Rigid-motion artifacts, such as cortical bone streaking and trabecular smearing, hinder in vivo assessment of bone microstructures in high-resolution peripheral quantitative computed tomography (HR-pQCT). Despite various motion grading techniques, no motion correction methods exist due to the lack of standardized degradation models. We optimize a conventional sinogram-based method to simulate motion artifacts in HR-pQCT images, creating paired datasets of motion-corrupted images and their corresponding ground truth, which enables seamless integration into supervised learning frameworks for motion correction. As such, we propose an Edge-enhanced Self-attention Wasserstein Generative Adversarial Network with Gradient Penalty (ESWGAN-GP) to address motion artifacts in both simulated (source) and real-world (target) datasets. The model incorporates edge-enhancing skip connections to preserve trabecular edges and self-attention mechanisms to capture long-range dependencies, facilitating motion correction. A visual geometry group (VGG)-based perceptual loss is used to reconstruct fine micro-structural features. The ESWGAN-GP achieves a mean signal-to-noise ratio (SNR) of 26.78, structural similarity index measure (SSIM) of 0.81, and visual information fidelity (VIF) of 0.76 for the source dataset, while showing improved performance on the target dataset with an SNR of 29.31, SSIM of 0.87, and VIF of 0.81. The proposed methods address a simplified representation of real-world motion that may not fully capture the complexity of in vivo motion artifacts. Nevertheless, because motion artifacts present one of the foremost challenges to more widespread adoption of this modality, these methods represent an important initial step toward implementing deep learning-based motion correction in HR-pQCT.

Objective To determine whether decreased femoral head enhancement on MRI differentiates septic arthritis from transient synovitis. Materials and methods This retrospective study included children < 10 years old with hip effusion on post-contrast MRI for suspected musculoskeletal infection. Two pediatric radiologists independently assessed femoral head enhancement. Kocher and modified Kocher scores were calculated from clinical and lab data. Differences between septic arthritis and transient synovitis were analyzed using Student’s t -tests and Fisher’s exact tests. Sensitivity and specificity for diagnosing septic arthritis were calculated for Kocher scores, their individual components, decreased femoral head enhancement, and muscle edema. Interobserver agreement was assessed. Results Thirty-four children were included (20 transient synovitis, 14 septic arthritis). Kocher and modified Kocher scores were significantly higher in septic arthritis ( p = 0.003, 0.008). Interobserver agreement for femoral head enhancement was substantial (kappa = 0.70). On consensus read, decreased femoral head enhancement was seen in 71.4% of septic arthritis and 50.0% of transient synovitis cases ( p = 0.296). Bone marrow edema was present in two septic arthritis cases. Muscle edema had moderate to high sensitivity (71.4%, 92.9%) but moderate to low specificity (75.0%, 50.0%) for septic arthritis. Conclusion Decreased femoral head enhancement does not reliably distinguish septic arthritis from transient synovitis. Relying on this finding alone may lead to unnecessary interventions in children with transient synovitis. Muscle edema and bone marrow edema may support the diagnosis of septic arthritis. Clinical evaluation and inflammatory markers remain critical in guiding decisions for hip aspiration.

Classic metaphyseal lesions (CMLs) are considered specific for child abuse, but the reliability of radiologists in distinguishing CMLs from metaphyseal variations is unclear. To evaluate the diagnostic performance of pediatric and adult emergency radiologists in differentiating CMLs from metaphyseal variations in the knees. We retrospectively reviewed distal femur and proximal tibia radiographs in children under 1 year of age who underwent skeletal surveys for suspected child abuse. A consensus diagnosis for CMLs and metaphyseal variations—serving as the ground truth—was established by two pediatric radiologists. The CML group comprised children diagnosed with abuse and confirmed CMLs. The metaphyseal variation group included children not diagnosed with abuse, who exhibited metaphyseal variations and had either no fractures or only an isolated skull fracture. Radiographs were trimmed to exclude other injuries. Four pediatric and four adult radiologists reviewed anonymized studies and categorized each case as CML, metaphyseal variation, normal, or indeterminate, with confidence levels (high, moderate, low). We analyzed diagnoses with moderate or high confidence. Interobserver agreement was assessed using kappa statistics. There were 44 children with CMLs (10 initial, 7 follow-up, 27 initial and follow-up) and 22 with metaphyseal variations (10 initial, 7 follow-up, 5 initial and follow-up). Metaphyseal fragmentation was the most common variation, identified in 249 of 344 femurs (72.4

Prenatal hydrocolpos is characterized by fluid distension of the vagina. Hydrocolpos can be caused by multiple underlying etiologies and often demonstrates overlapping imaging features compared to other cystic abdominal and pelvic lesions. The purpose of the current pictorial essay is to provide a systematic prenatal magnetic resonance imaging (MRI) approach to differentiating the primary etiologies leading to hydrocolpos. After discussing the fundamental embryological processes involved in vaginal development, the current essay discusses the most common causes of hydrocolpos with their associated prenatal and postnatal imaging features. An approach to distinguishing the more common differential diagnoses is provided. Given the implications of parental counseling and postnatal management, this essay provides an important approach for narrowing differential diagnoses based on prenatal imaging.

Background/Hypothesis: Brief resolved unexplained events (BRUEs) are events in infants characterized by cyanosis, abnormal breathing, abnormal tone, and altered responsiveness. Practice guidelines define high-risk and low-risk BRUEs and do not recommend imaging in low-risk patients. We evaluated imaging in these patients and hypothesized that high-risk patients would have more imaging studies and abnormalities. Methods: Using the radiology information system, a retrospective review was performed between 2016-2022 for patients <1 year presenting with BRUE. Defined search terms were used to identify imaging within one week of presentation. Patients were evaluated for clinical presentation, medical history, physical examination, imaging studies ordered, and final diagnoses. Results: 126 patients were identified. 113 patients (46 female; 93 high-risk), between 3 and 355 days old (average age 97 days), met inclusion criteria. Imaging included chest radiographs (99), head CTs (24), brain MRIs (19), skeletal surveys (16), and others (22). There was no difference in the number of imaging studies obtained between these groups (p=0.423, Mann-Whitney U test). However, a greater proportion of high-risk patients had imaging abnormalities (p=0.023, Fisher’s exact test). Only 1/20 (5%) low-risk patients had abnormal imaging (PCR proven viral bronchiolitis). 26/93 (28%) high-risk patients had abnormal findings, most commonly on chestradiographs (15), brain MRIs (9), head CTs (4), and skeletal surveys (3). 18/26 high-risk patients had imaging abnormalities leading to a diagnosis other than BRUE (viral bronchiolitis, bronchopulmonary dysplasia, nonaccidental trauma, perinatal HSV infection, ventricular septal defect, double aortic arch, intestinal malrotation, and neurofibromatosis). Overall, 7/93 (7.5%) high-risk BRUE patients had significant pathology. Conclusion: High-risk patients were more likely to have an imaging abnormality compared to low-risk patients, which is consistent with current imaging recommendations given only one low-risk imaging abnormality. Interestingly, 7.5% of the high-risk patients had significant pathology diagnosed by imaging.

Introduction: Conventional bone imaging methods primarily use X-ray techniques to assess bone mineral density (BMD), focusing exclusively on the mineral phase. This approach lacks information about the organic phase and bone water content, resulting in an incomplete evaluation of bone health. Recent research highlights the potential of ultrashort echo time magnetic resonance imaging (UTE MRI) to measure cortical porosity and estimate BMD based on signal intensity. UTE MRI also provides insights into bone water distribution and matrix organization, enabling a comprehensive bone assessment with a single imaging technique. Our study aimed to establish quantifiable UTE MRI-based biomarkers at clinical field strength to estimate BMD and microarchitecture while quantifying bound water content and matrix organization. Methods: Femoral bones from 11 cadaveric specimens (n = 4 males 67-92 yrs of age, n = 7 females 70-95 yrs of age) underwent dual -echo UTE MRI (3.0 T, 0.45 mm resolution) with different echo times and high resolution peripheral quantitative computed tomography (HR-pQCT) imaging (60.7 mu m voxel size). Following registration, a 4.5 mm HR-pQCT region of interest was divided into four quadrants and used across the multi -modal images. Statistical analysis involved Pearson correlation between UTE MRI porosity index and a signal -intensity technique used to estimate BMD with corresponding HR-pQCT measures. UTE MRI was used to calculate T1 relaxation time and a novel bound water index (BWI), compared across subregions using repeated measures ANOVA. Results: The UTE MRI-derived porosity index and signal -intensity -based estimated BMD correlated with the HRpQCT variables (porosity: r = 0.73, p = 0.006; BMD: r = 0.79, p = 0.002). However, these correlations varied in strength when we examined each of the four quadrants (subregions, r = 0.11-0.71). T1 relaxometry and the BWI exhibited variations across the four subregions, though these differences were not statistically significant. Notably, we observed a strong negative correlation between T1 relaxation time and the BWI (r = -0.87, p = 0.0006). Conclusion: UTE MRI shows promise for being an innocuous method for estimating cortical porosity and BMD parameters while also giving insight into bone hydration and matrix organization. This method offers the potential to equip clinicians with a more comprehensive array of imaging biomarkers to assess bone health without the need for invasive or ionizing procedures.

Chronic kidney disease (CKD) is characterized by secondary hyperparathyroidism and an increased risk of hip fractures predominantly related to cortical porosity. Unfortunately, bone mineral density measurements and high-resolution peripheral computed tomography (HR-pQCT) imaging have shortcomings that limit their utility in these patients. Ultrashort echo time magnetic resonance imaging (UTE-MRI) has the potential to overcome these limitations by providing an alternative assessment of cortical porosity. The goal of the current study was to determine if UTE-MRI could detect changes in porosity in an established rat model of CKD. Cy/+ rats (n = 11), an established animal model of CKD-MBD, and their normal littermates (n = 12) were imaged using microcomputed tomography (microCT) and UTE-MRI at 30 and 35 weeks of age (which approx-imates late-stage kidney disease in humans). Images were obtained at the distal tibia and the proximal femur. Cortical porosity was assessed using the percent porosity (Pore%) calculated from microCT imaging and the porosity index (PI) calculated from UTE-MRI. Correlations between Pore% and PI were also calculated. Cy/+ rats had higher Pore% than normal rats at both skeletal sites at 35 weeks (tibia = 7.13 % +/-5.59 % vs. 0.51 % +/-0.09 %, femur = 19.99 % +/-7.72 % vs. 2.72 % +/-0.32 %). They also had greater PI at the distal tibia at 30 weeks of age (0.47 +/-0.06 vs. 0.40 +/-0.08). However, Pore% and PI were only correlated in the proximal femur at 35 weeks of age (rho = 0.929, Spearman). These microCT results are consistent with prior studies in this animal model utilizing microCT imaging. The UTE-MRI results were inconsistent, resulting in variable correlations with microCT imaging, which may be related to suboptimal bound and pore water discrimination at higher magnetic field strengths. Nevertheless, UTE-MRI may still provide an additional clinical tool to assess fracture risk without using ionizing radiation in CKD patients.

Purpose: Chronic kidney disease (CKD) leads to increased bone fragility and risk of fracture. Cortical deteriorations, including cortical porosity, are key factors in fracture susceptibility in CKD. Since secondary hyperparathyroidism is common in CKD individuals and contributes to cortical deterioration, we hypothesized that reducing parathyroid hormone (PTH) may modulate CKD-induced cortical porosity. The goal of this pilot study was to assess the effects of lowering PTH, via the preclinical analogue of the FDA-approved calcimimetic etelcalcetide (KP-2326), on the development and progression of cortical pores in the setting of CKD. Methods: Male Cy/+ Sprague Dawley rats with clinical biochemistries consistent with CKD (N = 8) were assigned to the study. At 30-32 weeks of age, cortical bone was assessed via In vivo uCT and blood collected for biochemistries to create baseline measures. Calcimimetic treatment with KP-2326 (KP) was then administered 3x weekly for 2-4 weeks. Cortical bone and biochemical parameters were repeated at study endpoint (33-37 wks of age). A group of age- and cohort-matched CKD rats (N = 4) were utilized as untreated controls. Results: Untreated CKD rats had significantly increased cortical porosity over time, while porosity in KP-treated CKD rats was not significantly changed over time. Individual pore analysis revealed that pore area was significantly higher for expanding pores in untreated CKD rats compared to KP-treated CKD rats. Mechanical properties of KP-treated animal femora were similar to historical values of age-matched CKD animals and lower than those of age-matched non-diseased animals. Conclusion: Our pilot preclinical study demonstrates that etelcalcetide treatment can mitigate the progression of cortical bone changes in an animal model of CKD through suppression of pre-existing cortical pore expansion and limiting the size of new pore development. While stabilization of porosity is beneficial it remains likely that infilling of porosity will be needed to positively affect mechanical properties of bones in the setting of CKD.

Cortical porosity develops in chronic kidney disease (CKD) and increases with progressing disease. Cortical porosity is likely a prominent contributor to skeletal fragility/fracture. The degree to which cortical porosity occurs throughout the skeleton is not fully known. In this study, we assessed cortical bone porosity via micro -computed tomography at multiple skeletal sites in rats with progressive chronic kidney disease. We hypothe-sized that cortical porosity would occur in long bones throughout the body, but to a lesser degree in flat bones and irregular bones. Porosity was measured, using micro-CT, at 17 different skeletal sites in 6 male rats with CKD. Varying degrees of porosity were seen throughout the skeleton with higher porosity in flat and irregular bone (i.e. parietal bone, mandible) vs. long bones (p = 0.01) and in non-weightbearing bones vs. weightbearing bones (p = 0.01). Porosity was also higher in proximal sites vs. distal sites in long bones (p < 0.01 in all comparisons). There was large heterogeneity in porosity within skeletal sites across rats and within the same rat across skeletal sites. Correlations showed cortical porosity of the proximal tibia was positively associated with porosity at the other sites with the strongest correlation to the parietal bone and the weakest to the ulna. Overall, our data demonstrates varying and significant cortical bone porosity across the skeleton of animals with chronic kidney disease. These data point to careful selection of skeletal sites to assess porosity in pre-clinical studies and the potential for fractures at multiple skeletal sites in patients with CKD.

The ductus venosus serves as an important vascular pathway for intrauterine circulation. This case presents a description of an absent ductus venosus in a female patient with Noonan syndrome, including both prenatal and postnatal imaging of the anomaly. In the setting of the anomalous vascular connection, the umbilical vein courses inferiorly to the iliac vein in parallel configuration with the umbilical artery. This finding was suspected based on prenatal imaging and the case was brought to attention when placement of an umbilical catheter was thought to be malpositioned given its appearance on radiography. Ultrasound imaging confirmed the anomalous course. This is in keeping with prior descriptions in the literature of an association between Noonan syndrome and aberrant umbilical venous drainage. This case illustrates the need for awareness of this condition by the radiologist, allowing for identification on radiographs and the recommendation for further confirmatory imaging. Further, the case illustrates the value of paying particular attention to the fetal course of the umbilical vessels in patients with suspected Noonan syndrome, as this population is particularly at risk for anomalous vasculature.

A growing number of studies have investigated combination treatment as an approach to treat bone disease. The goal of this study was to investigate the combination of alendronate and raloxifene with a particular focus on mechanical properties. To achieve this goal we utilized a large animal model, the beagle dog, used previously by our laboratory to study both alendronate and raloxifene monotherapies. Forty-eight skeletally mature female beagles (1-2 years old) received daily oral treatment: saline vehicle (VEH), alendronate (ALN), raloxifene (RAL) or both ALN and RAL. After 6 and 12 months of treatment, all animals underwent assessment of bone material properties using in vivo reference point indentation (RPI) and skeletal hydration using ultra-short echo magnetic resonance imaging (UTE-MRI). End point measures include imaging, histomorphometry, and mechanical properties. Bone formation rate was significantly lower in iliac crest trabecular bone of animals treated with ALN (-71%) and ALN+RAL (-81%) compared to VEH. In vivo assessment of properties by RPI yielded minimal differences between groups while UTE-MRI showed a RAL and RAL+ALN treatment regimens resulted in significantly higher bound water compared to VEH (+23 and +18%, respectively). There was no significant difference among groups for DXA- or CT-based measures lumbar vertebra, or femoral diaphysis. Ribs of RAL-treated animals were smaller and less dense compared to VEH and although mechanical properties were lower the material-level properties were equivalent to normal. In conclusion, we present a suite of data in a beagle dog model treated for one year with clinically-relevant doses of alendronate and raloxifene monotherapies or combination treatment with both agents. Despite the expected effects on bone remodeling, our study did not find the expected benefit of ALN to BMD or structural mechanical properties, and thus the viability of the combination therapy remains unclear.

The OsteoProbe is a second-generation reference point indentation (RPI) device without a reference probe that is designed to simplify RPI testing for clinical use. Successful clinical implementation of the OsteoProbe would benefit from a better understanding of how its output, bone material strength index (BMSi), relates to the material properties of bone and under what conditions it reliably correlates with fracture risk. Large animal models have the potential to help fill this knowledge gap, as cadaveric studies are retrospective and limited by incomplete patient histories (including the potential use of bone matrix altering drugs such as bisphosphonates). The goal of this study was to assess the intra and inter-animal variability of OsteoProbe measures in untreated beagle dogs (n=12), and to evaluate this variability in comparison to traditional mechanical testing. OsteoProbe measurements were performed in vivo on the left tibia of each dog and repeated 6months later on the day of sacrifice. Within-animal variation of BMSi (CV of 5–10 indents) averaged 8.9 and 9.0% at the first and second timepoints, respectively. In contrast, inter-animal variation of BMSi increased from 5.3% to 9.1%. The group variation of BMSi was on par with that of traditional 3-point mechanical testing; inter-animal variation was 10% for ultimate force, 13% for stiffness, and 12% for total work as measured on the femur. There was no significant change in mean BMSi after 6months, but the individual change with time across the 12 dogs was highly variable, ranging from −12.4% to +21.7% (mean 1.6%, SD 10.6%). No significant correlations were found between in vivo tibia BMSi and femur mechanical properties measured by ex vivo 3-pt bending, but this may be a limitation of sample size or the tests being performed on different bones. No relationship was found between BMSi and tissue mineral density, but a strong positive correlation was found between BMSi and tibia cortical thickness (ρ=0.706, p=0.010). This report shows that while the OsteoProbe device has inter-individual variability quite similar to that of traditional mechanical testing, the longitudinal changes show high levels of heterogeneity across subjects. We further highlight the need for standardization in post-testing data processing and further study of the relationships between OsteoProbe and traditional mechanical testing.

Background: Chronic kidney disease (CKD) leads to complex metabolic changes and an increased risk of fracture. Currently, calcitriol is the standard of care as it effectively suppresses parathyroid hormone (PTH) levels in CKD patients. While calcitriol and its analogs improve BMD and reduce fractures in the general population, the extension of these benefits to patients with advanced kidney disease is unclear. Here, the impact of calcitriol on the skeleton was examined in the setting of reduction in PTH. Methods: Male Cy/+ rats, a PKD-like CKD model, were treated with either vehicle or calcitriol for 5 weeks. Their normal littermates served as controls. Animals were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole bone mechanics and bone quality). Results: PTH levels were significantly higher (12-fold) in animals with CKD compared to normal controls. CKD animals also exhibited negative changes in bone structural and mechanical properties. Calcitriol treatment resulted in a 60% suppression of PTH levels in animals with CKD. Despite these changes, it had no impact on bone volume (cortical or cancellous), bone turnover, osteoclast number or whole bone mechanical properties. Conclusions: These data indicate that while calcitriol effectively lowered PTH in rats with CKD, it did little to prevent the negative effects of secondary hyperparathyroidism on the skeleton.

Pre-clinical data have shown that tissue level effects stemming from bisphosphonate-induced suppression of bone remodeling can result in bone that is stronger yet more brittle. Raloxifene has been shown to reduce bone brittleness through non-cellular mechanisms. The goal of this work was to test the hypothesis that raloxifene can reverse the bone brittleness resulting from bisphosphonate treatment. Dog and mouse bone from multiple bisphosphonate dosing experiments were soaked in raloxifene and then assessed for mechanical properties. Mice treated with zoledronate in vivo had lower post-yield mechanical properties compared to controls. Raloxifene soaking had significant positive effects on select mechanical properties of bones from both vehicle and zoledronate treated mice. Although the effects were blunted in zoledronate bones relative to vehicle, the soaking was sufficient to normalize properties to control levels. Additional studies showed that raloxifene-soaked bones had a significant positive effect on cycles to failure (+114%) compared to control-soaked mouse bone. Finally, raloxifene soaking significantly improved select properties of ribs from dogs treated for 3 years with alendronate. These data show that ex vivo soaking in raloxifene can act through non-cellular mechanisms to enhance mechanical properties of bone previously treated with bisphosphonate. We also document that the positive effects of raloxifene soaking extend to enhancing fatigue properties of bone.

Patients with chronic kidney disease (CKD) have an increased risk of fracture. Raloxifene is a mild antiresorptive agent that reduces fracture risk in the general population. Here we assessed the impact of raloxifene on the skeletal properties of animals with progressive CKD. Male Cy/+ rats that develop autosomal dominant cystic kidney disease were treated with either vehicle or raloxifene for five weeks. They were assessed for changes in mineral metabolism and skeletal parameters (microCT, histology, whole-bone mechanics, and material properties). Their normal littermates served as controls. Animals with CKD had significantly higher parathyroid hormone levels compared with normal controls, as well as inferior structural and mechanical skeletal properties. Raloxifene treatment resulted in lower bone remodeling rates and higher cancellous bone volume in the rats with CKD. Although it had little effect on cortical bone geometry, it resulted in higher energy to fracture and modulus of toughness values than vehicle-treated rats with CKD, achieving levels equivalent to normal controls. Animals treated with raloxifene had superior tissue-level mechanical properties as assessed by nanoindentation, and higher collagen D-periodic spacing as assessed by atomic force microscopy. Thus, raloxifene can positively impact whole-bone mechanical properties in CKD through its impact on skeletal material properties.

ABSTRACT Chronic kidney disease (CKD) is associated with abnormalities in bone quantity and quality, leading to increased fractures. Recent studies suggest abnormalities of Wnt signaling in animal models of CKD and elevated sclerostin levels in patients with CKD. The goal of this study was to evaluate the effectiveness of anti-sclerostin antibody treatment in an animal model of progressive CKD with low and high parathyroid hormone (PTH) levels. Cy/+ male rats (CKD) were treated without or with calcium in the drinking water at 25 weeks of age to stratify the animals into high PTH and low PTH groups, respectively, by 30 weeks. Animals were then treated with anti-sclerostin antibody at 100 mg/kg i.v. weekly for 5 doses, a single 20-µg/kg subcutaneous dose of zoledronic acid, or no treatment, and were then euthanized at 35 weeks. As a positive control, the efficacy of anti-sclerostin antibody treatment was also evaluated in normal littermates. The results demonstrated that the CKD animals with high PTH had lower calcium, higher phosphorus, and lower FGF23 compared to the CKD animals with low PTH. Treatment with anti-sclerostin antibody had no effect on any of the biochemistries, whereas zoledronic acid lowered dkk-1 levels. The anti-sclerostin antibody increased trabecular bone volume/total volume (BV/TV) and trabecular mineralization surface in animals with low PTH, but not in animals with high PTH. Neither anti-sclerostin antibody nor zoledronic acid improved biomechanical properties in the animals. Cortical porosity was severe in high-PTH animals and was unaffected by either treatment. In contrast, in normal animals treated with anti-sclerostin antibody, there was an improvement in bone volume, cortical geometry, and biomechanical properties. In summary, this is the first study to test the efficacy of anti-sclerostin antibody treatment on animals with advanced CKD. We found efficacy in improving bone properties only when the PTH levels were low. © 2014 American Society for Bone and Mineral Research

ABSTRACT Raloxifene positively affects mechanical properties of the bone matrix in part through modification of skeletal-bound water. The goal of this study was to determine if raloxifene-induced alterations in skeletal hydration could be measured in vivo using ultra-short echotime magnetic resonance imaging (UTE-MRI). Twelve skeletally mature female beagle dogs (n = 6/group) were treated for 6 months with oral doses of saline vehicle (VEH, 1 mL/kg/d) or raloxifene (RAL, 0.5 mg/kg/d). After 6 months of treatment, all animals underwent in vivo UTE-MRI of the proximal tibial cortical bone. UTE-MRI signal intensity versus echotime curves were analyzed by fitting a double exponential to determine the short and long relaxation times of water with the bone (dependent estimations of bound and free water, respectively). Raloxifene-treated animals had significantly higher bound water (+14%; p = 0.05) and lower free water (–20%) compared with vehicle-treated animals. These data provide the first evidence that drug-induced changes in skeletal hydration can be noninvasively assessed using UTE-MRI. © 2015 American Society for Bone and Mineral Research. © 2015 American Society for Bone and Mineral Research.

Background/Aims: Patients with chronic kidney disease mineral and bone disorder (CKD-MBD) have a significantly higher vertebral and non-vertebral fracture risk than the general population. Several preclinical models have documented altered skeletal properties in long bones, but few data exist for vertebral bone. The goal of this study was to examine the effects of progressive CKD on vertebral bone structure and mechanics and to determine the effects of treatment with either bisphosphonates or anti-sclerostin antibody in groups of animals with high or low PTH.Methods: Animals with progressive kidney disease were left untreated, treated with calcium to lower PTH, zoledronic acid to lower remodeling without affecting PTH, anti-sclerostin antibody, or anti-sclerostin antibody plus calcium. Non-diseased, untreated littermates served as controls. Vertebral bone morphology (trabecular and cortical) and mechanical properties (structural and material-level) were assessed at 35 weeks of age by microCT and mechanical testing, respectively.Results: CKD with high PTH resulted in 6-fold higher bone formation rate, significant reductions in the amount of trabecular and cortical bone, and compromised whole bone mechanical properties in the vertebra compared to normal animals. Treatments that reduced bone remodeling were effective in normalizing vertebral structure and mechanical properties only if the treatment reduced serum PTH. Similarly, treatment with anti-sclerostin antibody was effective in enhancing bone mass and mechanical properties but only if combined with PTH-suppressive treatment.Conclusions: CKD significantly altered both cortical and trabecular bone properties in the vertebra resulting in compromised mechanical properties and these changes can be normalized by interventions that involve reductions in PTH levels. (C) 2015 Elsevier Inc. All rights reserved.