Micro-CT, Mechanical, and Histological Examination of the Effect of Local Adjuvants on Porcine Cortical Bone Following Intralesional Curettage of Bone Tumors.

BACKGROUND AND OBJECTIVES: Curettage is the removal of a tumor from the bone while preserving the surrounding healthy cortical bone, and is associated with higher rates of local recurrence. To lower these rates, curettage should be combined with local adjuvants, although their use is associated with damage to nearby healthy bone. OBJECTIVE: The purpose of this analysis is to determine the effect of local adjuvants on cortical porcine bone by using micro-computed tomography (micro-CT) along with histological and mechanical examination. METHODS: Local adjuvants were applied to porcine specimens under defined conditions. To assess changes in bone mineral density (BMD), a micro-CT scan was used. The pixel gray values of the volume of interest (VOI) were evaluated per specimen and converted to BMD values. The Vickers hardness test was employed to assess bone hardness (HV). The depth of necrosis was measured histologically using hematoxylin and eosin-stained tissue sections. RESULTS: A noticeable change in BMD was observed on the argon beam coagulation (ABC) sample. Comparable hardness values were measured on samples following electrocautery and ABC, and lowering of bone hardness was obtained in the case of liquid nitrogen. Extensive induced depth of necrosis was registered in the specimen treated with liquid nitrogen. CONCLUSION: This study determined the effect of local adjuvants on cortical bone by using micro-CT along with histological and mechanical examination. Phenolization and liquid nitrogen application caused a decrease in bone hardness. The bone density was affected in the range of single-digit percentage values. Liquid nitrogen induced extensive depth of necrosis with a wide variance of values.

The morphology of alveolar bone of the mandibular second and third molars in skeletal Class III patients.

OBJECTIVES: To investigate the alveolar bone morphology of the mandibular second and third molars in skeletal Class III patients from a buccolingual direction. METHODS: Sixty skeletal Class III patients were recruited. The alveolar bone width, buccal cortical bone thickness and lingual cortical bone thickness were measured in five planes from mesial to distal and at five depths from gingival to root. The effects of the gender of the patients, the second molar lingual inclination and the third molar on alveolar bone width and cortical bone thickness were evaluated. To explore the effect of third molar extraction on alveolar bone morphology, the measurements before and after third molar extraction were compared. RESULTS: The impacted third molar had significantly greater alveolar bone width and thicker buccal cortical bone at the cervical third of the molar, while the erupted third molar had greater alveolar bone width at the apical third. Three weeks after third molar extraction, these advantages would weaken owing to the reconstruction of the alveolar bone. Patients with lingually inclined molar were observed to own thicker lingual cortical bone. Males tended to have greater alveolar bone width, but no significant differences were shown in this study. CONCLUSIONS: The growth of the third molar and the second molar lingual inclination affect the alveolar bone morphology of the mandibular second and third molars significantly, but gender has trivial effects on the morphology. The alveolar bone morphology of the mandibular second and third molars would change 3 weeks after third molar extraction.

Investigation of Skull Cortical Thickness Changes in Healthy Population and Patients With Schizophrenia on Computed Tomography Images.

Cortical bone thickness is essential for the mechanical function of bone. Some factors including aging, sex, body size, hormone levels, behavior, and genetics lead to changes in cranial cortical robusticity. Moreover, the skull is one of the hardest and most durable structures in the human body. Schizophrenia is defined as a psychiatric disease characterized by delusions and hallucinations, and these patients have reduced brain volume; however, there is no study including cortical bone structure. For this reason, the aim of this study was to determine whether there is a difference in the skull cortical thickness of patients with schizophrenia and, compare it with healthy subjects. The cranial length, cranial width, anterior cortical thickness, right and left anterior cortical thickness, right and left lateral cortical thickness, right and left posterior lateral thickness, and posterior cortical thickness were measured with axial computed tomography images of 30 patients with schizophrenia and 132 healthy individuals aged between 18 and 69years. A statistically significant difference was found between the two groups in the measurements of right and left posterior lateral thickness, and posterior cortical thickness ( P = 0.006, P = 0.001, and P = 0.047, respectively). The sexes were compared, and it was found that the cranial width, anterior thickness, left anterior thickness, and right and left posterior thickness measurements of patients with schizophrenia showed a statistically significant difference compared with the control group ( P < 0.001, P = 0.003, P = 0.001, P < 0.001 and P < 0.001, respectively). The authors observed that skull cortical thickness may be different in schizophrenia. The results obtained from this study may be beneficial for evaluating these structures for clinical and pathological processes. Furthermore, knowledge about the skull cortical thickness in planning surgical procedures will increase the reliability and effectiveness of the surgical method, and this will minimize the risk of complications.

CCR3 deficiency is associated with increased osteoclast activity and reduced cortical bone volume in adult male mice.

Increasing evidence emphasizes the importance of chemokines and chemokine receptors as regulators of bone remodeling. The C-C chemokine receptor 3 (CCR3) is dramatically upregulated during osteoclastogenesis, but the role of CCR3 in osteoclast formation and bone remodeling in adult mice is unknown. Herein, we used bone marrow macrophages derived from adult male CCR3-proficient and CCR3-deficient mice to study the role of CCR3 in osteoclast formation and activity. CCR3 deficiency was associated with formation of giant hypernucleated osteoclasts, enhanced bone resorption when cultured on bone slices, and altered mRNA expression of related chemokine receptors and ligands. In addition, primary mouse calvarial osteoblasts isolated from CCR3-deficient mice showed increased mRNA expression of the osteoclast activator-related gene, receptor activator of nuclear factor kappa-B ligand, and osteoblast differentiation-associated genes. Microcomputed tomography analyses of femurs from CCR3-deficient mice revealed a bone phenotype that entailed less cortical thickness and volume. Consistent with our in vitro studies, the total number of osteoclasts did not differ between the genotypes in vivo. Moreover, an increased endocortical osteoid mineralization rate and higher trabecular and cortical bone formation rate was displayed in CCR3-deficient mice. Collectively, our data show that CCR3 deficiency influences osteoblast and osteoclast differentiation and that it is associated with thinner cortical bone in adult male mice.

Sfrp4 repression of the Ror2/Jnk cascade in osteoclasts protects cortical bone from excessive endosteal resorption.

Loss-of-function mutations in the Wnt inhibitor secreted frizzled receptor protein 4 (SFRP4) cause Pyle's disease (OMIM 265900), a rare skeletal disorder characterized by wide metaphyses, significant thinning of cortical bone, and fragility fractures. In mice, we have shown that the cortical thinning seen in the absence of Sfrp4 is associated with decreased periosteal and endosteal bone formation and increased endocortical resorption. While the increase in Rankl/Opg in cortical bone of mice lacking Sfrp4 suggests an osteoblast-dependent effect on endocortical osteoclast (OC) activity, whether Sfrp4 can cell-autonomously affect OCs is not known. We found that Sfrp4 is expressed during bone marrow macrophage OC differentiation and that Sfrp4 significantly suppresses the ability of early and late OC precursors to respond to Rankl-induced OC differentiation. Sfrp4 deletion in OCs resulted in activation of canonical Wnt/ß-catenin and noncanonical Wnt/Ror2/Jnk signaling cascades. However, while inhibition of canonical Wnt/ß-catenin signaling did not alter the effect of Sfrp4 on OCgenesis, blocking the noncanonical Wnt/Ror2/Jnk cascade markedly suppressed its regulation of OC differentiation in vitro. Importantly, we report that deletion of Ror2 exclusively in OCs (CtskCreRor2fl/fl ) in Sfrp4 null mice significantly reversed the increased number of endosteal OCs seen in these mice and reduced their cortical thinning. Altogether, these data show autocrine and paracrine effects of Sfrp4 in regulating OCgenesis and demonstrate that the increase in endosteal OCs seen in Sfrp4-/- mice is a consequence of noncanonical Wnt/Ror2/Jnk signaling activation in OCs overriding the negative effect that activation of canonical Wnt/ß-catenin signaling has on OCgenesis.

Biomechanical Behavior of All-on-4 and M-4 Configurations in an Atrophic Maxilla: A 3D Finite Element Method.

BACKGROUND In edentulous patients, the concept of 4 implants with early loading has been widely used in clinical settings. In the case of bone atrophy in the anterior maxilla, using short implants or an angulated implant may be a good choice for treatment. The occlusal scheme remains a key aspect of All-on-4. The aim of this study was to use the 3-dimensional (3D) finite element method (FEM) to evaluate how different All-on-4 designs for canine-guided and group function occlusion affected the distribution of stress in the atrophic premaxilla. MATERIAL AND METHODS A 3D edentulous maxilla model was created and in 3D FEM, 3 different configurations - M4, All-on-4, and short implant - were modeled by changing the anterior implants and using 2 different occlusal schemes. For each model, the occlusal load was applied to simulate lateral movements. For cortical bone, the maximum and minimum principal stress values were generated, and for ductile materials, von Mises stress values were obtained. RESULTS No significant differences were detected among the models; generally, however, the highest stress values were observed in the M-4 model and the models with short implants. Slightly higher stress values were observed in the group function occlusion group than in the canine-guided occlusion group. CONCLUSIONS To promote better primary stabilization, M-4 or short implant configurations with canine-guided occlusion appear to be preferable for patients who have severe atrophy in the anterior maxilla.

Prediction of Long Bone Fractures in Multiple Myeloma Patients in an Advanced Imaging World.

BACKGROUND: Multiple myeloma (MM) affects the long bones in 25% of patients. The advent of positron-emission tomography/computed tomography (PET/CT) scanners offers the possibility of both metabolic and radiographic information and may help determine fracture risk. To the best of our knowledge, no published study correlates these two factors with long bone fractures. OBJECTIVES: To evaluate the impact of PET/CT on fracture risk assessment in multiple myeloma patients. METHODS: We identified all bone marrow biopsy proven multiple myeloma patients from 1 January 2010 to 31 January 2015 at a single institution. We prospectively followed patients with long bone lesions using PET/CT scan images. RESULTS: We identified 119 patients (59 males/60 females) with 256 long bone lesions. Mean age at diagnosis was 58 years. The majority of lesions were in the femur (n=150, 59%) and humerus (n=84, 33%); 13 lesions in 10 patients (8%) required surgery for impending (n=4) or actual fracture (n=9). Higher median SUVmax was measured for those with cortical involvement (8.05, range 0-50.8) vs. no involvement (5.0, range 2.1-18.1). SUVmax was found to be a predictor of cortical involvement (odds ratio = 1.17, P = 0.026). No significant correlation was found between SUVmax and pain or fracture (P = 0.43). CONCLUSIONS: Improved medical treatment resulted improvement in 8% of patients with an actual or impending fracture. The orthopedic surgeons commonly use the Mirels classification for long bone fracture prediction. Adding PET/CT imaging to study in myeloma long bone lesions did not predict fracture risk directly but suggested it indirectly by cortical erosion.

Distal Femoral Cortical Irregularity at Knee MRI: Increased Prevalence in Youth Competitive Alpine Skiers.

Background Tumor-like cortical irregularities at the posterior distal femur are common incidental findings in adolescents, but the origin of these irregularities is debated. Purpose To compare the prevalence of distal femoral cortical irregularities (DFCIs) at different tendon attachment sites in youth competitive alpine skiers with that in young adults. Materials and Methods In this secondary analysis of a prospective trial, unenhanced 3-T knee MRI scans obtained in youth competitive alpine skiers were compared with images in control participants of the same age from 2014 to 2019 (Cantonal Ethics Committee Zurich registry number: KEK-ZH-2017-01395) for presence of DFCIs at the femoral attachment of the medial head of the gastrocnemius muscle (MHG) and/or lateral head of the gastrocnemius muscle (LHG) and adductor magnus tendon by two radiologists. DFCI size and tendon attachment position were measured. Tendon attachment position and associated MRI findings (meniscus, cartilage, bone marrow edema, joint effusion, ligaments, tendons) were examined for an association with DFCI. Pearson χ2, Student t test, logistic regression, and κ statistics were applied. Results Unilateral knee MRI scans obtained in 105 skiers (mean age, 14.8 years ± 0.6 [standard deviation]; 66 boys) and in 105 control participants (mean age, 14.6 years ± 0.5; 59 boys) were evaluated. DFCIs were found in 61 of 105 skiers (58%; 95% confidence interval [CI]: 48.5%, 67.2%) compared with 28 of 105 control participants (27%; 95% CI: 18.9%, 35.7%) (P < .001). Two skiers had more than one DFCI. Distribution of DFCIs for skiers and control participants was 60 of 63 (95.2%) and 26 of 28 (92.8%) at the MHG, three of 63 (4.8%) and one of 28 (3.6%) at the LHG, and zero of 63 (0%) and one of 28 (3.6%) at the adductor magnus attachment site, respectively. Interreader agreement was almost perfect (κ = 0.87; 95% CI: 0.80, 0.93). The mean size of MHG-related DFCIs in skiers (3.7 mm) was not different compared to the size of those in control participants (3.4 mm) (P = .32), nor was a difference found for the MHG tendon attachment position in knees with DFCI (63.9 mm vs 63.0 mm, P = .83) or without DFCI (63.6 mm vs 62.8 mm, P = .86). Regarding associated MRI findings, increased signal intensity of the MHG tendon showed a significant association with MHG-related DFCI in both groups (P = .01 for both). Conclusion A distal femoral cortical irregularity at the attachment sites of tendons was a frequent incidental finding on knee MRI scans, with an increased prevalence in youth competitive alpine skiers. © RSNA, 2020 Online supplemental material is available for this article.

Cortical Bone Microarchitecture in Dialysis Patients.

BACKGROUND: The incidence of skeletal fractures is high in dialysis patients. Current available tools are insufficient to predict bone fragility. We analyzed the microarchitecture in patients on dialysis therapy using bone biopsies and peripheral microcomputed tomography. METHODS: We analyzed 12 trans-iliac bone biopsies of patients with recent fractures. Bone microarchitecture was assessed in the bone cores by histology (2D-), microcomputed tomography (3D-µCT), and high-resolution peripheral quantitative computed tomography (HR-pQCT) at the tibia. RESULTS: Trabecular bone volume/tissue volume was similar in 2D histology and 3D-µCT (p = 0.40), while lower in HR-pQCT (p < 0.01). There was no correlation in trabecular microarchitectural indices between 2-histology and 3D-µCT, or HR-pQCT. The 3D-µCT cortical thickness (Ct.Th) were positively correlated with 2D (p < 0.05), but with HR-pQCT (p = 0.33). Ct.Th was lower in patients with ≥2 vertebral fractures than with one fracture. CONCLUSIONS: 3D-µCT is a reliable method for the measurement of cortical bone in bone biopsies. Prospective studies are awaited to address its value in discriminating fracture risk.

Deterioration of bone microstructure by aging and menopause in Japanese healthy women: analysis by HR-pQCT.

INTRODUCTION: Second-generation high-resolution peripheral quantitative computed tomography (HR-pQCT) has provide higher quality of bone images with a voxel size of 61 µm, enabling direct measurements of trabecular thickness. In addition to the standard parameters, the non-metric trabecular parameters such as trabecular morphology (plate to rod-like structures), connectivity, and anisotropy can also be analyzed. The purpose of this study is to investigate deterioration of bone microstructure in healthy Japanese women by measuring standard and non-metric parameters using HR-pQCT. MATERIALS AND METHODS: Study participants were 61 healthy Japanese women (31-70 years). The distal radius and tibia were scanned using second-generation HR-pQCT, and microstructures of trabecular and cortical bone were measured. Non-metric trabecular parameters included structure model index (SMI), trabecular bone pattern factor (TBPf), connectivity density (Conn.D), number of nodes (N.Nd/TV), degree of anisotropy (DA), and star volume of marrow space (V*ms). Estimated bone strength was evaluated by micro finite element analysis. Associations between bone microstructure, estimated bone strength, age, and menopause were analyzed. RESULTS: Trabecular number declined with age, and trabecular separation increased. SMI and TBPf increased, Conn.D and N.Nd/TV declined, and V*ms increased. Cortical BMD and thickness declined with age, and porosity increased. Stiffness and failure load decreased with age. Cortical thickness and estimated bone strength were affected by menopause. Cortical thickness was most associated with estimated bone strength. CONCLUSIONS: Trabecular and cortical bone microstructure were deteriorated markedly with age. Cortical thickness decreased after menopause and was most related to bone strength. Non-metric parameters give additional information about osteoporotic changes of trabecular bone.

Effects of mild hyperbaric oxygen on osteoporosis induced by hindlimb unloading in rats.

INTRODUCTION: Disuse-induced bone loss is caused by a suppression of osteoblastic bone formation and an increase in osteoclastic bone resorption. There are few data available for the effects of environmental conditions, i.e., atmospheric pressure and/or oxygen concentration, on osteoporosis. This study examined the effects of mild hyperbaric oxygen at 1317 hPa with 40% oxygen on unloading-induced osteoporosis. MATERIALS AND METHODS: Eighteen 8-week old male Wistar rats were randomly divided into three groups: the control for 21 days without unloading and mild hyperbaric oxygen (NOR, n = 6), the unloading for 21 days and recovery for 10 days without mild hyperbaric oxygen (HU + NOR, n = 6), and the unloading for 21 days and recovery for 10 days with mild hyperbaric oxygen (HU + MHO, n = 6). RESULTS: The cortical thickness and trabecular bone surface area were decreased in the HU + NOR group compared to the NOR group. There were no differences between the NOR and HU + MHO groups. Osteoclast surface area and Sclerostin (Sost) mRNA expression levels were decreased in the HU + MHO group compared to the HU + NOR group. These results suggested that the loss of the cortical and trabecular bone is inhibited by mild hyperbaric oxygen, because of an inhibition of osteoclasts and enhancement of bone formation with decreased Sost expression. CONCLUSIONS: We conclude that exposure to mild hyperbaric oxygen partially protects from the osteoporosis induced by hindlimb unloading.

Definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma: A report from the International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH).

BACKGROUND: The International Working Group on Staging Evaluation and Response Criteria Harmonization (SEARCH) seeks to provide a universally acceptable definition of cortical bone involvement in the staging of newly diagnosed pediatric Hodgkin lymphoma. PROCEDURE: A comprehensive literature search was performed using PubMed and Google Scholar with the search terms "Hodgkin lymphoma," "osseous lesions," "bony involvement," and "pediatric." Publications reviewed included case reports, retrospective analyses, and literature reviews. Each was evaluated for study design, number of participants, median age and age range at diagnosis, percentage of pediatric patients, criteria of interest definition, diagnostic tools, study objectives, and level of evidence. The final definition was based on the available data and consensus of the SEARCH working group. RESULTS: Twenty-five papers specifically addressing cortical bone involvement in Hodgkin lymphoma met the inclusion criteria. Eighteen papers were case reports with literature reviews; the remainder were observational cohort studies. Of these, 14 included pediatric patients (aged 0-21 years). The criteria for cortical bone involvement were not clearly defined in any paper, often varied within a study, and were inconsistent between publications. CONCLUSIONS: The SEARCH group for Childhood, Adolescent, and Young Adult Hodgkin Lymphoma (CAYAHL) proposes the following criteria as defining cortical bone involvement: any cortical bone biopsy-proven lesion; a positive bony window lesion on computer tomography (CT), with an FDG-PET positive correlate in a patient with biopsy-proven Hodgkin lymphoma, if there is no other typical skeletal pathology; auspicious skeletal lesions on FDG-PET or magnetic resonance imaging should be confirmed by CT or Tc-99m scan to distinguish cortical lesions from bone marrow involvement. Nodal masses that extend into bone with bony destruction are considered extranodal extension or "E" lesions and do not represent metastatic or stage IV disease.

Risk of reoperation within 12 months following osteosynthesis of a displaced femoral neck fracture is linked mainly to initial fracture displacement while risk of death may be linked to bone quality: a cohort study from Danish Fracture Database.

Background and purpose - Most guidelines use patient age as a primary decision factor when choosing between osteosynthesis or arthroplasty in displaced femoral neck fractures. We evaluate reoperation and death risk within 1 year after osteosynthesis, and estimate the influence of age, sex, degree of displacement, and bone quality.Patients and methods - All surgeries for femoral neck fractures with parallel implants (2 or 3 screws or pins) performed between December 2011 and November 2015 were collected from the Danish Fracture Database. Radiographs were analyzed for initial displacement, quality of reduction, protrusion, and angulation of implants. The bone quality was estimated using the cortical thickness index (CTI). Garden I and II type fractures with posterior tilt < 20° were excluded.Results - 654 patients with a mean age of 69 years were included. 59% were female. 54% were Garden II with posterior tilt > 20° or Garden III, and 46% were Garden IV. Only 38% were adequately reduced. 19% underwent reoperation and 18% died within 12 months. Female sex, surgical delay between 12 and 24 hours vs. < 12 hours, Garden IV type fracture, inadequate reduction, and protrusion of an implant were associated with statistically significant increased reoperation risk. No significant association between reoperation and age, CTI, or the initial angulation of implants was found. Notably, CTI was linked inversely with death risk.Interpretation - Reoperation risk is linked mainly to primary displacement and reduction of the fracture, with no apparent effect of age or bone quality. Bone quality may be linked with risk of death.

Is there a significant decrease in the femoral cortical bone around Furlong® stems after 18 years of follow-up?

INTRODUCTION: In the context of total hip arthroplasty (THA), there are several reasons that have motivated the development of short stems. It has been postulated that short stems allow a better conservation of the bone stock if compared to conventional stems. As far as we have knowledge, the quantitative loss of diaphyseal bone stock in patients with standard femoral stems has not been fully described. The aim of this study was to provide evidences about the thickness of the cortical bone at the diaphysis in patients who have undergone unilateral THA with Furlong® stems with a minimum follow-up of 18 years. PATIENTS AND METHODS: A retrospective study of patients who underwent THA in a single hospital was performed. The inclusion criteria were patients who had undergone a non-cemented elective THA with a Furlong® stem, minimum follow-up of 18 years, and contralateral femur and hip without history of previous surgical procedures. The follow-up analysis was performed by means of radiological examinations performed at the last follow-up visit. Data related to the sex, age at surgery and adverse events registered during the follow-up were gathered. The cortical thickness index (CTI) and cortical thickness (CT) assessed at the last follow-up visit in anteroposterior pelvic X-rays were analyzed, both in the operated hip and in the non-operated hip (which was used as control). Calibration of the measurements was done by means of using the circumference of the head of the THA. RESULTS: The total number of patients who met the inclusion criteria was 22. There were 14 women and eight men. There were 12 left hips. The mean age at the time of surgery was 59.32 ± 6.83 (range 50-70) years. The mean follow-up was 20.86 ± 1.90 (range 18-24) years. The CTI was found to be 11.93% greater in the non-operated hips. The CT measured at 3 cm and 6 cm from lesser trochanter, and at 9 cm from the greater trochanter, was found to be 21.64%, 15.33% and 18.73% greater in the non-operated hips, respectively. CONCLUSION: After a minimum of 18 years from the implantation of a Furlong® stem, the bone density that surrounds the implant seems to involve a cortical bone ten percent less thick than the cortical bone of the non-operated contralateral side. With this stem, the cortical zones with less CT seem to be the lateral cortex at 9 cm from the greater trochanter, and the medial cortex at 3 and 6 cm from the lesser trochanter. LEVEL OF EVIDENCE: III, retrospective case-control study.

Altered bone microarchitecture in a type 1 diabetes mouse model Ins2Akita.

Type 1 diabetes mellitus (T1DM) has been associated to several cartilage and bone alterations including growth retardation, increased fracture risk, and bone loss. To determine the effect of long term diabetes on bone we used adult and aging Ins2 Akita mice that developed T1DM around 3-4 weeks after birth. Both Ins2 Akita and wild-type (WT) mice were analyzed at 4, 6, and 12 months to assess bone parameters such as femur length, growth plate thickness and number of mature and preapoptotic chondrocytes. In addition, bone microarchitecture of the cortical and trabecular regions was measured by microcomputed tomography and gene expression of Adamst-5, Col2, Igf1, Runx2, Acp5, and Oc was quantified by quantitative real-time polymerase chain reaction. Ins2 Akita mice showed a decreased longitudinal growth of the femur that was related to decreased growth plate thickness, lower number of chondrocytes and to a higher number of preapoptotic cells. These changes were associated with higher expression of Adamst-5, suggesting higher cartilage degradation, and with low expression levels of Igf1 and Col2 that reflect the decreased growth ability of diabetic mice. Ins2 Akita bone morphology was characterized by low cortical bone area (Ct.Ar) but higher trabecular bone volume (BV/TV) and expression analysis showed a downregulation of bone markers Acp5, Oc, and Runx2. Serum levels of insulin and leptin were found to be reduced at all-time points Ins2 Akita . We suggest that Ins2 Akita mice bone phenotype is caused by lower bone formation and even lower bone resorption due to insulin deficiency and to a possible relation with low leptin signaling.

Liver-derived IGF-I is not required for protection against osteoarthritis in male mice.

Insulin-like growth factor-I (IGF-I) is anabolic for cartilage and important for cartilage integrity, which might suggest a connection between IGF-I and osteoarthritis (OA) development. However, the results of studies performed so far are conflicting, and we aimed to clarify the role of endocrine IGF-I in rodent OA. Male mice with inducible inactivation of circulating, liver-derived IGF-I (LI-IGF-I-/- mice, serum IGF-I reduced by ~80%) were used. Experimental OA was induced in young adult LI-IGF-I-/- and control mice by destabilization of the medial meniscus (DMM); age-related OA was also evaluated in 1-yr-old mice. DMM-operated LI-IGF-I-/- mice had thinner lateral subchondral bone plate in tibia compared with control mice, whereas osteophyte volume and articular cartilage damage were unaffected at the medial side of the DMM knee. However, the control mice but not the LI-IGF-I-/- mice also developed mild OA on the lateral side of the DMM knee compared with the unoperated knee. One-year-old LI-IGF-I-/- mice had lower mid-diaphyseal cortical bone area than the 1-yr-old control mice, whereas analyses of joint tissues displayed smaller osteophyte volume and thicker calcified cartilage than the control mice. There was no difference in OA severity in the articular cartilage between old LI-IGF-I-/- and control mice. Our study is the first to investigate whether there is an association between circulating IGF-I and OA in mice. We conclude that, although there is an ~80% reduction of circulating IGF-I and a decrease in cortical bone in male LI-IGF-I-/- mice, cartilage damage is clearly not intensified and may instead be slightly reduced.

Morphological profile of atypical femoral fractures: age-related changes to the cross-sectional geometry of the diaphysis.

The use of bisphosphonates for osteoporosis patients has markedly decreased the incidence of femoral neck or trochanteric fractures. However, anti-osteoporosis drugs have been reported to increase the incidence of atypical femoral fractures, which involve stress fractures in the subtrochanteric region or the proximal diaphysis. In this study, the morphological characteristics of the cortical bone in human femoral diaphysis samples were analyzed from individuals who lived before bisphosphonate drugs were available in Japan. A total of 90 right femoral bones were arbitrarily selected (46 males and 44 females) from modern Japanese skeletal specimens. Full-length images of these femurs were acquired using a computed tomography scanner. An image processing method for binarization was used to calculate the threshold values of individual bones for determining their contours. The range between the lower end of the lesser trochanter and the adductor tubercle of each femur was divided at regular intervals to obtain 10 planes. The mean value of cortical bone thickness, periosteal border length, and the cortical cross-sectional area was evaluated for all planes. Moreover, the ratio of the area of the cortical bone to the total area of cross-section at the mid-diaphysis was calculated. A comparison between males and females demonstrated that most females had lower cortical bone area ratios at the mid-diaphysis. The femoral outer shape did not differ markedly according to age or sex; however, substantial individual differences were observed in the shape of the inner surface of the cortical bone. The cortical bone thickness and the cross-sectional area decreased with age in the femoral diaphysis; furthermore, in females, the decrease was higher for the former than for the latter. This may be due to a compensatory increase in the circumference of the femoral diaphysis. In addition, in about half of the subjects there was a discrepancy between the region with maximal value of the cortical bone thickness and that of the total cross-sectional area. Biological responses to mechanical stresses to the femoral diaphysis are thought not to be uniform. Bisphosphonates inhibit bone resorption and may promote non-physiological bone remodeling. Thus, a nonhomogeneous decrease in cortical thickness may be related to the fracture occurrence in the femoral diaphysis in some cases. Thus, long-term administration of bisphosphonates in patients with morphological vulnerability in the femoral cortical bones may increase the occurrence of atypical femoral fractures.

Dietary inflammatory index® and cortical bone outcomes in healthy adolescent children.

Diet is thought to modulate inflammation. This study shows no relationships between the dietary inflammatory index (DII) and biomarkers of inflammation or bone after adjusting for covariates. Monocyte chemoattractant protein-1 was inversely associated with peripheral tibia cortical thickness and prospective childhood studies should be conducted to better understand this relationship and to determine if there are long-term consequences in adulthood. INTRODUCTION: Examine the relationships between the DII-scores and bone and biomarkers of inflammation in 290 adolescents, ages 9-13 years. METHODS: DII-scores were calculated from 3-day diet records and categorized into tertiles, low (< - 1.34), medium (- 1.34 to 1.41), and high (> 1.41) inflammation. Radius and tibia bone were assessed via peripheral quantitative computed tomography (Stratec XCT 2000) at the 66% site relative to the distal growth plate. Fasting serum was measured for tumor necrosis factor alpha (TNF-α), interleukin-6 (IL-6), vascular endothelial growth factor (VEGF), and monocyte chemoattractant protein-1 (MCP-1). The relationships between DII-scores and bone and biomarkers of inflammation were assessed using bivariate and partial correlations adjusting for sexual maturation, sex, race, muscle cross-sectional area, and height. ANOVA/ANCOVA models were used to compare DII-tertiles with dependent variables. RESULTS: DII-scores were negatively associated with tibia trabecular area (TtAr; r = - .141, P = .019), periosteal perimeter (PsPM; r = - .145, P = .016), endosteal perimeter (r = - .145, P = .016), strength strain index (SSI; r = - .129, P = .032), and radius TtAr (r = - .140, P = .020), PsPM (r = -.138, P = .027) and SSI (r = -.131, P = .036) but nullified when adjusting for covariates. Tibia PsPM was higher in the low DII group compared to the medium (P = .050) and high (P = .046) groups but nullified after controlling for covariates. DII-scores were not associated with TNF-α, VEGF, or IL-6, but were associated with MCP-1 only in the unadjusted model (r = .125, P = .042). In the adjusted model, MCP-1 was inversely associated with tibia cortical thickness (r = -.150 P = .030). CONCLUSION: The DII-scores were not related to biomarkers of inflammation or bone; however, the biomarker of inflammation, MCP-1 was negatively associated with tibia CtTh. Future prospective pediatric studies should be conducted to better understand this relationship and determine if there are long-term implications in adulthood.

Bone microarchitecture and bone turnover in hepatic cirrhosis.

Liver cirrhosis leads to bone loss. To date, information on bone quality (three-dimensional microarchitecture) and, thus, bone strength is scarce. We observed decreased bone quality at both assessed sites, independent of disease severity. Therefore, all patients should undergo early-stage screening for osteoporosis. INTRODUCTION: Recent studies found low bone mineral density in cirrhosis, but data on bone microstructure are scarce. This study assessed weight-bearing and non-weight-bearing bones in patients with cirrhosis and healthy controls. The primary objective was to evaluate trabecular and cortical microarchitecture. METHODS: This was a single-center study in patients with recently diagnosed hepatic cirrhosis. Thirty-two patients and 32 controls participated in this study. After determining the type of cirrhosis, the parameters of bone microarchitecture were assessed by high-resolution peripheral quantitative computed tomography. RESULTS: Both cortical and trabecular microarchitectures showed significant alterations. At the radius, trabecular bone volume fraction was 17% lower (corrected p = 0.028), and, at the tibia, differences were slightly more pronounced. Trabecular bone volume fraction was 19% lower (p = 0.024), cortical bone mineral density 7% (p = 0.007), and cortical thickness 28% (p = 0.001), while cortical porosity was 32% higher (p = 0.023), compared to controls. Areal bone mineral density was lower (lumbar spine - 13%, total hip - 11%, total body - 9%, radius - 17%, and calcaneus - 26%). There was no correlation between disease severity and microarchitecture. Areal bone mineral density (aBMD) measured by dual-energy X-ray absorptiometry (DXA) correlated well with parameters of cortical and trabecular microarchitecture. CONCLUSIONS: Hepatic cirrhosis deteriorates both trabecular and cortical microarchitecture, regardless of disease severity. Areal bone mineral density is diminished at all sites as a sign of generalized affection. In patients with hepatic cirrhosis, regardless of its origin or disease severity, aBMD measurements are an appropriate tool for osteologic screening.

Comparison of clinical, biochemical and histomorphometric analysis of bone biopsies in dialysis patients with and without fractures.

Chronic kidney disease-mineral bone disorders (CKD-MBD) are associated with increased risk of fracture. Studies report about 3% of fractures in CKD patients, and these occur earlier than in the general population, namely 16 and 13 years earlier for men and women, respectively. Better understanding of the pathophysiology of fractures would probably contribute to new therapeutic approaches. This study aimed to evaluate report of long bone fractures from a bone biopsies bank from patients on hemodialysis and compare clinical and biochemical characteristics, as well as the results of the histomorphometric analysis of trabecular and cortical bone of these patients with a control group (without fractures), paired for age, gender, and time on hemodialysis. Bone proteins (SOST, DMP1 and MEPE) were evaluated by immunohistochemistry. Seventeen patients with fracture and controls were studied. Fracture prevalence was 0.82/1000 patients/year. Serum phosphorus levels were significantly lower in the fracture group. Histomorphometric analysis revealed that all the patients had high turnover disease, and the fracture group had smaller volume and trabecular thickness, greater osteoid surface, smaller eroded surface, smaller mineralizing surface, formation rate and longer mineralization lag time when compared to controls; the DMP1 expression in the cortical bone was smaller and the SOST in the trabecular bone was higher in fractured patients. As conclusion, we found low prevalence of fractures. Both groups had high turnover disease, but the fractured ones presented more impaired bone microarchitecture, as well as lower formation and greater mineralization defect. Bone proteins expression correlated with parameters involved in bone remodeling.