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 18-36 years) 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.

Bone microarchitectural alterations associated with spinal cord injury: Relation to sex hormones, metabolic factors, and loading.

CONTEXT: People living with spinal cord injury (SCI) are at high risk for bone fractures. Neural, hormonal and metabolic contributors to bone microarchitectural alterations are incompletely understood. OBJECTIVE: To determine the relationship of physical, metabolic and endocrine characteristics with bone microarchitecture, characterized using high-resolution peripheral quantitative computed tomography (HRpQCT) in SCI. DESIGN: Cross-sectional analyses of bone properties in people with SCI. PARTICIPANTS: Twenty adults with SCI and paraplegia (12) or motor incomplete quadriplegia (8). OUTCOME MEASURES: Distal tibia and radius HRpQCT parameters, including density, microstructure and strength by microfinite element anaysis (µFEA); sex hormones; metabolic and inflammatory markers. RESULTS: The mean age of the participants with SCI was 41.5 ± 10.3 years, BMI 25.7 ± 6.2 kg/m2, time since injury 10.4 ± 9.0 years. Participants with SCI had significantly lower median total (Z score - 3.3), trabecular (-2.93), and cortical vBMD (-1.87), and Failure Load by µFEA (-2.48) at the tibia than controls. However, radius vBMD, aBMD and microarchitecture were similar in participants with SCI and un-injured controls. Unexpectedly, C-Reactive Protein (CRP) was positively associated with tibial trabecular vBMD (ß = 0.77, p = 0.02), thickness (ß = 0.52, p = 0.04) and number (ß = 0.92, p = 0.02). At the radius, estradiol level was positively associated with total vBMD (ß = 0.59, p = 0.01), trabecular thickness (ß = 0.43, p = 0.04), cortical thickness (ß = 0.63, p = 0.01) and cortical porosity (ß = 0.74 p = 0.04). CONCLUSIONS: Radius vBMD and microarchitecture is preserved but tibial total, cortical and trabecular vBMD, and estimated bone strength are markedly lower and bone microarchitectural parameters substantially degraded in people with SCI. The alterations in bone microarchitecture in people with SCI are likely multifactorial, however marked degradation of bone microarchitecture in tibia but not radius suggests that unloading is an important contributor of site-specific alterations of bone microarchitecture after SCI. Fracture prevention in SCI should focus on strategies to safely increase bone loading. CLINICALTRIALS: gov registration #: (NCT03576001).

Factors Associated With High-Risk and Low-Risk Bone Stress Injury in Female Runners: Implications for Risk Factor Stratification and Management.

Background: Bone stress injury (BSI) is a common overuse injury in active women. BSIs can be classified as high-risk (pelvis, sacrum, and femoral neck) or low-risk (tibia, fibula, and metatarsals). Risk factors for BSI include low energy availability, menstrual dysfunction, and poor bone health. Higher vertical load rates during running have been observed in women with a history of BSI. Purpose/Hypothesis: The purpose of this study was to characterize factors associated with BSI in a population of premenopausal women, comparing those with a history of high-risk or low-risk BSI with those with no history of BSI. It was hypothesized that women with a history of high-risk BSI would be more likely to exhibit lower bone mineral density (BMD) and related factors and less favorable bone microarchitecture compared with women with a history of low-risk BSI. In contrast, women with a history of low-risk BSI would have higher load rates. Study Design: Cross-sectional study; Level of evidence, 3. Methods: Enrolled were 15 women with a history of high-risk BSI, 15 with a history of low-risk BSI, and 15 with no history of BSI. BMD for the whole body, hip, and spine was standardized using z scores on dual-energy x-ray absorptiometry. High-resolution peripheral quantitative computed tomography was used to quantify bone microarchitecture at the radius and distal tibia. Participants completed surveys characterizing factors that influence bone health-including sleep, menstrual history, and eating behaviors-utilizing the Eating Disorder Examination Questionnaire (EDE-Q). Each participant completed a biomechanical assessment using an instrumented treadmill to measure load rates before and after a run to exertion. Results: Women with a history of high-risk BSI had lower spine z scores than those with low-risk BSI (-1.04 ± 0.76 vs -0.01 ± 1.15; P < .05). Women with a history of high-risk BSI, compared with low-risk BSI and no BSI, had the highest EDE-Q subscores for Shape Concern (1.46 ± 1.28 vs 0.76 ± 0.78 and 0.43 ± 0.43) and Eating Concern (0.55 ± 0.75 vs 0.16 ± 0.38 and 0.11 ± 0.21), as well as the greatest difference between minimum and maximum weight at current height (11.3 ± 5.4 vs 7.7 ± 2.9 and 7.6 ± 3.3 kg) (P < .05 for all). Women with a history of high-risk BSI were more likely than those with no history of BSI to sleep <7 hours on average per night during the week (80% vs 33.3%; P < .05). The mean and instantaneous vertical load rates were not different between groups. Conclusion: Women with a history of high-risk BSI were more likely to exhibit risk factors for poor bone health, including lower BMD, while load rates did not distinguish women with a history of BSI.

Impact loading in female runners with single and multiple bone stress injuries during fresh and exerted conditions.

BACKGROUND: Bone stress injuries (BSIs) are common in female runners, and recurrent BSI rates are high. Previous work suggests an association between higher impact loading during running and tibial BSI. However, it is unknown whether impact loading and fatigue-related loading changes discriminate women with a history of multiple BSIs. This study compared impact variables at the beginning of a treadmill run to exertion and the changes in those variables with exertion among female runners with no history of BSI as well as among those with a history of single or multiple BSIs. METHODS: We enrolled 45 female runners (aged 18-40 years) for this cross-sectional study: having no history of diagnosed lower extremity BSI (N-BSI, n = 14); a history of 1 lower extremity BSI (1-BSI, n = 16); and diagnosed by imaging, or a history of multiple (≥3) lower extremity BSIs (M-BSI, n = 15). Participants completed a 5-km race speed run on an instrumented treadmill while wearing an Inertial Measurement Unit. The vertical average loading rate (VALR), vertical instantaneous loading rate (VILR), vertical stiffness during impact via instrumented treadmill, and tibial shock determined as the peak positive tibial acceleration via Inertial Measurement Unit were measured at the beginning and the end of the run. RESULTS: There were no differences between groups in VALR, VILR, vertical stiffness, or tibial shock in a fresh or exerted condition. However, compared to N-BSI, women with M-BSI had greater increase with exertion in VALR (-1.8% vs. 6.1%, p = 0.01) and VILR (1.5% vs. 4.8%, p = 0.03). Similarly, compared to N-BSI, vertical stiffness increased more with exertion among women with M-BSI (-0.9% vs. 7.3%, p = 0.006) and 1-BSI (-0.9% vs. 1.8%, p = 0.05). Finally, compared to N-BSI, the increase in tibial shock from fresh to exerted condition was greater among women with M-BSI (0.9% vs. 5.5%, p = 0.03) and 1-BSI (0.9% vs. 11.2%, p = 0.02). CONCLUSION: Women with 1-BSI or M-BSIs experience greater exertion-related increases in impact loading than women with N-BSI. These observations imply that exertion-related changes in gait biomechanics may contribute to risk of BSI.

Serum 25-Hydroxyvitamin D is Associated With Bone Microarchitecture and Strength in a Multiracial Cohort of Young Adults.

PURPOSE: To determine whether 25-hydroxyvitamin D (25-OH D) levels are associated with bone outcomes in a multiracial cohort of young adults. METHODS: This cross-sectional study included 165 participants (83 men, 82 women, 18-30 years of age) who self-identified as Asian, Black, or White. We measured bone microarchitecture and strength of the distal radius and tibia using high-resolution peripheral quantitative computed tomography. We used linear regression to estimate the association between 25-OH D (ng/mL) and bone measurements, adjusting for race, sex, age, weight, height, calcium intake, physical activity, and season. RESULTS: A total of 43.6% of participants were 25-OH D deficient (<20 ng/mL) with greater prevalence in Asian (38.9%) and Black (43.1%) compared with White (18.0%) participants (P < 0.001). At the distal radius, 25-OH D was positively associated with cortical area, trabecular density, cortical thickness, cortical porosity, and failure load (P < 0.05 for all). At the distal tibia, higher 25-OH D was associated with higher cortical area, trabecular density, trabecular number, failure load, and lower trabecular separation and cortical density (P < 0.05 for all). After multivariable adjustment, those with 25-OH D deficiency had generally worse bone microarchitecture than those with 25-OH D sufficiency. Black individuals had largely more favorable bone outcomes than Asian and White individuals, despite higher prevalence of 25-OH D deficiency. CONCLUSIONS: We found a high prevalence of 25-OH D deficiency in a multiracial cohort of young adults. Lower 25-OH D was associated with worse bone outcomes at the distal radius and tibia at the time of peak bone mass, warranting further attention to vitamin D status in young adults.

Physical Activity, Menstrual History, and Bone Microarchitecture in Female Athletes with Multiple Bone Stress Injuries.

PURPOSE: To determine differences in health and physical activity history, bone density, microarchitecture, and strength among female athletes with a history of multiple BSI, athletes with ≤1 BSI, and nonathletes. METHODS: We enrolled 101 women (age, 18-32 yr) for this cross-sectional study: nonathlete controls (n = 17) and athletes with a history of ≥3 BSIs (n = 21) or ≤1 BSI (n = 63). We collected subjects' health and training history and measured bone microarchitecture of the distal tibia via high-resolution peripheral quantitative computed tomography (HR-pQCT) and areal bone mineral density of the hip and spine by dual-energy X-ray absorptiometry. RESULTS: Groups did not differ according to age, body mass index, age at menarche, areal bone mineral density, or tibial bone microarchitecture. Women with multiple BSI had a higher prevalence of primary and secondary amenorrhea (P < 0.01) compared with other groups. Total hours of physical activity in middle school were similar across groups; however, women with multiple BSI performed more total hours of physical activity in high school (P = 0.05), more hours of uniaxial loading in both middle school and high school (P = 0.004, P = 0.02), and a smaller proportion of multiaxial loading activity compared with other groups. CONCLUSIONS: These observations suggest that participation in sports with multiaxial loading and maintaining normal menstrual status during adolescence and young adulthood may reduce the risk of multiple bone stress injuries.

Assimilation of Cholesterol by Monascus purpureus.

Monascus purpureus, a filamentous fungus known for its fermentation of red yeast rice, produces the metabolite monacolin K used in statin drugs to inhibit cholesterol biosynthesis. In this study, we show that active cultures of M. purpureus CBS 109.07, independent of secondary metabolites, use the mechanism of cholesterol assimilation to lower cholesterol in vitro. We describe collection, extraction, and gas chromatography-flame ionized detection (GC-FID) methods to quantify the levels of cholesterol remaining after incubation of M. purpureus CBS 109.07 with exogenous cholesterol. Our findings demonstrate that active growing M. purpureus CBS 109.07 can assimilate cholesterol, removing 36.38% of cholesterol after 48 h of incubation at 37 °C. The removal of cholesterol by resting or dead M. purpureus CBS 109.07 was not significant, with cholesterol reduction ranging from 2.75-9.27% throughout a 72 h incubation. Cholesterol was also not shown to be catabolized as a carbon source. Resting cultures transferred from buffer to growth media were able to reactivate, and increases in cholesterol assimilation and growth were observed. In growing and resting phases at 24 and 72 h, the production of the mycotoxin citrinin was quantified via high-performance liquid chromatography-ultraviolet (HPLC-UV) and found to be below the limit of detection. The results indicate that M. purpureus CBS 109.07 can reduce cholesterol content in vitro and may have a potential application in probiotics.