Are Synovial Inflammatory Markers Increased in Patients Who Have Aseptic Total Hip Arthroplasty Dislocation Indicated for Revision?

BACKGROUND: Previous studies have speculated on elevated synovial inflammatory markers in patients undergoing surgical revision for total hip arthroplasty (THA) dislocation. However, this assumption is based on small patient series and a full investigation according to International Consensus Meeting (ICM) criteria has not yet been performed. METHODS: Patients who had aseptic THA dislocation indicated for revision surgery were identified retrospectively. Only patients who had available diagnostic workup according to ICM 2018 criteria, including preoperative and intraoperative parameters, were included. For comparison, we analyzed a matched cohort of patients indicated for aseptic THA revision for other conditions. The 2 cohorts each consisted of 55 patients and were not different regarding age, sex, BMI, or implant fixation. RESULTS: There was no difference in synovial white blood cell count (2,238 ± 2,544 versus 2,533 ± 3,448 c/µL; P = .601), alpha-defensin quotient (0.14 ± 0.11 versus 0.19 ± 0.28; P = .207), or polymorphonuclear neutrophil percentage (% PMN) (36.7 ± 22.6 versus 31.3 ± 24.5%; P = .312) between the groups. In the dislocation cohort, 20% of patients had a synovial white blood cell count of 3,000 c/µL or higher, compared with 18% in the control cohort. However, all patients in the dislocation cohort were below the cutoff for alpha-defensin or % PMN. CONCLUSION: In patients who have aseptic THA dislocation, synovial inflammatory markers are not elevated compared with patients undergoing aseptic revision for other complications. A detailed preoperative analysis of synovial inflammatory markers using ICM criteria appears critical in patients who have a THA dislocation to exclude periprosthetic joint infection. LEVEL OF EVIDENCE: Level III, retrospective, comparative study.

Effects of Infantile Hypophosphatasia on Human Dental Tissue.

Hypophosphatasia (HPP) is an inherited, systemic disorder, caused by loss-of-function variants of the ALPL gene encoding the enzyme tissue non-specific alkaline phosphatase (TNSALP). HPP is characterized by low serum TNSALP concentrations associated with defective bone mineralization and increased fracture risk. Dental manifestations have been reported as the exclusive feature (odontohypophosphatasia) and in combination with skeletal complications. Enzyme replacement therapy (asfotase alfa) has been shown to improve respiratory insufficiency and skeletal complications in HPP patients, while its effects on dental status have been understudied to date. In this study, quantitative backscattered electron imaging (qBEI) and histological analysis were performed on teeth from two patients with infantile HPP before and during asfotase alfa treatment and compared to matched healthy control teeth. qBEI and histological methods revealed varying mineralization patterns in cementum and dentin with lower mineralization in HPP. Furthermore, a significantly higher repair cementum thickness was observed in HPP compared to control teeth. Comparison before and during treatment showed minor improvements in mineralization and histological parameters in the patient when normalized to matched control teeth. HPP induces heterogeneous effects on mineralization and morphology of the dental status. Short treatment with asfotase alfa slightly affects mineralization in cementum and dentin. Despite HPP being a rare disease, its mild form occurs at higher prevalence. This study is of high clinical relevance as it expands our knowledge of HPP and dental involvement. Furthermore, it contributes to the understanding of dental tissue treatment, which has hardly been studied so far.

Impact of polyethylene glenoid cementation technique on cement mantle integrity and stability after cyclic loading: a computed tomography and biomechanical study.

BACKGROUND: There are no generally accepted guidelines for polyethylene (PE) glenoid component cementation techniques. In particular, it is not known whether the backside of a PE glenoid should be fully or partially cemented-or not cemented at all. We hypothesized that cementing techniques would have an impact on cement mantle volume and integrity, as well as biomechanical stability, measured as micromotion under cyclic loading. METHODS: To address our hypothesis, 3 different cementation techniques using a single 2-peg PE glenoid design with polyurethane foam were compared regarding (1) the quality and quantity of the cement mantle and (2) biomechanical stability after cyclic loading in vitro. Eight identically cemented glenoids per group were used. Group A underwent cement application only into the peg holes, group B received additional complete cement mantle application on the backside of the glenoid, and group C received the same treatment as group B but with additional standardized drill holes in the surface of the glenoid bone for extra cement interdigitation. All glenoids underwent cyclic edge loading by 105 cycles according to ASTM F2028-14. Before and after loading, cement mantle evaluation was performed by XtremeCT and biomechanical strength and loosening were evaluated by measuring the relative motion of the implants. RESULTS: The cement mantle at the back of the implant was incomplete in group A as compared with groups B and C, in which the complete PE backside was covered with a homogeneous cement mantle. The cement mantle was thickest in group C, followed by group B (P = .006) and group A (P < .001). We did not detect any breakage of the cement mantle in any of the 3 groups after testing. Primary stability during cyclic loading was similar in all groups after the "running-in" phase (up to 4000 cycles). Gross loosening did not occur in any implant. CONCLUSIONS: Coverage of the PE glenoid with cement was reproducible in the fully cemented groups (ie, groups B and C) as compared with relevant cement defects in group A. The addition of cement to the back of the PE glenoid and additional drill holes in the glenoid surface did not improve primary stability in the tested setting.

Prevalence of osteoporosis and osteopenia in elderly patients scheduled for total knee arthroplasty.

INTRODUCTION: Osteoporosis is a common comorbidity in elderly patients with osteoarthritis (OA) and may increase perioperative complications in orthopedic surgery (e.g., component migration, periprosthetic fractures). As there is no investigation of bone mineral density (BMD) in elderly patients prior to total knee arthroplasty (TKA) in Europe, we investigated this issue with a particular focus on a potential treatment gap. MATERIALS AND METHODS: We assessed the BMD by dual-energy X-ray absorptiometry (DXA) in 109 consecutive elderly patients (age ≥ 70 years) scheduled for TKA. In addition to a detailed assessment of osteoporosis and osteopenia, the influence of clinical risk factors and radiological OA severity on BMD was evaluated using group comparisons and linear regression models. In addition, we analyzed differences in BMD between patients scheduled for TKA vs. total hip arthroplasty (THA). RESULTS: Of the included 109 patients, 19 patients (17.4%) were diagnosed with osteoporosis and 50 (45.9%) with osteopenia. In the osteoporotic patients, a clinically relevant underdiagnosis concomitant with a serious treatment gap was observed in 95.0% of the patients. Body mass index, OA grade, and glucocorticoid use were identified as independent factors associated with BMD. No differences in BMD were found between the patients scheduled for TKA vs. THA. CONCLUSIONS: Considering the high prevalence of osteoporosis and osteopenia in elderly patients, DXA screening should be recommended for patients ≥ 70 years indicated for TKA.

Ultrasound as a diagnostic tool for femoral head containment disorders in children between one and 12 years of age.

PURPOSE: Ultrasound has been used to diagnose hip dysplasia in neonates and to screen until the end of their first year. For older children, femoral head containment disorders such as developmental dysplasia of the hip, Legg-Calvé-Perthes disease or cerebral palsy are usually diagnosed with plain radiographs. The aim of the present study was to evaluate ultrasound in comparison with radiographic imaging in children up to age 12 years and to determine reference values for sonographic containment parameters. METHODS: Hip ultrasound and radiographic imaging were acquired on the same day and then compared. As a reference, normal acetabular angle and acetabulum head index were determined on radiographs. Lateral cartilage distance (LCD), lateral head distance (LHD) and femoral head extrusion angle (HA) were measured on ultrasound images. RESULTS: We included 96 patients with 167 healthy hips in the study. A total of 55 patients were female and 41 male. The mean age was 5.2 years (sd 3.3; 1.0 to 11.9). LCDultrasound, LHDultrasound and HAultrasound correlated significantly with radiographic parameters. The following ultrasound values were calculated as limits for impending loss of containment: LCDultrasound ≥ 6.5 mm, LHDultrasound ≥ 3.3 mm and HAultrasound ≥ 27.6°. CONCLUSION: Ultrasound is a simple, radiation-free diagnostic tool to detect femoral head containment disorders, even in children older than one year. This study provides reference values for hip ultrasound in children up to 12 years. LEVEL OF EVIDENCE: III.

Bone mineral density assessment by DXA in rheumatic patients with end-stage osteoarthritis undergoing total joint arthroplasty.

BACKGROUND: Patients with rheumatic diseases have a high risk for joint destruction and secondary osteoarthritis (OA) as well as low bone mineral density (BMD, i.e., osteoporosis). While several factors may lead to low BMD in these patients, the value of BMD measurements in rheumatic patients with end-stage OA scheduled for total joint arthroplasty is unknown. METHODS: In this retrospective cross-sectional study of 50 adults with secondary OA due to rheumatic diseases, we evaluated dual energy X-ray absorptiometry (DXA) measurements of both hips and the spine performed within 3 months prior to arthroplasty (n = 25 total hip arthroplasty, THA; n = 25 total knee arthroplasty, TKA). We analyzed various demographic and disease-specific characteristics and their effect on DXA results by using group comparisons and multivariate linear regression models. RESULTS: Although patients undergoing TKA were younger (63.2 ± 14.2 vs. 71.0 ± 10.8 yr., p = 0.035), osteoporosis was observed more frequently in patients scheduled for TKA than THA (32% vs. 12%). Osteopenia was detected in 13/25 patients (52%) in both the THA and TKA cohort. In the THA cohort, female sex, lower BMI and prednisolone use were associated with lower T-score in the hip. In TKA patients, higher OA grade determined by Kellgren-Lawrence score was associated with lower T-score in the hip of the affected side. CONCLUSIONS: Osteoporosis is present in a considerable frequency of rheumatic patients with end-stage OA, and THA and TKA patients show distinct frequencies and risk factors of low BMD. Our findings point to a potential value of DXA regarding preoperative evaluation of bone status.

Diagnostic yield of cone beam computed tomography for small foreign body detection in the hand in comparison with radiography, MSCT and MRI: an ex vivo study.

INTRODUCTION: Detection of symptomatic foreign bodies (FB) after penetrating hand injuries can be challenging. Multiplanar radiography is most frequently used for FB detection and may be complemented by multislice computed tomography (MSCT) if suspected FBs cannot be identified and clinical symptoms are persisting. Cone beam computed tomography (CBCT) is a promising imaging modality for traumatology aside from fracture detection. The aim of this study was to evaluate the diagnostic yield of CBCT for different small FBs in the hand in comparison with radiography, MSCT and magnetic resonance imaging (MRI). METHODS: In ten cadaveric hands of voluntary body donors, 20 different FBs (metal, glass, stone, wood, thorn) in predefined sizes (0.5, 1 and 2mm) were randomly placed in the central hand and the basal phalanges. All hands were imaged using radiography, 256-slice CT, CBCT, and 3T MRI. A total of 200 subcutaneous and intramuscular particles were analyzed for their visibility by two observers at two time points. The Cohens Kappa coefficient was calculated as a measure of interobserver agreement and intraobserver reliability. The particle detection rate between different imaging modalities was compared using McNemar Chi2-tests. RESULTS: CBCT and MSCT provided a higher detection rate (94.6% and 86.3%) for detecting metal, glass and stone particles compared to standard radiography (70.0%; each p<0.001). MRI did not provide a diagnostic benefit. Wood particles and thorns were not reliably recognizable by any imaging technique. The interobserver agreement (K=0.768; p<0.001) and the intraobserver reliability for both observers (K1=0.914 and K2=0.907; p<0.001) were good. The dose length product (DLP) was 2-fold lower in CBCT than in MSCT (39.2 ± 2.1 vs. 81.4 ± 2.9 mGy*cm; p<0.001). CONCLUSIONS: In this ex vivo study, CBCT provided a high detection rate for small metal, glass, and stone particles while the radiation exposure was significantly lower compared to MSCT. These results suggest that CBCT instead of MSCT seems a reasonable option in supplementary diagnostics to exclude of FBs. The primary use of CBCT instead of radiography may be considered for symptomatic patients with expected small radiopaque particles <1mm. Organic FBs can be visualized indirectly in MRI and CBCT/MSCT by entrapped surrounding air. LEVEL OF EVIDENCE: Level I, diagnostic study.

Clinical and Radiological Characterization of Patients with Immobilizing and Progressive Stress Fractures in Methotrexate Osteopathy.

Methotrexate (MTX) is one of the most commonly prescribed drugs for autoimmune rheumatic diseases. As there is no consensus on its negative effects on bone, the purpose of this investigation was to determine the clinical spectrum of patients with stress fractures due to long-term MTX treatment (i.e., MTX osteopathy). We have retrospectively analyzed data from 34 patients with MTX treatment, severe lower extremity pain and immobilization. MRI scans, bone turnover markers, bone mineral density (DXA) and bone microarchitecture (HR-pQCT) were evaluated. Stress fractures were also imaged with cone beam CT. While the time between clinical onset and diagnosis was prolonged (17.4 ± 8.6 months), the stress fractures had a pathognomonic appearance (i.e., band-/meander-shaped, along the growth plate) and were diagnosed in the distal tibia (53%), the calcaneus (53%), around the knee (62%) and at multiple sites (68%). Skeletal deterioration was expressed by osteoporosis (62%) along with dissociation of low bone formation and increased bone resorption. MTX treatment was discontinued in 27/34 patients, and a combined denosumab-teriparatide treatment initiated. Ten patients re-evaluated at follow-up (2.6 ± 1.5 years) had improved clinically in terms of successful remobilization. Taken together, our findings provide the first in-depth skeletal characterization of patients with pathognomonic stress fractures after long-term MTX treatment.

Bone healing and reactivation of remodeling under asfotase alfa therapy in adult patients with pediatric-onset hypophosphatasia.

Hypophosphatasia (HPP) is a hereditary musculoskeletal disorder caused by inactivating variants in the ALPL gene and subsequently reduced serum tissue-nonspecific alkaline phosphatase (TNSALP) activity. This inborn error of metabolism results in decreased bone quality, accumulations of osteoid, and reduced bone mineralization. Increased incidence of fractures and prolonged bone healing are characteristic features for HPP. Available enzyme replacement therapy (asfotase alfa), was reported to recover bone mineralization and bone quality in adult HPP patients. Moreover, it was shown that asfotase alfa improved fracture healing of former nonunions in two adult HPP patients. We hypothesized that the nonunions are filled partially with osteoid, offering great potential to benefit from the treatment with asfotase alfa to promote bone healing. In the present study, we report three adult patients with pediatric-onset HPP and detected ALPL-mutations with prolonged bone healing after arthrodesis, tibial stress fracture, and osteotomy. After the initiation of asfotase alfa, immediately increased levels of alkaline phosphatase (ALP) and bone-specific ALP, as well as decreased levels of pyridoxal-5-phosphate (PLP), were detected in biochemical analysis. Importantly, even after up to 5 years of non-healing, a progredient consolidation was shown, assessed by a custom three-dimensional evaluation of repeated cone-beam computed tomography (CBCT) images, characterized by rapidly increasing levels of bone volume per tissue volume (BV/TV) within the volume of interest (i.e., the region of the non-healing bone). These radiographical findings were in line with the reported restoration of functional ability and pain-free full weight-bearing, as well as increased neuromuscular parameters (e.g., improved muscle strength). Taken together, our findings indicate that asfotase alfa improves the osseous consolidation of nonunions likely due to re-mineralization of osteoid tissue filling the former gap and improving the functional ability in adult HPP patients, characterized by increasing levels of BV/TV assessed via an innovative three-dimensional evaluation of CBCT images.

Bilateral Looser zones or pseudofractures in the anteromedial tibia as a component of medial tibial stress syndrome in athletes.

PURPOSE: Medial tibial stress syndrome (MTSS) represents a common diagnosis in individuals exposed to repetitive high-stress loads affecting the lower limb, e.g., high-performance athletes. However, the diagnostic approach and therapeutic regimens are not well established. METHODS: Nine patients, diagnosed as MTSS, were analyzed by a comprehensive skeletal analysis including laboratory bone turnover parameters, dual-energy X-Ray absorptiometry (DXA), and high-resolution peripheral quantitative computed tomography (HR-pQCT). RESULTS: In 4/9 patients, bilateral pseudofractures were detected in the mid-shaft tibia. These patients had significantly lower levels of 25-hydroxycholecalciferol compared to patients with MTSS but similar levels of bone turnover parameters. Interestingly, the skeletal assessment revealed significantly higher bone mineral density (BMD) Z-scores at the hip (1.3 ± 0.6 vs. - 0.7 ± 0.5, p = 0.013) in patients with pseudofractures and a trend towards higher bone microarchitecture parameters measured by HR-pQCT at the distal tibia. Vitamin D supplementation restored the calcium-homeostasis in all patients. Combined with weight-bearing as tolerated, pseudofractures healed in all patients and return to competition was achieved. CONCLUSION: In conclusion, deficient vitamin D levels may lead to pseudofractures due to localized deterioration of mineralization, representing a pivotal component of MTSS in athletes with increased repetitive mechanical loading of the lower limbs. Moreover, the manifestation of pseudofractures is not a consequence of an altered BMD nor microarchitecture but appears in patients with exercise-induced BMD increase in combination with reduced 25-OH-D levels. The screening of MTSS patients for pseudofractures is crucial for the initiation of an appropriate treatment such as vitamin D supplementation to prevent a prolonged course of healing or recurrence. LEVEL OF EVIDENCE: III.

Genotype-Phenotype Associations in 72 Adults with Suspected ALPL-Associated Hypophosphatasia.

Hypophosphatasia (HPP) is a rare inborn error of metabolism due to a decreased activity of tissue nonspecific alkaline phosphatase (TNSALP). As the onset and severity of HPP are heterogenous, it can be challenging to determine the pathogenicity of detected rare ALPL variants in symptomatic patients. We aimed to characterize patients with rare ALPL variants to propose which patients can be diagnosed with adult HPP. We included 72 patients with (1) clinical symptoms of adult HPP or positive family history and (2) low TNSALP activity and/or high pyridoxal 5'-phosphate (PLP) levels, who underwent ALPL gene sequencing. The patients were analyzed and divided into three groups depending on ALPL variant pathogenicity according to the classification of the American College of Medical Genetics and Genomics (ACMG). Reported pathogenic (n = 34 patients), rare (n = 17) and common (n = 21) ALPL variants only were found. Muscular complaints were the most frequent symptoms (> 80%), followed by bone affection (> 50%). Tooth involvement was significantly more common in patients with pathogenic or rare ALPL variants. Seven rare variants could be classified as likely pathogenic (ACMG class 4) of which five have not yet been described. Inconclusive genetic findings and less specific symptoms make diagnosis difficult in cases where adult HPP is not obvious. As not every pathogenic or rare ALPL variant leads to a manifestation of HPP, only patients with bone complications and at least one additional complication concerning teeth, muscle, central nervous and mental system, repeated low TNSALP activity and high PLP levels should be diagnosed as adult HPP if rare ALPL gene variants of ACMG class 4 or higher support the diagnosis.

Large osteocyte lacunae in iliac crest infantile bone are not associated with impaired mineral distribution or signs of osteocytic osteolysis.

The enlargement of osteocyte lacunae via osteocytic osteolysis was previously detected in situations of increased calcium demand (e.g., lactation, vitamin D deficiency). However, it is unclear whether similar processes occur also in the growing infantile skeleton and how this is linked to the mineral distribution within the bone matrix. Human iliac crest biopsies of 30 subjects (0-6 months, n = 14; 2-8 years, n = 6 and 18-25 years, n = 10) were acquired. Bone microarchitecture was assessed by micro-CT, while cellular bone histomorphometry was performed on undecalcified histological sections. Quantitative backscattered electron imaging (qBEI) was conducted to determine the bone mineral density distribution (BMDD) as well as osteocyte lacunar size and density. We additionally evaluated cathepsin K positive osteocytes using immunohistochemistry. Infantile bone was characterized by various signs of ongoing bone development such as higher bone (re)modeling, lower cortical and trabecular thickness compared to young adults. Importantly, a significantly higher osteocyte lacunar density and increased lacunar area were detected. Large osteocyte lacunae were associated with a more heterogeneous bone mineral density distribution of the trabecular bone matrix due to the presence of hypermineralized cartilage remnants, whereas the mean mineralization (i.e., CaMean) was not different in infantile bone. Absence of cathepsin K expression in osteocyte lacunae indicated nonexistent osteocytic osteolysis. Taken together, we demonstrated that the overall mineralization distribution in infantile bone is not altered compared to young adults besides high trabecular mineralization heterogeneity. Our study also provides important reference values for bone microstructure, BMDD and osteocyte characteristics in infants, children and young adults. Infantile bone displays large osteocyte lacunae indicating a developmental phenomenon rather than osteocytic osteolysis. Larger osteocytes may have superior mechanosensory abilities to enable bone adaption during growth.

Impaired Bone Microarchitecture in Patients with Hereditary Hemochromatosis and Skeletal Complications.

Hereditary hemochromatosis (HHC) is characterized by excessive intestinal iron absorption resulting in a pathological increase of iron levels. Parenchyma damage may be a consequence of iron deposition in affected organs (e.g., liver, pancreas, gonads) as well as bones and joints, leading to osteoporosis with increased fracture risk and arthropathy. Up to date, it is not known whether HHC can also be considered as a risk factor for osteonecrosis. Likewise, the underlying skeletal changes are unknown regarding, e.g., microstructural properties of bone. We aimed to study the spectrum of skeletal complications in HHC and the possible underlying microarchitectural changes. Therefore, we retrospectively analyzed all patients with HHC (n = 10) presenting in our outpatient clinic for bone diseases. In addition to dual-energy X-ray absorptiometry (DXA), high-resolution peripheral quantitative computed tomography (HR-pQCT) was performed and bone turnover markers, 25-OH-D3, ferritin and transferrin saturation were measured. Cortical volumetric bone mineral density (Ct.BMD) and cortical thickness (Ct.Th) were reduced, whereas trabecular microstructure (Tb.Th) and volumetric bone mineral density (Tb.BMD) were preserved compared to age- and gender-adjusted reference values from the literature. Interestingly, the occurrence of bone complications was age dependent; while younger patients presented with osteonecroses or transient bone marrow edema, patients older than 65 years presented with fractures. Our study provides first insights into altered bone microarchitecture in HHC and sheds new light on the occurrence of osteonecrosis. If available, HR-pQCT is a useful complement to fracture risk assessment and to determine microstructural deterioration and volumetric bone mineralization deficits.

Total Hip Arthroplasty in Multiple Sclerosis. / Hüftendoprothetik bei multipler Sklerose.

Systemic neurological disease represents a risk factor for complications after total hip arthroplasty (THA), especially for dislocation, infections, gait disorders and fall-related periprosthetic fractures. There is little specific literature on total hip arthroplasty in patients with multiple sclerosis. However, increased revision rates have been reported, which are in part due to dislocations. Implants with increased dislocation safety, e.g. tripolar acetabular systems, can represent a reasonable alternative. Due to gait disorders and a higher prevalence of osteoporosis, specific osteological evaluation and treatment should be considered to prevent periprosthetic fractures. This short review summarizes the current literature on total hip arthroplasty in patients with multiple sclerosis.

Outcome of Teriparatide Treatment on Fracture Healing Complications and Symptomatic Bone Marrow Edema in Four Adult Patients With Hypophosphatasia.

The response to teriparatide has been described in very few cases of hypophosphatasia (HPP). In this cross-sectional study, we report the prevalence of symptomatic bone marrow edema (BME) and fracture healing complications in a large cohort of childhood and adult HPP patients and discuss the results of teriparatide treatment in four cases. From 2016 to 2018, 51 patients with a diagnosis of HPP were seen at our institution. The diagnosis of HPP was established by low serum alkaline phosphatase (ALP), elevated serum pyridoxal-5-phosphate (PLP), at least one typical clinical symptom of HPP and supported by ALPL mutation analysis. In this study cohort, 28 (56%) and 14 (27%) patients had a history of fracture or a history of BME, respectively. Four patients, including middle-aged to elderly women and men who all presented with persistent symptomatic BME or fracture healing complications, were treated with teriparatide. DXA was performed prior to treatment and laboratory values were measured on a regular basis during treatment. Treatment with teriparatide showed variable effects in terms of clinical and biochemical response. Although all four patients displayed a temporary increase in ALP activity, only two patients with a mild form of adult HPP and moderately increased PLP levels showed definite clinical and radiological improvement after teriparatide treatment. In conclusion, fracture healing complications and BME occur frequently in HPP patients. Teriparatide shows variable clinical and biochemical effects depending on the severity of the disease. PLP levels and the number of ALPL alleles might be good parameters to predict treatment outcomes. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.