Increased local bone turnover in patients with chronic periprosthetic joint infection.

Aims: The management of periprosthetic joint infection (PJI) remains a major challenge in orthopaedic surgery. In this study, we aimed to characterize the local bone microstructure and metabolism in a clinical cohort of patients with chronic PJI. Methods: Periprosthetic femoral trabecular bone specimens were obtained from patients suffering from chronic PJI of the hip and knee (n = 20). Microbiological analysis was performed on preoperative joint aspirates and tissue specimens obtained during revision surgery. Microstructural and cellular bone parameters were analyzed in bone specimens by histomorphometry on undecalcified sections complemented by tartrate-resistant acid phosphatase immunohistochemistry. Data were compared with control specimens obtained during primary arthroplasty (n = 20) and aseptic revision (n = 20). Results: PJI specimens exhibited a higher bone volume, thickened trabeculae, and increased osteoid parameters compared to both control groups, suggesting an accelerated bone turnover with sclerotic microstructure. On the cellular level, osteoblast and osteoclast parameters were markedly increased in the PJI cohort. Furthermore, a positive association between serum (CRP) but not synovial (white blood cell (WBC) count) inflammatory markers and osteoclast indices could be detected. Comparison between different pathogens revealed increased osteoclastic bone resorption parameters without a concomitant increase in osteoblasts in bone specimens from patients with Staphylococcus aureus infection, compared to those with detection of Staphylococcus epidermidis and Cutibacterium spp. Conclusion: This study provides insights into the local bone metabolism in chronic PJI, demonstrating osteosclerosis with high bone turnover. The fact that Staphylococcus aureus was associated with distinctly increased osteoclast indices strongly suggests early surgical treatment to prevent periprosthetic bone alterations.

Dynamics of Skeletal Status under Optimized Management during Subsequent Pregnancy in Three Women with a History of Pregnancy- and Lactation-Associated Osteoporosis Carrying pathogenic Variants in WNT1 and LRP5.

Pregnancy- and lactation-associated osteoporosis (PLO) is a rare but clinically highly relevant condition, characterized by reduced bone mineral density (BMD) and acute onset of severe pain due to symptomatic bone marrow edema of the hip or vertebral and/or insufficiency fractures, among others. Previous reports showed a high frequency of hereditary bone disorders unmasked by PLO, predisposing for more severe forms. To date, no data on the risk for additional fractures during subsequent pregnancy in women with PLO and genetic bone disorder have been available. To address this question, we retrospectively analyzed the clinical, biochemical, and densitometric course of three women with a history of PLO and detected variants in WNT1 or LRP5 and subsequent pregnancies. Calcium homeostasis and bone turnover were optimized by basic treatment, and timely initiation of weaning was recommended. Teriparatide treatment for 12 months under strict contraception was initiated in one woman after the diagnosis of PLO. In none of the women did additional fractures or symptomatic bone marrow edemas occur, and BMD by dual-energy X-ray absorptiometry as bone microarchitecture by high-resolution peripheral quantitative computed tomography remained stable. In conclusion, this report expands the understanding of this rare but severe condition and helps to improve clinical counseling and management. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Does Juvenile Idiopathic Arthritis Affect the Course of Legg-Calvé-Perthes Disease? A Case-Control Study with a Mean Follow-Up of 8 Years.

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.

Allograft Chip Incorporation in Acetabular Reconstruction: Multiscale Characterization Revealing Osteoconductive Capacity.

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.

Relevant genetic variants are common in women with pregnancy and lactation-associated osteoporosis (PLO) and predispose to more severe clinical manifestations.

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.

Clinical Phenotype and Relevance of LRP5 and LRP6 Variants in Patients With Early-Onset Osteoporosis (EOOP).

Reduced bone mineral density (BMD; ie, Z-score ≤-2.0) occurring at a young age (ie, premenopausal women and men <50 years) in the absence of secondary osteoporosis is considered early-onset osteoporosis (EOOP). Mutations affecting the WNT signaling pathway are of special interest because of their key role in bone mass regulation. Here, we analyzed the effects of relevant LRP5 and LRP6 variants on the clinical phenotype, bone turnover, BMD, and bone microarchitecture. After exclusion of secondary osteoporosis, EOOP patients (n = 372) were genotyped by gene panel sequencing, and segregation analysis of variants in LRP5/LRP6 was performed. The clinical assessment included the evaluation of bone turnover parameters, BMD by dual-energy X-ray absorptiometry, and microarchitecture via high-resolution peripheral quantitative computed tomography (HR-pQCT). In 50 individuals (31 EOOP index patients, 19 family members), relevant variants affecting LRP5 or LRP6 were detected (42 LRP5 and 8 LRP6 variants), including 10 novel variants. Seventeen variants were classified as disease causing, 14 were variants of unknown significance, and 19 were BMD-associated single-nucleotide polymorphisms (SNPs). One patient harbored compound heterozygous LRP5 mutations causing osteoporosis-pseudoglioma syndrome. Fractures were reported in 37 of 50 individuals, consisting of vertebral (18 of 50) and peripheral (29 of 50) fractures. Low bone formation was revealed in all individuals. A Z-score ≤-2.0 was detected in 31 of 50 individuals, and values at the spine were significantly lower than those at the hip (-2.1 ± 1.3 versus -1.6 ± 0.8; p = .003). HR-pQCT analysis (n = 34) showed impaired microarchitecture in trabecular and cortical compartments. Significant differences regarding the clinical phenotype were detectable between index patients and family members but not between different variant classes. Relevant variants in LRP5 and LRP6 contribute to EOOP in a substantial number of individuals, leading to a high number of fractures, low bone formation, reduced Z-scores, and impaired microarchitecture. This detailed skeletal characterization improves the interpretation of known and novel LRP5 and LRP6 variants. © 2020 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

A novel, multi-level approach to assess allograft incorporation in revision total hip arthroplasty.

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.

Primary intraosseous meningioma: clinical, histological, and differential diagnostic aspects.

OBJECTIVE: Primary 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. METHODS: In 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. RESULTS: In 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. CONCLUSIONS: PIM 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.

Th17 cell frequency is associated with low bone mass in primary sclerosing cholangitis.

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.

Bone microstructure is significantly altered in CRPS-affected distal tibiae as detected by HR-pQCT: a retrospective cross-sectional study.

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.

Incorporation and Remodeling of Structural Allografts in Acetabular Reconstruction: Multiscale, Micro-Morphological Analysis of 13 Pelvic Explants.

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.

Trabecular bone microarchitecture predicts fragility fractures in postmenopausal women on denosumab treatment.

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 ±â€¯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.

Iterative Model Reconstruction (IMR) in MDCT Below 2 mSv for the Detection of Urinary Calculi: Diagnostic Accuracy and Image Quality in Comparison to Filtered Back-Projection and 4th Generation Iterative Reconstruction (iDose4).

PURPOSE: 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. MATERIALS AND METHODS: 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 ±â€Š0.8 mGy, mean DLP: 126 ±â€Š38 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. RESULTS: 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 ±â€Š0.6 mSv was calculated. CONCLUSION: 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. KEY POINTS: · Urinary tract. · urolithiasis. · iterative reconstruction. CITATION FORMAT: · 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.

Low physical performance determined by chair rising test muscle mechanography is associated with prevalent fragility fractures.

This study examined associations between physical performance assessed by chair rising test muscle mechanography and DXA T-score as well as body composition in a large patient cohort. Next to various significant interrelationships between these muscle and bone parameters, lower physical performance was associated with prevalent fragility fractures. PURPOSE: Although the interaction between muscle and bone has been demonstrated in various aspects, the clinical focus in the diagnosis of musculoskeletal disorders mainly lies on the skeletal assessments. Accordingly, the association between muscle function, bone mineral density (BMD), and fragility fractures remains to be further elucidated with a feasible muscle assessment in a clinical setting. METHODS: Patient data (2076 patients, 1538 women, 538 men) were evaluated retrospectively from a large dual energy X-ray absorptiometry (DXA) database as well as from chair rising test (CRT) that was performed on a muscle mechanograph. To determine potential predictors of the CRT time and maximum force, a multivariate regression analysis was performed including age, DXA T-score, and body composition indices. Furthermore, CRT results were compared between non-fracture and fracture cases. RESULTS: We determined independent predictors for CRT time such as age, femoral DXA T-score, and total fat mass, whereas CRT force was only influenced by total lean mass. Both women and men with previous fragility fractures displayed a longer CRT time (women p = 0.009, men p = 0.001) and lower CRT force (women p < 0.001, men p < 0.001) than those with no fractures, while no clear differences in CRT results could be detected between normal BMD, osteopenia, and osteoporosis based on DXA T-scores. CONCLUSIONS: Our study demonstrates that in addition to the associations between chair rising time and femoral T-score assessed by DXA, low muscle strength is associated with previous fragility fractures.

Comparison of Bone Microarchitecture Between Adult Osteogenesis Imperfecta and Early-Onset Osteoporosis.

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.

Cartilage calcification of the ankle joint is associated with osteoarthritis in the general population.

BACKGROUND: Cartilage calcification (CC) is associated with osteoarthritis (OA) in weight-bearing joints, such as the hip and the knee. However, little is known about the impact of CC and degeneration on other weight-bearing joints, especially as it relates to the occurrence of OA in the ankles. The goal of this study is to analyse the prevalence of ankle joint cartilage calcification (AJ CC) and to determine its correlation with factors such as histological OA grade, age and BMI in the general population. METHODS: CC of the distal tibia and talus in 160 ankle joints obtained from 80 donors (mean age 62.4 years, 34 females, 46 males) was qualitatively and quantitatively analysed using high-resolution digital contact radiography (DCR). Correlations with factors, such as the joint's histological OA grade (OARSI score), donor's age and BMI, were investigated. RESULTS: The prevalence of AJ CC was 51.3% (95% CI [0.40, 0.63]), independent of gender (p = 0.18) and/or the joint's side (p = 0.82). CC of the distal tibia was detected in 35.0% (28/80) (95% CI [0.25, 0.47]) and talar CC in 47.5% (38/80) (95% CI [0.36, 0.59]) of all cases. Significant correlations were noted between the mean amount of tibial and talar CC (r = 0.59, p = 0.002), as well as between the mean amount of CC observed in one ankle joint with that of the contralateral side (r = 0.52, p = 0.02). Furthermore, although the amount of AJ CC observed in the distal tibia and talus correlated with the histological OA-grade of the joint (r = 0.70, p < 0.001 and r = 0.72, p < 0.001, respectively), no such correlation was seen in the general population with relation to age (p = 0.32 and p = 0.49) or BMI (p = 0.51 and p = 0.87). CONCLUSION: The prevalence of AJ CC in the general population is much higher than expected. The relationship between the amount of AJ CC and OA, independent of the donors' age and BMI, indicates that CC may play a causative role in the development of OA in ankles.

Pulmonary cement embolism is not associated with the cause of death in a post-mortem cohort of cement-augmented interventions in the spine.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Disease Duration and Stage Influence Bone Microstructure in Patients With Primary Biliary Cholangitis.

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.

Early bone tissue aging in human auditory ossicles is accompanied by excessive hypermineralization, osteocyte death and micropetrosis.

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.

Skeletal dissemination in Paget's disease of the spine.

PURPOSE: 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. METHODS: Case report. RESULTS: 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. CONCLUSIONS: 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.