Dual energy x-ray absorptiometry analysis contributes to the prediction of hip osteoarthritis progression

Introduction: To determine if structural bone parameters obtained from dual energy X-ray absorptiometry (DXA) contribute to the prediction of progression of hip osteoarthritis (OA) and to test if the difference between the most affected (OA) hip and the contralateral hip adds to this prediction.Methods: The study group involves a prospective cohort of 189 patients that met the American College of Rheumatology (ARC) classification criteria for hip osteoarthritis. Progression was defined as 20% joint space narrowing or total hip replacement within a two years follow up. Software was developed to calculate geometrical aspects and bone mineral density (BMD) in different regions of interest of the proximal femur. Logistic regression was used to test if Kellgren and Lawrence (K-L) scores and DXA parameters can predict progression of OA. Models were compared using -2log likelihood tests, R2Nagelkerke and areas under the Receiver Operator Characteristic curves, assessed using 10-fold cross validation.Results: The model that included the DXA variables was significantly better in predicting hip OA progression than the model with K-L score of the affected side

Current clinical practice of knee osteotomy in the Netherlands

Background: Realignment osteotomies is gaining popularity amongst Dutch orthopaedic surgeons. Exact numbers and used standards in clinical practice concerning osteotomies are unknown due to the absence of a national registry. The aim of this study was to investigate the national statistics of performed osteotomies, utilized clinical workups, surgical techniques, and post-operative rehabilitation standards in the Netherlands. Method: Dutch orthopaedic surgeons, all members of the Dutch Knee Society, received a web-based survey between January and March 2021. This electronic survey contained 36 questions, subdivided into: general surgeon-related information, number of performed osteotomies, inclusion of patients, clinical workup, surgical techniques, and post-operative management. Results: 86 orthopaedic surgeons filled in the questionnaire, of whom 60 perform realignment osteotomies around the knee. All the 60 responders (100%) perform high tibial osteotomies and 63.3% additionally perform distal femoral osteotomies, while 30% perform double level osteotomies. Discrepancies in surgical standards were reported regarding to inclusion criteria, clinical workup, surgical techniques, and post-operative strategies. Conclusions: In conclusion, this study got more insight in knee osteotomy clinical practices as applied by Dutch orthopaedic surgeons. However, there are still important discrepancies which pleads for more standardization based on available evidence. A (inter)national knee osteotomy registry, and even more so, a (inter)national registry for joint preserving surgeries could be helpful to achieve more standardization and treatment insights. Such a registry could improve all aspects of osteotomies and its combinations with other joint-preserving interventions towards evidence for personalised treatments

Visual Inspection for Lower Limb Malalignment Diagnosis Is Unreliable

Objective: Visual inspection of the lower limb is often part of standard clinical practice during a physical examination at the outpatient clinic. This study aims to investigate how reliable visual inspections are in terms of detecting lower limb malalignments without additional tools and physical examinations. Design: This study enrolled 50 patients. Each patient underwent a whole leg radiograph (WLR); in addition, a standardized digital photograph was taken of the lower limbs. Four persons (different experience levels) visually rated the digital photograph twice (unaware of the hip knee angle [HKA] on the WLR) and placed them in the category: severe valgus (>5°); moderate valgus (2°-5°); neutral, moderate varus (2°-5°); and severe varus (>5°). Visual ratings were compared with the measured HKA on WLRs for correlation using Spearman’s rho. Linear ordinal regression models with significance when P < 0.05 were used to test whether body mass index (BMI), age, gender, and HKA were possible risk factors for incorrect visual HKA assessment. Results: Spearman’s rho between the visual assessment and measured HKA on the WLR was moderate with 0.478 (P < 0.01). Women had an increased odds ratio of 3.7 (P = 0.001) for incorrect visual assessment. Higher HKA also increased the odds ratio for erroneous visual assessment with 1.4 (P = 0.003). BMI and age did not significantly increase the odds of erroneous visual leg axis assessments in this study. Conclusions: Visual assessment of the lower limb alignment does not provide clinically relevant information. Lower limb malalignment diagnoses cannot be performed using only a visual inspection. Physical examination tests and radiographical assessments are advised. Level of evidence: Diagnostic level II

Physiological effects of oral glucosamine on joint health: Current status and consensus on future research priorities

The aim of this paper was to provide an overview of the current knowledge and understanding of the potential beneficial physiological effects of glucosamine (GlcN) on joint health. The objective was to reach a consensus on four critical questions and to provide recommendations for future research priorities. To this end, nine scientists from Europe and the United States were selected according to their expertise in this particular field and were invited to participate in the Hohenheim conference held in Aug

Magnetic resonance imaging-based bone imaging of the lower limb: Strategies for generating high-resolution synthetic computed tomography

This study aims at assessing approaches for generating high-resolution magnetic resonance imaging- (MRI-) based synthetic computed tomography (sCT) images suitable for orthopedic care using a deep learning model trained on low-resolution computed tomography (CT) data. To that end, paired MRI and CT data of three anatomical regions were used: high-resolution knee and ankle data, and low-resolution hip data. Four experiments were conducted to investigate the impact of low-resolution training CT data on sCT generation and to find ways to train models on low-resolution data while providing high-resolution sCT images. Experiments included resampling of the training data or augmentation of the low-resolution data with high-resolution data. Training sCT generation models using low-resolution CT data resulted in blurry sCT images. By resampling the MRI/CT pairs before the training, models generated sharper images, presumably through an increase in the MRI/CT mutual information. Alternatively, augmenting the low-resolution with high-resolution data improved sCT in terms of mean absolute error proportionally to the amount of high-resolution data. Overall, the morphological accuracy was satisfactory as assessed by an average intermodal distance between joint centers ranging from 0.7 to 1.2 mm and by an average intermodal root-mean-squared distances between bone surfaces under 0.7 mm. Average dice scores ranged from 79.8% to 87.3% for bony structures. To conclude, this paper proposed approaches to generate high-resolution sCT suitable for orthopedic care using low-resolution data. This can generalize the use of sCT for imaging the musculoskeletal system, paving the way for an MR-only imaging with simplified logistics and no ionizing radiation

The Association Between the Development of Cam Morphology During Skeletal Growth in High-Impact Athletes and the Presence of Cartilage Loss and Labral Damage in Adulthood:A Prospective Cohort Study With a 12-Year Follow-up

Background: Cam morphology develops during skeletal growth, but its influence on cartilage and the labrum in high-impact athletes later in life is unknown. Purpose: To (1) explore the association between the presence and duration of cam morphology during adolescence and the cartilage and labral status 7 to 12 years later and (2) report the prevalence of cartilage loss and labral damage in a population of young male athletes (&lt;32 years old) who played professional soccer during skeletal growth. Study Design: Cohort study (Prognosis); Level of evidence, 2. Methods: A total of 89 healthy male academy soccer players from the Dutch soccer club Feyenoord (aged 12-19 years) were included at baseline. At baseline and 2.5- and 5-year follow-ups, standardized supine anteroposterior pelvis and frog-leg lateral radiographs of each hip were obtained. At 12-year follow-up, magnetic resonance imaging of both hips was performed. Cam morphology was defined by a validated alpha angle ≥60° on radiographs at baseline or 2.5- or 5-year follow-up when the growth plates were closed. Hips with the presence of cam morphology at baseline or at 2.5-year follow-up were classified as having a “longer duration” of cam morphology. Hips with cam morphology only present since 5-year follow-up were classified as having a “shorter duration” of cam morphology. At 12-year follow-up, cartilage loss and labral abnormalities were assessed semiquantitatively. Associations were estimated using logistic regression, adjusted for age and body mass index. Results: Overall, 35 patients (70 hips) with a mean age of 28.0 ± 2.0 years and mean body mass index of 24.1 ± 1.8 participated at 12-year follow-up. Cam morphology was present in 56 of 70 hips (80%). The prevalence of cartilage loss was 52% in hips with cam morphology and 21% in hips without cam morphology (adjusted odds ratio, 4.52 [95% CI, 1.16-17.61]; P =.03). A labral abnormality was present in 77% of hips with cam morphology and in 64% of hips without cam morphology (adjusted odds ratio, 1.99 [95% CI, 0.59-6.73]; P =.27). The duration of cam morphology did not influence these associations. Conclusion: The development of cam morphology during skeletal growth was associated with future magnetic resonance imaging findings consistent with cartilage loss in young adults but not with labral abnormalities.</p

FK506 protects against articular cartilage collagenous extra-cellular matrix degradation

Objective: Osteoarthritis (OA) is a non-rheumatologic joint disease characterized by progressive degeneration of the cartilage extra-cellular matrix (ECM), enhanced subchondral bone remodeling, activation of synovial macrophages and osteophyte growth. Inhibition of calcineurin (Cn) activity through tacrolimus (FK506) in invitro monolayer chondrocytes exerts positive effects on ECM marker expression. This study therefore investigated the effects of FK506 on anabolic and catabolic markers of osteoarthritic chondrocytes in 2D and 3D invitro cultures, and its therapeutic effects in an invivo rat model of OA. Methods: Effects of high and low doses of FK506 on anabolic (QPCR/histochemistry) and catabolic (QPCR) markers were evaluated invitro on isolated (2D) and ECM-embedded chondrocytes (explants, 3D pellets). Severe cartilage damage was induced unilaterally in rat knees using papain injections in combination with a moderate running protocol. Twenty rats were treated with FK506 orally and compared to twenty untreated controls. Subchondral cortical and trabecular bone changes (longitudinal microCT) and macrophage activation (SPECT/CT) were measured. Articular cartilage was analyzed exvivo using contrast enhanced microCT and histology. Results: FK506 treatment of osteoarthritic chondrocytes invitro induced anabolic (mainly collagens) and reduced catabolic ECM marker expression. In line with this, FK506 treatment clearly protected ECM integrity invivo by markedly decreasing subchondral sclerosis, less development of subchondral pores, depletion of synovial macrophage activation and lower osteophyte growth. Conclusion: FK506 protected cartilage matrix integrity invitro and invivo. Additionally, FK506 treatment invivo reduced OA-like responses in different articular joint tissues and thereby makes Cn an interesting target for therapeutic intervention of OA

Bone fragility and decline in stem cells in prematurely aging DNA repair deficient trichothiodystrophy mice

Trichothiodystrophy (TTD) is a rare, autosomal recessive nucleotide excision repair (NER) disorder caused by mutations in components of the dual functional NER/basal transcription factor TFIIH. TTD mice, carrying a patient-based point mutation in the Xpd gene, strikingly resemble many features of the human syndrome and exhibit signs of premature aging. To examine to which extent TTD mice resemble the normal process of aging, we thoroughly investigated the bone phenotype. Here, we show that female TTD mice exhibit accelerated bone aging from 39 weeks onwards as well as lack of periosteal apposition leading to reduced bone strength. Before 39 weeks have passed, bones of wild-type and TTD mice are identical excluding a developmental defect. Albeit that bone formation is decreased, osteoblasts in TTD mice retain bone-forming capacity as in vivo PTH treatment leads to increased cortical thickness. In vitro bone marrow cell cultures showed that TTD osteoprogenitors retain the capacity to differentiate into osteoblasts. However, after 13 weeks of age TTD females show decreased bone nodule formation. No increase in bone resorption or the number of osteoclasts was detected. In conclusion, TTD mice show premature bone aging, which is preceded by a decrease in mesenchymal stem cells/osteoprogenitors and a change in systemic factors, identifying DNA damage and repair as key determinants for bone fragility by influencing osteogenesis and bone metabolism

Unfocused Extracorporeal Shock Waves Induce Anabolic Effects in Rat Bone

Abstract. BACKGROUND: Extracorporeal shock waves are known to stimulate the differentiation of mesenchymal stem cells toward osteoprogenitors and induce the expression of osteogenic-related growth hormones. The aim of this study was to investigate if and how extracorporeal shock waves affected new bone formation, bone microarchitecture, and the mechanical properties of bone in a healthy rat model, in order to evaluate whether extracorporeal shock wave therapy might be a potential treatment for osteoporosis. METHODS: Thirteen rats received 1000 electrohydraulically generated unfocused extracorporeal shock waves to the right tibia. The contralateral, left tibia was not treated and served as a control. At two, seven, twenty-one, and forty-nine days after administration of the shock waves, in vivo single-photon-emission computed tomography (SPECT) scanning was performed to measure new bone formation on the basis of uptake of technetium-labeled methylene diphosphonate ((99m)Tc-MDP) (n = 6). Prior to and forty-nine days after the extracorporeal shock wave therapy, micro-computed tomography (micro-CT) scans were made to examine the architectural bone changes. In addition, mechanical testing, microcrack, and histological analyses were performed. RESULTS: Extracorporeal shock waves induced a strong increase in (99m)Tc-MDP uptake in the treated tibia compared with the uptake in the untreated, control tibia. Micro-CT analysis showed that extracorporeal shock waves stimulated increases in both trabecular and cortical volume, which resulted in higher bone stiffness compared with that of the contro