Estimated Bone Strength Research Articles

Aromatase inhibitors, bone microstructure, and estimated bone strength in postmenopausal women with breast cancer: a 5-year prospective study.

Aromatase inhibitors (AIs) are the standard treatment for early breast cancer (EBC) and are typical causative agents of cancer treatment-induced bone loss. However, the effects of long-term treatment with these drugs on bone microstructure remain unclear. This prospective, single-arm observational study included postmenopausal, non-osteoporotic women with hormone receptor-positive EBC. Patients who underwent dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type I N-terminal propeptide levels were compared at baseline and at 60months after commencing AI treatment. Fifteen women were included in the study, with a median age of 58years and a quartile range of 56.5-62.5years. At 60months, HR-pQCT revealed that the cortical area and thickness decreased with increased cortical porosity in the cortical bone. In addition, the number of trabeculae decreased and trabecular separation increased trabecular bones decreases, and trabecular bone separation opens, resulting in a decrease in the trabecular bone volume fraction. Total bone mineral density (BMD), trabecular volumetric BMD, and cortical volumetric BMD, and estimated bone strength significantly decreased. DXA BMD values significantly decreased in the total hip and femoral neck but not the lumbar spine. TRACP-5b values after 5years of AI treatment showed a significant negative correlation with the rate of change in the total volumetric BMD in the distal tibia. Postmenopausal women who received AIs for 5years for EBC experienced significant deterioration in the bone microstructure, BMD, and estimated bone strength.

Prediction of Femoral Bone Strength in the Presence of Tumors and Tumor-like Lesions Using Finite Element Analysis.

Patients with bone tumors in their femurs are at risk of developing pathological fractures. Tumors with high fracture risk, especially fragile malignant lesions, are treated surgically. However, it is difficult to estimate bone strength based on clinical and radiographic findings. This study aimed to determine whether finite element analysis (FEA) provides useful information on the bone strength of femurs with tumors and tumor-like lesions. Total femoral computed tomography (CT) data (slice thickness, 0.5 mm) were retrospectively obtained from 18 patients with femoral bone tumors. Three-dimensional FEA of femurs were developed using CT data. The virtual femoral head compression test and direct three-point bending test were performed on the femurs using FEA to predict bone strength and fracture location. The compression direction was parallel to the mechanical axis, whereas that of the three-point bending test was applied to the tumor itself. In the femoral head compression test using FEA, 13 out of 18 femurs with bone tumors fractured at the femoral head, while 14 out of 18 femurs fractured at the tumor site during the virtual direct three-point bending test. The median loads predicted using the femoral head compression test were significantly higher than those predicted by the direct three-point bending test. The FEA results indicated that pathological fractures are unlikely to occur during normal walking. Direct external forces applied to the tumor body may lead to fractures.

Setrusumab for the treatment of osteogenesis imperfecta: 12-month results from the phase 2b asteroid study.

Osteogenesis imperfecta (OI) is a rare genetic disorder commonly caused by variants of the type I collagen genes COL1A1 and COL1A2. OI is associated with increased bone fragility, bone deformities, bone pain, and reduced growth. Setrusumab, a neutralizing antibody to sclerostin, increased areal bone mineral density (aBMD) in a 21-week phase 2a dose escalation study. The phase 2b Asteroid (NCT03118570) study evaluated the efficacy and safety of setrusumab in adults. Adults with a clinical diagnosis of OI type I, III, or IV, a pathogenic variant in COL1A1/A2, and a recent fragility fracture were randomized 1:1:1:1 to receive 2, 8, or 20mg/kg setrusumab doses or placebo by monthly intravenous infusion during a 12-mo treatment period. Participants initially randomized to the placebo group were subsequently reassigned to receive setrusumab 20mg/kg open label. Therefore, only results from the 2, 8, and 20mg/kg double-blind groups are presented herein. The primary endpoint of Asteroid was change in distal radial trabecular volumetric bone mineral density (vBMD) from baseline at month 12, supported by changes in high-resolution peripheral quantitative computed tomography micro-finite element (microFE)-derived bone strength. A total of 110 adults were enrolled with similar baseline characteristics across treatment groups. At 12mo, there was a significant increase in mean (SE) failure load in the 20mg/kg group (3.17% [1.26%]) and stiffness in the 8 (3.06% [1.70%]) and 20mg/kg (3.19% [1.29%]) groups from baseline. There were no changes in radial trabecula vBMD (p>05). Gains in failure load and stiffness were similar across OI types. There were no significant differences in annualized fracture rates between doses. Two adults in the 20mg/kg group experienced related serious adverse reactions. Asteroid demonstrated a beneficial effect of setrusumab on estimates of bone strength across the different types of OI and provides the basis for additional phase 3 evaluation.

Denosumab Prevents Bone Loss and Microarchitectural Deterioration in Premenopausal Women With Breast Cancer Receiving Estradiol Suppression Therapy: A Randomized Controlled Trial.

Suppression of ovarian function and aromatase inhibition (AI) increases disease-free survival in premenopausal women with estrogen receptor (ER)-positive early-stage breast cancer but accelerates bone loss. We therefore hypothesized that suppressing bone remodeling using denosumab (DMAB) would prevent bone loss in these women. In a 12-month double-blind randomized trial, 68 women with ER-positive early-stage breast cancer commencing ovarian function suppression and AI were randomly assigned to 60 mg DMAB (n = 34) or placebo (PBO; n = 34) once every 6 months (at 0 and 6 months). Volumetric bone mineral density (BMD), microarchitecture, and estimated bone strength of the distal tibia and distal radius were measured using high-resolution peripheral quantitative computed tomography, and spine and hip BMD were measured using dual-energy X-ray absorptiometry at 0, 6, and 12 months. The primary end point and treatment effect was the mean adjusted between group difference (MAD; [95% CI]) in distal tibial total volumetric BMD over 12 months, with a single P value tested over all time points. The study is registered with the Australian New Zealand Clinical Trials Registry (anzctr.org.au; identifier: ACTRN12616001051437). Intention-to-treat analysis included all 68 randomly assigned women. Over 12 months, compared with PBO, DMAB prevented the decrease in distal tibial total BMD (MAD, 20.8 mg HA/cm3 [95% CI, 17.3 to 24.2]), cortical BMD (42.9 mg HA/cm3 [95% CI, 32.1 to 53.9]), trabecular BMD (3.32 mg HA/cm3 [95% CI, 1.45 to 5.20], P = .004), estimated stiffness (11.6 kN/m [95% CI, 7.6 to 15.6]), and failure load (563 N [95% CI, 388 to 736]). Findings were similar at the distal radius. Decreases in BMD at the lumbar spine (MAD, 0.13 g/cm2 [95% CI, 0.11 to 0.15]), total hip (0.08 g/cm2 [95% CI, 0.07 to 0.09], and femoral neck (0.06 g/cm2 [95% CI, 0.05 to 0.07]) were also prevented. All P < .001 unless otherwise noted. Treatment with DMAB at commencement of estradiol suppression therapy preserves BMD, bone microarchitecture, and estimated strength, and is likely to increase fracture-free survival.

The impact of androgen deprivation therapy on bone microarchitecture in men with prostate cancer: A longitudinal observational study (The ANTELOPE Study)

IntroductionAndrogen Deprivation Therapy (ADT) for prostate cancer (PC) has substantial negative impacts on the musculoskeletal system and body composition. Many studies have focused on the effects of ADT on areal bone mineral density (aBMD), but aBMD does not capture key determinants of bone strength and fracture risk, for example volumetric bone density (vBMD), geometry, cortical thickness and porosity, trabecular parameters and rate of remodelling. More specialist imaging techniques such as high-resolution peripheral quantitative computed tomography (HR-pQCT) have become available to evaluate these parameters. Although it has previously been demonstrated that bone microarchitectural deterioration occurs in men undergoing ADT, the aim of the ANTELOPE study was to examine longitudinal changes in bone microstructure alongside a range of musculoskeletal parameters and frailty, comparing men with PC receiving ADT alone or ADT plus chemotherapy for metastatic disease, with a healthy age-matched population. MethodsWe used HR-pQCT to investigate effects of 12 months of ADT on vBMD and microstructural parameters, complemented by assessment of changes in aBMD, serum bone turnover markers, sex hormones, body composition, grip strength, physical and muscle function, frailty and fracture risk. We studied three groups: Group A − men with localised/locally advanced PC due to commence ADT; Group B − men with newly diagnosed hormone-sensitive, metastatic PC, starting ADT alongside docetaxel chemotherapy and steroids; Group C − healthy, age-matched men. The primary endpoint was change in vBMD (Group A vs Group C) at the distal radius. ResultsNinety-nine participants underwent baseline study assessments (Group A: n = 38, Group B: n = 30 and Group C: n = 31). Seventy-five participants completed all study assessments (Group A (29), Group B (18), Group C (28). At baseline, there were no significant differences between Groups A and C in any of the BMD or bone microstructure outcomes of interest. After 12 months of ADT treatment, there was a significantly greater decrease in vBMD (p < 0.001) in Group A (mean 12-month change = -13.7 mg HA/cm3, −4.1 %) compared to Group C (mean 12-month change = -1.3 mg HA/cm3, −0.4 %), demonstrating achievement of primary outcome. Similar effects were observed when comparing the change in vBMD between Group B (mean 12-month change = -13.5 mg HA/cm3, −4.3 %) and Group C. These changes were mirrored in aBMD. ADT resulted in microstructural deterioration, a reduction in estimated bone strength and an increase in bone turnover. There was evidence of increase in total fat mass and trunkal fat mass in ADT-treated patients, with marked loss in upper limb mass, along with BMI gain. Frailty increased and physical performance and strength deteriorated in both ADT groups, relative to the healthy control group. ConclusionThe study showed that ADT has profound effects on vBMD, aBMD, bone microstructure and strength and body composition, and important impacts on frailty and physical performance. Whilst DXA remains a valuable tool (changes in aBMD are of the same magnitude as those observed for vBMD), HR-pQCT should be considered for assessing the effects of anti-androgens and other newer PC therapies on bone, as well as potential mitigation by bone-targeted agents.

Changes in bone density and structure of proximal humerus with aging in Chinese women

AimsThis study aimed to investigate age- and menopause-related differences in bone mineral density (BMD), bone structure and estimated bone strength at surgical neck of humerus in Chinese female sample. MethodsWe conducted a cross-sectional cohort study of 171 Chinese women. Bone mass, indices of geometric properties and estimated mechanical strength of the surgical neck were evaluated by quantitative computed tomography (QCT). Comparisons were performed across menstrual status categories. Age-related changes in QCT-derived bone parameters were calculated. ResultsThe age-related difference of BMD and cortical thickness was 40.25 % and 32.86 % between the age of 20 and 86 years. Progressive periosteal and endosteal expansion was associated linearly with age. Estimated mechanical strength indexes showed significant quadratic associations with age, with their peak occurred at the age of 46–55 years. The quartile of women with the greatest medullary diameter also had the lowest valve of BMD and cortical thickness and the greatest in skeletal width. Compared to premenopausal individuals, perimenopausal women were distinguished by lower cortical thickness (18.63 %) and BMD (20.05 %). The continued decrease in cortical thickness and BMD was noted after menopause. The medullary and periosteal diameter increased by 17.98 % and 9.34 % respectively in perimenopausal period, but not after menopause. The accelerated loss of the maximum and polar section modulus was observed in late postmenopausal women. ConclusionsThe increase in bone size only occurred during the menopause transition. Obvious loss of resistance to bending was in late postmenopausal period.

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

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

3D-DXA Based Finite Element Modelling for Femur Strength Prediction: Evaluation Against QCT.

Osteoporosis is characterised by the loss of bone density resulting in an increased risk of fragility fractures. The clinical gold standard for diagnosing osteoporosis is based on the areal bone mineral density (aBMD) used as a surrogate for bone strength, in combination with clinical risk factors. Finite element (FE) analyses based on quantitative computed tomography (QCT) have been shown to estimate bone strength better than aBMD. However, their application in the osteoporosis clinics is limited due to exposure of patients to increased X-rays radiation dose. Statistical modelling methods (3D-DXA) enabling the estimation of 3D femur shape and volumetric bone density from dual energy X-ray absorptiometry (DXA) scan have been shown to improve osteoporosis management. The current study used 3D-DXA based FE analyses to estimate femur strength from the routine clinical DXA scans and compared its results against 151 QCT based FE analyses, in a clinical cohort of 157 subjects. The linear regression between the femur strength predicted by QCT-FE and 3D-DXA-FE models correlated highly (coefficient of determination R2 = 0.86) with a root mean square error (RMSE) of 397 N. In conclusion, the current study presented a 3D-DXA-FE modelling tool providing accurate femur strength estimates noninvasively, compared to QCT-FE models.

Rapid bone microarchitecture decline in older men with high bone turnover-the prospective STRAMBO study.

Older men with high bone turnover have faster bone loss. We assessed the link between the baseline levels of bone turnover markers (BTMs) and the prospectively assessed bone microarchitecture decline in men. In 825 men aged 60-87yr, we measured the serum osteocalcin (OC), bone alkaline phosphatase (BAP), N-terminal propeptide of type I procollagen (PINP), and C-terminal telopeptide of type I collagen (CTX-I), and urinary total deoxypyridinoline (tDPD). Bone microarchitecture and strength (distal radius and distal tibia) were estimated by high-resolution pQCT (XtremeCT, Scanco Medical) at baseline and then after 4 and 8yr. Thirty-seven men took medications affecting bone metabolism. Statistical models were adjusted for age and BMI. At the distal radius, the decrease in the total bone mineral density (Tt.BMD), cortical BMD (Ct.BMD), cortical thickness (Ct.Thd), and cortical area (Ct.Ar) and failure load was faster in the highest vs the lowest CTX-I quartile (failure load: -0.94 vs -0.31% yr-1, P < .001). Patterns were similar for distal tibia. At the distal tibia, bone decline (Tt.BMD, Ct.Thd, Ct.Ar, Ct.BMD, and failure load) was faster in the highest vs the lowest tDPD quartile. At each skeletal site, the rate of decrease in Tb.BMD differed between the extreme OC quartiles (P < .001). Men in the highest BAP quartile had a faster loss of Tt.BMD, Tb.BMD, reaction force, and failure load vs the lowest quartile. The link between PINP and bone decline was poor. The BTM score is the sum of the nos. of the quartiles for each BTM. Men in the highest quartile of the score had a faster loss of cortical bone and bone strength vs the lowest quartile. Thus, in the older men followed prospectively for 8yr, the rate of decline in bone microarchitecture and estimated bone strength was 50%-215% greater in men with high bone turnover (highest quartile, CTX-I above the median) compared to the men with low bone turnover (lowest quartile, CTX-I below the median).

Predicting Non-traumatic Incident Fractures on Rheumatic Disease Patients on Long-term Glucocorticoids

Background: To identify contributors to non-traumatic incident fractures on rheumatic disease patients who are on long term glucocorticoids (LTGC) Methods: Two hundred and twenty patients on LTGC (110 with vertebral fracture and 110 without vertebral fracture) who participated in a cross-sectional study in 2014-2015 were invited to have repeated assessments on 1) aBMD using dual-energy X-ray absorptiometry (DXA), 2) volumetric BMD (vBMD), microstructure and bone strength assessment of the wrist and tibia using high-resolution peripheral quantitative computed tomography (HR-pQCT) and 3) spine radiographs in the 5th year. Clinical covariates were recorded on questionnaires, and Fracture Risk Assessment Tool (FRAX) score was calculated accordingly. Non-traumatic incident fracture over the 5-year were documented. Receiver operating characteristic curve (ROC) analysis was performed to compare the strength of fracture prediction tools. Results: Out of the 140 patients who completed the 5th year assessments, 47 (33.6%) developed incident fractures. History of previous fracture, aBMD at hip and lumbar spine, T-score, trabecular vBMD, trabecular bone volume fraction and estimated bone strength at the tibia at baseline remained significantly different after adjusting for age between the group with and without incident fractures. The area under curve (AUC) of a prediction model comprised of age, history of previous fracture and average trabecular vBMD at tibia was comparable with that of the FRAX score (0.710 vs 0.679-0.702), and slightly outperformed than the AUC of DXA aBMD at hip and lumbar spine (0.628-0.668) under ROC analysis. Conclusion: Age, history of previous fracture and average trabecular vBMD at tibia could be the main contributors in building a prediction model for non-traumatic incident fracture in rheumatic disease patients on LTGC.

Quantifying Bone Strength Deficits in Young Adults Born Extremely Preterm or Extremely Low Birth Weight.

The long-term bone health of young adults born extremely preterm (EP; <28 weeks' gestation) or extremely low birth weight (ELBW; <1000 g birth weight) in the post-surfactant era (since the early 1990s) is unclear. This study investigated their bone structure and estimated bone strength using peripheral quantitative computed tomography (pQCT)-based finite element modeling (pQCT-FEM). Results using this technique have been associated with bone fragility in several clinical settings. Participants comprised 161 EP/ELBW survivors (46.0% male) and 122 contemporaneous term-born (44.3% male), normal birth weight controls born in Victoria, Australia, during 1991-1992. At age 25 years, participants underwent pQCT at 4% and 66% of tibia and radius length, which was analyzed using pQCT-FEM. Groups were compared using linear regression and adjusted for height and weight. An interaction term between group and sex was added to assess group differences between sexes. Parameters measured included compressive stiffness (kcomp ), torsional stiffness (ktorsion ), and bending stiffness (kbend ). EP/ELBW survivors were shorter than the controls, but their weights were similar. Several unadjusted tibial pQCT-FEM parameters were lower in the EP/ELBW group. Height- and weight-adjusted ktorsion at 66% tibia remained lower in EP/ELBW (mean difference [95% confidence interval] -180 [-352, -8] Nm/deg). The evidence for group differences in ktorsion and kbend at 66% tibia was stronger among males than females (pinteractions <0.05). There was little evidence for group differences in adjusted radial models. Lower height- and weight-adjusted pQCT-FEM measures in EP/ELBW compared with controls suggest a clinically relevant increase in predicted long-term fracture risk in EP/ELBW survivors, particularly males. Future pQCT-FEM studies should utilize the tibial pQCT images because of the greater variability in the radius possibly related to lower measurement precision. © 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).

Risk of wrist fracture, estimated by the load-to-strength ratio, declines following sleeve gastrectomy in adolescents and young adults.

Vertical sleeve gastrectomy (VSG) improves metabolic health in young people with obesity but is accompanied by substantial loss of bone mass and estimated bone strength. We thus estimated fracture risk following VSG using the load-to-strength ratio (LSR), which integrates bone strength estimates with the predicted force of a fall. Prospective 2-year study of youth ages 13-24years with obesity undergoing VSG (n = 24) or lifestyle therapy (n = 34). We performed high-resolution peripheral quantitative computed tomography of the distal radius and microfinite element analysis to estimate bone strength and calculated LSR. VSG participants lost 26.4 ± 8.1% weight at year 1 (p < 0.001), which was sustained at year 2, while control participants gained weight at year 2 (4.5 ± 8.3%, p = 0.009). The predicted impact force decreased at years 1 and 2 following VSG (p < 0.001) but increased at year 2 among controls (p = 0.011). Estimated bone strength was unchanged at year 1 but decreased (p < 0.001) at year 2 following VSG, while bone strength did not change in controls. At year 1, the LSR decreased among VSG participants (p < 0.001), implying a lower risk of fracture. At year 2, the LSR was lower than baseline (p < 0.001), but higher compared to year 1 (p = 0.001). LSR did not change in the control group. Short-term estimated fracture risk at the radius following VSG decreases. However, ongoing bone loss despite stable weight between years 1 and 2 leads to a concerning rise in estimated fracture risk. Longer follow-up will be critical to evaluate the trajectory of fracture risk. (ClinicalTrials.gov NCT02557438, registered 9/23/2015).

FRI038 Differences In Bone Accrual Over One Year In Young Girls With Obesity Compared To Normal Weight Controls

Abstract Disclosure: S. Kaur: None. V. Singhal: None. L.A. Haidar: None. M. Bredella: None. M. Misra: None. Introduction: Despite higher bone mineral density (BMD), women with obesity are at an increased risk of fracture compared to normal-weight women. Optimal adolescent bone accrual is critical for normal peak bone mass acquisition and future bone health. Whereas several studies have examined the impact of low body weight on bone accrual in youth, data are lacking regarding the impact of obesity on bone accrual. We aimed to assess changes in areal and volumetric BMD, bone geometry and microarchitecture, and estimates of bone strength over one year in young females with moderate to severe obesity compared to their normal-weight counterparts. Methods: We recruited females between 13-25 years of age with moderate to severe obesity (OB) (n=21) and compared their bone accrual over one year with normal-weight controls (NWC) (n=50). Dual-energy X-ray absorptiometry to assess areal BMD (aBMD), high-resolution peripheral quantitative computed tomography (distal radius and tibia) to assess volumetric BMD (vBMD), bone geometry, and microarchitecture, and micro finite element analysis for estimates of bone strength was used. Analyses were controlled for age and race. Results: The mean age was 18.7 ± 2.7 years. OB and NWC were similar for age, race, height, and physical activity at baseline. OB had higher weight and BMI (p&amp;lt;0.0001 for both) and younger menarchal age (p=0.022) than NWC. Over one year, there was no difference between the groups for change in height, weight, and BMI. However, OB did not demonstrate the increase in total hip BMD observed in NWC (p=0.03) over a year. OB also had lesser increases in percent cortical area, cortical thickness, cortical and total vBMD at the radius over a year than the NWC group (p≤0.037 for all). The groups did not differ for tibial bone accrual. Conclusions: Our study demonstrates that longitudinal bone accrual over one year is impaired at the total hip and radius in adolescents and young adult females with obesity compared to normal-weight controls, while no differences are observed in tibial bone accrual. This raises concerns regarding future bone health in women with obesity, particularly at certain skeletal sites. Presentation: Friday, June 16, 2023

OR13-04 Risk Of Wrist Fracture In Gastric Bypass Compared To Gastric Banding As Estimated By The Load-To-Strength Ratio

Abstract Disclosure: G.H. Jung: None. B. Zahedi: None. K. Lindeman: None. C.C. Rushin: None. M.C. Cheney: None. M.L. Bouxsein: None. E.W. Yu: Grant Recipient; Self; Amgen Inc. Background: Bariatric surgeries such as Roux-en-Y gastric bypass (RYGB) and adjustable gastric banding (AGB) lead to long-term deficits in bone density but are also accompanied by decreased weight, which may lower the impact force with falls. Given that risk of fracture is dependent on both bone strength and the external force applied to bone, the clinical implications of these opposing effects are unclear. The aim of this study is to compare the long-term skeletal impact of RYGB and AGB using a biomechanical evaluation of load-to-strength ratio as a surrogate for fracture risk. Methods: We examined a cohort of adults who received RYGB and AGB surgery ≥ 10 years ago (RYGB: n=25; AGB: n=25). We computed the load-to-strength ratio at the distal radius as a ratio of impact force to bone strength, with higher load-to-strength ratios representing a higher susceptibility to fracture. Impact force (F) was calculated for a forward fall via a single-spring biomechanical model. High-resolution peripheral quantitative CT was used to estimate bone strength via microfinite element analysis. Participants also had dual-energy X-ray absorptiometry measurements of areal bone mineral density (aBMD) at the spine, hip, and distal radius, along with laboratory evaluations (parathyroid hormone, PTH; C-telopeptide, CTX; type 1 procollagen, P1NP; 25OH-vitamin D). Differences in bone outcomes between RYGB and AGB groups were compared using generalized linear modeling in R version 4.2.2 and adjusted for age, sex/menopausal status, and race/ethnicity. Results: The RYGB and AGB groups were each comprised of 22 women and 3 men. Compared to AGB, the RYGB group was younger (56 vs 62 years), had more premenopausal women (41% vs 9%), more individuals who identified as Black (36% vs 8%) and longer duration since surgery (13 vs 11 years) (p&amp;lt;0.05 for all). Current BMI (34.5 kg/m^2) was similar between groups, although postsurgical weight loss was higher in RYGB (45 vs. 27 kg, p&amp;lt;0.001). In multivariate analysis, in comparison to AGB, the RYGB group had 98% higher CTX and 34% higher P1NP levels (P&amp;lt;0.01 for both), as well as 20% lower total vBMD at the distal radius, 12% lower total hip, 10% lower femoral neck and 8% lower spinal aBMD (P&amp;lt;0.05 for all). Although impact forces were similar in the 2 groups, RYGB had a 12% lower estimated bone strength (3768 ± 182 vs. 4236 ± 193 N, p=0.01). Load-to-strength ratio was numerically higher in RYGB as compared with AGB (0.78 ± 0.05 vs 0.69± 0.06, p=0.1), suggestive of higher fracture risk, although this did not reach statistical significance. Conclusions: Despite achieving similar postoperative weight as AGB, RYGB patients had lower estimated bone strength at the distal radius, higher bone turnover markers, lower BMD and a trend for higher load-to-strength ratio ≥10 years after surgery. Taken together, these results indicate the long-term deleterious skeletal effects are more concerning with RYGB than AGB. Presentation: Friday, June 16, 2023

Bone Density, Geometry, Structure and Strength Estimates in Adolescent and Young Adult Women with Atypical Anorexia Nervosa versus Typical Anorexia Nervosa and Normal-Weight Healthy Controls.

Our objective was to characterize bone outcomes in adolescent and young adult women with atypical anorexia nervosa (AAN) compared to typical AN and normal-weight healthy controls (HC) based on DSM-5 criteria. Four hundred thirty-two participants (141 AN, 131 AAN and 160 HC), ages 12-21 years, underwent dual-energy X-ray absorptiometry for areal BMD, and a subset had high-resolution peripheral quantitative CT assessment of the distal radius and tibia for volumetric BMD (vBMD), bone geometry and microarchitecture, and microfinite element analysis for estimated strength. The groups did not differ for age, pubertal stage, menarcheal age or physical activity. BMI and bone outcomes overall were intermediate in AAN compared with AN and HC. This applied to spine, total hip and femoral neck BMD measures and many distal tibial measures. However, the mean whole-body less head BMD Z-score did not differ between AAN and AN, and it was lower in both vs. HC. Similarly, many distal radius measures did not differ between AAN vs. AN or HC but were lower in AN than HC. Lower BMI, lean mass and bone age, older menarcheal age and longer illness duration correlated with greater impairment of bone outcomes. These data indicate that individuals with AAN overall have bone outcomes that are intermediate between AN and HC.

Comparison of Bone Quality Among Winter Endurance Athletes with and Without Risk Factors for Relative Energy Deficiency in Sport (REDs): A Cross-Sectional Study.

Relative Energy Deficiency in Sport (REDs) is a syndrome describing the relationship between prolonged and/or severe low energy availability and negative health and performance outcomes. The high energy expenditures incurred during training and competition put endurance athletes at risk of REDs. The objective of this study was to investigate differences in bone quality in winter endurance athletes classified as either low-risk versus at-risk for REDs. Forty-four participants were recruited (M = 18; F = 26). Bone quality was assessed at the distal radius and tibia using high resolution peripheral quantitative computed tomography (HR-pQCT), and at the hip and spine using dual X-ray absorptiometry (DXA). Finite element analysis was used to estimate bone strength. Participants were grouped using modified criteria from the REDs Clinical Assessment Tool Version 1. Fourteen participants (M = 3; F = 11), were classified as at-risk of REDs (≥ 3 risk factors). Measured with HR-pQCT, cortical bone area (radius) and bone strength (radius and tibia) were 6.8%, 13.1% and 10.3% lower (p = 0.025, p = 0.033, p = 0.027) respectively, in at-risk compared with low-risk participants. Using DXA, femoral neck areal bone density was 9.4% lower in at-risk compared with low-risk participants (p = 0.005). At-risk male participants had 21.9% lower femoral neck areal bone density (via DXA) than low-risk males (p = 0.020) with no significant differences in females. Overall, 33.3% of athletes were at-risk for REDs and had lower bone quality than those at low-risk.

Alteration of Volumetric Bone Mineral Density Parameters in Men with Spinal Cord Injury.

Spinal cord injury (SCI) induces severe losses of trabecular and cortical volumetric bone mineral density (vBMD), which cannot be discriminated with conventional dual-energy X-ray absorptiometry (DXA) analysis. The objectives were to: (i) determine the effects of SCI on areal BMD (aBMD) and vBMD determined by advanced 3D-DXA-based methods at various femoral regions and (ii) model the profiles of 3D-DXA-derived parameters with the time since injury. Eighty adult males with SCI and 25 age-matched able-bodied (AB) controls were enrolled in this study. Trabecular and cortical vBMD, cortical thickness and derived strength parameters were assessed by 3D-SHAPER® software at various femoral subregions. Individuals with SCI had significantly lower integral vBMD, trabecular vBMD, cortical vBMD, cortical thickness and derived bone strength parameters (p < 0.001 for all) in total proximal femur compared with AB controls. These alterations were approximately to the same degree for all three femoral subregions, and the difference between the two groups tended to be greater for cortical vBMD than trabecular vBMD. There were minor differences according to the lesion level (paraplegics vs tetraplegics) for all 3D-DXA-derived parameters. For total proximal femur, the decreasing bone parameters tended to reach a new steady state after 5.1years for integral vBMD, 7.4years for trabecular vBMD and 9.2years for cortical vBMD following SCI. At proximal femur, lower vBMD (integral, cortical and trabecular) and cortical thickness resulted in low estimated bone strength in individuals with SCI. It remains to be demonstrated whether these new parameters are more closely associated with fragility fracture than aBMD.

Assessment of Bone Healing: Opportunities to Improve the Standard of Care.

➤ Bone healing is commonly evaluated by clinical examination and serial radiographic evaluation. Physicians should be mindful that personal and cultural differences in pain perception may affect the clinical examination. Radiographic assessment, even with the Radiographic Union Score, is qualitative, with limited interobserver agreement.➤ Physicians may use serial clinical and radiographical examinations to assess bone healing in most patients, but in ambiguous and complicated cases, they may require other methods to provide assistance in decision-making.➤ In complicated instances, clinically available biomarkers, ultrasound, and magnetic resonance imaging may determine initial callus development. Quantitative computed tomography and finite element analysis can estimate bone strength in later callus consolidation phases.➤ As a future direction, quantitative rigidity assessments for bone healing may help patients to return to function earlier by increasing a clinician's confidence in successful progressive healing.

Deficits in volumetric bone mineral density, bone microarchitecture, and estimated bone strength in women with atypical anorexia nervosa compared to healthy controls.

Anorexia nervosa is associated with low bone mineral density (BMD) and deficits in bone microarchitecture and strength. Low BMD is common in atypical anorexia nervosa, in which criteria for anorexia nervosa are met except for low weight. We investigated whether women with atypical anorexia nervosa have deficits in bone microarchitecture and estimated strength at the peripheral skeleton. Measures of BMD and microarchitecture were obtained in 28 women with atypical anorexia nervosa and 27 controls, aged 21-46 years. Mean tibial volumetric BMD, cortical thickness, and failure load were lower, and radial trabecular number and separation impaired, in atypical anorexia nervosa versus controls (p < .05). Adjustingfor weight, deficits in tibial cortical bone variables persisted (p < .05). Women with atypical anorexia nervosa and amenorrhea had lower volumetric BMD and deficits in microarchitecture and failure load versus those with eumenorrhea and controls. Those with a history of overweight/obesity or fracture had deficits in bone microarchitecture versus controls. Tibial deficits were particularly marked. Less lean mass and longer disease duration were associated with deficits in high-resolution peripheral quantitative computed tomography (HR-pQCT) variables in atypical anorexia nervosa. Women with atypical anorexia nervosa have lower volumetric BMD and deficits in bone microarchitecture and strength at the peripheral skeleton versus controls, independent of weight, and particularly at the tibia. Women with atypical anorexia nervosa and amenorrhea, less lean mass, longer disease duration, history of overweight/obesity, or fracture history may be at higher risk. This is salient as deficits in HR-pQCT variables are associated with increased fracture risk. Atypical anorexia nervosa is a psychiatric disorder in which psychological criteria for anorexia nervosa are met despite weight being in the normal range. We demonstrate that despite weight in the normal range, women with atypical anorexia nervosa have impaired bone density, structure, and strength compared to healthy controls. Whether this translates to an increased risk of incident fracture in this population requires further investigation.

Comparison of bone microstructure and strength in the distal radius and tibia between the different types of primary hypertrophic osteoarthropathy: an HR-pQCT study

SummaryPrimary hypertrophic osteoarthropathy (PHO) is a hereditary bone disease that is grouped into PHO autosomal recessive 1 (PHOAR1) and PHO autosomal recessive 2 (PHOAR2) due to different causative genes. Data comparing bone microstructure between the two subtypes are scarce. This is the first study to find that PHOAR1 patients had inferior bone microstructure compared with PHOAR2 patients.PurposeThe primary goal of this study was to assess bone microarchitecture and strength in PHOAR1 and PHOAR2 patients and to compare them with age- and sex-matched healthy controls (HCs). The secondary goal was to assess the differences between PHOAR1 and PHOAR2 patients.MethodsTwenty-seven male Chinese PHO patients (PHOAR1 = 7; PHOAR2 = 20) were recruited from Peking Union Medical College Hospital. The areal bone mineral density (aBMD) was assessed by dual-energy X-ray absorptiometry (DXA). Peripheral bone microarchitecture at the distal radius and tibia were evaluated by high-resolution peripheral quantitative computed tomography (HR-pQCT). Biochemical markers of PGE2, bone turnover, and Dickkopf-1 (DKK1) were investigated.ResultsCompared with HCs, PHOAR1 and PHOAR2 patients had distinctively larger bone geometry, substantially lower vBMD at the radius and tibia, and compromised cortical microstructure at the radius. For trabecular bone, PHOAR1 and PHOAR2 patients showed different changes at the tibia. PHOAR1 patients had significant deficits in the trabecular compartment, resulting in lower estimated bone strength. Conversely, PHOAR2 patients showed a higher trabecular number, narrower trabecular separation, and lower trabecular network inhomogeneity than HCs, translating into preserved or slightly high estimated bone strength.ConclusionPHOAR1 patients had inferior bone microstructure and strength compared with PHOAR2 patients and HCs. Additionally, this study was the first to find differences in the bone microstructure between PHOAR1 and PHOAR2 patients.