Bone Strength Index Research Articles

Picking a bone with fluoride – dose-response meta-analysis on exposure to fluoride and bone density

Abstract There are still uncertainties around the effects, beneficial and adverse, of water fluoride exposure on bone density and strength. We selected bone mineral density (BMD) for investigation as it is recognized as the major non-invasive indicator of bone strength, representing its clinical assessment standard. The aim of this systematic review and meta-analysis was to characterize for the first time the relation between fluoride exposure and BMD through a dose-response approach, using a one-stage dose-response meta-analysis based on a cubic spline random-effects model. Out of 1201 potentially relevant literature records retrieved, after removing duplicates, title/abstract screening, and full-text evaluation, 16 studies were eligible for this review, 12 of which were also suitable for the dose-response meta-analysis. We observed an almost linear association between fluoride and BMD, yielding a mean difference of 2.60 (95% CI 0.17 to 0.40) at 4 mg/L of fluoride exposure. This pattern was also confirmed for hip BMD (MD = 2.83; 95% CI 0.11 to 0.40 at 4 mg/L). However, sex-specific analyses showed different patterns of association. In males, the relation between fluoride exposure and BMD was almost linear until 0.75 mg/L (MD = 0.24; 95% CI -0.22to 0.37), after which it plateaued. Females showed a slight increased BMD at 1 mg/L (MD = 0.05; 95% CI -0.02 to 0.16) but decreasing values above 2.5 mg/L (MD=-0.22; 95% CI -2.72 to 2.38 at 4 mg/L), with an indication of an inverted U-shaped association. This pattern was clearer when we restricted our analysis to hip BMD (MD=-0.56; 95% CI -2.98 to 1.85 at 4 mg/L). Sensitivity analyses examining both bone-specific BMD and conducting risk of bias assessments are currently underway. Moreover, imprecision of the estimates, especially in stratified analyses, and potential for residual confounding, underscore the need for further prospective studies, to more adequately assess the relation between fluoride exposure and bone density and strength. Key messages • At fluoride exposure below 1 mg/L, we observed a linear correlation between fluoride exposure and increase bone density in the overall pooled dose-response analysis of eligible studies. • Sex-specific patterns: males show positive response until certain exposure threshold; while females demonstrate an increase only at low doses of exposure and a downward trend at higher exposures.

Influence of Conditions for Obtaining Polylactide-Based Materials on Their Physico-Mechanical and Rheological Characteristics

The work is devoted to the study of the influence of the conditions for obtaining materials based on the synthetic polymer polylactide on their physico-mechanical and rheological characteristics. These materials are promising for the creation of biodegradable polymer implants of temporary action to maintain the mechanical properties of broken bones during the healing period. They are designed to replace the titanium fixators currently used for these purposes, which is due not only to the need for repeated surgery to extract them, but also to the fact that the strength and modulus of elasticity of titanium fixators exceed the values of bone strength indicators by an order of magnitude, which can cause the phenomenon of bone resorption and a decrease in its strength. It has been established that with an increase in temperature in the plasticization and pressing zone, as well as with an increase in pressure in the press, there is a natural decrease in the viscosity of the polylactide melt, as well as the values of the elastic modulus and breaking stress of solid samples. Varying the cooling rate of the material during the pressing process affects the degree of its crystallinity. At the same time, the lower the cooling rate, the greater the degree of crystallinity of the polylactide and the greater the values of the elastic modulus and breaking stress.

Generation and Validation of Normative, Age-Specific Reference Curves for Bone Strain Index in Women.

Bone Strain Index (BSI), based on dual-energy X-ray absorptiometry (DXA), is a densitometric index of bone strength of the femur and lumbar spine. Higher BSI values indicate a higher strain applied to bone, predisposing to higher fracture risk. This retrospective, multicentric study on Italian women reports the BSI normative age-specific reference curves. A cohort of Caucasian Italian women aged 20 to 90 years was selected from three different clinical centres. Bone mineral density (BMD) and BSI measurements were obtained for the lumbar spine vertebrae (L1-L4) and for the femur (neck, trochanter and intertrochanter) using Hologic densitometers scans. The data were compared with BMD normative values provided by the densitometer manufacturer. Then, the age-specific BSI curve for the femur and lumbar spine was generated. No significant difference was found between the BMD of the subjects in this study and BMD reference data provided by Hologic (p = 0.68 for femur and p = 0.90 for lumbar spine). Spine BSI values (L1-L4) increase by 84% between 20 and 90 years of age. The mean BSI of the total femur increases about 38% in the same age range. The BSI age-specific reference curve could help clinicians improve osteoporosis patient management, allowing an appropriate patient classification according to the bone resistance to the applied loads and fragility fracture risk assessment.

Effects of a manganese complex with lysine and glutamic acid on growth performance, manganese deposition, and emission, antioxidant capacity and metacarpal strength in weaned piglets.

The present study sought to assess the effects of manganese complexes with lysine and glutamic acid (Mn-LG) as manganese (Mn) sources on growth performance, trace element deposition, antioxidant capacity, and metacarpal strength in weaned piglets. The study involved 288 healthy Duroc × Landrace × Yorkshire piglets that were weaned at 25 to 28 d of age and weighed 8.66 ± 0.96kg. These piglets were randomly divided into six groups: a control group (Mn-LG-0, receiving a basal diet without Mn supplementation), a Mn sulfate group (basal diet supplemented with 40 mg·kg-1 diet of Mn, Mn-S-40 group), and four Mn-LG groups (Mn-LG-20, Mn-LG-40, Mn-LG-60, Mn-LG-80, supplemented with 20, 40, 60, and 80 mg·kg-1 Mn from Mn-LG in the basal diet). Grouping began at weaning on the 0th day of the experiment. The corn-soybean-based basal diet during the early (days 0 to 14) and late (days 15 to 42) phases of the experiment contained 20.88 and 30.12 mg·kg-1 Mn, respectively. Blood samples were collected on days 14 and 42, and pigs were sacrificed for sample collection on day 42. The results indicated no significant differences in average daily gain, average daily feed intake, or feed-to-gain ratio among the groups (P > 0.05). The diarrhea rates of all Mn-LG groups and the Mn-S-40 group were significantly lower in the 0 to 14 d and during the entire experimental period than in the Mn-LG-0 group (P < 0.001). The Mn-LG-40 group exhibited a significant increase in liver Mn concentration and serum Mn superoxide dismutase (Mn-SOD) activity on day 42 (P < 0.01), as well as a significant decrease in fecal Mn concentration (P < 0.05), compared to those of the Mn-S-40 group. Significant differences (P < 0.05) were detected in the serum, liver, and fecal Mn concentrations, as well as in the serum and liver Mn-SOD activity, across the different Mn-LG groups. The serum and fecal Mn concentrations and serum Mn-SOD activity increased linearly or quadratically (P < 0.01) with increasing Mn-LG supplementation. No significant differences (P > 0.05) were found in kidney, heart, or metacarpal bone Mn concentrations or in bone strength indices. In summary, compared with the Mn-LG-0 diet, dietary supplementation with Mn-LG enhanced serum Mn deposition and Mn-SOD activity and decreased the incidence of diarrhea. Additionally, the fecal Mn concentration was lower in the Mn-LG group than in the inorganic group at equivalent dosages.

Potential Effects of an Exoskeleton-Assisted Overground Walking Program for Individuals With Spinal Cord Injury Who Uses a Wheelchair on Imaging and Serum Markers of Bone Strength: Pre-Post Study.

As many as 60% of individuals use a wheelchair long term after a spinal cord injury (SCI). This mode of locomotion leads to chronic decline in lower-extremity weight-bearing activities and contributes to the development of severe sublesional osteoporosis and high rates of fragility fracture. Overground exoskeleton-assisted walking programs provide a novel opportunity to increase lower-extremity weight bearing, with the potential to improve bone health. The aim of the study is to measure the potential effects of an exoskeleton-assisted walking program on lower-extremity bone strength and bone remodeling biomarkers in individuals with chronic (≥18 months) SCI who use a wheelchair. In total, 10 participants completed a 16-week exoskeleton-assisted walking program (34 individualized 1-hour sessions, progressing from 1 to 3 per week). Bone mineral density and bone strength markers (dual-energy x-ray absorptiometry: total body, left arm, leg, total hip, and femoral neck and peripheral quantitative computed tomography: 25% of left femur and 66% of left tibia) as well as bone remodeling biomarkers (formation=osteocalcin and resorption=C-telopeptide) were measured before and after intervention and compared using nonparametric tests. Changes were considered significant and meaningful if the following criteria were met: P<0.1, effect size ≥0.5, and relative variation >5%. Significant and meaningful increases were observed at the femur (femoral neck bone mineral content, bone strength index, and stress-strain index) and tibia (cortical cross-sectional area and polar moment of inertia) after the intervention (all P<.10). We also noted a decrease in estimated femoral cortical thickness. However, no changes in bone remodeling biomarkers were found. These initial results suggest promising improvements in bone strength markers after a 16-week exoskeleton-assisted walking program in individuals with chronic SCI. Additional research with larger sample sizes, longer interventions (possibly of greater loading intensity), and combined modalities (eg, pharmacotherapy or functional electrical stimulation) are warranted to strengthen current evidence. ClinicalTrials.gov NCT03989752; https://clinicaltrials.gov/ct2/show/NCT03989752. RR2-10.2196/19251.

Deterioration of apatite orientation in the cholecystokinin B receptor gene (Cckbr)-deficient mouse femurs.

The discrepancy between bone mineral density (BMD), the gold standard for bone assessment, and bone strength is a constraint in diagnosing bone function and determining treatment strategies for several bone diseases. Gastric hypochlorhydria induced by clinically used proton pump inhibitor (PPI) therapy indicates a discordance between changes in BMD and bone strength. Here, we used Cckbr-deficient mice with gastric hypochlorhydria to examine the effect of gastric hypochlorhydria on bone mass, BMD, and preferential orientation of the apatite crystallites, which is a strong indicator of bone strength. Cckbr-deficient mice were created, and their femurs were analyzed for BMD and preferential orientation of the apatite c-axis along the femoral long axis. Cckbr-deficient mouse femurs displayed a slight osteoporotic bone loss at 18weeks of age; however, BMD was comparable to that of wild-type mice. In contrast, apatite orientation in the femur mid-shaft significantly decreased from 9 to 18weeks. To the best of our knowledge, this is the first report demonstrating the deterioration of apatite orientation in the bones of Cckbr-deficient mice. Lesions in Cckbr-deficient mice occurred earlier in apatite orientation than in bone mass. Hence, bone apatite orientation may be a promising method for detecting hypochlorhydria-induced osteoporosis caused by PPI treatment and warrants urgent clinical applications.

Relationship between CT-Derived Bone Mineral Density and UTE-MR-Derived Porosity Index in Equine Third Metacarpal and Metatarsal Bones.

Fatigue-related subchondral bone injuries of the third metacarpal/metatarsal (McIII/MtIII) bones are common causes of wastage, and they are welfare concerns in racehorses. A better understanding of bone health and strength would improve animal welfare and be of benefit for the racing industry. The porosity index (PI) is an indirect measure of osseous pore size and number in bones, and it is therefore an interesting indicator of bone strength. MRI of compact bone using traditional methods, even with short echo times, fail to generate enough signal to assess bone architecture as water protons are tightly bound. Ultra-short echo time (UTE) sequences aim to increase the amount of signal detected in equine McIII/MtIII condyles. Cadaver specimens were imaged using a novel dual-echo UTE MRI technique, and PI was calculated and validated against quantitative CT-derived bone mineral density (BMD) measures. BMD and PI are inversely correlated in equine distal Mc/MtIII bone, with a weak mean r value of -0.29. There is a statistically significant difference in r values between the forelimbs and hindlimbs. Further work is needed to assess how correlation patterns behave in different areas of bone and to evaluate PI in horses with and without clinically relevant stress injuries.

#5559 BONE SPECIFIC ALKALINE PHOSPHATASE AS A POTENTIAL BIOMARKER OF AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE PROGRESSION

Abstract Background and Aims Autosomal dominant polycystic kidney disease (ADPKD) is a systemic disease, resulting in a dysfunction of the primary cilium, a sensory organelle ubiquitously present in human cells. Ciliopathies are characterized by disorders of seemingly unrelated organs and functions, which depend on integrity of the primary cilium, among them the skeleton and the kidneys. A distinct bone phenotype has been reported in ADPKD patients in several cohort studies. Findings, however, were heterogenous. Present study aimed to measure bone turnover biomarkers in patients with ADPKD across disease severity measured by eGFR and height-adjusted total kidney volume (HtTKV). Method In this cross-sectional study, we included 80 ADPKD patients with different chronic kidney disease (CKD) stages (G1 and G2 (n = 39), and G3 and G4 (n = 41)) with median age 44.0 (33.5-50.5) years, 62.5% men, and BMI 25.1 (23.3-28.7) kg/m2. HtTKV was measured with magnetic resonance imaging. We measured biochemical parameters of mineral metabolism, including bone specific alkaline phosphatase (BALP) and total ALP, calcium (Ca), parathyroid hormone (PTH), and 25(OH) vitamin D (25(OH)D) and bone strength index (BSi) with microindentation, using an OsteoProbe® (Active Life Scientific, USA). Microindentation is minimally invasive technique assessing bone quality. The cortical bone at the mid-shaft of the tibia is penetrated with the indenter to measure bone resistance. Results Bone biomarkers expressed as median and interquartile range were as follow: Ca 9.6 (9.3-9.9) mg/dL, BALP 9.0 (7.0-12.5) ug/L, ALP 59.0 (46.0-72.0) U/L, PTH 43.5 (26.6-72.0) pg/mL and 25(OH)D 25.4 (16.6-33.5) ng/mL. Median BSi was 79.1(73.5-82.1) in men and 68.5 (62.1-78.6) in women (lower than the average score in healthy caucasians). Among analyzed bone markers only BALP significantly associated with severity of ADPKD. BALP - but not eGFR - associated with HtTKV and was different across HtTKV tertiles. BALP was also higher in the highest BSi group, but BSi did not associate with HtTKV (Figure 1). Conclusion In patients with ADPKD and different stages of CKD, BALP associates with bone strength and kidney volume, suggesting that it may be a sensitive marker of systemic ADPKD manifestations. Further studies should elucidate whether BALP may be a more sensitive marker for ADPKD progression than GFR.

Bone-specific physical activity questionnaire-derived skeletal loading score predicts bone geometry, density, and strength indices: a cross-sectional study.

The bone-specific physical activity questionnaire (BPAQ) provides a bone-relevant index of physical activity participation according to the mechanical loads experienced across the life span. We aimed to examine relationships between historical bone-relevant physical activity and pQCT-derived parameters of bone strength. We recruited 532 healthy volunteers (277 males, 255 females) across a broad age range (4-97years). Peripheral quantitative computed tomography (XCT-3000, Stratec, Germany) was used to examine volumetric bone density, area, and strength indices of the non-dominant tibia and radius. Exercise loading history from birth was determined using the past BPAQ (pBPAQ) score. Pearson correlation analysis was used to examine relationships between pBPAQ scores and pQCT parameters. Independent of sex, pBPAQ scores were associated with total density at the 38% and 66% tibial sites and the 66% radial site (r = 0.145-0.261, p ˂ 0.05), total area at the 38% tibial site and 4% and 66% radial sites (r = 0.129-0.156, p ˂ 0.05), and strength indices at all measured sites (r = 0.123-0.234, p < 0.05). We conclude that, independent of sex, historical bone-relevant physical activity is associated with pQCT-derived indices of bone strength, indicating that pBPAQ captures the characteristics of bone loading history that are likely to be relevant adaptive stimuli.A larger sample is required to examine the influence of age on this relationship.

Associations between blood antioxidant levels and femoral neck strength

BackgroundStudies have confirmed that antioxidants contribute to a lower risk of osteoporosis, which is an independent factor for femoral neck fracture (FNF). However, the associations between blood antioxidant levels and femoral neck strength remain unclear.ObjectiveOur aim was to test the hypothesis that levels of blood antioxidants are positively associated with composite indices of bone strength in femoral neck, which integrate the bending strength index (BSI), compressive strength index (CSI), and impact strength index (ISI), in a population of middle-aged and elderly individuals.MethodsThis cross-sectional study utilized data from the Midlife in the United States (MIDUS) study. Blood levels of antioxidants were measured and analyzed.ResultsIn total, data from 878 participants were analyzed. Results of Spearman correlation analyses indicated that blood levels of 6 antioxidants (total lutein, zeaxanthin, alpha-carotene, 13-cis-beta-carotene, trans-beta-carotene and total lycopene) were positively associated with CSI, BSI, or ISI in middle-aged and elderly individuals. Conversely, blood gamma-tocopherol and alpha-tocopherol levels were negatively associated with CSI, BSI, or ISI scores. Furthermore, linear regression analyses suggested that only blood zeaxanthin levels remained positively associated with CSI (odds ratio, OR 1.27; 95% CI: 0.03, 2.50; p = 0.045), BSI (OR, 0.54; 95% CI: 0.03–1.06; p = 0.037), and ISI (OR, 0.06; 95% CI: 0.00, 0.13; p = 0.045) scores in the study population after adjusting for age and sex.ConclusionsOur results indicated that elevated blood zeaxanthin levels were significantly and positively associated with femoral neck strength (CSI, BSI, or ISI) in a population of middle-aged and elderly individuals. These findings suggest that zeaxanthin supplementation may reduce FNF risk independently.

Time Trends in Trajectories of Forearm Mineral Content and Bone Size during Childhood-Results from Cross-Sectional Measurements with the Same Apparatus Four Decades Apart.

Evidence suggests that single photon absorptiometry (SPA)-measured forearm bone mineral density (BMD) is lower in contemporary children in Malmö than it was four decades ago, but the fracture incidence in the at-risk population (all Malmö children) has been stable during the same period. The aim of this study was to evaluate if improvements in skeletal structure over time may explain this observation. In 2017-2018 we measured distal forearm bone mineral content (BMC; mg/cm) and periosteal diameter (mm) in 238 boys and 204 girls aged 7-15 using SPA. Based on the SPA measurements, we calculated forearm BMD (mg/cm2), bone mineral apparent density (BMAD, mg/cm3), section modulus, and strength index (BMAD × section modulus). The results were compared with those derived from measurements of 55 boys and 61 girls of the same ages using the same scanner in 1979-1981. We used log-linear regression with age, sex, and cohort as predictors to investigate differences in trait trajectories (trait versus age slopes [mean percent difference in beta values (95% confidence interval)]). SPA-measured forearm BMC was lower at each age in 2017-2018 compared to 1979-1981 (a mean age and sex adjusted relative difference of 9.1%), the forearm BMC trajectory was similar in 2017-2018 to that in 1979-1981 (reference) [0.0%/year (-1.0%, 1.0%)], while the 2017-2018 forearm periosteal diameter trajectory was steeper [1.1%/year (0.3%, 2.0%)]. Since bone size influences both BMD (BMC divided by scanned area) and mechanical characteristics, the forearm BMD trajectory was flatter in 2017-2018 [-1.1%/year (-2.0%, -0.2%)] and the forearm section modulus trajectory steeper [3.9%/year (1.4%, 6.4%)]. Forearm strength index trajectory was similar [1.8%/year (-0.5%, 4.1%)]. The lower SPA-measured forearm BMD trajectory in contemporary children compared to four decades ago may be offset by changes in forearm bone structure, resulting in similar overall bone strength. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Road cycling and bone health: a scoping review

Introduction&#x0D; In competitive road cycling, low body mass is a common focus for many athletes. Due to the high energy expenditure and non-weight bearing nature of competitive road cycling, there are associated health risks including relative energy deficiency and low bone mineral density. Untreated, this can lead to an increased susceptibility to fracture. This can be a particular problem in competitive road cycling where the prevalence of falls is high.&#x0D; Methods&#x0D; A scientific literature search on studies investigating relative energy deficiency and bone mineral density in the sport of road cycling was performed. &#x0D; Results&#x0D; Twenty-four studies investigated the relationship between road cycling and relative energy deficiency, bone mineral density, bone structure, calcium and vitamin D, markers for bone metabolism and strength training. Road cyclists were generally found to be at risk of relative energy deficiency and reduced bone mineral density. However, bone strength indices on peripheral quantitative computed tomography were not reduced. There was also conflicting evidence on the effect of consuming calcium and vitamin D on markers for bone metabolism and bone mineral density. Studies supported evidence that the inclusion of strength training can have a positive effect on bone mineral density in road cyclists.&#x0D; Discussion&#x0D; Relative energy deficiency in road cyclists is particularly concerning due to its detrimental impact on bone health and general increased risk of injury. Similarly, low bone mineral density is worrying due to high prevalence of falls and subsequent fracture risk. While it remains to be seen whether calcium and vitamin D supplementation provide adequate bone protection, increased education among competitive road cyclists on the benefits of energy balance and strength training in terms of bone health could be useful and should be advocated by their support team.&#x0D; Conclusion&#x0D; There was evidence of increased risk of relative energy deficiency, low bone mineral density and increased bone resorption in road cyclists. However, there was also evidence that strength and impact training could improve bone health in competitive road cyclists

Bone Strength of the Calcaneus Is Associated with Dietary Calcium Intake in Older Japanese Men, but Not Women.

The relationship between calcium intake and bone strength in older Asian individuals, including Japanese, is controversial; therefore, we herein investigated this relationship in older Japanese populations. We performed a cross-sectional analysis of 314 participants older than 65 years who voluntarily participated in a medical examination and responded to questionnaires. The osteo-sono assessment index (OSI) measured at the right calcaneus using a quantitative ultrasonic device was used as an indicator of bone strength. The daily dietary intake of calcium was assessed using a brief-type self-administered diet history questionnaire. A two-way analysis of covariance revealed a significant interaction between sex and calcium intake on the OSI (p &lt; 0.01). A multiple regression analysis showed a positive correlation between calcium intake and the OSI in males (p &lt; 0.01), but not females (p = 0.27). In females, grip strength divided by body weight positively correlated with the OSI (p = 0.04). The present results suggest that a higher calcium intake contributes to bone strength in older Japanese males. Although a higher grip strength may contribute to bone strength in females, the potential of estrogen as a confounding factor needs to be considered.

Trabecular bone score and phalangeal quantitative ultrasound are associated with muscle strength and fracture risk in hemodialysis patients.

There is growing interest in the relationship between chronic kidney disease (CKD) and fragility fracture risk. Bone mineral density (BMD) is a major determinant of bone strength, although its role as a predictor of fracture in advanced CKD and hemodialysis is still under debate. We aimed to further investigate surrogates of bone quality and their associations with muscle strength and fracture risk in hemodialysis. Multiple clinical risk factors for fracture and an estimated 10-year probability of fracture, BMD at lumbar spine and femur, trabecular bone score (TBS), X-ray vertebral morphometry, phalangeal bone quantitative ultrasonography (QUS), tibial pulse-echo ultrasonography (PEUS), and handgrip strength were evaluated in a setting of hemodialysis patients in treatment with acetate-free biofiltration (AFB) or bicarbonate hemodialysis. The bone ultrasound measurements, both at phalangeal and tibial sites, were significantly associated with lumbar and femoral DXA values. Handgrip strength was significantly associated with the 10-year probability of fracture (r = −0.57, p < 0.001 for major fractures and r = −0.53, p < 0.001 for hip fracture, respectively), with femur neck, total femur, and L1–L4 BMD values (r = 0.47, p = 0.04; r = 0.48, p = 0.02; r = 0.58, p = 0.007, respectively), with TBS at the lumbar spine (r = 0.71, p < 0.001) and with the phalangeal QUS measure of AD-SoS (r = 0.369, p = 0.023). In the hemodialysis group, 10 participants (24.3%) reported at least one morphometric vertebral fracture (Vfx); conversely, only six participants (15%) showed Vfx in the control group. In the hemodialysis group, participants with Vfx compared with participants without Vfx reported significantly different TBS, bone transmission time (BTT), cortical thickness, and handgrip strength (p < 0.05). At multiple regression analysis, by identifying as dependent variable the 10-year fracture risk for major fracture, after correcting for age, BMI, time since dialysis, AD-SoS, cortical bone thickness, and handgrip strength, only BTT (β = −15.21, SE = 5.91, p = 0.02) and TBS (β = −54.69, SE = 21.88, p = 0.02) turned out as independently associated with fracture risk. In conclusion, hemodialysis patients showed a higher fracture risk and lower surrogate indices of bone strength as TBS and QUS parameters. In this cohort of patients, handgrip strength measurements appeared to be a useful instrument to identify high-fracture-risk subjects.

Hind limb muscles influence the architectural properties of long bones in frogs.

The Mechanostat Theory states that osteocytes sense both the intensity and directionality of the strains induced by mechanical usage and modulate the bone design accordingly. In long bones, this process may adapt anterior-posterior and lateral-medial strength to their mechanical environment showing regional specificity. Anuran species are ideal for analyzing the muscle-bone relationships related to the different mechanical stresses induced by their many locomotor modes and habitat uses. This work aimed to explore the relationships between indicators of the force of the most relevant muscles to locomotion and the mechanical properties of femur and tibia fibula in preserved samples of three anuran species with different habitat use (aquatic, arboreal) and locomotion modes (swimmer, jumper, walker/climber). For that purpose, we measured the anatomical cross-sectional area of each dissected muscle and correlated it with the moments of inertia and bone strength indices. Significant, species-specific covariations between muscle and bone parameters were observed. Pseudis platensis, the aquatic swimmer, showed the largest muscles, followed by Boana faber, the jumper and Phyllomedusa sauvagii, the walker/climber. As we expected, bigger muscles correlate with bone parameters in all the species. Nevertheless, smaller muscles also play an important role in bone design. In aquatic species, muscle interaction enhances mostly lateral bending strength throughout the femur and lateral and antero-posterior bending strength in the tibia fibula. In the jumper species, muscles affected the femur and tibia fibula mostly in anterior-posterior bending. In the walker/climber species, responses involving both antero-posterior and lateral bending strengths were observed in the femur and tibia fibula. These results show that bones will be more or less resistant to lateral and antero-posterior bending according to the different mechanical challenges of locomotion in aquatic vs. arboreal habitats. This study provides new evidence of the muscle-bone relationships in three frog species associated with their different locomotion and habitat uses, highlighting the crucial role of muscle in determining the architectural properties of bones.

High-Intensity Exercise and Geometric Indices of Hip Bone Strength in Postmenopausal Women on or off Bone Medication: The MEDEX-OP Randomised Controlled Trial

To compare the effects of high-intensity resistance and impact training (HiRIT) to low-intensity, Pilates-based exercise (LiPBE) on proximal femur geometry and explore the influence of antiresorptive medication on those effects. Postmenopausal women with low bone mass, on or off antiresorptive bone medications were randomly allocated, stratified on medication intake, to eight months of twice-weekly, supervised HiRIT (Onero™) or LiPBE (Buff Bones®). 3D hip software was used to analyse proximal femur DXA scans. Outcomes included femoral neck (FN) and total hip (TH), volumetric (e.g. vBMC, vBMD) and geometric (e.g. cortical thickness, cross-sectional area [CSA], section modulus [Z]) indices of bone strength. Data were analysed using analysis of variance. Scans of 102 women were examined: LiPBE, 43; HiRIT, 37; LiPBE-med, 11; HiRIT-med, 11. HiRIT improved TH trabecular vBMC and vBMD (3.1 ± 1.1% versus − 1.2 ± 1.2%, p = 0.008; and 1.5 ± 1.0% versus − 1.6 ± 1.2%, p = 0.042, respectively) and FN and TH total vBMC (2.0 ± 0.8% versus − 0.2 ± 0.7%, p = 0.032; and 0.7 ± 0.4% versus − 0.8 ± 0.6%, p = 0.032, respectively), compared to losses in LiPBE. HiRIT also increased Z while LiPBE did not (p = 0.035). The combination of HiRIT and medication achieved greater improvements in FN total and trabecular vBMD, total BMC, CSA and Z than HiRIT alone. HiRIT improved geometric parameters of proximal femur strength, while LiPBE exercise was largely ineffective. Medication may enhance some HiRIT effects. Findings suggest reduced hip fracture risk in response to HiRIT.Trial registration number ACTRN12617001511325.

One-Year Mean A1c of > 7% is Associated with Poor Bone Microarchitecture and Strength in Men with Type 2 Diabetes Mellitus.

Type 2 diabetes mellitus (T2DM) is associated with normal or slightly elevated bone mineral density (BMD) but paradoxically increased fracture risk. Although multiple mechanisms have been proposed to explain this observation, one thing is clear from prior studies, T2DM is associated with poor bone quality rather than a defect in bone quantity. The objective of our study is to evaluate the effect of longitudinal glycemic control on bone quality and bone turnover in men with T2DM. This was a secondary analysis of baseline data from 169 male participants, aged 35-65 in 3 clinical trials. Participants were grouped according to the average of all their A1C measurements between 9 and 15months prior to study entry (group 1: no T2DM, group 2: T2DM with A1C ≤ 7%, group 3: T2DM with A1C > 7%). At study entry serum osteocalcin and C-terminal telopeptide of type 1 collagen (CTx) were measured by ELISA, and testosterone and estradiol by liquid-chromatography/mass-spectrometry. Areal BMD, trabecular bone score and body composition were measured by dual-energy X-ray absorptiometry while volumetric BMD, bone microarchitecture, and bone strength were assessed by high-resolution peripheral quantitative computed tomography. At the tibia, trabecular separation was higher and trabecular number was significantly lower in group 3 compared to both groups 2 and 1, even after adjustments for covariates (p = 0.02 for both). Bone strength indices at the tibia such as stiffness and failure load were lowest in group 3, the difference being significant when compared to group 1 (p = 0.01, p = 0.009 respectively) but not to group 2, after adjustments for covariates. Bone turnover markers (osteocalcin and CTx) were significantly lower in group 3 relative to group 1, with CTx also being significantly lower in group 3 compared with group 2 (p < 0.001, p = 0.001 respectively). Poor glycemic control over the course of a year in men with T2DM is associated with poorer bone microarchitecture and strength, and reduced bone turnover. Conversely, good glycemic control in the setting of T2DM appears to attenuate this observed impairment in bone quality.

Are Children Suffering From Congenital Pseudarthrosis of the Tibia Associated With Decreased Bone Strength?

Background:Congenital pseudarthrosis of the tibia (CPT) is a rare and difficult-to-treat congenital disease in neonates. Our previous study found that exosomes derived from serum of children with CPT inhibit bone formation. In this study, we used ultrasound bone densitometry to detect the bone strength differences between hospitalized children with CPT and with non-metabolic diseases to determine the bone strength of children with CPT.MethodsA total of 37 children with CPT with a mean age of 3.14 ± 1.81 years and 40 hospitalized children with a mean age of 3.32 ± 2.66 years with supracondylar fracture of the humerus and without a bone metabolic disease (control group) were recruited in our hospital. The ultrasonic bone densitometer was used to examine the bilateral calcaneus of the subjects. We collected the broadband ultrasonic attenuation (BUA), speed of sound (SOS), quantitative ultrasound index (QUI), bone strength index (STI) and bone mineral density estimation (BMDe) values. Multivariable regression was used to examine the associations between quantitative ultrasound measurement differences and age, body mass index (BMI), neurofibromatosis type 1 (NF1) and CPT Crawford type. Intra-class correlation coefficient (ICC) was calculated to estimate intra- and inter-rater agreements.Results74 calcaneus scans were taken from CPT patients (23 boys and 14 girls) and 80 calcaneus scans were taken from the control (24 boys and 16 girls). The CPT patients exhibited significantly lower SOS (1,368.75 ± 136.78 m/s), STI (7.2319 ± 38.6525), QUI (8.2532 ± 56.1720), and BMDe (−0.0241 ± 0.3552 g/cm3) than the control (SOS: 1,416.02 ± 66.15 m/s, STI: 7.96 ± 16.884, QUI: 28.8299 ± 25.461, BMDe: 0.0180 ± 0.1610 g/cm3). Multiple regression revealed that SOS, STI and QUI were statistically significant and negatively correlated with CPT Crawford classification.ConclusionsWe found the incidence of decreased bone strength in CPT group was higher than that in the non-bone metabolic disease group. This phenomenon was not related to NF1 but related to CPT Crawford classification, which suggested that the higher the grade of the CPT Crawford classification, the lower the bone strength and the higher the risk of fracture.

The Bone Strain Index: An Innovative Dual X-ray Absorptiometry Bone Strength Index and Its Helpfulness in Clinical Medicine.

Bone strain Index (BSI) is an innovative index of bone strength that provides information about skeletal resistance to loads not considered by existing indexes (Bone Mineral Density, BMD. Trabecular Bone Score, TBS. Hip Structural Analysis, HSA. Hip Axis Length, HAL), and, thus, improves the predictability of fragility fractures in osteoporotic patients. This improved predictability of fracture facilitates the possibility of timely intervention with appropriate therapies to reduce the risk of fracture. The development of the index was the result of combining clinical, radiographical and construction-engineering skills. In fact, from a physical point of view, primary and secondary osteoporosis, leading to bone fracture, are determined by an impairment of the physical properties of bone strength: density, internal structure, deformation and fatigue. Dual X-ray absorptiometry (DXA) is the gold standard for assessing bone properties, and it allows measurement of the BMD, which is reduced mainly in primary osteoporosis, the structural texture TBS, which can be particularly degraded in secondary osteoporosis, and the bone geometry (HSA, HAL). The authors recently conceived and developed a new bone deformation index named Bone Strain Index (BSI) that assesses the resistance of bone to loads. If the skeletal structure is equated to engineering construction, these three indexes are all considered to determine the load resistance of the construct. In particular, BSI allows clinicians to detect critical information that BMD and TBS cannot explain, and this information is essential for an accurate definition of a patient’s fracture risk. The literature demonstrates that both lumbar and femoral BSI discriminate fractured osteoporotic people, that they predict the first fragility fracture, and further fragility fractures, monitor anabolic treatment efficacy and detect patients affected by secondary osteoporosis. BSI is a new diagnostic tool that offers a unique perspective to clinical medicine to identify patients affected by primary and, specially, secondary osteoporosis. This literature review illustrates BSI’s state of the art and its ratio in clinical medicine.

The bone strain index predicts fragility fractures. The OFELY study.

Recently, the bone strain index (BSI), a new index of bone strength based on a finite element model (FEA) from dual X-ray absorptiometry (DXA), has been developed. BSI represents the average equivalent strain inside the bone, assuming that a higher strain level (high BSI) indicates a condition of higher risk. Our study aimed to analyze the relationship between BSI and age, BMI and areal BMD in pre- and postmenopausal women and to prospectively investigate fracture prediction (Fx) by BSI in postmenopausal women. Methods. At the 14th annual follow-up of the OFELY study, BSI was measured at spine (Spine BSI) and femoral scans (Neck and Total Hip BSI), in addition to areal BMD with DXA (Hologic QDR 4500) in 846 women, mean (SD) age 60yr (15). The FRAX® (fracture risk assessment tool) for major osteoporotic fractures (MOF) was calculated with FN areal BMD (aBMD) at baseline; incident fragility fractures were annually registered until January 2016. Results. In premenopausal women (n=261), Neck and Total Hip BSI were slightly negatively correlated with age (Spearman r=-0.13 and -0.15 respectively, p=0.03), whereas all BSIs were positively correlated with BMI (r=+0.20 to 0.37, p<0.01) and negatively with BMD (r=-0.69 to -0.37, p<0.0001). In postmenopausal women (n=585), Neck and Total Hip BSI were positively correlated with age (Spearman r=+0.26 and +0.31 respectively, p<0.0001), whereas Spine BSI was positively correlated with BMI (r=+0.22, p<0.0001) and all BSIs were negatively correlated with BMD (r=-0.81 to -0.60, p<0.0001). During a median [IQ] 9.3 [1.0] years of follow-up, 133 postmenopausal women reported an incident fragility Fx, including 80 women with a major osteoporotic Fx (MOF) and 26 women with clinical vertebral Fx (VFx). Each SD increase of BSI value was associated with a significant increase of the risk of all fragility Fx with an age-adjusted HR of 1.23 for Neck BSI (p=0.02); 1.27 for Total Hip BSI (p=0.004) and 1.35 for Spine BSI (p<0.0001). After adjustment for FRAX®, the association remained statistically significant for Total Hip BSI (HR 1.24, p=0.02 for all fragility Fx; 1.31, p=0.01 for MOF) and Spine BSI (HR 1.33, p<0.0001 for all fragility Fx; 1.33, p=0.005 for MOF; 1.67, p=0.002 for clinical VFx). In conclusion, spine and femur BSI, an FEA DXA derived index, predict incident fragility fracture in postmenopausal women, regardless of FRAX®.