Bone Material Strength Index Research Articles

Impaired Bone Tissue Quality Associated with Inflammation in HIV-Immunological Non-Responders: A Cross-Sectional Analysis.

People with HIV (PWH) with poor immune response despite adequate antiretroviral treatment (ART) are susceptible to non-AIDS-related health issues. This study seeks to evaluate bone quality in Immunological Non-Responders (INRs) in comparison to those with proper immune response (IRs) using in vivo microindentation to quantify bone quality, in addition to conventional bone mineral density (BMD) evaluations. A cross-sectional study was conducted at Hospital del Mar in Barcelona from January 2019 to June 2023. Participants were matched in a 1:2-ratio (INRs:IR) based on age, sex, body mass index (BMI), and ART. Participants underwent bone quality assessment using in vivo microindentation, BMD and analysis of bone turnover and inflammation markers. Statistical analyses involved multivariable regression to adjust for potential confounding variables. A total of 159 PWH were included, 53 INRs and 106 IRs. INRs had worse bone quality, with lower median Bone Material Strength index (BMSi) compared to IRs (79 (76-87) vs. 86 (82-89); p<0.001), and similar BMD. INRs shown increased high-sensitive C-Reactive Protein levels with lower 25-(OH)-Vitamin D3. A significant negative correlation between inflammation and bone quality was found, especially noticeable in INRs. Multivariable linear regression shown that INR status is a major predictor of decreased bone quality, regardless of conventional risk factors. INRs condition is significantly associated with higher inflammatory levels, which may contribute to a deleterious effect on bone quality as measured by in vivo microindentation. Further studies are needed to confirm these results and to focus on non-AIDS comorbidities in this subgroup of PWH.

Type 2 Diabetes and Fracture Risk in Older Women

The reasons for the increased fracture risk in type 2 diabetes (T2D) are not fully understood. To determine if poorer skeletal characteristics or worse physical function explain the increased fracture risk in T2D. This prospective observational study is based on the population-based Sahlgrenska University Hospital Prospective Evaluation of Risk of Bone Fractures study cohort of older women, performed in the Gothenburg area between March 2013 and May 2016. Follow-up of incident fracture data was completed in March 2023. Data analysis was performed between June and December 2023. Data were collected from questionnaires and through examination of anthropometrics, physical function, and bone measurements using bone densitometry (dual-energy x-ray absorptiometry), and high-resolution peripheral computed tomography. A subsample underwent bone microindentation to assess bone material strength index (BMSi). Baseline assessment of bone characteristics and physical function and radiograph verified incident fractures. Of 3008 women aged 75 to 80 years, 294 women with T2D (mean [SD] age, 77.8 [1.7] years) were compared with 2714 women without diabetes (mean [SD] age, 77.8 [1.6] years). Women with T2D had higher bone mineral density (BMD) at all sites (total hip, 4.4% higher; femoral neck (FN), 4.9% higher; and lumbar spine, 5.2% higher) than women without. At the tibia, women with T2D had 7.4% greater cortical area and 1.3% greater density, as well as 8.7% higher trabecular bone volume fraction. There was no difference in BMSi (T2D mean [SD], 78.0 [8.3] vs controls, 78.1 [7.3]). Women with T2D had lower performance on all physical function tests. The study found 9.7% lower grip strength, 9.9% slower gait speed, and 13.9% slower timed up-and-go time than women without diabetes. During a median (IQR) follow-up of 7.3 (4.4-8.4) years, 1071 incident fractures, 853 major osteoporotic fractures (MOF), and 232 hip fractures occurred. In adjusted (for age, body mass index, clinical risk factors, and FN BMD) Cox regression models, T2D was associated with an increased risk of any fracture (HR, 1.26; 95% CI, 1.04-1.54) and MOF (HR, 1.25; 95% CI, 1.00-1.56). In this cohort study of older women, T2D was associated with higher BMD, better bone microarchitecture, and no different BMSi but poorer physical function, suggesting that poor physical function is the main reason for the increased fracture risk in T2D women.

Assessment of bovine cortical bone fracture behavior using impact microindentation as a surrogate of fracture toughness.

The fracture behavior of bone is critically important for evaluating its mechanical competence and ability to resist fractures. Fracture toughness is an intrinsic material property that quantifies a material's ability to withstand crack propagation under controlled conditions. However, properly conducting fracture toughness testing requires the access to calibrated mechanical load frames and the destructive testing of bone samples, and therefore fracture toughness tests are clinically impractical. Impact microindentation mimicks certain aspects of fracture toughness measurements, but its relationship with fracture toughness remains unknown. In this study, we aimed to compare measurements of notched fracture toughness and impact microindentation in fresh and boiled bovine bone. Skeletally mature bovine bone specimens (n = 48) were prepared, and half of them were boiled to denature the organic matrix, while the other half remained preserved in frozen conditions. All samples underwent a notched fracture toughness test to determine their resistance to crack initiation (KIC) and an impact microindentation test using the OsteoProbe to obtain the Bone Material Strength index (BMSi). Boiling the bone samples increased the denatured collagen content, while mineral density and porosity remained unaffected. The boiled bones also showed significant reduction in both KIC (P < .0001) and the average BMSi (P < .0001), leading to impaired resistance of bone to crack propagation. Remarkably, the average BMSi exhibited a high correlation with KIC (r = 0.86; P < .001). A ranked order difference analysis confirmed the excellent agreement between the 2 measures. This study provides the first evidence that impact microindentation could serve as a surrogate measure for bone fracture behavior. The potential of impact microindentation to assess bone fracture resistance with minimal sample disruption could offer valuable insights into bone health without the need for cumbersome testing equipment and sample destruction.

The practicality of using bone impact microindentation in a population-based study of women: A Geelong-Osteoporosis Study

Impact microindentation (IMI) is a minimally invasive technique that allows the assessment of bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. In this study, we aimed to assess the practicality of its application in 99 women aged 42-84 yr from the Geelong Osteoporosis Study. Impact microindentation was performed in the mid-shaft of the right tibia using the OsteoProbe. Immediately following measurement, each participant was requested to rate on a Visual Analogue Scale [0−10] the level of discomfort anticipated and experienced, any initial reluctance towards the measurement and whether they were willing to repeat the measurement. Of 99 potential participants who attended this assessment phase, 55 underwent IMI measurement. Reasons for non-measurement in 44 women were existing skin conditions (n = 8, 18.2 %) and excessive soft tissue around mid-tibial region (n = 32, 72.2 %). An additional four (9.1 %) participants did not provide any reasons for declining. For 55 participants who had underwent IMI, the expectation for pain when briefed about the procedure was low (2.28 ± 2.39), as was pain experienced during the measurement (0.72 ± 1.58). Participants were not reluctant to undergo the measurement (0.83 ± 1.67), and all indicated a willingness to repeat the measurement. Results of this study showed that the IMI technique is well tolerated and accepted by women participating in the Geelong Osteoporosis Study, suggesting that the technique shows promise in a research or clinical setting.

For older individuals there is greater variance in low mean Bone Material Strength Index values obtained with the OsteoProbe

PurposeBone Material Strength Index (BMSi) quantifies the resistance of bone to a specified force in vivo at the mid tibia using impact microindentation (IMI). Anecdotal evidence suggests that within-participant variance in BMSi may be associated with the individual's mean BMSi. This study aimed to investigate associations between mean and variance of IMI measures in a population-based study. MethodsParticipants were men (n = 420) and women (n = 55) from the Geelong Osteoporosis Study who underwent BMSi measurement using the OsteoProbe at recent follow-up phases (men 2016–2022; women 2022–2023). Median age was 63.7 yr (IQR 53.0–71.8). BMSi standard deviation was skewed and therefore natural log transformed (referred to as ln-SD). Linear regression models were developed with ln-SD as the dependent variable and mean BMSi as the independent variable adjusting for sex, age, height and weight. ResultsIn unadjusted models, greater BMSi was associated with lower ln-SD (β = −1.58, p = 0.042). This association was sustained after adjustment (p = 0.013), and an interaction between BMSi and age was observed (p = 0.004). In those aged 63.7 yr and over (median age), mean BMSi was inversely associated with ln-SD (β = −3.22, p = 0.002). Sex was not identified as an effect modifier. In younger participants, no BMSi*ln-SD association was observed. ConclusionIn older men and women, there was greater variance in low BMSi values. This suggests that standard deviation of the BMSi measure may provide additional information in the assessment of bone health and is worthy of further investigation. Mini abstractIn older men and women, greater variance is observed when BMSi values are low, reflecting potential variation in the bone surface.

Associations Between Aldosterone-Renin-Ratio and Bone Parameters Derived from Peripheral Quantitative Computed Tomography and Impact Microindentation in Men

Components of the renin–angiotensin–aldosterone system (RAAS) are present on bone cells. One measure of RAAS activity, the aldosterone-renin-ratio (ARR), is used to screen for primary aldosteronism. Associations between ARR and bone mineral density are conflicting. This study investigated associations between ARR and peripheral quantitative computed tomography (pQCT) and impact microindentation (IMI). Male participants (n = 431) were from the Geelong Osteoporosis Study. “Likely” primary aldosteronism was defined as ARR ≥ 70 pmol/mIU. Another group, “possible” primary aldosteronism, was defined as either ARR ≥ 70 pmol/mIU or taking a medication that affects the RAAS, but not a beta blocker, and renin < 15 mU/L. Using pQCT, images at 4% and 66% of radial (n = 365) and tibial (n = 356) length were obtained. Using IMI measurements, bone material strength index (BMSi; n = 332) was determined. Associations between ARR or likely/possible primary aldosteronism and IMI or pQCT-derived bone parameters were tested using median regression. ARR and aldosterone values were not associated with any of the pQCT-derived bone variables in either unadjusted or adjusted analyses. Men with likely primary aldosteronism (n = 16), had lower adjusted total bone area (radial 66% site, − 12.5%). No associations were observed for men with possible primary aldosteronism (unadjusted or adjusted). No associations with BMSi were observed (p > 0.05). There were no associations between ARR or aldosterone and pQCT-derived bone parameters. Men with likely primary aldosteronism had lower bone area, suggesting clinically high levels of ARR may have a negative impact on bone health.

Correlation between reference point indentation and mechanical properties of 3D-printed polymers

Reference point indentation (RPI) is a novel experimental technique designed to evaluate bone quality. This study utilizes two RPI instruments, BioDent and Osteoprobe, to investigate the mechanical responses of several 3D-printed polymers. We correlated the mechanical properties from a tensile test with the RPI parameters obtained from the BioDent and OsteoProbe. In addition, we tested the same polymers five years later (Age 5). The results show that for Age 0 polymers, the elastic modulus is highly correlated with average unloading slope (r = 0.87), first unloading slope (r = 0.85), bone material strength index (BMSi) (r = 0.85), average loading slope (r = 0.82), first indentation distance (r = 0.79), and total indentation distance (r = 0.76). The ultimate stress correlates significantly with first unloading slope (r = 0.85), average unloading slope (r = 0.83), BMSi (r = 0.81), first indentation distance (r = 0.73), average loading slope (r = 0.71), and total indentation distance (r = 0.70). The elongation has no significant correlation with the RPI parameters except with the average creep indentation distance (r = 0.60). For Age 5 polymers, correlations between mechanical properties and RPI parameters are low. This study illustrates the potential of RPI to assess the mechanical properties of polymers nondestructively with simple sample requirements. Furthermore, for the first time, 3D-printed polymers and aged polymers are investigated with RPI.

#6641 BONE MATERIAL STRENGTH INDEX AND DUAL ENERGY X-RAY ABSORPTIOMETRY IN EVALUATION OF BONE HEALTH IN AUTOSOMAL POLYCYSTIC KIDNEY DISEASE

Abstract Background and Aims Bone material strength measured with the use of impact microindentation technique (OsteoProbe®) has emerged recently as potentially beneficial tool in evaluating bone quality in metabolic bone disorders. Patients with autosomal polycystic kidney disease (ADPKD) carry an increased risk of skeletal complications, both due to deficiency of polycystins and development of chronic kidney disease-mineral bone disorder (CKD-MBD). In our preliminary study, we found that bone material strength index (BMSi) associated with bone mineral density (BMD) measured with the use of dual energy X-ray absorptiometry (DXA) in chronic kidney disese patients (CKD). The aim of the present study was to find if the same applies to patients with ADPKD. We evaluated bone health by measuring BMSi and performing DXA in patients with ADPKD. Method BMSi was measured (OsteoProbe®, Active Life Scientific, USA) in 64 adult patients (37 men, mean age 43 years) with ADPKD in CKD stages G1-4. The measurement of BMSi compared the resistance to impact of microindentation in bone and reference material. After applying local anaesthesia, we impacted the cortical bone in the midshaft tibia in 10 different points. BMD was measured using Hologic Discovery Wi densitometer in multiple sites: lumbar spine, hip, 1/3 distal non-dominant forearm and whole-body. Trabecular bone score (TBS) was calculated using Medimaps TBS iNsight software. Results Mean values of BMSi, TBS and BMD are presented in the Table 1. BMSi in ADPKD patients was lower than average value observed in healthy individuals (85 men and 80 women). A positive linear relationship between BMSi and BMD was found in all of the examined sites with the highest standardized regression coefficient for 1/3 distal forearm (R2 = 0.315, beta = 0.57, p &amp;lt; 0.001) and weakest for lumbar spine (R2 = 0.003, beta = 0.33, p = 0.003). There was no association between BMSi and TBS. Conclusion This is the first report on BMSi in ADPKD patients. In agreement with the notion of a distinct bone phenotype in ADPKD, we observed a median bone material strength index in patients with ADPKD that was lower than the reference value. BMSi associated with BMD, but not with TBS. However, the association with BMD overall is weak, with BMD explaining only 3 to 31% of the variability of BMSi. This observation suggests complementarity and warrants additional studies investigating whether BMSi associates with hard bone endpoints, independent of BMD.

Changes in bone quality after switching from a TDF to a TAF based ART: A pilot randomized study.

The impact of tenofovir disoproxil fumarate (TDF) antiretroviral (ART) regimens on bone health has been characterized mostly by bone mineral density (BMD), but recently also by bone quality (BQ). The aim of this pilot study is to assess the changes in BMD and BQ after switch from TDF to tenofovir alafenamide (TAF) ART. HIV individuals receiving TDF-based ART were randomized to switch to Bictegravir-TAF-Emtricitabine or to remain in the same regimen. At baseline and 24-weeks after randomization, participants underwent bone mineral density (BMD) by DXA and BQ assessment using bone microindentation, a validated technique that measures bone tissue quality expressed as bone material strength index (BMSi). A panel of plasma bone turnover biomarkers were measured by ELISA at the same time-points. Values are expressed as median [interquartile range] and non-parametric tests were used where appropriate. A total of 24 HIV individuals were included in the study, 19 of which were men (80%). Median age at baseline was 43 years (IQR 38-54). Half of individuals were allocated in the TDF group while the other half changed to TAF treatment. No differences at baseline between both groups were detected in any parameter. Non-significant changes nor in lumbar or femoral BMD at week 24 was found in any regimen. In contrast, there was an increase in BMSi in the TAF arm at 24 weeks, and thus an improvement in BQ[81.6 (79-83) to 86 (80-88) (+5.1%);p=0.041], whereas the TDF arm remained stable from 82 (76-85) at baseline to 82 (73-83);p=0.812. Hence, at week 24 there were significant differences in BQ between arms (p=0.049). A reduction in bone formation markers was found at week 24 in both regimens: N-terminal propeptide of type-1 collagen decreased a 20% (-35 - -0.6); p=0.031 with TAF and -16% (-25 - -5); p=0.032 with TDF. Also a decrease in bone resorption marker C-telopeptide with TAF was detected [-10% (-19 - -5);p=0.028] but not with TDF (p=0.232), suggesting a less metabolically active bone after switching to TAF. A bone quality improvement was found after switching from a TDF to a TAF based ART independently of BMD, suggesting that the bone health benefits of TAF may extend beyond BMD. Future research should be directed to confirm these findings and to identify the underlying mechanisms of ART related bone toxicity.

Reference Intervals for Bone Impact Microindentation in Healthy Adults: A Multi-Centre International Study

Impact microindentation (IMI) is a novel technique for assessing bone material strength index (BMSi) in vivo, by measuring the depth of a micron-sized, spherical tip into cortical bone that is then indexed to the depth of the tip into a reference material. The aim of this study was to define the reference intervals for men and women by evaluating healthy adults from the United States of America, Europe and Australia. Participants included community-based volunteers and participants drawn from clinical and population-based studies. BMSi was measured on the tibial diaphysis using an OsteoProbe in 479 healthy adults (197 male and 282 female, ages 25 to 98 years) across seven research centres, between 2011 and 2018. Associations between BMSi, age, sex and areal bone mineral density (BMD) were examined following an a posteriori method. Unitless BMSi values ranged from 48 to 101. The mean (± standard deviation) BMSi for men was 84.4 ± 6.9 and for women, 79.0 ± 9.1. Healthy reference intervals for BMSi were identified as 71.0 to 97.9 for men and 59.8 to 95.2 for women. This study provides healthy reference data that can be used to calculate T- and Z-scores for BMSi and assist in determining the utility of BMSi in fracture prediction. These data will be useful for positioning individuals within the population and for identifying those with BMSi at the extremes of the population.

Restrictive Eating and Prior Low-Energy Fractures Are Associated With History of Multiple Bone Stress Injuries.

Bone stress injuries (BSIs) are common among athletes and have high rates of recurrence. However, risk factors for multiple or recurrent BSIs remain understudied. Thus, we aimed to explore whether energy availability, menstrual function, measures of bone health, and a modified Female Athlete Triad Cumulative Risk Assessment (CRA) tool are associated with a history of multiple BSIs. We enrolled 51 female runners (ages 18-36years) with history of ≤1 BSI (controls; n = 31) or ≥3 BSIs (multiBSI; n = 20) in this cross-sectional study. We measured lumbar spine, total hip, and femoral neck areal bone mineral density by dual-energy X-ray absorptiometry, bone material strength index using impact microindentation, and volumetric bone mineral density, microarchitecture, and estimated strength by high-resolution peripheral quantitative computed tomography. Participants completed questionnaires regarding medical history, low-energy fracture history, and disordered eating attitudes. Compared with controls, multiBSI had greater incidence of prior low-energy fractures (55% vs. 16%, p = .005) and higher modified Triad CRA scores (2.90 ± 2.05 vs. 1.84 ± 1.59, p = .04). Those with multiBSI had higher Eating Disorder Examination Questionnaire (0.92 ± 1.03 vs. 0.46 ± 0.49, p = .04) scores and a greater percentage difference between lowest and highest body mass at their current height (15.5% ± 6.5% vs. 11.5% ± 4.9% p = .02). These preliminary findings indicate that women with a history of multiple BSIs suffered more prior low-energy fractures and have greater historical and current estimates of energy deficit compared with controls. Our results provide strong rationale for future studies to examine whether subclinical indicators of energy deficit contribute to risk for multiple BSIs in female runners.

Bone-microarchitecture and bone-strength in a sample of adults with hypophosphatasia and a matched reference population assessed by HR-pQCT and impact microindentation.

Hypophosphatasia (HPP) is an autosomal recessive or dominate disease affecting bone mineralization, and adults with HPP are in risk to develop metatarsal stress fractures and femoral pseudofractures. Given to the scarce data on the bone quality and its association to the fracture risk in adults with HPP, this study aimed to evaluate bone turnover, bone strength and structure in adults with HPP. In this cross-sectional study, we included 14 adults with genetically verified HPP and 14 sex-, age-, BMI-, and menopausal status-matched reference individuals. We analyzed bone turnover markers, and measured bone material strength index (BMSi) by impact microindentation. Bone geometry, volumetric density and bone microarchitecture as well as failure load at the distal radius and tibia were evaluated using a second-generation high-resolution peripheral quantitative computed tomography system. Bone turnover markers did not differ between patients with HPP and reference individuals. BMSi did not differ between the groups (67.90 [63.75-76.00] vs 65.45 [58.43-69.55], p=0.149). Parameters of bone geometry and volumetric density did not differ between adults with HPP and the reference group. Patients with HPP had a tendency toward higher trabecular separation (0.664 [0.613-0.724] mm vs 0.620 [0.578-0.659] mm, p=0.054) and inhomogeneity of trabecular network (0.253 [0.235-0.283] mm vs 0.229 [0.208-0.252] mm, p=0.056) as well as lower trabecular bone volume fraction (18.8 [16.4-22.7] % vs 22.8 [20.6-24.7] %, p=0.054) at the distal radius. In addition, compound heterozygous adults with HPP had a significantly higher cortical porosity at the distal radius than reference individuals (1.5 [0.9-2.2] % vs 0.7 [0.6-0.7] %, p=0.041). BMSi is not reduced in adults with HPP. Increased cortical porosity may contribute to the occurrence of femoral pseudofractures in compound heterozygous adults with HPP. However, further studies investigating larger cohorts of adults with HPP using methods of bone histomorphometry are recommended to adequately assess the bone quality in adults with HPP.

Intraoperative use of impact microindentation to assess distal radius bone quality.

Impact microindentation is a new technique that measures the resistance of a patient's bone to micro-indentation but has not yet been implemented in an intraoperative setting. To assess the technique's safety and utility, we acquired microindentation measurements of bone material strength index (BMSi) using the OsteoProbe prior to distal radius fixation with a volar locking plate. Subsequently, the patients received a dual-energy x-ray absorptiometry scan to measure the areal bone mineral density of the proximal femur, lumbar spine, and contralateral distal radius. By assigning the patients to low-energy, fragility fracture (n = 17) and high-energy fracture (n = 11) groups based on clinical history, we investigated whether intraoperative BMSi was sensitive to osteoporosis. Impact microindentation added a maximum of 10minof operative time and did not result in any intraoperative or postoperative complications. There were, however, no significant differences in BMSi at the radius between these two groups. This study demonstrates the feasibility of performing intraoperative impact microindentation to directly assess a patient's bone quality, but additional research is necessary to establish whether intraoperative microindentation can identify patients with inferior bone matrix quality.

Bone material strength index as measured by in vivo impact microindentation is normal in subjects with high-energy trauma fractures

SummaryBone material properties were assessed using impact microindentation in patients with high-energy trauma fractures. Compared to patients with low-energy trauma fractures, bone material strength index was significantly higher in patients with high-energy trauma fractures, and did not differ between patients with osteopenia and those with osteoporosis within each trauma group.IntroductionImpact microindentation (IMI) is a technique to assess tissue-level properties of bone at the tibia. Bone material strength index (BMSi), measured by IMI, is decreased in patients with low-energy trauma fractures, independently of areal bone mineral density (aBMD), but there is no information about BMSi in patients with high-energy trauma fractures. In the present study, we evaluated tissue-level properties of bone with IMI in patients with high-energy trauma fractures.MethodsBMSi was measured 3.0 months (IQR 2.0–5.8) after the fracture in 40 patients with high-energy trauma and 40 age- and gender-matched controls with low-energy trauma fractures using the OsteoProbe® device.ResultsMean age of high- and low-energy trauma patients was 57.7 ± 9.1 and 57.2 ± 7.7 years, respectively (p = 0.78). Fracture types were comparable in high- vs low-energy trauma patients. Lumbar spine (LS)-aBMD, but not femoral neck (FN)-aBMD, was higher in high- than in low-energy trauma patients (LS 0.96 ± 0.13 vs 0.89 ± 0.13 g/cm2, p = 0.02; FN 0.75 ± 0.09 vs 0.72 ± 0.09 g/cm2, p = 0.09). BMSi was significantly higher in high- than in low-energy trauma patients (84.4 ± 5.0 vs 78.0 ± 4.6, p = 0.001), also after adjusting for aBMD (p = 0.003). In addition, BMSi did not differ between patients with osteopenia and those with osteoporosis within each trauma group.ConclusionOur data demonstrate that BMSi and LS-aBMD, but not FN-aBMD, are significantly higher in high-energy trauma patients compared to matched controls with similar fractures from low-energy trauma. Further studies of non-osteoporotic patients with high-energy trauma fracture with measurements of BMSi are warranted to determine whether IMI might help in identifying those with reduced bone strength.

Associations between parameters of peripheral quantitative computed tomography and bone material strength index.

Bone material strength index (BMSi) is measured in vivo using impact microindentation (IMI). However, the associations between BMSi and other bone measures are not clear. This study investigated whether bone parameters derived by peripheral quantitative computed tomography (pQCT) are associated with BMSi. Participants were men (n=373, ages 34-96yr) from the Geelong Osteoporosis Study. BMSi was measured using an OsteoProbe (Active Life Scientific, USA). Bone measures were obtained at both the radius (n=348) and tibia (n=342) using pQCT (XCT 2000 Stratec Medizintechnik, Germany). Images were obtained at 4% and 66% of radial and tibial length. Associations between pQCT parameters and BMSi were tested using Spearman's correlation and multivariable regression used to determine independent associations after adjustment for potential confounders. Models were checked for interaction terms. Weak associations were observed between total bone density (radius 4%; r=+0.108, p=0.046, tibia 4%; r=+0.115, p=0.035), cortical density (tibia 4%; r=+0.123, p=0.023) and BMSi. The associations were independent of weight, height, and glucocorticoid use (total bone density: radius 4%; β=0.020, p=0.006, tibia 4%; β=0.020, p=0.027 and cortical density: radius 4%; β=4.160, p=0.006, tibia 4%; β=0.038, p=0.010). Associations with bone mass were also observed at the 66% radial and tibial site, independent of age, weight, and glucocorticoid use (β=4.160, p=0.053, β=1.458, p=0.027 respectively). Total area at the 66% tibial site was also associated with BMSi (β=0.010, p=0.012), independent of weight and glucocorticoid use. No interaction terms were identified. There were weak associations detected between some pQCT-derived bone parameters and BMSi.

Longitudinal Changes in Serum Markers of Bone Metabolism and Bone Material Strength in Premenopausal Women with Distal Radial Fracture.

Markers of bone metabolism (MBM) play an important role in fracture evaluation, and changes have been associated with increased fracture risk. The purpose of the present study was to describe changes in MBM in premenopausal women with distal radial fractures. Premenopausal women with distal radial fractures (n = 34) and without fractures (controls) (n = 39) were recruited. Serum MBM in patients with distal radial fractures were obtained at the time of the initial presentation, 6 weeks, and 3, 6, and 12 months. MBM included 25(OH) vitamin D, PTH, osteocalcin, P1NP, BSAP, CTX, sclerostin, DKK1, periostin, and TRAP5b. Areal bone mineral density (aBMD) was assessed with dual x-ray absorptiometry, and the bone material strength index (BMSi) was assessed with microindentation. Most MBM reached peak levels at 6 weeks after the injury, including osteocalcin (+17.7%), sclerostin (+23.5%), and DKK1 (12.6%). Sclerostin was lower (-27.4%) and DKK1 was higher (+22.2%) at 1 year after the fracture. CTX declined below baseline levels at 6 and 12 months, whereas TRAP5b, BSAP, and periostin did not significantly change. At 12 months, sclerostin was lower (p = 0.003) and DKK1 was higher (p = 0.03) in the distal radial fracture group than in the control group. Greater fracture severity was associated with greater increases in P1NP and BSAP. aBMD and BMSi were not associated with fracture. Distal radial fractures caused increases in several MBM, which typically peaked at 6 weeks after injury and gradually decreased over 6 months. Sclerostin and DKK1 remained below and above baseline at 1 year, respectively. Increasing fracture severity resulted in larger changes in MBM. aBMD and BMSi did not discriminate between patients with distal radial fractures and controls. Continued efforts to identify markers of skeletal fragility in young women are warranted to mitigate future fracture risk. Prognostic Level II. See Instructions for Authors for a complete description of levels of evidence.

Evidence of impaired bone quality in men with type 1 diabetes: a cross-sectional study.

ObjectiveType 1 diabetes (T1D) is associated with substantial fracture risk. Bone mineral density (BMD) is, however, only modestly reduced, suggesting impaired bone microarchitecture and/or bone material properties. Yet, the skeletal abnormalities have not been uncovered. Men with T1D seem to experience a more pronounced bone loss than their female counterparts. Hence, we aimed to examine different aspects of bone quality in men with T1D.Design and MethodsIn this cross-sectional study, men with T1D and healthy male controls were enrolled. BMD (femoral neck, total hip, lumbar spine, whole body) and spine trabecular bone score (TBS) were measured by dual x-ray absorptiometry, and bone material strength index (BMSi) was measured by in vivo impact microindentation. HbA1c and bone turnover markers were analyzed.ResultsAltogether, 33 men with T1D (43 ± 12 years) and 28 healthy male controls (42 ± 12 years) were included. Subjects with T1D exhibited lower whole-body BMD than controls (P = 0.04). TBS and BMSi were attenuated in men with T1D vs controls (P = 0.016 and P = 0.004, respectively), and T1D subjects also had a lower bone turnover. The bone parameters did not differ between subjects with or without diabetic complications. Duration of disease correlated negatively with femoral neck BMD but not with TBS or BMSi.ConclusionsThis study revealed compromised bone material strength and microarchitecture in men with T1D. Moreover, our data confirm previous studies which found a modest decrease in BMD and low bone turnover in subjects with T1D. Accordingly, bone should be recognized as a target of diabetic complications.

MO567PILOT STUDY OF BONE RESISTANCE MEASURED IN VIVO BY IMPACT MICROINDENTATION IN KIDNEY TRANSPLANTATION

Abstract Background and Aims Impact microindentation (IMI) is a new technique that measures bone material strength (BMS). Results are expressed as a BMS index (BMSi) which represents the ratio between the IMI distance [penetration of the needle-probe in patient’s bone (mid-shaft tibia)] versus a reference material (polimethylmethacrylate). Method Observational, prospective, single-center study. Baseline IMI (Osteoprobe®, Active Life Scientific, USA) and bone densitometry (iDXA, Lunar Health Care GE) were performed and data collected in the peritransplantation period of kidney transplant (KT) patients from May 2019 to May 2020, following our current clinical bone and transplant protocols. Based on the individual risk of fracture and current Spanish Society of Rheumathology/Nephrology guidelines, antirresorptive treatment (bisphosphonates or denosumab) was added on top of calcium and vitamin D supplements. We hereby present preliminary results of the control IMI performed 6 months after KT. Results Baseline IMI was performed in 45 patients, 62% men, 56±14 y/o, and a BMI of 24.9±3.5 kg/m2, reasonably controlled for classical serum bone mineral parameters. 70% were on dialysis prior to KT, 20% were diabetic, and 33.3% of women suffered from early menopause. 15.9% had a history of previous fragility fracture, 13% had a parent history of hip fracture, and 14% fell more than twice during the last year. Mean baseline FRAX® (https://www.sheffield.ac.uk/FRAX/tool.aspx?lang=sp) for a major osteoporotic fracture and hip were 4.3% and 2.3%, respectively. Baseline lumbar, femoral neck, hip and ultradistal radius DXA T-score were respectively -0.9, -1.7, -1.5, -2.0 SD. Mean BMSi was 78.5±7.6. Osteopenic/osteoporotic patients had a significantly lower BMSi than those who were not (76.3 vs 83; r = 0.37; p = 0.012). A statistically significant positive correlation was observed between BMSi and the trabecular bone score [(TBS), r = 0.346 ; p = 0.036). On a visual-analogic scale of pain, puncture was rated on average 1.1±1.6 over 10 (82% 0-2). 37.2% of patients began bisphosphonates (alendronic acid) and 9.3% denosumab. Control IMI was performed at 6 months in 24 patients, with a mean BMSi of 76.9±10.5. Mean difference between baseline and 6 months BMSi in this subgroup was 1.18±11.5. The group of patients treated with antiresorptives showed on average an increase in BMSi at 6 months, compared with a decrease in the control group (+5.2 vs -5.3; p = 0.054). Conclusion IMI is a technique with excellent tolerance that may offer complementary information on bone quality in the global assessment of bone resistance. IMI may allow the detection of EARLY changes in bone resistance in corticosteroid-treated KT patients with/without antiresorptives added to prophylactic treatment with calcium and vitamin D.

MO576ASSOCIATION OF BONE MATERIAL STRENGTH WITH BONE DENSITY IN PATIENTS WITH END-STAGE RENAL DISEASE

Abstract Background and Aims Patients with end-stage renal disease (ESRD) have an increased risk of skeletal complications, including an increased fracture risk, which is only partially identified by determination of bone mineral density (BMD). Experimentally, the complex bone-and mineral disorders in ESRD cause disturbances of bone material properties, but these have not been studied in vivo. Determination of bone material strength index (BMSi) by reference point indentation (RPI) is a novel method to determine bone material quality in vivo and can identify patients at increased fracture risk, even in the presence of normal BMD. We determined BMSi in ESRD patients and investigated its association with BMD and serum markers of mineral metabolism. Method 15 Adult patients with ESRD, scheduled for a living-donor kidney transplantation, were included in this cross-sectional study. Laboratory analyses included calcium, phosphate, PTH 1-84 and alkaline phosphatase. BMSi was determined by RPI with the OsteoProbe RUO in the tibia. Bone mineral density was measured by dual X-ray absorptiometry. Results Patients with bone mineral strenght index above median had higher bone mineral density of the right hip and total body than patients below median (p = 0.04). Alkaline phosphatase was lower in patients with BMSi below the median (47 (35-71) U/L vs. 103 (53-318) U/L, p = 0.009). There was a trend towards a significant relationship between length and BMSi (p = 0.09). Conclusion We identified for the first time an association of BMSi with BMD and alkaline phosphatase in patients with ESRD. Our findings of an association of BMSi with BMD are in accordance with findings in other populations with increased fracture risk.

Bone material strength index is altered in patients with Cushing’s syndrome even after long-term remission

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