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Background Impacted bone-grafting with morselized allograft chips is commonly used to reconstruct acetabular bone defects in revision total hip arthroplasty (THA). While the overall clinical outcome of this procedure is described to be excellent, the microstructural basis and histological determinants of allograft incorporation remained to be further elucidated. Methods The acetabula of 23 individuals with documented previous use of allograft chips during revision THA were explanted post mortem. The time that the allografts were in situ averaged 10.3 ± 4.5 years (range, 1.2 to 19.8 years). The host bone (HB)-allograft bone (AB) interface was characterized using a suite of high-resolution (HR) imaging techniques including HR-peripheral quantitative computed tomography (HR-pQCT), histological analysis, cellular histomorphometry, and scanning electron microscopy. Results AB could be identified in 16 of the 23 cases. The HB and AB showed overlap (i.e., ingrowth) in 91.3% of the total interface. The mean ingrowth was 2.2 ± 1.0 mm with a maximum of 4.7 ± 2.1 mm. The periphery of the AB showed a tight interconnection with the HB associated with increased bone remodeling indices and increased trabecular thickness. While no association between the time in situ and the ingrowth was observed, the bone defect area was positively associated with the thickness of a fibrosis layer separating the ingrowth zone from the AB. Conclusions Allograft chips in revision THA form an adequate osseous foundation with successful incorporation through ingrowth of the HB (i.e., osteoconduction). While complete remodeling was not observed, larger defects were associated with fibrosis formation, which may compromise stability. Clinical relevance Our study provides the first systematic, multiscale long-term evaluation of chip allograft incorporation in revision THA to underscore its successful clinical use. As larger defects were associated with fibrous ingrowth, structural allografts may be superior for larger defects in terms of long-term outcomes.

OBJECTIVEPrimary intraosseous meningioma (PIM) is a rare manifestation of meningioma, a benign, neoplastic lesion of the meninges. Its characteristic appearance is hyperostosis, while no or only minimal dural changes can be observed. This study aims to characterize this rare entity from both a clinical and histopathological point of view in order to improve clinical management.METHODSIn the years 2009–2017, 26 cases of PIM were diagnosed using MRI and CT scans. In 16 cases the indication for resection was given, and specimens were further examined using a multilevel approach, including histological and immunohistochemical analyses. Additionally, the local database was searched for all cases of meningiomas, as well as osteosclerotic differential diagnoses—i.e., fibrous dysplasia, Paget’s disease of bone, and other benign osteosclerotic lesions.RESULTSIn this study, PIM represented 2.4% of all meningiomas with a predominant occurrence in females (85%). Regarding the initial manifestation, PIMs show a slightly earlier onset than meningiomas. While most PIMs are located in the sphenoid bone, associated calcifications were visible in 58% of the cases on CT scans. Most of the cases were classified as WHO grade I (93%) and meningotheliomatous meningiomas (91%). Tumor growth was associated with an increased bone resorption followed by massive osteoid deposition and consecutive sclerosis. The frequently observed frayed appearance results from multiple bony canals, which contain blood vessels for the blood supply of the highly vascularized tumor tissue.CONCLUSIONSPIM is a rare but important differential diagnosis for osteosclerotic lesions of the skull, especially in women. Tumor-induced, cellular-mediated bone resorption and formation may play a central role in the underlying pathogenesis.

Background: This study aimed to determine the clinical and radiological course in children who had Legg–Calvé–Perthes disease (LCPD) associated with juvenile idiopathic arthritis (JIA). Methods: In a retrospective chart review between 2007 and 2019, eight consecutive JIA patients diagnosed with concomitant LCPD were identified and compared with a case-control group of 10 children with LCPD only. Results: LCPD was diagnosed at a mean age of 8.1 years (3.0–14.7) in children with JIA as compared to 6.1 years (2.9–10.0) in controls. According to the modified Harris Hip Score (mHHS), four children with JIA and all controls had an excellent result. Regarding the fragmentation severity and the duration of each stage, we found no differences using the lateral pillar and modified Elizabethtown classification. Five hips were classified as Stulberg I/II, two hips as Stulberg III, and one hip as Stulberg V with no evidence of hip dysplasia or severe overcoverage in either group. Conclusions: The radiological outcome of LCPD did not differ between both groups, while the clinical outcome was slightly better in controls. Physicians should be aware that children with LCPD may have JIA too. In suspicious cases, further investigations are recommended, and patients should be referred to pediatric rheumatologists.

Background & Aims Osteoporotic fractures are a major cause of morbidity and reduced quality of life in patients with primary sclerosing cholangitis (PSC), a progressive bile duct disease of unknown origin. Although it is generally assumed that this pathology is a consequence of impaired calcium homeostasis and malabsorption, the cellular and molecular causes of PSC-associated osteoporosis are unknown. Methods We determined bone mineral density by dual-X-ray absorptiometry and assessed bone microstructure by high-resolution peripheral quantitative computed tomography in patients with PSC. Laboratory markers of liver and bone metabolism were measured, and liver stiffness was assessed by FibroScan. We determined the frequency of Th17 cells by the ex vivo stimulation of peripheral blood mononuclear cells in a subgroup of 40 patients with PSC. To investigate the potential involvement of IL-17 in PSC-associated bone loss, we analyzed the skeletal phenotype of mice lacking Abcb4 and/or Il-17. Results Unlike in patients with primary biliary cholangitis, bone loss in patients with PSC was not associated with disease duration or liver fibrosis. However, we observed a significant negative correlation between the bone resorption biomarker deoxypyridinoline and bone mineral density in the PSC cohort, indicating increased bone resorption. Importantly, the frequency of Th17 cells in peripheral blood was positively correlated with the urinary deoxypyridinoline level and negatively correlated with bone mass. We observed that Abcb4-deficient mice displayed a low-bone-mass phenotype, which was corrected by an additional Il-17 deficiency or anti-IL-17 treatment, whereas the liver pathology was unaffected. Conclusions Our findings demonstrate that an increased frequency of Th17 cells is associated with bone resorption in PSC. Whether antibody-based IL-17 blockade is beneficial against bone loss in patients with PSC should be addressed in future studies. Lay summary Primary sclerosing cholangitis (PSC) is a cholestatic liver disease characterized by progressive bile duct destruction. One serious complication of PSC is reduced bone mass resulting in increased fracture risk. Herein, we demonstrate that Th17 cells mediate bone loss in PSC by inducing bone resorption, which suggests that antibody-based IL-17 blockade might be beneficial for the treatment of bone loss in affected patients.

This cross-sectional study examined the associations between c-terminal FGF23 levels, laboratory markers of bone metabolism and bone microarchitecture in 82 patients with osteoporosis. Higher FGF23 levels were associated with impaired trabecular but not cortical bone microarchitecture, and this was confirmed after adjusting for confounding variables such as age or BMI. Fibroblast growth factor 23 (FGF23) is an endocrine hormone-regulating phosphate and vitamin D metabolism. While its mode of action is well understood in diseases such as hereditary forms of rickets or tumor-induced osteomalacia, the interpretation of FGF23 levels in patients with osteoporosis with regard to bone microarchitecture is less clear. C-terminal FGF23 levels and bone turnover markers were assessed in 82 patients with osteoporosis (i.e., DXA T-score ≤ − 2.5 at the lumbar spine or total hip). Bone microarchitecture was measured by high-resolution peripheral quantitative computed tomography (HR-pQCT) at the distal radius and tibia. Data were analyzed in a cross-sectional design using correlation and regression models. We found a significant negative logarithmic correlation between FGF23 levels and trabecular but not cortical bone microarchitecture at both skeletal sites. Furthermore, using a multiple linear regression model, we confirmed FGF23 as a predictor for reduced trabecular parameters even when adjusting for confounding factors such as age, BMI, phosphate, bone-specific alkaline phosphatase, vitamin D3, and PTH. Taken together, high FGF23 levels are associated with impaired trabecular bone microarchitecture in osteoporosis patients, and this association seems to occur after adjustment of confounding variables including phosphate and vitamin D. Future longitudinal studies are now needed to validate our findings and investigate FGF23 in relation to fracture risk.

The successful use of allografts in reconstructive orthopedic surgery, including revision total hip arthroplasty (THA), has been outlined repeatedly. Nonetheless, as previous studies were primarily based on clinical follow-ups, we aimed to create an algorithm that accurately determines the extent of allograft incorporation in the acetabulum and femur using a suite of high-resolution imaging techniques. This study is based on a large patient database including > 4,500 patient data with previous revision THA and simultaneous use of allografts. While the database was continuously matched with the deceased individuals at the local forensic medicine department, complete hips were retrieved in case of a positive match. A positive match was achieved for n = 46 hips at a mean follow-up of 11.8 ± 5.1 years. Comprehensive imaging included contact radiography, high-resolution computed tomography (HR-pQCT), undecalcified histology of ground sections and quantitative backscattered electron imaging (qBEI). We here define a histomorphometric toolkit of parameters to precisely characterize the incorporation of structural (bulk) and morselized (chip) allografts in the acetabulum (n = 38) and femur (n = 8), including the defect area and interface length, microstructural and cellular bone turnover parameters as well as overlap and fibrosis thickness. This collection of samples, through its unique study design and precise definition of incorporation parameters, will provide the scientific community with a valuable source for further in-depth investigation of allograft incorporation and, beyond that, the regenerative potential of this osteoconductive scaffold.

Reduced bone mineral density (BMD; ie, Z-score ≤-2.0) occurring at a young age (ie, premenopausal women and men

Background High-resolution peripheral quantitative computed tomography (HR-pQCT) represents a three-dimensional tool for the screening of osteoporosis patients i.e., regarding fracture risk. The purpose of this study was to determine the baseline and follow-up bone microarchitecture in relation to incident fracture risk in postmenopausal women on denosumab treatment. Methods We have retrospectively evaluated data from 182 postmenopausal women treated with denosumab that underwent an initial HR-pQCT scan before the initiation of the treatment; and at least one second HR-pQCT after 12 months. Women were assigned to two groups based on documented fragility fractures for the following 2.9 ± 1.1 years: fracture (n = 22) and no fracture (n = 160). Baseline parameters from DXA, HR-pQCT and bone turnover were compared between the two groups. Furthermore, ROC and multiple regression analyses of the baseline and follow-up data were performed to evaluate the predictive value regarding incident fractures. Results At baseline, trabecular parameters were significantly reduced in the fracture group and showed the best predictive value for new fractures, while DXA results could not predict fractures. A multiple regression model identified BV/TV and age as the best baseline parameters for incident fracture risk. At 12 months, cortical and trabecular parameters increased in the non-fracture group, while no significant increase was noted in the fracture group. However, no significant differences regarding the changes of these parameters could be detected between the non-fracture and fracture cohort. Conclusions Trabecular bone microstructure at baseline is crucial for incident fracture risk in postmenopausal women on denosumab treatment, especially in comparison to DXA values. In this context, the microstructural follow-up results seemed to be of lesser importance regarding fracture risk. The results of this exploratory study should be validated in independent populations.

Background Total hip arthroplasty (THA) is frequently accompanied by acetabular bone loss, which constitutes a major challenge in revision procedures. Structural allografts can be implanted to restore a stable osseous foundation for the acetabular prosthesis. As previous studies were limited to clinical data or included very few cases, the extent to which the graft bone is incorporated over time has remained unclear. Methods Thirteen acetabula were retrieved post mortem, and the incorporation properties of the bone allografts were analyzed using a hierarchical approach of imaging techniques including contact radiography, high-resolution peripheral quantitative computed tomography (HR-pQCT), histological analysis of undecalcified specimens, and quantitative backscattered electron imaging (qBEI). The distance between the current allograft bone and host bone borders (i.e., current overlap) as well as the distance between the original allograft bone and host bone borders (i.e., total ingrowth) were assessed. Results In 10 of 13 cases, the complete interface (100%) was characterized by direct contact and additional overlap of the allograft bone and host bone, while the remaining 3 cases demonstrated direct contact along 25% to 80% of the interface. The allograft bone showed an intact trabecular structure and significantly higher mineralization compared with the host bone. The mean current overlap (and standard deviation) was 2.3 ± 1.0 mm, with a maximum of 5.3 ± 2.4 mm. Importantly, the total ingrowth reached much further, to a mean of 7.2 ± 2.3 mm (maximum, 10.5 ± 4.0 mm). Neither the time that the allograft was in situ nor the degree of contact between the host and allograft bone correlated with the current overlap and the time in situ did not correlate with total ingrowth. Conclusions This study showed bone remodeling with subsequent interconnection of the host and allograft bone along the majority of the interface, leading to adequate incorporation of the allograft. The lack of complete incorporation of the graft did not lead to graft collapse up to 22 years after revision surgery. Clinical relevance Our study provides the first systematic multiscale evaluation of successfully implanted structural allografts and forms the scientific basis for their clinical use in revision THA.

The purpose of the study was to assess the impact of iterative model reconstruction (IMR) on reader confidence with respect to stone detection and image quality in comparison to filtered back-projection (FBP) and iDose level 4 (iDose4) in abdominal MDCT with radiation doses below 2 mSv.For 32 consecutive patients with suspected ureteral stone disease, the raw data of unenhanced 256 slice MDCT (120 kV, 40 reference mAs, mean CTDIvol: 2.7 ± 0.8 mGy, mean DLP: 126 ± 38 mGy × cm) were reconstructed using a prototype version of IMR (levels 1 - 3), iDose4 (level 4) and FBP at a 3 mm slice thickness. Image analysis was independently performed by two radiologists in a blinded fashion. The reader confidence level with respect to stone detection was recorded based on a 5-point scale (1 - certain exclusion; 5 - concrement definitely present) as well as for the evaluation of image quality regarding the depiction of anatomical details (1 - poor; 5 - excellent). A clinical reference standard for stone detection was not established. Statistical evaluation included weighted kappa analysis and Wilcoxon test.17 pelvic and ureteral stones were found. 11 further concrements were located within the ostium of the urinary bladder or the bladder itself. Applying IMR, a distinct improvement in image quality was observed at every level (mean value for FBP, 2.0; iDose4, 2.9; IMR L1, 4.2; IMR L2, 4.0; IMR L3, 3.9; all p 0.001). Applying the higher IMR levels L2 and L3, a certain level of so-called "blotchiness" of anatomical contours was observed. Reader confidence was significantly improved and was independent of IMR level (certain stone detection FBP, 69 %; iDose4, 81 %; IMR L1 to L3, 95 %; all p 0.001). With increasing IMR levels, the reduction in streak artifacts was quantified by a decrease in image noise. A loss of anatomical information was not observed. The sensitivity rates for stone detection were equivalent for all MDCTs reconstructed with FBP, iDose4 and IMR. A mean effective dose of 1.9 ± 0.6 mSv was calculated.In comparison to FBP and iDose4, a significant increase in mean image quality, reduction in image noise and improvement in subjective reader confidence can be achieved by applying IMR even at significantly reduced dose settings below 2 mSv. Results indicate that a further dose reduction might be possible with IMR.· Urinary tract. · urolithiasis. · iterative reconstruction.· Schmidt-Holtz J, Laqmani A, Butscheidt S et al. Iterative Model Reconstruction (IMR) in MDCT Below 2mSv for the Detection of Urinary Calculi: Diagnostic Accuracy and Image Quality in Comparison to Filtered Back-Projection and 4th Generation Iterative Reconstruction (iDose4). Fortschr Röntgenstr 2018; 190: 630 - 636.ZIEL: Das Ziel dieser Studie war es, die Auswirkungen der iterativen Modellrekonstruktion (IMR) auf die Sicherheit des Radiologen bei der Steindetektion und auf die Bildqualität im Vergleich zu gefilterten Rückprojektionen (FBP) und iDose Level 4 (iDose4) im Stein-MDCT mit Strahlendosen unter 2 mSv zu beurteilen.Für 32 aufeinanderfolgende Patienten mit Verdacht auf ein Harnleiterkonkrement wurden die Rohdaten der nativen Scans (256 Slice MDCT, 120 kV, 40 Referenz mAs, mittleres CTDIvol: 2,7 ± 0,8 mGy, mittleres DLP: 126 ± 38 mGy × cm) unter Verwendung einer Prototypversion von IMR (Level 1 – 3), iDose4 (Level 4) und FBP mit einer Schichtdicke von 3 mm rekonstruiert. Die Bildanalyse wurde jeweils unabhängig von zwei geblindeten Radiologen durchgeführt. Die diagnostische Sicherheit des Radiologen bei der Steindetektion erfolgte auf der Grundlage einer 5-Punkte-Skala (1 – sicherer Ausschluss, 5 – Konkrement definitiv vorhanden) wie auch für die Auswertung der Bildqualität in Bezug auf die Darstellung von anatomischen Details (1 – mangelhaft; 5 – Ausgezeichnet). Ein klinischer Referenzstandard für die Steindetektion wurde nicht erhoben. Die statistische Auswertung beinhaltet die weighted kappa-analysis und den Wilcoxon-Test.17 Nierenbecken- und Uretersteine wurden gefunden. 11 weitere Konkremente wurden im Harnblasenostium oder der Harnblase selber lokalisiert. Bei der Anwendung von IMR wurde mit jeder Iterationsstufe eine deutliche Verbesserung der Bildqualität beobachtet (Mittelwert für FBP, 2,0, iDose4, 2,9, IMR L1, 4,2, IMR L2, 4,0, IMR L3, 3,9, alle p 0,001). Mit den höheren IMR-Stufen L2 und L3 wurde ein gewisses Maß an sogenannter „blotchiness“ (Unschärfe) anatomischer Konturen beobachtet. Die Sicherheit des Radiologen wurde so unabhängig vom IMR-Level signifikant verbessert (sichere Steindetektion FBP, 69 %; iDose4, 81 %; IMR L1 bis L3, 95 %, alle p 0,001). Mit zunehmenden IMR-Werten wurde die Reduktion von Streifenartefakten durch eine Abnahme des Bildrauschens quantifiziert. Ein Verlust anatomischen Informationen wurde nicht beobachtet. Die Sensitivität der Steindetektion waren äquivalent für alle MDCTs, die mit FBP, iDose4 oder IMR rekonstruiert wurden. Es wurde eine mittlere effektive Dosis von 1,9 ± 0,6 mSv berechnet.Eine Urolithiasis kann zuverlässig durch MDCT bei deutlich reduzierten Dosiseinstellungen unter 2 mSv detektiert werden. Im Vergleich zu FBP und iDose4 kann eine signifikante Erhöhung der durchschnittlichen Bildqualität, eine Verringerung des Bildrauschens und eine Verbesserung der subjektiven diagnostischen Sicherheit des Radiologen bei der Konkrementdetektion mit Hilfe von IMR erreicht werden. Dies deutet darauf hin, dass mit IMR weiterreichende Dosisreduktionen möglich sein könnten.· Urogenitaltrakt. · Urolithiasis. · Iterative Reconstruction.

Diagnosis and management of adult individuals with low bone mass and increased bone fragility before the age of 50 can be challenging. A number of these patients are diagnosed with mild osteogenesis imperfecta (OI) through detection of COL1A1 or COL1A2 mutations; however, a clinical differentiation from early-onset osteoporosis (EOOP) may be difficult. The purpose of this study was to determine the bone microstructural differences between mild OI and EOOP patients. 29 patients showed mutations in COL1A1 or COL1A2 and were classified as OI. Skeletal assessment included dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and bone turnover serum analyses. Bone microstructure of 21/29 OI patients was assessed and compared to 23 age- and sex-matched patients clinically classified EOOP but without mutations in the known disease genes as well as to 20 healthy controls. In the OI patients, we did not observe an age-dependent decrease in DXA Z-scores. HR-pQCT revealed a significant reduction in volumetric BMD and microstructural parameters in the distal radius and tibia in both the OI and EOOP cohorts compared to the healthy controls. When comparing the bone microstructure of OI patients with the EOOP cohort, significant differences were found in terms of bone geometry in the radius, while no significant changes were detected in all other HR-pQCT parameters at the radius and tibia. Taken together, adult mild OI patients demonstrate a predominantly high bone turnover trabecular bone loss syndrome that shows minor microstructural differences compared to EOOP without mutation detection.

Primary biliary cholangitis (PBC) is known to be a major risk factor for osteoporosis reflected by a reduction of bone mineral density (BMD). However, both the extent of the macro- and microstructural alterations of bone as well as the causative factors are unknown. We have retrospectively analyzed a total of 96 patients with PBC and 53 healthy controls matched for age, sex, and body mass index. In addition to dual-energy X-ray absorptiometry (DXA) measurements at the lumbar spine and hip, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to assess the geometric, volumetric, and microstructural changes of bone at the distal radius and tibia. Furthermore, serum analyses and measures of disease duration and stage including transient elastography were performed. Total, cortical, and trabecular volumetric BMD as well as geometric parameters were significantly reduced in PBC patients. Microstructural analysis revealed a significantly lower cortical thickness (p < 0.001) and bone volume per tissue volume (p < 0.001) in the radius and tibia but unchanged trabecular number in patients with PBC (radius: p = 0.42; tibia: p = 0.12). Multivariate regression models pointed out that disease duration and stage are the primary factors that are independently associated with bone loss in PBC. A subgroup analysis of patients with additional autoimmune hepatitis (AIH) revealed no significant changes in bone structure compared with PBC only. Taken together, PBC patients demonstrate severe alterations in bone microstructure that are positively associated with disease duration and stage. By applying HR-pQCT in the distal radius and tibia, a combined bone loss syndrome expressed by a predominant decrease in BMD and cortical thickness could be detected. © 2018 American Society for Bone and Mineral Research.

Paget’s disease of bone (PDB) is a common skeletal disorder that is associated with locally increased bone turnover, skeletal deformity and pain. We report a case of skeletal dissemination in PDB of the spine. Case report. A 46-year-old former professional athlete suffered from disseminated PDB throughout the spine and hips after various surgical interventions including spondylodesis, bone grafting and bone morphogenetic protein (rhBMP-2) administration. Only intravenous zoledronic acid prevented the further progression of skeletal dissemination, which was expressed by a normalization of (bone-specific) alkaline phosphatase levels. The biopsy obtained from the lumbar spine confirmed the diagnosis of PDB in the absence of malignant transformation. We outline skeletal dissemination as a possibly surgery-related complication in a patient with PDB in the lumbar spine. Bisphosphonates remain the treatment of first choice in PDB and surgical interventions should be considered very carefully.

Einleitung Vitamin D spielt eine Rolle in der Kalziumhomoostase und beeinflusst die Expression von uber 900 Genen mit Folgen fur die muskuloskelettale Gesundheit und Funktion. Daruber hinaus konnten durch Nachweis des Vitamin D-Rezeptors (VDR) in vielen Geweben des Organismus weitere Effekte von Vitamin D beobachtet werden. Material und Methoden Im Rahmen der vorliegenden Arbeit wurde die Literatur im Hinblick auf die Bedeutung von Vitamin D fur die muskuloskelettale Gesundheit und die maximale sportliche Leistungsfahigkeit untersucht. Ergebnisse und Diskussion Die hohe Pravalenz fur einen Vitamin D-Mangel, die bereits aus der Allgemeinbevolkerung bekannt ist, konnte fur Athleten unterschiedlicher Sportarten bestatigt werden. Somit ergibt sich eine Relevanz fur den Leistungssport. Hierfur sind u. a. die geografische Lage, das vorherrschende Klima, die Tages- und Jahreszeit sowie die Sportart (Indoor/Outdoor) verantwortlich. Es konnten Zusammenhange zwischen verschiedenen Serumkonzentrationen von 25-OH-D3 und unterschiedlichen Aspekten des Leistungssports beobachtet werden. So gewahrleistet eine Serumkonzentration oberhalb von 30 ng/ml eine regelrechte Mineralisation der Knochenmatrix und tragt entscheidend zur Knochengesundheit bei. Auch konnte in diesem Bereich ein positiver Zusammenhang mit einer beschleunigten Regeneration der muskularen Kraft gezeigt werden. Hohere Werte, oberhalb von 40 ng/ml, hatten einen protektiven Effekt bei der Genese von Stressfrakturen. Hinsichtlich der Leistungsfahigkeit vermuten Forscher Werte von ≥ 50 ng/ml als Voraussetzung fur die Entwicklung der maximalen korperlichen Leistung. Wahrend der Nutzen von hoheren Serumkonzentrationen umstritten ist, zeigen sich deutliche Defizite der Mineralisation (Rachitis, Osteomalazie) und muskularen Funktion (Reversible Myopathie) bei Unterschreiten einer Konzentration 30 ng/ml. Schlussfolgerung Sportmedizinische Untersuchungen sollten die laborchemische Bestimmung von 25-OH-D3, Kalzium, Kreatinin und Parathormon enthalten und somit die Vitamin D-abhangige Kalziumhomoostase adressieren. Im Falle eines Mangelzustandes kann durch Optimierung der Lebensweise und ggf. orale Substitution von Cholecalciferol eine Normalisierung auf ≥ 30 ng/ml herbeigefuhrt werden. Eine solche Konzentration zeigt einen protektiven und leistungssteigernden Effekt. Sie ist wichtig fur die Wiederherstellung und Erhaltung der muskuloskelettalen Gesundheit und Leistungsfahigkeit.

Objectives To investigate if cartilage calcification (CC) is a systemic process, the purpose of this study was to determine the prevalence and the amount of meniscal/hyaline CC of the knee joint in the general population by high-resolution imaging (DCR) and to evaluate the association between CC with cartilage degeneration and age. Methods Cross-sectional DCR-study of 180 knee joints of 90 donors (42 female/48 male, mean age 62.3y). Histological hyaline (OARSI) and meniscal (Krenn) cartilage degeneration was determined of all knees. Results CC was observed in 100% of the donors (bilaterally in 98%), hyaline cartilage calcification (HCC) in 92% and meniscal calcification (MC) in 100%. CC was detected in more than three out of six distinct cartilage areas in 84.4% of all knees. The mean amount of CC correlated between both sides of donors, the different analyzed areas of the knee joint and between the various types of cartilage structures. There was more calcification in meniscal than in hyaline cartilage (factor 5.3) and in the medial than the lateral compartment (factor 1.2). HCC/MC were already detectable with only mild cartilage lesions and the amount correlated with histological cartilage degeneration, but not with age. Conclusions The present study provides evidence that meniscal and hyaline CC occurs in a pattern that is compatible with CC being a systemically driven process and that meniscal fibrocartilage is more prone to calcification than hyaline cartilage. Furthermore, the age-independent association between the amount of CC and the grade of degeneration in both hyaline and meniscal cartilage, suggests that CC is an obligatory early event in initiating cartilage degeneration.

Pregnancy and lactation-associated osteoporosis (PLO) is a rare skeletal disorder characterized by early-onset osteoporosis typically manifestating with vertebral compression fractures or transient osteoporosis of the hip. We hypothesized that genetic variants may play a role in the development of PLO. This study aimed to analyze the presence of genetic variants and a potential association with the clinical presentation in PLO. 42 women with PLO were included from 2013 to 2019 in a multicenter study in Germany. All cases underwent comprehensive genetic analysis based on a custom-designed gene panel including genes relevant for skeletal disorders. The skeletal status was assessed using dual-energy X-ray absorptiometry (DXA). Subgroups were further analyzed by serum bone turnover markers (n = 31) and high-resolution peripheral computed tomography (HR-pQCT; n = 23). We detected relevant genetic variants in 21 women (50%), with LRP5, WNT1 and COL1A1/A2 being the most commonly involved genes. The mean number of vertebral compression fractures was 3.3 ± 3.4 per case with a significantly higher occurrence in the subgroup with genetic variants (4.8 ± 3.7 vs. 1.8 ± 2.3, p = 0.02). Among the total cohort, DXA Z-scores were significantly lower at the lumbar spine compared to the femoral neck (p = 0.002). HR-pQCT revealed a pronounced reduction of trabecular and cortical thickness, while trabecular number was within the reference range. Eighteen women (43%) received a bone-specific therapy (primarily teriparatide). Overall, a steep increase in bone mass (+37.7%) was observed after 3 years. In conclusion, pregnancy and lactation represent skeletal risk factors, which may unmask hereditary bone disorders leading to PLO. These cases were affected more severely. Nevertheless, a timely diagnosis and adequate treatment can ensure a substantial recovery potential even without specific therapy. Patients with genetically induced low bone turnover (e.g.; LRP5, WNT1) may especially benefit from osteo-anabolic medication.

Objective To compare both image quality and visibility of normal and abnormal findings at submillisievert chest CT (smSv-CT) using filtered back projection (FBP) and the two different iterative reconstruction (IR) techniques iterative model reconstruction (IMR) and iDose 4 ™. Materials and methods This institutional review board approved study was based on retrospective interpretation of clinically indicated acquired data. The requirement to obtain informed consent was waived. 81 patients with suspected pneumonia underwent smSv-CT (Brilliance iCT, Philips Healthcare; mean effective dose: 0.86±0.2mSv). Data were reconstructed using FBP and two different IR techniques iDose 4 ™ and IMR (Philips Healthcare) at various iteration levels. Objective image noise (OIN) was measured. Two experienced readers independently assessed all images for image noise, image appearance and visibility of normal anatomic and abnormal findings. A random intercept model was used for statistical analysis. Results Compared to FBP and iDose 4 ™, IMR reduced OIN up to 88% and 72%, respectively (p 4 ™ images provided satisfactory to good image quality for visibility of normal and abnormal findings and were superior to FBP (p 4 ™, while being superior for visibility of abnormal findings except for reticular pattern (p Conclusion IMR results for visibility of normal and abnormal lung findings are heterogeneous, indicating that IMR may not represent a priority technique for clinical routine. iDose 4 ™ represents a suitable method for evaluation of lung tissue at submillisievert chest CT.

In the course of complex regional pain syndrome (CRPS), local osteopenia in the subchondral/subcortical areas of the affected limb represents a central manifestation. Mechanistic aspects of CRPS-associated pathologies remain unclear, and knowledge about bone morphology in CRPS-affected areas is rare. The aim of this study was to assess trabecular and cortical bone microstructure in patients with CRPS of the distal tibiae. We retrospectively analysed 14 women diagnosed with unilateral CRPS type I of the lower limb whose affected and unaffected distal tibiae were examined by high-resolution peripheral quantitative computed tomography (HR-pQCT). Laboratory tests included serum levels of calcium, phosphate, 25-hydroxyvitamin D, bone alkaline phosphatase, parathyroid hormone, osteocalcin and urinary levels of deoxypyridinoline (DPD). Bone mineral density was measured by dual-energy X-ray absorptiometry (DXA) at the lumbar spine and both proximal femurs. Average urinary DPD levels, a biochemical marker of bone resorption, were elevated in the examined patient cohort (7.1 ± 1.9 nmol/mmol, reference 3.0–7.0 nmol/mmol). According to HR-pQCT, CRPS-affected distal tibiae showed significantly lower values of cortical BMD and cortical thickness compared to the unaffected contralateral side. Also, bone volume relative to total volume was significantly lower. Trabecular number and trabecular thickness tended to be lower in the affected tibiae. CRPS is associated with significant alterations in bone microstructure of the affected tibiae. Increased bone resorption seems to play a crucial role within a multifactorial process of CRPS-mediated bone atrophy. HR-pQCT could possibly serve as a diagnostic tool in specific CRPS therapy.

Metaphyseal changes in rickets and child abuse-related fractures may be difficult to distinguish; therefore, it is important to follow a standardized procedure in order to detect mineralization defects of the skeleton and differentiate them from healing fractures. We present a typical post-mortem case of rickets in a 3.5-year-old boy where different diagnostic tools were applied to confirm this condition. At autopsy a rachitic rosary was seen. Vitamin D insufficiency found in laboratory analyses, metaphyseal fraying in radiography and an accumulation of non-mineralized bone (osteoid) in undecalcified histological preparations led to the correct diagnosis. This case shows that the appropriate methodology to use undecalcified bone preparations is of paramount importance to detect mineralization defects. Moreover, as in this case which involved a combination of rickets and child abuse, the situation is often more complex where neglect and abuse may lead to vitamin D insufficiency.

Within the mineralized bone, osteocytes form a multifunctional mechanosensitive network orchestrating bone remodelling. A preserved osteocyte population is a crucial determinant of bone quality. In human auditory ossicles, the early decrease in osteocyte numbers but maintained integrity remains an unexplained phenomenon that might serve for sound transmission from air to the labyrinth. Here we analysed the frequency, size and composition of osteocyte lacunae in the auditory ossicles of 22 individuals from early postnatal period to old age. Mineralization of the bone matrix was determined using backscattered electron imaging. No signs of bone remodelling were observed above the age of 1 year. We detected characteristics of early bone tissue aging, such as decrease in osteocytes, lower total lacunar density and lacunar area, as well as high matrix mineralization accompanied by distinct accumulation of micropetrotic lacunae and decreased indentation depths. The majority of these changes took place in the first months and years of life, while afterwards only minor reorganization was present. With osteocyte apoptosis potentially being a consequence of low mechanical stimuli, the early loss of osteocytes without initiation of bone remodelling indicates an adaptive response conserving the architecture of the auditory ossicles and ensuring stable sound transmission throughout life.

Pregnancy was found to be a skeletal risk factor promoting the initial onset of previously unrecognized monogenic bone disorders, thus explaining a proportion of cases with pregnancy-associated osteoporosis. Therapeutic measures should focus in particular on the normalization of the disturbed calcium homeostasis in order to enable the partial skeletal recovery. Pregnancy-associated osteoporosis (PAO) is a rare skeletal condition, which is characterized by a reduction in bone mineral density (BMD) in the course of pregnancy and lactation. Typical symptoms include vertebral compression fractures and transient osteoporosis of the hip. Since the etiology is not well understood, this prospective study was conducted in order to elucidate the relevance of pathogenic gene variants for the development of PAO. Seven consecutive cases with the diagnosis of PAO underwent a skeletal assessment (blood tests, DXA, HR-pQCT) and a comprehensive genetic analysis using a custom-designed gene panel. All cases showed a reduced BMD (DXA T-score, lumbar spine − 3.2 ± 1.0; left femur − 2.2 ± 0.5; right femur − 1.9 ± 0.5), while the spine was affected more severely (p

Complications of cement-augmented interventions (e.g., kyphoplasty) in the spine include local cement leakage and pulmonary cement embolisms (PCE). This study was conducted to determine their extent in a unique post-mortem cohort. Retrospective analysis of post-mortem whole-body CT scans and review of autopsy results in 29 consecutive cases with cement-augmented interventions in the spine. PCE findings were graded based on cement deposits: grade 0 (no PCE), grade 1 (1-3 PCE), grade 2 (4-6 PCE), and grade 3 (> 6 or branch-shaped PCE). Bone and lung tissue specimens were obtained in representative cases to confirm the findings histologically. Local cement leakage was detected in 69%: intravenous (34%), intervertebral (31%), intraspinal (14%), and retrograde (17%). Lung sections showed PCE in 52%: grade 0 (48%), grade 1 (31%), grade 2 (10%), and grade 3 (10%). Matching with autopsy findings revealed that none of the cases died due to the impact of PCE. The presented data reveal a high frequency of PCE making it a notable finding—especially since not only single but also branch-like embolisms were detected. Thus, it is of great importance that none of the causes of death were related to the impact of PCE. Nevertheless, it is crucial to consider the underlying diseases for increased PCE risk and to apply latest surgical techniques and preventive measures. These slides can be retrieved under Electronic Supplementary material.

Primary biliary cholangitis (PBC) is known to be a major risk factor for osteoporosis reflected by a reduction of bone mineral density (BMD). However, both the extent of the macro- and microstructural alterations of bone as well as the causative factors are unknown. We have retrospectively analyzed a total of 96 patients with PBC and 53 healthy controls matched for age, sex, and body mass index. In addition to dual-energy X-ray absorptiometry (DXA) measurements at the lumbar spine and hip, high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to assess the geometric, volumetric, and microstructural changes of bone at the distal radius and tibia. Furthermore, serum analyses and measures of disease duration and stage including transient elastography were performed. Total, cortical, and trabecular volumetric BMD as well as geometric parameters were significantly reduced in PBC patients. Microstructural analysis revealed a significantly lower cortical thickness (p 0.001) and bone volume per tissue volume (p 0.001) in the radius and tibia but unchanged trabecular number in patients with PBC (radius: p = 0.42; tibia: p = 0.12). Multivariate regression models pointed out that disease duration and stage are the primary factors that are independently associated with bone loss in PBC. A subgroup analysis of patients with additional autoimmune hepatitis (AIH) revealed no significant changes in bone structure compared with PBC only. Taken together, PBC patients demonstrate severe alterations in bone microstructure that are positively associated with disease duration and stage. By applying HR-pQCT in the distal radius and tibia, a combined bone loss syndrome expressed by a predominant decrease in BMD and cortical thickness could be detected. © 2018 American Society for Bone and Mineral Research.

The main hallmark of high bone mass (HBM) disorders is increased bone mineral density, potentially visible in conventional radiographs and quantifiable by other radiographic methods. While one of the most common forms of HBM is CLCN7-related autosomal dominant osteopetrosis type II (ADO II), there is no consensus on diagnostic thresholds. We therefore wanted to assess whether CLCN7-osteopetrosis patients differ from benign HBM cases in terms of (1) bone mineral density, (2) bone structure, and (3) microarchitectural abnormalities. 16 patients meeting the criteria of HBM (DXA T/Z-score ≥ 2.5 at all sites) were included in this retrospective study. Osteologic assessment using dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT), and serum analyses was performed. The presence of CLCN7 and/or other HBM gene mutations affecting bone mass were tested using a custom designed bone panel. While a DXA threshold for ADO II could be implemented (DXA Z-score ≥ + 6.0), the differences in bone microarchitecture were of lesser extent compared to the benign HBM group. All adult patients with ADO II suffered from elevated fracture rates independent from Z-score. In HR-pQCT, structural alterations, such as bone islets were found only inconsistently. In cases of HBM, a DXA Z-score ≥ 6 may be indicative for an inheritable HBM disorder, such as ADO II. Microarchitectural bone alterations might represent local microfracture repair or accumulation of cartilage remnants due to impaired osteoclast function, but seem not to be correlated with fracture risk.

PURPOSE:To assess image quality of CT pulmonary angiography (CTPA) at reduced radiation exposure (RD-CTPA) and contrast medium (CM) volume using two different iterative reconstruction (IR) algorithms (iDose4 and iterative model reconstruction (IMR)) in comparison to filtered back projection (FBP). MATERIALS AND METHODS:52 patients (body weight < 100 kg, mean BMI: 23.9) with suspected pulmonary embolism (PE) underwent RD-CTPA (tube voltage: 80 kV; mean CTDIvol: 1.9 mGy) using 40 ml CM. Data were reconstructed using FBP and two different IR algorithms (iDose4 and IMR). Subjective and objective image quality and conspicuity of PE were assessed in central, segmental, and subsegmental arteries. RESULTS:Noise reduction of 55% was achieved with iDose4 and of 85% with IMR compared to FBP. Contrast-to-noise ratio significantly increased with iDose4 and IMR compared to FBP (p