Publications by authors named "Danielle E Whittier"

Mechanical unloading causes bone loss, but it remains unclear whether disuse-induced changes to bone microstructure are permanent or can be recovered upon reloading. We examined bone loss and recovery in 17 astronauts using time-lapsed high-resolution peripheral quantitative computed tomography and biochemical markers to determine whether disuse-induced changes are permanent. During 6 months in microgravity, resorption was threefold higher than formation.

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Article Synopsis
  • Identifying individuals at risk for short-term fractures is critical, as many fractures happen in those without osteoporosis, and researchers studied bone microarchitecture's role in predicting these risks.
  • In a study of over 7,000 participants, they found measures of radius and tibia bone microarchitecture were significant predictors of 2-year fracture risk, even when factoring in traditional assessments like DXA-BMD and FRAX.
  • The results indicated that decreases in certain bone measures significantly increased fracture risk in both men and women, suggesting that HR-pQCT could enhance current methods for assessing fracture risk in older adults.
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  • Osteoporotic fractures pose a significant risk for older adults, yet safe treatments are often underutilized among those most at risk, highlighting the need for better assessment methods.
  • * Artificial intelligence (AI) and machine learning (ML) can improve the identification of individuals at high fracture risk by analyzing complex data from medical records and devices.
  • * While AI-ML has the potential to enhance osteoporosis management through personalized approaches, it's essential to address concerns like model explainability, biases, and the overall impact on clinical practice.
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Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60-87 yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD).

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Introduction: The continued development of high-resolution peripheral quantitative computed tomography (HR-pQCT) has led to a second-generation scanner with higher resolution and longer scan region. However, large multicenter prospective cohorts were collected with first-generation HR-pQCT and have been used to develop bone phenotyping and fracture risk prediction (μFRAC) models. This study establishes whether there is sufficient universality of these first-generation trained models for use with second-generation scan data.

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Type 1 diabetes mellitus (T1DM) has been linked to increased osteocyte apoptosis, local accumulation of mineralized lacunar spaces, and microdamage suggesting an impairment of the mechanoregulation network in affected individuals. Diabetic neuropathy might exacerbate this dysfunction through direct effects on bone turnover, and indirect effects on balance, muscle strength, and gait. However, the in vivo effects of impaired bone mechanoregulation on bone remodeling in humans remain underexplored.

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Article Synopsis
  • * Researchers analyzed data from 6,835 individuals aged 40 to 96, identifying a significant number of fractures and finding consistent associations between HR-pQCT bone measures and fracture risk across all age groups.
  • * The results indicate that low bone density is a persistent factor for fracture risk regardless of age, suggesting that the lower fracture risk observed in older adults with lower aBMD might arise from limitations in the DXA method rather than actual differences in bone health.
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Purpose Of Review: Summarize the recent literature that investigates how advanced medical imaging has contributed to our understanding of skeletal phenotypes and fracture risk across the lifespan.

Recent Findings: Characterization of bone phenotypes on the macro-scale using advanced imaging has shown that while wide bones are generally stronger than narrow bones, they may be more susceptible to age-related declines in bone strength. On the micro-scale, HR-pQCT has been used to identify bone microarchitecture phenotypes that improve stratification of fracture risk based on phenotype-specific risk factors.

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Background: Recent applications of high-resolution peripheral quantitative computed tomography (HR-pQCT) have demonstrated that changes in local bone remodelling can be quantified in vivo using longitudinal three-dimensional image registration. However, certain emerging applications, such as fracture healing and joint analysis, require larger multi-stack scan regions that can result in stack shift image artifacts. These artifacts can be detrimental to the accurate alignment of the bone structure across multiple timepoints.

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Article Synopsis
  • Local mechanical stimuli are crucial for maintaining bone health and adaptation, and their disruption can lead to bone loss.
  • This study used data from two participant groups to enhance detection methods for bone remodeling and assess the precision of measuring these changes in living humans.
  • Key findings showed no significant differences in scan results over time, with precision rates indicating that bone formation is most likely in high-strain areas while resorption occurs in low-strain regions.
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Most fracture risk assessment tools use clinical risk factors combined with bone mineral density (BMD) to improve assessment of osteoporosis; however, stratifying fracture risk remains challenging. This study developed a fracture risk assessment tool that uses information about volumetric bone density and three-dimensional structure, obtained using high-resolution peripheral quantitative compute tomography (HR-pQCT), to provide an alternative approach for patient-specific assessment of fracture risk. Using an international prospective cohort of older adults (n = 6802) we developed a tool to predict osteoporotic fracture risk, called μFRAC.

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Rapid loss of areal bone mineral density (aBMD) is associated with higher fracture risk after adjustment for confounders including initial aBMD. However, the link between bone microarchitecture decline and fracture is not clear. We studied the association between bone microarchitecture deterioration assessed prospectively over 4 years and the subsequent fracture risk in older men.

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High-resolution peripheral quantitative computed tomography (HR-pQCT) is an emerging in vivo imaging modality for quantification of bone microarchitecture. However, extraction of quantitative microarchitectural parameters from HR-pQCT images requires an accurate segmentation of the image. The current standard protocol using semi-automated contouring for HR-pQCT image segmentation is laborious, introduces inter-operator biases into research data, and poses a barrier to streamlined clinical implementation.

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Unlabelled: In older men, higher high-sensitivity C-reactive protein (hsCRP) concentrations were associated with faster prospectively assessed endocortical expansion (distal radius, distal tibia) and slightly higher cortical bone loss at distal tibia, but not with the fracture risk. High hsCRP level has a limited impact on bone decline in older men.

Purpose: Data on the link of the high-sensitivity C-reactive protein (hsCRP) with bone loss and fracture risk are discordant.

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Purpose Of Review: Diabetes mellitus is defined by elevated blood glucose levels caused by changes in glucose metabolism and, according to its pathogenesis, is classified into type 1 (T1DM) and type 2 (T2DM) diabetes mellitus. Diabetes mellitus is associated with multiple degenerative processes, including structural alterations of the bone and increased fracture risk. High-resolution peripheral computed tomography (HR-pQCT) is a clinically applicable, volumetric imaging technique that unveils bone microarchitecture in vivo.

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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.

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Poor vitamin D status and high parathyroid hormone (PTH) level are associated with impaired bone microarchitecture, but these data are mainly cross-sectional. We studied the association of the baseline PTH and 25-hydroxycholecalciferol (25OHD) levels with the prospectively assessed deterioration of bone microarchitecture and in estimated bone strength in older men. Distal radius and tibia bone microarchitecture was assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT) at baseline, then after 4 and 8 years in 826 men aged 60-87 years.

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Prevalence of osteoporosis is more than 50% in older adults, yet current clinical methods for diagnosis that rely on areal bone mineral density (aBMD) fail to detect most individuals who have a fragility fracture. Bone fragility can manifest in different forms, and a "one-size-fits-all" approach to diagnosis and management of osteoporosis may not be suitable. High-resolution peripheral quantitative computed tomography (HR-pQCT) provides additive information by capturing information about volumetric density and microarchitecture, but interpretation is challenging because of the complex interactions between the numerous properties measured.

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Context: High fracture risk in individuals with low muscle strength is attributed to high risk of falls.

Objective: This work aims to study the association of muscle mass and physical performance with bone microarchitecture decline and risk of fall and nonvertebral fracture in men.

Methods: A prospective, 8-year follow-up of a cohort was conducted among the general population.

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Injury to the ACL significantly increases the risk of developing post-traumatic osteoarthritis. Following injury, considerable focus is placed on visualizing soft tissue changes using MRI, but there is less emphasis on the alterations to the underlying bone. It has recently been shown using high-resolution peripheral quantitative computed tomography (HR-pQCT) that significant reductions in bone quality occur in the knee post ACL-injury.

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Bone strength determined from finite element (FE) modelling provides an estimate of fracture healing progression following a distal radius fracture (DRF), but how these measures relate to patient-reported outcomes and functional outcomes remains unknown. We hypothesized that changes in bone stiffness and bone mineral density measured using high-resolution peripheral quantitative computed tomography (HR-pQCT) are associated with clinically available measures of functional and patient-reported outcomes. We also aimed to identify which clinical outcome measures best predict fracture stiffness and could therefore be used to inform cast removal.

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High resolution peripheral quantitative computed tomography (HR-pQCT) was designed to study bone mineral density (BMD) and microarchitecture in peripheral sites at the distal radius and tibia. With the introduction of the second generation HR-pQCT scanner (XtremeCT II, Scanco Medical) that has a larger, longer gantry it is now possible to study the human knee in vivo using HR-pQCT. Previous validation of HR-pQCT measurements at the distal radius and tibia against micro-CT is not representative of the knee because the increased cross-sectional area, greater amount of soft tissue surrounding the scan region, and different imaging protocol result in potentially increased beam hardening effects and photon scatter and different signal-to-noise ratio.

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Article Synopsis
  • No existing population-based reference datasets for volumetric bone mineral density and microarchitecture are available for the second-generation HR-pQCT technology, despite its rising use in bone studies.
  • This study generated site- and sex-specific centile curves for bone properties using data from 1236 adults (both male and female) in Calgary, scanned at the distal tibia and radius.
  • The findings offer reference curves that can help assess bone health in predominantly white adult populations, facilitating more tailored approaches in clinical settings.
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The application of high resolution peripheral quantitative computed tomography (HR-pQCT) for the study of bone health has provided valuable insight into the role bone microarchitecture has in determining bone strength and fracture risk. However, conventional density and morphological parameters struggle to distinguish whether localized bone loss is present, visible as heterogeneous deterioration in the trabecular network. This is because current HR-pQCT parameters quantify a global average of properties in the cortical or trabecular compartment.

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Due to difficulty assessing healing of distal radius fractures using conventional radiography, there is interest in using high resolution peripheral quantitative computed tomography (HR-pQCT) to track healing at the microarchitectural level. Unfortunately, the plaster-of-Paris and fiberglass casts used to immobilize fractures affect HR-pQCT measurements due to beam hardening, and increased noise. The challenge is compounded because casts have variable thickness, and an individual patient will often have their cast changed 2-3 times during the course of treatment.

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