Measures Of Bone Strength Research Articles

Improving the identification of bone-specific physical activity using wrist-worn accelerometry: A cross-sectional study in 11-12-year-old Australian children.

Physical activity (PA) during childhood and adolescence is important for the accrual of maximal peak bone mass. The precise dose that benefits bone remains unclear as methods commonly used to analyze PA data are unsuitable for measuring bone-relevant PA. Using improved accelerometry methods, this study identified the amount and intensity of PA most strongly associated with bone outcomes in 11-12-year-olds. Participants (n=770; 382 boys) underwent tibial peripheral quantitative computed tomography to assess trabecular and cortical density, endosteal and periosteal circumference and polar stress-strain index. Seven-day wrist-worn raw acceleration data averaged over 1-s epochs was used to estimate time accumulated above incremental PA intensities (50 milli-gravitational unit (mg) increments from 200 to 3000mg). Associations between time spent above each 50mg increment and bone outcomes were assessed using multiple linear regression, adjusted for age, sex, height, weight, maturity, socioeconomic position, muscle cross-sectional area and PA below the intensity of interest. There was a gradual increase in mean R2 change across all bone-related outcomes as the intensity increased in 50mg increments from >200 to >700mg. All outcomes became significant at >700mg (R2 change=0.6%-1.3% and p=0.001-0.02). Any further increases in intensity led to a reduction in mean R2 change and associations became non-significant for all outcomes >1500mg. Using more appropriate accelerometry methods (1-s epochs; no a priori application of traditional cut-points) enabled us to identify that ∼10min/day of PA >700mg (equivalent to running ∼10km/h) was positively associated with pQCT-derived measures of bone density, geometry and strength in 11-12-year-olds.

Abaloparatide is more potent than teriparatide in restoring bone mass and strength in type 1 diabetic male mice

This study investigated the efficacy of the two FDA-approved bone anabolic ligands of the parathyroid hormone receptor 1 (PTH1R), teriparatide or human parathyroid hormone 1–34 (PTH) and abaloparatide (ABL), to restoring skeletal health using a preclinical murine model of streptozotocin-induced T1-DM. Intermittent daily subcutaneous injections of equal molar doses (12 pmoles/g/day) of PTH (50 ng/g/day), ABL (47.5 ng/g/day), or vehicle, were administered for 28 days to 5-month-old C57Bl/6 J male mice with established T1-DM or control (C) mice. ABL was superior to PTH in increasing or restoring bone mass in control or T1-MD mice, respectively, which was associated with superior stimulation of trabecular and periosteal bone formation, upregulation of osteoclastic/osteoblastic gene expression, and increased circulating bone remodeling markers. Only ABL corrected the reduction in ultimate load, which is a measure of bone strength, induced by T1-DM, and it also increased energy to ultimate load. In addition, bones from T1-DM mice treated with PTH or ABL exhibited increased ultimate stress, a material index, compared to T1-DM mice administered with vehicle. And both PTH and ABL prevented the increased expression of the Wnt antagonist Sost/sclerostin displayed by T1-DM mice. Further, PTH and ABL increased to a similar extent the circulating bone resorption marker CTX and the bone formation marker P1NP in T1-DM after 2 weeks of treatment; however, only ABL sustained these increases after 4 weeks of treatment. We conclude that at equal molar doses, ABL is more effective than PTH in increasing bone mass and restoring the cortical and trabecular bone lost with T1-DM, due to higher and longer-lasting increases in bone remodeling.

Gut microbial community and fecal metabolomic signatures in different types of osteoporosis animal models.

The gut microbiota (GM) constitutes a critical factor in the maintenance of physiological homeostasis. Numerous studies have empirically demonstrated that the GM is closely associated with the onset and progression of osteoporosis (OP). Nevertheless, the characteristics of the GM and its metabolites related to different forms of OP are poorly understood. In the present study, we examined the changes in the GM and its metabolites associated with various types of OP as well as the correlations among them. We simultaneously established rat postmenopausal, disuse-induced, and glucocorticoid-induced OP models. We used micro-CT and histological analyses to observe bone microstructure, three-point bending tests to measure bone strength, and enzyme-linked immunosorbent assay (ELISA) to evaluate the biochemical markers of bone turnover in the three rat OP models and the control. We applied 16s rDNA to analyze GM abundance and employed untargeted metabolomics to identify fecal metabolites in all four treatment groups. We implemented multi-omics methods to explore the relationships among OP, the GM, and its metabolites. The 16S rDNA sequencing revealed that both the abundance and alterations of the GM significantly differed among the OP groups. In the postmenopausal OP model, the bacterial genera g__Bacteroidetes_unclassified, g__Firmicutes_unclassified, and g__Eggerthella had changed. In the disuse-induced and glucocorticoid-induced OP models, g__Akkermansia and g__Rothia changed, respectively. Untargeted metabolomics disclosed that the GM-derived metabolites significantly differed among the OP types. However, a Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis showed that it was mainly metabolites implicated in lipid and amino acid metabolism that were altered in all cases. An association analysis indicated that the histidine metabolism intermediate 4-(β-acetylaminoethyl) imidazole was common to all OP forms and was strongly correlated with all bone metabolism-related bacterial genera. Hence, 4-(β-acetylaminoethyl) imidazole might play a vital role in OP onset and progression. The present work revealed the alterations in the GM and its metabolites that are associated with OP. It also disclosed the changes in the GM that are characteristic of each type of OP. Future research should endeavor to determine the causal and regulatory effects of the GM and the metabolites typical of each form of OP.

The Impact of Whole Egg Consumption on Bone Accrual in Healthy Children: A Randomized Controlled Trial.

Dietary interventions designed to examine the role of nutrition on childhood bone accrual have often focused on the role of individual micronutrients (eg, calcium, vitamin D, and zinc) and macronutrients (eg, protein). The osteogenic benefits of whole foods, such as eggs, are not well understood despite eggs being a source of high-quality nutrients and bioactive compounds known to positively influence bone. A significant positive cross-sectional association between whole egg consumption and tibia cortical bone mass has recently been shown in young children; however, randomized controlled trials (RCTs) have not been conducted. This study is a double-blind RCT in male and female children ages 9-13 years of different ancestries, designed to determine if consuming food products with whole eggs (equivalent to 8-10 eggs/wk) versus foods with milk or gelatin (placebo) over a 9-month period will improve measures of bone strength. Total body less head (TBLH) and lumbar spine bone mineral content (BMC) and areal bone mineral density (aBMD) were assessed using dual-energy X-ray absorptiometry (DXA). DXA Z-scores were computed using published pediatric growth charts and were adjusted for height-for-age Z-score (HAZ). Mid-tibia cortical volumetric BMD, BMC, cortical area, total bone area, cortical thickness, and strength strain index were measured using peripheral quantitative computed tomography. Overall, there were no significant intervention effects for any bone outcomes. The increase in spine BMCHAZ Z-score in the egg group versus the gelatin group approached significance (p = 0.07). Significant time effects in TBLH aBMDHAZ Z-score occurred as all groups decreased over 9 months (p < 0.03). Most tibia cortical bone outcomes increased over time (all p < 0.02), but changes did not differ across intervention groups. Whole eggs provide important nutritional benefits for children, but the bone responses to consumption of 8-10 eggs/wk over a period of 9 months in children entering the early stages of puberty were small. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Indices of sarcopenic obesity are important predictors of finite element analysis-derived bone strength in older adults with obesity.

The expanding population of older adults with obesity is a public health challenge, in part, because of the increased risk of fractures despite normal or high bone mineral density. Potential factors predisposing to fractures in this group include sarcopenia associated with obesity and impaired bone quality. We aimed to determine the contribution of sarcopenic obesity (SO) indices to bone strength as assessed by microfinite element analysis (μFEA) of high-resolution peripheral quantitative computed tomography (HR-pQCT). One-hundred eighty-nine older (age ≥ 65 years) adults with obesity (BMI ≥ 30 kg/m2) participated in lifestyle intervention trials at our medical center. All underwent baseline measurements of bone strength (failure load and stiffness) using μFEA from HR-pQCT of the distal radius and tibia. In addition, SO indices [appendicular lean mass/weight (ALM/W) and percent body fat (FM%)] by dual-energy X-ray absorptiometry and handgrip strength (HGS) by dynamometry were assessed. SO was diagnosed and staged based on the 2022 ESPEN and EASO expert consensus statement. Both ALM/W and HGS were positively correlated explaining 28% to 36% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). In contrast, FM% was negatively correlated explaining 22% to 31% of the variance in failure load and stiffness at the distal radius and tibia (all p < 0.001). The associations of SO indices with failure load and stiffness remained significant after controlling for age, sex, race/ethnicity, diabetes, and 25-OH vitamin D (ALM/W: R 2=0.301 to 0.448, HGS: R 2=0.346 to 0.472, FM%: R 2=0.299 to 0.432) (p < 0.001 to 0.011). SO was diagnosed in 75/189 (40%) participants with 66/75 (88%) having functional or metabolic complications (stage II). Participants with SO had lower failure load and stiffness at the distal radius than participants with no SO (both p < 0.05). These findings demonstrate that lower muscle mass and strength and higher fat mass may impair bone quality. Therefore, interventions that focus on preserving muscle mass and strength while reducing fat mass may be important to decrease fracture risk when older adults with obesity undertake lifestyle intervention therapy.

Bone health in childhood and adolescence: an overview on dual-energy X-ray absorptiometry scanning, fracture surveillance and bisphosphonate therapy for low-middle-income countries.

Bone accrual in childhood determines bone health in later life. Loss of bone strength in early life can lead to increased morbidity and reduced quality of life in childhood and adolescence. Increased availability of assessment tools and bisphosphonate therapy, together with increased awareness on the significance of fracture history and risk factors, have led to greater opportunities, to improve detection and optimize management of children and adolescents with bone fragility globally, including those in lower resource settings. Bone mineral density z-scores and bone mineral content are surrogate measures of bone strength, which can be measured by dual-energy X-ray absorptiometry (DXA), in growing individuals. DXA can aid in the diagnosis and management of primary and secondary bone fragility disorders in childhood. DXA helps evaluate children with clinically significant fractures, and monitor those with bone fragility disorders, or at high risk for compromised bone strength. Obtaining DXA images can however be challenging, especially in younger children, due to difficulty in positioning and movement artefacts, while paediatric DXA interpretation can be confounded by effects of growth and puberty. Furthermore, access to DXA facilities as well as appropriate paediatric reference norms and expertise for interpretation, may not be easily available especially in lower resource settings. Pediatric bone experts are now placing increasing emphasis on the fracture phenotype and clinical context to diagnose osteoporosis over bone mineral density (BMD) by DXA. Low trauma vertebral fractures are now recognized as a hallmark of bone fragility, and spinal fracture surveillance by either conventional lateral thoracolumbar radiographs or vertebral fracture assessment by DXA is gaining increasing importance in diagnosing childhood osteoporosis, and initiating bone protective therapy. Furthermore, it is now understood that even a single, low-trauma long bone fracture can signal osteoporosis in those with risk factors for bone fragility. Intravenous bisphosphonate therapy is the mainstay of treatment for childhood bone fragility disorders. Other supportive measures to improve bone strength include optimizing nutrition, encouraging weight bearing physical activity within the limits of the underlying condition, and treating any associated endocrinopathies. With this paradigm shift in childhood osteoporosis evaluation and management, lack of DXA facilities to assess BMD at baseline and/or provide serial monitoring is not a major barrier for initiating IV bisphosphonate therapy in children in whom it is clinically indicated and would benefit from its use. DXA is useful, however, to monitor treatment response and optimal timing for treatment discontinuation in children with transient risk factors for osteoporosis. Overall, there is lack of awareness and paucity of guidelines on utilizing and adopting available resources to manage paediatric bone disorders optimally in lower-resource settings. We provide an evidence-based approach to the assessment and management of bone fragility disorders in children and adolescents, with appropriate considerations for lower resource settings including LMIC countries.

Diagnosis, Follow-Up and Therapy for Secondary Osteoporosis in Vulnerable Children: A Narrative Review

By definition, children constitute a vulnerable population, especially when they are chronically ill and/or disabled. A characteristic of chronically ill and disabled children is that they also suffer from indirect effects of their disease, such as immobilization, chronic inflammation, reduced time outdoors in the sun, osteotoxic effects of disease-targeted therapy (like glucocorticoids), and poor nutrition. All these factors may lead to bone fragility due to secondary osteoporosis, a co-morbidity that may be overlooked in the context of serious underlying diseases. The ultimate goal of osteoporosis diagnosis and monitoring in this setting is the early identification, prevention, and treatment of low-trauma long bone and vertebral fractures; indeed, vertebral fractures are a frequently under-diagnosed manifestation of overt bone fragility in this context. Efforts to prevent first-ever fractures are also meritorious, including encouragement of weight-bearing activities, optimization of nutritional status, including calcium and vitamin D supplementation, and the diagnosis and treatment of delayed growth and puberty; however, these conservative measures may be insufficient in those at high risk. Numerous natural history studies have shown that vertebral fractures are more common than non-vertebral (i.e., long bone) fractures in at-risk children. Not surprisingly, the cornerstone of secondary osteoporosis monitoring is lateral spine imaging for the early detection of vertebral collapse. Although dual-energy x-ray absorptiometry (DXA) is the gold standard to measure bone mineral density, digital X-ray radiogrammetry may be used as a surrogate measure of bone strength if dual-energy x-ray absorptiometry is not available. In the event that preventive measures fail, treatment with bisphosphonates may be appropriate. Typically, treatment with intravenous bisphosphonates is reserved for children with overt bone fragility and limited potential for spontaneous recovery. However, there is increasing attention to very high-risk children, such as boys with Duchenne muscular dystrophy, who may benefit from bisphosphonate therapy prior to first-ever fractures (given their high fracture frequency and essentially absent potential for spontaneous recovery). This article provides a contemporary overview of the definition and diagnosis of osteoporosis in children with chronic illness, along with the approach to monitoring those at risk and the evidence for currently recommended intervention strategies.

Increased Dietary Protein to Energy Ratio in Pre-Weaning Lambs Increases Average Daily Gain and Cortical Bone Thickness in the Tibia

The objective of this study was to examine if diets differing in crude protein (CP) to metabolizable energy (ME) ratio (CP:ME) pre-weaning altered peripheral quantitative computed tomography (pQCT) measures of bone mass and strength in lambs. The left hind leg of lambs were available at the completion of a trial designed to examine the effect that altering the CP:ME ratio in milk replacer had on growth and body composition of pre-weaned lambs reared artificially. Treatments consisted of either normal commercial milk replacer (CMR, n = 10) containing 240 g/kg CP and 21.89 MJ/kg ME, high protein milk replacer (HPM, n = 9) containing CMR with additional milk protein concentrate to reach 478.7 g/kg CP and 19.15 MJ/kg ME or a mix of normal milk replacer and milk protein concentrate adjusted twice-weekly to match optimal CP:ME requirements (MB, n = 8) based on maintenance plus 300 g/d liveweight gain. At 22 kg live weight, lambs were euthanized and the tibia including the surrounding muscle was collected and scanned using pQCT at the mid-diaphysis. Lambs on the HPM and MB diets had a greater average daily gain (p &lt; 0.01). There were limited differences in bone morphology and muscle mass, though notably the higher protein diets (MB and HPM) were associated with greater cortical thickness (p &lt; 0.05) and, therefore, potentially greater peak bone mass at maturity This finding demonstrates that pre-weaning diets, and the protein content in particular, may influence the developmental potential of long bones and attainment of peak bone mass at maturity.

RF06 | PSAT171 Impact of GH Administration on Skeletal Endpoints in Adults with Overweight/Obesity

Abstract Background Obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. Methods 77 adults ages 18-65 years, BMI ≥25 kg/m2, and BMD T- or Z-score ≤ -1.0 were randomized in a double-blind protocol to daily subcutaneous GH or placebo for 18 months, targeting IGF-1 in the upper quartile of the age-appropriate normal range. There was a post-treatment observation period from 18-24 months. DXA and high-resolution peripheral quantitative CT were performed at baseline, 18 months and 24 months. Volumetric quantitative CT was performed at baseline and 18 months. Results are reported as mean ±SD or mean (95% confidence interval). Results There were no pretreatment differences between the GH (n=39) and placebo groups (n=38), including mean age (48±12y), BMI (33.1±5.7kg/m2) and BMD at any site. Forty-nine subjects (47% female) completed 18 months. P1NP, osteocalcin and CTX increased (p&amp;lt;0.005) and visceral adipose tissue decreased (p=0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased at 18 months in the GH vs placebo group (p&amp;lt;0.05). During the post-treatment observation period (18 to 24 months), total radius aBMD and tibia cortical thickness increased in the GH vs placebo group (p&amp;lt;0.05); there was also a trend toward an increase in total hip aBMD in the GH vs placebo group (p=0.06). At 24 months, none of the differences between the GH and placebo groups remained significant. There was a higher incidence of numbness and tingling (33% vs 8%, p=0.01) and joint pain or stiffness (33% vs 5%, p=0.003) in the GH vs placebo group. There were no other differences in adverse events between groups. Conclusions We demonstrated that GH administration for 18 months to individuals with overweight/obesity and low BMD decreased some measures of BMD, bone microarchitecture, and bone strength compared with placebo. None of these differences remained significant after 6 months off therapy. A longer duration of treatment, or a longer duration of observation post-treatment, may be necessary to see the expected biphasic decline and then increase in BMD reflecting an expanding remodeling space followed by mineralization that has previously been seen with GH administration in other populations, including individuals with and without GH deficiency. Although future investigation of the effects of GH on bone is required to assess the true long-term impact on skeletal integrity as well as fracture reduction, our study suggests that GH administration for 18 months to adults with overweight/obesity does not improve BMD, bone microarchitecture, or bone strength. Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m., Saturday, June 11, 2022 1:12 p.m. - 1:17 p.m.

Bone Robusticity Values - Non Weight Bearing Vs Weight Bearing Bones: The Iowa Bone Development Study

Adolescence is a key time for bone development with 25% of adult bone accrued in these years. Evidence also indicates that robusticity (bone width relative to length) may account for a 30%-80% difference in bone strength with slender bones being weaker and prone to stress fracture. Few studies have investigated robustness and bone strength in children. PURPOSE: To determine the variability in robusticity and bone strength pre puberty and at maturity of weight bearing and non-weight bearing bones. METHODS: Secondary analysis of data from the Iowa Bone Development Study (IBDS) was used. https://clinicaltrials.gov/ct2/show/NCT03547128 Using peripheral Quantitative Computed Tomography (pQCT) measures of bone strength from the tibia and radius from 11-25 years of age were obtained. Robusticity (total bone area/ bone length) was calculated and the variability of each measure was determined by calculating the Coefficient of Variation (CV) (mean/standard deviation). CV’s were compared for bone strength variables, bone mineral density, moment of inertia, cortical area, robusicity, total area and bone length between the non weight bearing radius and weight bearing tibia. RESULTS: At both 11 and 23 years of age, robusticity values in the radius were approximately 25-30% more variable compared to the tibia (Pre-puberty CV: Tibia 17.15%, Radius 24.52%. Post-puberty CV: Tibia 19.21%, Radius 25.69%) Similar CV’s were found in total area (Pre-puberty CV: Tibia: 22.91%, Radius 29.04%. Post-puberty CV: Tibia 26.18%, Radius 32.90%) but not in bone length (Pre-puberty CV: Tibia 9.57%, Radius 9.18%. Post-puberty CV: Tibia 10.14%, Radius 10.59%). CONCLUSIONS: Robusticity varied less in the tibia pre and post puberty. The increase in variability measured by the CV for the radius may be due to more variety in loading of the upper limb compared to the lower limb. Most ambulatory individuals consistently apply at least 1x body weight loading to their lower limb bones while walking. Normative data indicates healthy adults typically take between 4,000 and 18,000 steps/day. Also the variability in robusticity is from the changes in total area of the bone suggesting different osteoblast and osteoclast activity for the upper and lower limbs.

Effects of estradiol on bone in men undergoing androgen deprivation therapy: a randomized placebo-controlled trial.

In men, many effects of testosterone (T) on the skeleton are thought to be mediated by estradiol (E2), but trial evidence is largely lacking. This study aimed to determine the effects of E2 on bone health in men in the absence of endogenous T. This study is a 6-month randomized, placebo-controlled trial with the hypothesis that E2 would slow the decline of volumetric bone mineral density (vBMD) and bone microstructure, maintain areal bone mineral density (aBMD), and reduce bone remodelling. 78 participants receiving androgen deprivation therapy for prostate cancer were randomized to 0.9 mg of 0.1% E2 gel daily or matched placebo. The outcome measures were vBMD and microarchitecture at the distal tibia and distal radius by high-resolution peripheral quantitative CT, aBMD at the spine and hip by dual-energy x-ray absorptiometry, and serum bone remodelling markers. For the primary endpoint, total vBMD at the distal tibia, there was no significant difference between groups, mean adjusted difference (MAD) 2.0 mgHA/cm3 (95% CI: -0.8 to 4.8), P = 0.17. Cortical vBMD at the distal radius increased in the E2 group relative to placebo, MAD 14.8 mgHA/cm3 (95% CI: 4.5 to 25.0), P = 0.005. Relative to placebo, E2 increased estimated failure load at tibia, MAD 250 N (95% CI: 36 to 465), P = 0.02, and radius, MAD 193 N (95% CI: 65 to 320), P = 0.003. Relative to placebo, E2 increased aBMD at the lumbar spine, MAD 0.02 g/cm2 (95% CI: 0.01 to 0.03), P = 0.01, and ultra-distal radius, MAD 0.01 g/cm2 (95% CI: 0.00 to 0.02), P = 0.01, and reduced serum bone remodelling markers. Relative to placebo, E2 treatment increases some measures of bone density and bone strength in men and reduces bone remodelling, effects that occur in the absence of endogenous T.

Impact of GH administration on skeletal endpoints in adults with overweight/obesity.

Overweight/obesity is associated with relative growth hormone (GH) deficiency and increased fracture risk. We hypothesized that GH administration would improve bone endpoints in individuals with overweight/obesity. An 18-month, randomized, double-blind, placebo-controlled study of GH, followed by 6-month observation. In this study, 77 adults (53% men), aged 18-65 years, BMI ≥ 25 kg/m2, and BMD T- or Z-score ≤ -1.0 were randomized to daily subcutaneous GH or placebo, targeting IGF1 in the upper quartile of the age-appropriate normal range. Forty-nine completed 18 months. DXA, volumetric quantitative CT, and high-resolution peripheral quantitative CT were performed. Pre-treatment mean age (48 ± 12 years), BMI (33.1 ± 5.7 kg/m2), and BMD were similar between groups. P1NP, osteocalcin, and CTX increased (P < 0.005) and visceral adipose tissue decreased (P = 0.04) at 18 months in the GH vs placebo group. Hip and radius aBMD, spine and tibial vBMD, tibial cortical thickness, and radial and tibial failure load decreased in the GH vs placebo group (P < 0.05). Between 18 and 24 months (post-treatment observation period), radius aBMD and tibia cortical thickness increased in the GH vs placebo group. At 24 months, there were no differences between the GH and placebo groups in bone density, structure, or strength compared to baseline. GH administration for 18 months increased bone turnover in adults with overweight/obesity. It also decreased some measures of BMD, bone microarchitecture, and bone strength, which all returned to pre-treatment levels 6 months post-therapy. Whether GH administration increases BMD with longer treatment duration, or after mineralization of an expanded remodeling space post-treatment, requires further investigation.

Bone Mineral Density and Trabecular Bone Score in Predicting Vertebral Fractures in Male Employees of the Electricity Generating Authority of Thailand.

Purpose Osteoporotic VF is frequently asymptomatic and affects not only women but also men. Identifying patients at risk is essential for early management and prevention. BMD and the TBS are measurements of bone strength and trabecular microarchitecture, respectively. Their role in VF prediction in men is less well-studied. We determined the BMD and TBS predictive ability for osteoporotic VF in men. Methods A total of 115 male participants of the Electricity Generating Authority of Thailand (EGAT) cohorts without a history of VF who completed the baseline BMD and TBS measurements in 2012 and a thoracolumbar spine radiograph in 2017 were recruited. The VF was assessed using the Genant semiquantitative method. Logistic regression analysis was performed to identify factors associated with the fracture. The area under the receiving operator curve (AUC) was analyzed to define VF predictive ability. Results Forty subjects (34.78%) had VFs. The unadjusted relative risks (95% confidence interval) for VF for one standard deviation decrease in the TBS and low TBS were 1.319 (1.157–1.506) and 2.347 (1.496–3.682), respectively, and remained significant after BMD and age adjustment. For VF prediction, combined models had a greater AUC than models predicted from a single variable. The use of low TBS, femoral neck BMD, and age provided the best AUC (0.693). Conclusion BMD and the TBS could predict osteoporotic VF in male EGAT employees. The use of both BMD and the TBS in the VF prediction process improved predictive ability.

Tibial Bone Geometry Is Associated With Bone Stress Injury During Military Training in Men and Women.

Bone stress injuries (BSI) are a common musculoskeletal condition among exercising and military populations and present a major burden to military readiness. The purpose of this investigation was to determine whether baseline measures of bone density, geometry, and strength, as assessed via peripheral quantitative computed tomography (pQCT), are predictive of tibial BSI during Marine Officer Candidates School training. Tibial pQCT scans were conducted prior to the start of physical training (n = 504; Male n = 382; Female n = 122) to measure volumetric bone mineral density (vBMD), geometry, robustness, and estimates of bone strength. Bone parameters were assessed at three tibial sites including the distal metaphysis (4% of tibial length measured from the distal endplate), mid-diaphysis (38% of tibial length measured from the distal endplate), and proximal diaphysis (66% of tibial length measured from the distal endplate). Injury surveillance data was collected throughout training. Four percent (n = 21) of the sample were diagnosed with a BSI at any anatomical site during training, 10 injuries were of the tibia. Baseline bone parameters were then tested for associations with the development of a tibial BSI during training and it was determined that cortical bone measures at diaphyseal (38 and 66%) sites were significant predictors of a prospective tibial BSI. At the mid-diaphysis (38% site), in a simple model and after adjusting for sex, age, and body size, total area [Odds Ratio (OR): 0.987, 0.983], endosteal circumference (OR: 0.853, 0.857), periosteal circumference (OR: 0.863, 0.824), and estimated bending strength (SSI; OR: 0.998, 0.997) were significant predictors of a BSI during training, respectively, such that lower values were associated with an increased likelihood of injury. Similarly, at the proximal diaphysis (66% site), total area (OR: 0.989, 0.985), endosteal circumference (OR: 0.855, 0.854), periosteal circumference (OR: 0.867, 0.823), robustness (OR: 0.007, 0.003), and SSI (OR: 0.998, 0.998) were also significant predictors of BSI in the simple and adjusted models, respectively, such that lower values were associated with an increased likelihood of injury. Results from this investigation support that narrower bones, with reduced circumference, lower total area, and lower estimated strength are associated with increased risk for tibial BSI during military training.

Modelling of bone fracture using the fundamental functional unit – Osteon

Limited bone sample size and number, coupled with hierarchical microstructures and non-linear damage, make credible assessment of bone quality difficult. This study presents a simple non-Linear Elastic Fracture Mechanics (non-LEFM) model, which can be easily adopted to measure bone strength and toughness using a limited number of small bone samples. The new closed-form model assumes that osteon, the fundamental functional unit of cortical bone, plays the dominant role in bulk bone properties. Different to Griffith theory [1] or LEFM [2] containing 0 microstructure, the new non-LEFM model contains 1 microstructure, the osteon diameter OD or the characteristic microstructure Cch. The “0 to 1” leap in microstructure modelling is critical for the evaluation of the non-linear damage prior to a transverse fracture. And it leads to the fracture relation Pmax = ft × Ae (Fracture Load = Strength × Area), in which the longitudinal tensile strength ft is the slope of the linear Pmax – Ae relation while the equivalent area Ae contains sample dimensions as well as Cch. Fracture measurements from samples with different sizes or initial cracks are on one straight line through the origin (0, 0), i.e. ft can be determined from any sample group. Fracture toughness KIC can then be transferred from ft and Cch. A statistical analysis based on normal distribution has been combined into the model so that the reliability band for bone strength and toughness can be specified. Bone data from literature are analyzed by the present model, and non-linear damage zones at Pmax in dry and wet bones are estimated and compared.

A Measure of Strength: Developmental PFAS Exposures and Bone Mineral Content in Adolescence.

Vol. 129, No. 12 Science SelectionOpen AccessA Measure of Strength: Developmental PFAS Exposures and Bone Mineral Content in Adolescenceis accompanied byAssociations of Maternal Serum Perfluoroalkyl Substances Concentrations with Early Adolescent Bone Mineral Content and Density: The Health Outcomes and Measures of the Environment (HOME) Study Charles W. Schmidt Charles W. Schmidt Search for more papers by this author Published:17 December 2021CID: 124002https://doi.org/10.1289/EHP10551AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InRedditEmail AbstractThe amount of bone mass that accumulates during early childhood and adolescence is a significant factor governing skeletal strength and the risk of osteoporosis in older adults.1,2 Growing evidence suggests developing bone may be damaged by exposures to per- and polyfluoroalkyl substances (PFAS).3 A new study in Environmental Health Perspectives4 associates higher concentrations of PFAS in maternal blood during pregnancy with lower measures of bone strength in adolescent children. The study was led by Jessie Buckley, an associate professor of environmental health and engineering at the Johns Hopkins Bloomberg School of Public Health in Baltimore, Maryland.Resistance to bone diseases such as osteoporosis depends on maximizing bone mass during critical growth periods, which include adolescence. A new study reports associations between higher prenatal PFAS exposures and lower measures of bone strength in 12-year-olds, with potential implications for adult bone health. Image: © Sergey Novikov/Shutterstock.Commonly described as “forever chemicals” because they are exceedingly resistant to degradation, PFAS have been used as stain, oil, and water repellents and as surfactants in fire-fighting foam.5 Certain PFAS are being phased out of production, but other novel formulations are being introduced to take their place.6Buckley and colleagues analyzed data collected by the Health Outcomes and Measures of the Environment (HOME) study, which enrolled pregnant women from Cincinnati, Ohio, and the surrounding areas between 2003 and 2006. This ongoing study aims to assess how fetal and early-life chemical exposures affect children’s growth and development.7 The women provided blood samples at 16 and 26 weeks of pregnancy and within a day of their child’s delivery. For the current study, the investigators measured PFAS in one sample per participant, with all three sampling points represented in the study.Buckley’s team analyzed data for 206 children from the HOME cohort who had also undergone dual-energy X-ray absorptiometry bone scans at 12 years of age. These scans measure inorganic bone mineral, which gives the skeleton its strength.8 Using those data, the researchers calculated two bone measurements: bone mineral content (BMC) and bone mineral density (BMD). The team then looked at how BMC and BMD measures varied with maternal blood concentrations of four PFAS: perfluorooctanoic acid (PFOA), perfluorononanoic acid (PFNA), perfluorohexane sulfonic acid (PFHxS), and perfluorooctane sulfonic acid.Higher concentrations of PFOA and PFNA individually and of all four PFAS assessed as a mixture were associated with lower z-scores for BMC and BMD in the forearm and hip. The lower z-scores suggest that children with higher PFAS exposures had lower average bone mass compared with individuals of the same age, sex, and ancestry. “The mixture’s relationship with bone outcomes was stronger than the relationship [of any single] PFAS,” Buckley says. “This is important, since in the real world people tend to be exposed to mixtures of different PFAS all at once.”Abby Fleisch, a pediatric endocrinologist at Maine Medical Center in Portland, who was not involved in the research, says the study has several strengths. “It identifies gestation as a possible vulnerable window for PFAS exposures to impact bone health later in life,” she says. Furthermore, prospective data gathered so far have been limited to females, whereas Buckley and colleagues studied both sexes. Indeed, higher maternal PFOA concentrations were generally associated with lower z-scores in males compared with females. However, a key limitation, Buckley says, is that small sample sizes resulting from losses during follow-up made it difficult to assess sex-related differences.Still, the study addresses “important questions regarding prenatal exposure to both individual and mixtures of PFAS,” says Meghan Lynch, an environmental epidemiologist and PFAS expert at Abt Associates, an environmental consulting company headquartered in Rockville, Maryland. “Decreases in BMD in childhood are linked to an increase in fractures and the development of osteoporosis,” she says. “More research is needed to understand if this [association with PFAS] persists and if it is exacerbated by ongoing exposure to PFAS through adolescence and beyond.”Charles W. Schmidt, MS, is an award-winning journalist in Portland, ME, whose work has appeared in Scientific American, Nature, Science, Discover Magazine, Undark, the Washington Post, and many other publications.

Bone Health Among Transgender Youth: What Is a Clinician to Do?

Bone Health Among Transgender Youth: What Is a Clinician to Do?

The influence of snuff and smoking on bone accretion in late adolescence. The Troms\xf8 study, Fit Futures

SummaryAreal bone mineral density (aBMD) predicts future fracture risk. This study explores associations between use of tobacco and bone accretion in Norwegian adolescents. Our results indicate that use of snuff is negatively associated with accretion of aBMD in adolescence and may be a signal of increased future fracture risk.PurposeBone mineral accrual in childhood and adolescence is a long-term primary preventive strategy of osteoporosis. Areal bone mineral density (aBMD) is a surrogate measure of bone strength and a predictor of fracture risk. The aim of this population-based 2-year follow-up cohort study was to explore associations between use of snuff and smoking and changes (∆) in aBMD in Norwegian girls and boys aged 15–17 years at baseline.MethodsThe first wave of the Tromsø study, Fit Futures was conducted from 2010 to 2011. Femoral neck (FN), total hip (TH), and total body (TB) bone mineral content (BMC) and aBMD were measured by dual-energy X-ray absorptiometry. Information on use of snuff, smoking habits, and other lifestyle related variables were collected through self-administered questionnaires. Two years later, during 2012–2013, the measurements were repeated in the second wave. The present study included 349 girls and 281 boys and compared “non-users” (n = 243 girls, 184 boys) with “users” (n = 105 girls, 96 boys) of snuff and “non-smokers” (n = 327 girls, 249 boys) with “smokers” (n = 21 girls, 31 boys) using linear regression adjusted for age, baseline height and weight, change in height and weight, pubertal maturation, physical activity, ethnicity, alcohol consumption, diagnosis known to affect bone, and medication known to affect bone. The influence of “double use” on bone accretion was also explored.ResultsIn girls, no associations between use of snuff and ∆aBMD were found. In boys, use of snuff was associated with reduced bone accretion in all ∆aBMD models. Sensitivity analysis with exclusion of “sometimes” users of snuff strengthened associations at femoral sites in girls and attenuated all associations in boys. In girls, no associations between smoking and ∆aBMD were found. In boys, only the association with TB ∆aBMD was significant in the fully adjusted models. In girls, “double users” analyses showed similar association to smoking. In boys, nearly all models showed statistically significant associations with a difference of ~ 1–2% in ∆aBMD between “non-users” and “double users” during 2 years of follow-up.ConclusionsOur results indicate that tobacco use in late adolescence could be detrimental to bone accretion and may be a signal of increased fracture risk in adult life.

Examining effects of habitual physical activity and body composition on bone structure in early post-menopausal women: a pQCT analysis.

The menopausal transition is characterized by dramatic bone loss, leading to an increased risk of fracture. Few studies have examined how modifiable risk factors influence bone structure. Thus, the objective of this cross-sectional study was to examine the relationship between habitual physical activity (PA), body composition, and bone structure in post-menopausal women with low bone mass. Data was analyzed from 276 post-menopausal women with low bone mass enrolled in the Heartland Osteoporosis Prevention Study. Body composition and bone structure measures were collected using dual X-ray absorptiometry (DXA) and peripheral quantitative computed tomography (pQCT) at the tibia. Habitual PA was collected using the Human Activity Profile questionnaire. Multiple regression analysis was used to determine the relative impact of habitual PA and body composition on bone structure measures (density, area, and strength). Direct and/or indirect effects of PA on bone outcomes were assessed by path analysis. Mean (± SD) age of participants was 54.5 (± 3.2) years and average BMI was 25.7(± 4.7). Mean T-score of the total lumber spine and hip were - 1.5 (± .6) and - 0.8 (± .59), respectively, with all women classified with low bone mass. Habitual PA had a significant positive effect on bone area and strength measures at the 66% site, and trend effects at the 4% site. Lean mass had a significant positive effect on area and strength at the 66% site and 4% site. Fat mass showed no effect at the 66% site, with a positive effect on density and strength at the 4% site. Increased habitual activity was related to improved bone structure of the tibia. Our results in post-menopausal women emphasize that PA and lean mass preservation are important for maintaining bone structure in the years following menopause.

Side-Side Radial Strength Differences In The Cortex In Female Volleyball Players Compared To Controls

INTRODUCTION: Repetitive mechanical loading optimizes bone strength as reported in studies investigating side to side differences in within-subject models using athletes from sports with high repetitive loads and that require use of a dominant lower limb (Weatherholt and Warden, 2016). Similarly, racquet sport players yielded greater strength differences compared to controls in their racquet limb (Kontulainen et al., 2003). Such differences are not yet fully understood in female volleyball players; therefore, due to the highly repetitive striking of a dominant upper limb, the use of female volleyball players is an appropriate population to determine such strength differences. PURPOSE: To determine the percent differences in cortical strength traits between the dominant-non dominant radii in female volleyball players compared to a control group. METHODS: Division II female volleyball players (VB) (N = 16) and age-match controls (CON) (N = 15) underwent peripheral quantitative computed tomography (pQCT) scans to measure bone strength in both radii at the 66% site. Side to Side differences in cortical density (ΔCoD, mg/cm3), cortical area (ΔCoA mm2), strength strain index (ΔSSIp mm3), and moment of inertia (ΔMoI mm4) were assessed using a 2x4 mixed ANOVA. RESULTS: VB (19 yrs + 1.2); CON (22.5 yrs + 3.3). No significant differences between dominant-non dominant radii across all variables were found. Radii cortical strength variables resulted in the following ΔCoD: VB -0.96 % (CI -1.93-0.01); CON -0.45 % (CI -0.03-0.87), ΔCoA: VB 2.12% (CI -0.61-4.85); CON 1.49% (CI -0.21-3.19), ΔSSIp: VB 0.31% (CI -5.8-6.42); CON -2.66 % (CI -7.29-1.97), ΔMoI: VB 4.77 % (CI -1.39-10.93); CON 2.98% (CI -0.46-6.42). CONCLUSION: No significant differences between the dominant-non dominant radii were found in Division II female volleyball players compared to age-matched controls. However, the structural variables CoA and MoI show greater percent differences compared to control than CoD. These data suggest that volleyball may not be an appropriate model for within-subject analysis for bone adaptation due to the type of mechanical loading that is common in the sport. Factors such as start-to-play age, position, and career duration may affect these side to side differences; further investigations are needed on a larger sample size.