ts21) and results in skeletal deficits including shortened stature, low bone mineral density, and a predisposition to early onset osteoporosis. Ts21 causes significant alterations in skeletal development, morphology of the appendicular skeleton, bone homeostasis, age-related bone loss, and bone strength. However, the genetic or cellular origins of DS skeletal phenotypes remain unclear. Recent findings: New studies reveal a sexual dimorphism in characteristics and onset of skeletal deficits that differ between DS and typically developing individuals. Age-related bone loss occurs earlier in the DS as compared to general population. Perturbations of DS skeletal quality arise from alterations in cellular and molecular pathways affected by the overexpression of trisomic genes. Sex-specific alterations occur in critical developmental pathways that disrupt bone accrual, remodeling, and homeostasis and are compounded by aging, resulting in increased risks for osteopenia, osteoporosis, and fracture in individuals with DS.Item Foreword: Calcified Tissue International and Musculoskeletal Research Special Issue: Bone Material Properties and Skeletal Fragility.(Springer, 2015-09) Burr, David B.; Allen, Matthew R.; Department of Anatomy & Cell Biology, IU School of MedicineItem In Vivo Quantitative Imaging Biomarkers of Bone Quality and Mineral Density using Multi-Band-SWIFT Magnetic Resonance Imaging(Elsevier, 2021) Surowiec, Rachel K.; Ram, Sundaresh; Idiyatullin, Djaudat; Goulet, Robert; Schlecht, Stephen H.; Galban, Craig J.; Kozloff, Kenneth M.; Radiology and Imaging Sciences, School of MedicineBone is a composite biomaterial of mineral crystals, organic matrix, and water. Each contributes to bone quality and strength and may change independently, or together, with disease progression and treatment. Even so, there is a near ubiquitous reliance on ionizing x-ray-based approaches to measure bone mineral density (BMD) which is unable to fully characterize bone strength and may not adequately predict fracture risk. Characterization of treatment efficacy in bone diseases of altered remodeling is complicated by the lack of imaging modality able to safely monitor material-level and biochemical changes in vivo. To improve upon the current state of bone imaging, we tested the efficacy of Multi Band SWeep Imaging with Fourier Transformation (MB-SWIFT) magnetic resonance imaging (MRI) as a readout of bone derangement in an estrogen deficient ovariectomized (OVX) rat model during growth. MB-SWIFT MRI-derived BMD correlated significantly with BMD measured using micro-computed tomography (μCT). In this rodent model, growth appeared to overcome estrogen deficiency as bone mass continued to increase longitudinally over the duration of the study. Nonetheless, after 10 weeks of intervention, MB-SWIFT detected significant changes consistent with estrogen deficiency in cortical water, cortical matrix organization (T1), and marrow fat. Findings point to MB-SWIFT's ability to quantify BMD in good agreement with μCT while providing additive quantitative outcomes about bone quality in a manner consistent with estrogen deficiency. These results indicate MB-SWIFT as a non-ionizing imaging strategy with value for bone imaging and may be a promising technique to progress to the clinic for monitoring and clinical management of patients with bone diseases such as osteoporosis.Item Resonance in the mouse tibia as a predictor of frequencies and locations of loading-induced bone formation(Springer, 2014-01) Zhao, Liming; Dodge, Todd; Nemani, Arun; Yokota, Hiroki; Biomedical Engineering, School of Engineering and TechnologyTo enhance new bone formation for the treating of patients with osteopenia and osteoporosis, various mechanical loading regimens have been developed. Although a wide spectrum of loading frequencies is proposed in those regimens, a potential linkage between loading frequencies and locations of loading-induced bone formation is not well understood. In this study, we addressed a question: Does mechanical resonance play a role in frequency-dependent bone formation? If so, can the locations of enhanced bone formation be predicted through the modes of vibration? Our hypothesis is that mechanical loads applied at a frequency near the resonant frequencies enhance bone formation, specifically in areas that experience high principal strains. To test the hypothesis, we conducted axial tibia loading using low, medium, or high frequency to the mouse tibia, as well as finite element analysis. The experimental data demonstrated dependence of the maximum bone formation on location and frequency of loading. Samples loaded with the low-frequency waveform exhibited peak enhancement of bone formation in the proximal tibia, while the high-frequency waveform offered the greatest enhancement in the midshaft and distal sections. Furthermore, the observed dependence on loading frequencies was correlated to the principal strains in the first five resonance modes at 8.0-42.9 Hz. Collectively, the results suggest that resonance is a contributor to the frequencies and locations of maximum bone formation. Further investigation of the observed effects of resonance may lead to the prescribing of personalized mechanical loading treatments.