Kristin L. Popp

Bone Geometry, Strength, and Muscle Size in Runners with a History of Stress Fracture

PURPOSE Our primary aim was to explore differences in estimates of tibial bone strength, in female runners with and without a history of stress fractures. Our secondary aim was to explore differences in bone geometry, volumetric density, and muscle size that may explain bone strength outcomes. METHODS A total of 39 competitive distance runners aged 18-35 yr, with (SFX, n = 19) or without (NSFX, n = 20) a history of stress fracture were recruited for this cross-sectional study. Peripheral quantitative computed tomography (XCT 3000; Orthometrix, White Plains, NY) was used to assess volumetric bone mineral density (vBMD, mg x mm(-3)), bone area (ToA, mm(2)), and estimated compressive bone strength (bone strength index (BSI) = ToA x total volumetric density (ToD(2))) at the distal tibia (4%). Total (ToA, mm(2)) and cortical (CoA, mm(2)) bone area, cortical vBMD, and estimated bending strength (strength-strain index (SSIp), mm(3)) were measured at the 15%, 25%, 33%, 45%, 50%, and 66% sites. Muscle cross-sectional area (MCSA) was measured at the 50% and 66% sites. RESULTS Participants in the SFX group had significantly smaller (7%-8%) CoA at the 45%, 50%, and 66% sites (P <or= 0.05 for all), significantly lower SSIp (9%-10%) at the 50% and 66% sites, and smaller MCSA (7%-8%) at the 66% site. The remaining bone parameters including vBMD were not significantly different between groups. After adjusting for MCSA, there were no differences between groups for any measured bone outcomes. CONCLUSIONS These findings suggest that cortical bone strength, cortical area, and MCSA are all lower in runners with a history of stress fracture. However, the lower strength was appropriate for the smaller muscle size, suggesting that interventions to reduce stress fracture risk might be aimed at improving muscle size and strength.

Bone volumetric density, geometry, and strength in female and male collegiate runners

PURPOSE To explore differences in tibial bone geometry, volumetric density, and estimates of bone strength in runners and healthy controls. METHODS Male (n = 21) and female (n = 38) runners (49.1 +/- 13.2 miles x wk(-1)) and inactive healthy controls (17 males and 32 females; mean age = 22 +/- 3.3 yr) were recruited to participate. Peripheral quantitative computed tomography was used to assess total volumetric bone mineral density (vBMD, mg x mm(-3)), total bone area (ToA, mm2), and an estimate of compressive bone strength (bone strength index (BSI) = ToA x total bone volumetric density (ToD2)) at the distal (4%) site of the tibia. ToA (mm2) and cortical bone area (CoA, mm2), cortical vBMD (CoD, mg x mm(-3)), cortical thickness (CoTh, mm), and an estimate of bone bending strength (polar strength strain index (SSIp), mm3) were measured at 50% and 66% sites. RESULTS ToA and BSI were significantly greater (+11%-19%, P < 0.05) in female runners than controls at the 4% site. At the proximal sites, female runners had significantly greater ToA, CoA, CoTh, and SSIp (+9%-19%, all P < 0.001) compared with female controls. vBMD was similar at all tibia sites. Compared with controls, male runners had significantly greater CoTh at the 50% and 66% sites (+8% and 14%, respectively, P < 0.05) as well as greater CoA (+11%, P < 0.009) at the 66% site. There were no differences in bone strength or density at any site in the male runners. CONCLUSIONS Greater bone strength in female runners was attributable to greater bone area rather than density. Although male runners did not show greater bone strength, they did exhibit favorable bone geometric properties. These data further document that running has osteogenic potential.

Bone mass, microarchitecture and strength are influenced by race/ethnicity in young adult men and women

Lower rates of fracture in both Blacks compared to Whites, and men compared to women are not completely explained by differences in bone mineral density (BMD). Prior evidence suggests that more favorable cortical bone microarchitecture may contribute to reduced fracture rates in older Black compared to White women, however it is not known whether these differences are established in young adulthood or develop during aging. Moreover, prior studies using high-resolution pQCT (HR-pQCT) have reported outcomes from a fixed-scan location, which may confound sex- and race/ethnicity-related differences in bone structure. PURPOSE We determined differences in bone mass, microarchitecture and strength between young adult Black and White men and women. METHODS We enrolled 185 young adult (24.2±3.4yrs) women (n=51 Black, n=50 White) and men (n=34 Black, n=50 White) in this cross-sectional study. We used dual-energy X-ray absorptiometry (DXA) to determine areal BMD (aBMD) at the femoral neck (FN), total hip (TH) and lumbar spine (LS), as well as HR-pQCT to assess bone microarchitecture and failure load by micro-finite element analysis (μFEA) at the distal tibia (4% of tibial length). We used two-way ANOVA to compare bone outcomes, adjusted for age, height, weight and physical activity. RESULTS The effect of race/ethnicity on bone outcomes did not differ by sex, and the effect of sex on bone outcomes did not differ by race/ethnicty. After adjusting for covariates, Blacks had significantly greater FN, TH and LS aBMD compared to Whites (p<0.05 for all). Blacks also had greater cortical area, vBMD, and thickness, and lower cortical porosity, with greater trabecular thickness and total vBMD compared to Whites. μFEA-estimated FL was significantly higher among Blacks compared to Whites. Men had significantly greater total vBMD, trabecular thickness and cortical area and thickness, but greater cortical porosity than women, the net effects being a higher failure load in men than women. CONCLUSION These findings demonstrate that more favorable bone microarchitecture in Blacks compared to Whites and in men compared to women is established by young adulthood. Advantageous bone strength among Blacks and men likely contributes to their lower risk of fractures throughout life compared to their White and women counterparts.

Risk of Stress Fracture Varies by Race/Ethnic Origin in a Cohort Study of 1.3 Million U.S. Army Soldiers†

Stress fractures (SF) are common and costly injuries in military personnel. Risk for SF has been shown to vary with race/ethnicity. Previous studies report increased SF risk in white and Hispanic Soldiers compared with black Soldiers. However, these studies did not account for the large ethnic diversity in the US military. We aimed to identify differences in SF risk among racial/ethnic groups within the US Army. A retrospective cohort study was conducted using data from the Total Army Injury and Health Outcomes Database from 2001 until 2011. SF diagnoses were identified from ICD‐9 codes. We used Cox‐proportional hazard models to calculate time to SF by racial/ethnic group after adjusting for age, education, and body mass index. We performed a sex‐stratified analysis to determine whether the ethnic variation in SF risk depends on sex. We identified 21,549 SF cases in 1,299,332 Soldiers (more than 5,228,525 person‐years of risk), revealing an overall incidence rate of 4.12 per 1000 person‐years (7.47 and 2.05 per 1000 person‐years in women and men, respectively). Using non‐Hispanic blacks as the referent group, non‐Hispanic white women had the highest risk of SF, with a 92% higher risk of SF than non‐Hispanic black women (1.92 [1.81–2.03]), followed by American Indian/Native Alaskan women (1.72 [1.44–1.79]), Hispanic women (1.65 [1.53–1.79]), and Asian women (1.32 [1.16–1.49]). Similarly, non‐Hispanic white men had the highest risk of SF, with a 59% higher risk of SF than non‐Hispanic black men (1.59 [1.50–1.68]), followed by Hispanic men (1.19 [1.10–1.29]). When examining the total US Army population, we found substantial differences in the risk of stress fracture among racial/ethnic groups, with non‐Hispanic white Soldiers at greatest risk and Hispanic, American Indian/Native Alaskan, and Asian Soldiers at an intermediate risk. Additional studies are needed to determine the factors underlying these race‐ and ethnic‐related differences in stress fracture risk.

The role of adaptive bone formation in the etiology of stress fracture

Stress fractures are common injuries with load-bearing activities. Stress fractures have been reported in the scientific literature for over a century; however, the etiology continues to be investigated with important distinctions made between the contributions of the tissue-level processes of bone remodeling and modeling. In response to novel repetitive loading, increased bone remodeling may serve to replace fatigue-damaged bone while at the same time creating temporary porosity. Much attention has been given to the role of remodeling in the etiology of stress fracture; however, the role of bone modeling has received less attention. Modest increases in modeling, via bone formation on the periosteal surface of long bones in response to mechanical loading, greatly increases the fatigue resistance of bone. Thus, enhancing this adaptive bone formation is a promising target for stress fracture prevention, and a focus on adaptive bone formation may reveal novel risk factors for stress fracture.

Bone strength estimates relative to vertical ground reaction force discriminates women runners with stress fracture history

PURPOSE To determine differences in bone geometry, estimates of bone strength, muscle size and bone strength relative to load, in women runners with and without a history of stress fracture. METHODS We recruited 32 competitive distance runners aged 18-35, with (SFX, n=16) or without (NSFX, n=16) a history of stress fracture for this case-control study. Peripheral quantitative computed tomography (pQCT) was used to assess volumetric bone mineral density (vBMD, mg/mm3), total (ToA) and cortical (CtA) bone areas (mm2), and estimated compressive bone strength (bone strength index; BSI, mg/mm4) at the distal tibia. ToA, CtA, cortical vBMD, and estimated strength (section modulus; Zp, mm3 and strength strain index; SSIp, mm3) were measured at six cortical sites along the tibia. Mean active peak vertical (pkZ) ground reaction forces (GRFs), assessed from a fatigue run on an instrumented treadmill, were used in conjunction with pQCT measurements to estimate bone strength relative to load (mm2/N∗kg-1) at all cortical sites. RESULTS SSIp and Zp were 9-11% lower in the SFX group at mid-shaft of the tibia, while ToA and vBMD did not differ between groups at any measurement site. The SFX group had 11-17% lower bone strength relative to mean pkZ GRFs (p<0.05). CONCLUSION These findings indicate that estimated bone strength at the mid-tibia and mean pkZ GRFs are lower in runners with a history of stress fracture. Bone strength relative to load is also lower in this same region suggesting that strength deficits in the middle 1/3 of the tibia and altered gait biomechanics may predispose an individual to stress fracture.

Low energy availability surrogates correlate with health and performance consequences of Relative Energy Deficiency in Sport

Low energy availability (EA) is suspected to be the underlying cause of both the Female Athlete Triad and the more recently defined syndrome, Relative Energy Deficiency in Sport (RED-S). The International Olympic Committee (IOC) defined RED-S as a syndrome of health and performance impairments resulting from an energy deficit. While the importance of adequate EA is generally accepted, few studies have attempted to understand whether low EA is associated with the health and performance consequences posited by the IOC. Objective The purpose of this cross-sectional study was to examine the association of low EA with RED-S health and performance consequences in a large clinical population of female athletes. Methods One thousand female athletes (15–30 years) completed an online questionnaire and were classified as having low or adequate EA. The associations between low EA and the health and performance factors listed in the RED-S models were evaluated using chi-squared test and the odds ratios were evaluated using binomial logistic regression (p<0.05). Results Athletes with low EA were more likely to be classified as having increased risk of menstrual dysfunction, poor bone health, metabolic issues, haematological detriments, psychological disorders, cardiovascular impairment and gastrointestinal dysfunction than those with adequate EA. Performance variables associated with low EA included decreased training response, impaired judgement, decreased coordination, decreased concentration, irritability, depression and decreased endurance performance. Conclusion These findings demonstrate that low EA measured using self-report questionnaires is strongly associated with many health and performance consequences proposed by the RED-S models.

Regional variation of bone density, microarchitectural parameters, and elastic moduli in the ultradistal tibia of young black and white men and women

Whole-bone analyses can obscure regional heterogeneities in bone characteristics. Quantifying these heterogeneities might improve our understanding of the etiology of injuries, such as lower-extremity stress fractures. Here, we performed regional analyses of high-resolution peripheral quantitative computed tomography images of the ultradistal tibia in young, healthy subjects (age range, 18 to 30 years). We quantified bone characteristics across four regional sectors of the tibia for the following datasets: white women (n = 50), black women (n = 51), white men (n = 50), black men (n = 34), and all subjects (n = 185). After controlling for potentially confounding variables, we observed statistically significant variations in most of the characteristics across sectors (p < 0.05). Most of the bone characteristics followed a similar trend for all datasets but with different magnitudes. Regardless of race or sex, the anterior sector had the lowest trabecular and total volumetric bone mineral density and highest trabecular separation (p < 0.001), while cortical thickness was lowest in the medial sector (p < 0.05). Accordingly, the anterior sector also had the lowest elastic modulus in the anterior-posterior and superior-inferior directions (p < 0.001). In all sectors, the mean anisotropy was ~3, suggesting cross-sector similarity in the ratios of loading in these directions. In addition, the bone characteristics from regional and whole-bone analyses differed in all datasets (p < 0.05). Our findings on the heterogeneous nature of bone microarchitecture in the ultradistal tibia may reflect an adaptation of the bone to habitual loading conditions.

Low Bone Mineral Density in Male Athletes Is Associated With Bone Stress Injuries at Anatomic Sites With Greater Trabecular Composition

Background: While sports participation is often associated with health benefits, a subset of athletes may develop impaired bone health. Bone stress injuries (BSIs) are a common overuse injury in athletes; site of injury has been shown to relate to underlying bone health in female athletes. Hypothesis/Purpose: This case series characterizes the association of type of sports participation and anatomic site of BSIs with low bone mineral density (BMD), defined as BMD Z-score <–1.0. Similar to female athletes, it was hypothesized that male athletes who participate in running and sustain BSIs in sites of higher trabecular bone content would be more likely to have low BMD. Study Design: Cohort study; Level of evidence, 3. Methods: Chart review identified 28 male athletes aged 14 to 36 years with history of ≥1 lower-extremity BSI who were referred for evaluation of overall bone health, including assessment of lumbar spine, hip, and/or total body less head BMD per dual-energy x-ray absorptiometry. BMD Z-scores were determined via age, sex, and ethnicity normative values. Prior BSIs were classified by anatomic site of injury into trabecular-rich locations (pelvis, femoral neck, and calcaneus) and cortical-rich locations (tibia, fibula, femur, metatarsal and tarsal navicular). Sport type and laboratory values were also assessed in relationship to BMD. The association of low BMD to anatomic site of BSI and sport were evaluated with P value <.05 as threshold of significance. Results: Of 28 athletes, 12 (43%) met criteria for low BMD. Athletes with a history of trabecular-rich BSIs had a 4.6-fold increased risk for low BMD as compared with those with only cortical-rich BSIs (9 of 11 vs 3 of 17, P = .002). Within sport type, runners had a 6.1-fold increased risk for low BMD versus nonrunners (11 of 18 vs 1 of 10, P = .016). Laboratory values, including 25-hydroxy vitamin D, were not associated with BMD or BSI location. Conclusion: Low BMD was identified in 43% of male athletes in this series. Athletes participating in sports of running and with a history of trabecular-rich BSI were at increased risk for low BMD.

Nonsteroidal Anti-Inflammatory Drug Prescriptions are Associated with Increased Stress Fracture Diagnosis in the U.S. Army Population

Stress fractures are common in military personnel and endurance athletes, and nonsteroidal anti‐inflammatory drug (NSAID) use is widespread in these populations. NSAIDs inhibit prostaglandin synthesis, which blunts the anabolic response of bone to physical activity and could therefore increase risk of stress fracture. The objective of this study was to determine whether prescribed NSAIDs were associated with stress fracture diagnoses among US Army soldiers. We also aimed to establish whether acetaminophen, an analgesic alternative to NSAIDs, was associated with stress fracture risk. A nested case‐control study was conducted using data from the Total Army Injury and Health Outcomes Database from 2002 to 2011 (n = 1,260,168). We identified soldiers with a diagnosis of stress fracture (n = 24,146) and selected 4 controls per case matched on length of military service (n = 96,584). We identified NSAID and acetaminophen prescriptions 180 to 30 days before injury (or match date). We also identified soldiers who participated in basic combat training (BCT), a 10‐week period of heightened physical activity at the onset of Army service. Among these individuals, we identified 9088 cases and 36,878 matched controls. Conditional logistic regression was used to calculate incident rate ratios (RR) for stress fracture with adjustment for sex. NSAID prescription was associated with a 2.9‐fold increase (RR = 2.9, 95% confidence interval [CI] 2.8–2.9) and acetaminophen prescription with a 2.1‐fold increase (RR = 2.1, 95% CI 2.0–2.2) in stress fracture risk within the total Army population. The risk was more than 5‐fold greater in soldiers prescribed NSAIDs (RR = 5.3, 95% CI 4.9–5.7) and more than 4‐fold greater in soldiers prescribed acetaminophen (RR = 4.4, 95% CI 3.9–4.9) during BCT. Our results reveal an association between NSAID and acetaminophen prescriptions and stress fracture risk, particularly during periods of heightened physical activity. Prospective observational studies and randomized controlled trials are needed to support these findings before clinical recommendations can be made.