Publications by authors named "Mary Bouxsein"

We have proposed to the Food and Drug Administration (FDA) that treatment-related increases in total hip bone mineral density (TH BMD) at two years could be a surrogate endpoint for fracture risk reduction in clinical trials. The qualification of a surrogate includes a strong association of the surrogate with the clinical outcome. We compiled a large database of individual patient data (IPD) through the FNIH-ASBMR-SABRE project, and this analysis aimed to assess the relationship between baseline BMD and fracture risk in the placebo groups.

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Unlabelled: Up to 40% of elite athletes experience bone stress injuries (BSIs), with 20-30% facing reinjury. Early identification of runners at high risk of subsequent BSI could improve prevention strategies. However, the complex etiology and multifactorial risk factors of BSIs makes identifying predictive risk factors challenging.

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  • Astronauts in deep space are at risk for eye problems due to microgravity, which negatively impacts ocular health.
  • Researchers studied mice on the ISS, exposing them to microgravity and varying levels of artificial gravity to assess the effects on their optic nerves and retinas.
  • Results showed that microgravity raises oxidative stress, inflammation, and other negative changes in eye tissue, but adding artificial gravity can reduce these harmful effects.
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Type 1 diabetes (T1D) is associated with an increased risk of hip fracture beyond what can be explained by reduced bone mineral density, possibly due to changes in bone material from accumulation of advanced glycation end-products (AGEs) and altered matrix composition, though data from human cortical bone in T1D are limited. The objective of this study was to evaluate cortical bone material behavior in T1D by examining specimens from cadaveric femora from older adults with long-duration T1D (≥50 yr; n = 20) and age- and sex-matched nondiabetic controls (n = 14). Cortical bone was assessed by mechanical testing (4-point bending, cyclic reference point indentation, impact microindentation), AGE quantification [total fluorescent AGEs, pentosidine, carboxymethyl lysine (CML)], and matrix composition via Raman spectroscopy.

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  • Vertebral compression fractures (VFs) and spinal degeneration are prevalent causes of back pain in older adults, with this study exploring their connection through longitudinal data from the Framingham Heart Study.
  • The research found that individuals with existing VFs experienced a greater change in intervertebral disc height narrowing (DHN) over time, although the difference diminished after adjusting for various factors like age and body mass index.
  • For facet joint osteoarthritis (FJOA), there was a slight increase in the change of symptoms among participants with VFs, particularly those with severe fractures, suggesting that VFs could contribute to worsening spine osteoarthritis.
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  • Exposure to total body irradiation (TBI) in adult rhesus macaques shows that it leads to slight declines in cortical bone microstructure, like reduced thickness and area, but does not significantly affect material composition or mechanical properties compared to non-irradiated controls.
  • While TBI was administered after peak bone mass was achieved, the study suggests that skeletons of long-term survivors might maintain their mechanical integrity even with some radiation-induced structural changes.
  • Additionally, aging impacts the mechanical behavior of bones, particularly reducing toughness to fracture, indicating further research is needed to understand how radiation may cause bone fragility in both mature and immature bones for better patient care.
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  • 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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  • Older adults with type 1 diabetes (T1D) are at higher risk for hip fractures, but bone density and structure in this population have not been thoroughly studied.
  • This study analyzed 3D CT scans of the hip from 101 T1D patients and 181 non-diabetic controls, revealing T1D patients often have lower bone mass but only significant differences in those diagnosed before age 15, as well as those with nephropathy and neuropathy.
  • The findings suggest that early diagnosis of T1D, as well as kidney and nerve complications, may lead to poorer bone health, contributing to the increased hip fracture risks for these individuals.
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There is a strong association between total hip bone mineral density (THBMD) changes after 24 mo of treatment and reduced fracture risk. We examined whether changes in THBMD after 12 and 18 mo of treatment are also associated with fracture risk reduction. We used individual patient data (n = 122 235 participants) from 22 randomized, placebo-controlled, double-blind trials of osteoporosis medications.

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Context: Neuropathy and fracture are prevalent complications of type 1 diabetes (T1D). Although correlated in the clinical literature, it remains unknown whether neuropathy contributes to the initiation of bone loss at the earliest stages of disease.

Methods: We performed a single-center, cross-sectional study to quantify parameters of nerve and bone health in adolescent girls with T1D (n=21) and associated controls (n=12).

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  • Computed tomography (CT) measures subcutaneous and visceral adipose tissue (SAT and VAT), and this study aims to provide reference values specific to age, sex, and vertebral levels for these metrics.
  • The research analyzed data from the Framingham Heart Study, including nearly 15,000 measurements from over 3700 participants, focusing on how VAT and SAT change with age and differ between genders.
  • Results showed that VAT increases significantly with age, especially in males, while the ratio of VAT to SAT also increases, and the findings are available through an online tool for further reference.
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Objective: Less than half of servicewomen report loss of menses during initial military training. However, self-reported menstrual status may not accurately reflect hypothalamic-pituitary-ovarian (HPO) axis suppression and may underestimate reproductive health consequences of military training. Our aim was to characterise HPO axis function during US Army Basic Combat Training (BCT) in non-hormonal contraceptive-using women and explore potential contributors to HPO axis suppression.

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Context: Impaired bone microarchitecture, assessed by high-resolution peripheral quantitative computed tomography (HR-pQCT), may contribute to bone fragility in type 2 diabetes (T2DM) but data on men are lacking.

Objective: To investigate the association between T2DM and HR-pQCT parameters in older men.

Methods: HR-pQCT scans were acquired on 1794 participants in the Osteoporotic Fractures in Men (MrOS) study.

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Randomized trials have not been performed, and may never be, to determine if osteoporosis treatment prevents hip fracture in men. Addressing that evidence gap, we analyzed data from an observational study of new hip fractures in a large integrated healthcare system to compare the reduction in hip fractures associated with standard-of-care osteoporosis treatment in men versus women. Sampling from 271,389 patients aged ≥ 65 who had a hip-containing CT scan during care between 2005 and 2018, we selected all who subsequently had a first hip fracture (cases) after the CT scan (start of observation) and a sex-matched equal number of randomly selected patients.

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  • Bone stress injury (BSI) is a prevalent overuse injury among active women, classified into high-risk (pelvis, sacrum, femoral neck) and low-risk (tibia, fibula, metatarsals) categories with various risk factors.
  • This study aimed to assess differences in bone mineral density (BMD) and load rates between premenopausal women with a history of high-risk BSI, low-risk BSI, and no BSI history, hypothesizing that high-risk patients would have poorer bone health.
  • Results indicated that women with high-risk BSI had significantly lower spine BMD compared to those with low-risk BSI, highlighting the impact of BSI on bone health in pre
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Alzheimer's disease (AD) and osteoporosis often coexist in the elderly. Although observational studies suggest an association between these two diseases, the pathophysiologic link between AD and skeletal health has been poorly defined. We examined the skeletal phenotype of 5xFAD mice, an AD model with accelerated neuron-specific amyloid-β accumulation causing full-blown AD phenotype by the age of 8 months.

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  • Osteoporosis and cardiovascular disease often occur together in older adults, but no direct causal link has been established between them.
  • A study involving 1,391 participants from the Framingham Heart Study assessed the relationship between vascular function and bone health, hypothesizing that poor vascular function negatively impacts bone density and strength.
  • The findings indicated that while poorer vascular function was initially associated with lower bone quality metrics, these associations were not significant after considering factors like age and sex, suggesting that aging-related vascular dysfunction may not be a direct cause of osteoporosis in older individuals.
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Some osteoporosis drug trials have suggested that treatment is more effective in those with low BMD measured by DXA. This study used data from a large set of randomized controlled trials (RCTs) to determine whether the anti-fracture efficacy of treatments differs according to baseline BMD. We used individual patient data from 25 RCTs (103 086 subjects) of osteoporosis medications collected as part of the FNIH-ASBMR SABRE project.

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Diabetes, a disease marked by consistent high blood glucose levels, is associated with various complications such as neuropathy, nephropathy, retinopathy, and cardiovascular disease. Notably, skeletal fragility has emerged as a significant complication in both type 1 (T1D) and type 2 (T2D) diabetic patients. This review examines noninvasive imaging studies that evaluate skeletal outcomes in adults with T1D and T2D, emphasizing distinct skeletal phenotypes linked with each condition and pinpointing gaps in understanding bone health in diabetes.

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  • A study analyzed randomized controlled trials to investigate the effectiveness of antiosteoporosis medications in individuals aged 70 and older compared to those younger than 70.
  • Results showed that these medications significantly reduced fracture risks in both age groups, with similar effectiveness, although younger participants had a slightly greater reduction in hip fracture risk.
  • Additionally, older adults experienced greater improvements in bone mineral density (BMD) after 24 months of treatment, suggesting these meds are beneficial for both age groups without significant age-related differences in fracture prevention.
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  • * 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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