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Romosozumab, a humanized monoclonal antibody that binds and inhibits sclerostin produces a marked increase in bone formation with a concomitant decreased bone resorption. This transient rise in bone formation in the first two months of treatment is mainly due to an increased modeling-based bone formation. This requires the recruitment and differentiation of osteoblasts, one possibility being a preferential switch in commitment of precursors to osteoblasts over adipocytes. The purpose of this study was to analyze the marrow adiposity in transiliac bone biopsies at months 2 or 12 from the FRAME biopsy sub-study in patients receiving romosozumab or placebo. The total adipocyte area, number and density were measured on the total cancellous bone area. The size and shape at the individual adipocyte level were assessed including the mean adipocyte area, perimeter, min and max diameters and aspect ratio. No significant difference in total adipocyte area, number or density between placebo and romosozumab groups was observed at months 2 and 12, and no difference was observed between 2 and 12 months. After 2 or 12 months, romosozumab did not modify the size or shape of the adipocytes. No relationship between the adipocyte parameters and the dynamic parameters of bone formation could be evidenced. In conclusion, based on the analysis of a small number of biopsies, no effect of romosozumab on bone marrow adiposity of iliac crest was identified after 2 and 12 months suggesting that the modeling-based formation observed at month 2 was not due to a preferential commitment of the precursor to osteoblast over adipocyte cell lines but may result from a reactivation of bone lining cells and from a progenitor pool independent of the marrow adipocyte population.
Osteoporosis is characterized by bone loss resulting from an imbalance between the bone resorption and the bone formation in favor of the resorption. Romosozumab, a new medication to treat osteoporosis, has been shown to induce an early transient increase in bone formation that requires the differentiation of new bone forming cells called osteoblasts. Osteoblasts and fat-containing cells known as adipocytes present in the bone marrow originate from a common precursor cell. Thus, a preferential switch of this precursor to osteoblast over adipocyte is thought to be a possible cause for the increase in bone formation. The purpose of this study was to analyze the bone marrow adipocytes on bone biopsies from the pelvis in osteoporotic patients treated with romosozumab in order to evaluate that possibility. After treatment, the proportion of adipocytes, their size and shape, did not change when compared to untreated patients. In conclusion, no effect of romosozumab on bone marrow adipocytes was identified suggesting that the increased bone formation induced by romosozumab was not due to a preferential differentiation of precursor cells to osteoblasts over adipocytes.
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The aim of this study was to determine whether the Bone Strain Index (BSI), a recent DXA-based bone index, is related to bone mechanical behavior, microarchitecture and finally, to determine whether BSI improves the prediction of bone strength and the predictive role of BMD in clinical practice. PURPOSE: Bone Strain Index (BSI) is a new DXA-based bone index that represents the finite element analysis of the bone deformation under load. The current study aimed to assess whether the BSI is associated with 3D microarchitecture and the mechanical behavior of human lumbar vertebrae. METHODS: Lumbar vertebrae (L3) were harvested fresh from 31 human donors. The anteroposterior BMC (g) and aBMD (g/cm2) of the vertebral body were measured using DXA, and then the BSI was automatically derived. The trabecular bone volume (Tb.BV/TV), trabecular thickness (Tb.Th), degree of anisotropy (DA), and structure model index (SMI) were measured using µCT with a 35-µm isotropic voxel size. Quasi-static uniaxial compressive testing was performed on L3 vertebral bodies under displacement control to assess failure load and stiffness. RESULTS: The BSI was significantly correlated with failure load and stiffness (r = -0.60 and -0.59; p < 0.0001), aBMD and BMC (r = -0.93 and -0.86; p < 0.0001); Tb.BV/TV and SMI (r = -0.58 and 0.51; p = 0.001 and 0.004 respectively). After adjustment for aBMD, the association between BSI and stiffness, BSI and SMI remained significant (r = -0.51; p = 0.004 and r = -0.39; p = 0.03 respectively, partial correlations) and the relation between BSI and failure load was close to significance (r = -0.35; p = 0.06). CONCLUSION: The BSI was significantly correlated with the microarchitecture and mechanical behavior of L3 vertebrae, and these associations remained statistically significant regardless of aBMD.
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Absorciometría de Fotón , Densidad Ósea , Análisis de Elementos Finitos , Vértebras Lumbares , Estrés Mecánico , Microtomografía por Rayos X , Humanos , Vértebras Lumbares/fisiología , Vértebras Lumbares/diagnóstico por imagen , Vértebras Lumbares/fisiopatología , Femenino , Densidad Ósea/fisiología , Anciano , Masculino , Persona de Mediana Edad , Absorciometría de Fotón/métodos , Fenómenos Biomecánicos/fisiología , Microtomografía por Rayos X/métodos , Hueso Esponjoso/diagnóstico por imagen , Hueso Esponjoso/fisiología , Soporte de Peso/fisiología , Anciano de 80 o más Años , Fuerza Compresiva/fisiología , Adulto , AnisotropíaRESUMEN
The known host range of circoviruses is continuously expanding because of more intensive diagnostic activities and advanced sequencing tools. Recently, a new circovirus (penguin circovirus (PenCV)) was identified in the guano and cloacal samples collected from Adélie penguins (Pygoscelis adeliae) and chinstrap penguins (Pygoscelis antarcticus) in Antarctica. Although the virus was detected in several asymptomatic subjects, a potential association with feather disease was speculated. To investigate the occurrence and implications of PenCV in other penguin species located outside of Antarctica, a broad survey was undertaken in African penguins (Spheniscus demersus) on two islands off the southern Namibian coast. For this purpose, specific molecular biology assays were developed and validated. None of the 151 blood samples tested positive for PenCV. Several reasons could explain the lack of PenCV positive samples. African penguins and Pygoscelis species are separated by approximately 6000 km, so there is almost no opportunity for transmission. Similarly, host susceptibility to PenCV might be penguin genus-specific. Overall, the present study found no evidence of PenCV in African penguin colonies in Namibia. Further dedicated studies are required to assess the relevance of PenCV among different penguin species.
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BACKGROUND: Rodent models are commonly used experimentally to assess treatment effectiveness in spinal fusion. Certain factors are associated with better fusion rates. The objectives of the present study were to report the protocols most frequently used, to evaluate factors known to positively influence fusion rate, and to identify new factors. METHOD: A systematic literature search of PubMed and Web of Science found 139 experimental studies of posterolateral lumbar spinal fusion in rodent models. Data for level and location of fusion, animal strain, sex, weight and age, graft, decortication, fusion assessment and fusion and mortality rates were collected and analyzed. RESULTS: The standard murine model for spinal fusion was male Sprague Dawley rats of 295g weight and 13 weeks' age, using decortication, with L4-L5 as fusion level. The last two criteria were associated with significantly better fusion rates. On manual palpation, the overall mean fusion rate in rats was 58% and the autograft mean fusion rate was 61%. Most studies evaluated fusion as a binary on manual palpation, and only a few used CT and histology. Average mortality was 3.03% in rats and 1.56% in mice. CONCLUSIONS: These results suggest using a rat model, younger than 10 weeks and weighing more than 300 grams on the day of surgery, to optimize fusion rates, with decortication before grafting and fusing the L4-L5 level.
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Fusión Vertebral , Ratas , Masculino , Ratones , Animales , Fusión Vertebral/métodos , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , Columna Vertebral/cirugía , Vértebras Lumbares/cirugía , Trasplante Óseo , Modelos AnimalesRESUMEN
Despite their ability to reduce fracture-risk and increase Bone Mineral Density (BMD) in osteoporotic women, bisphosphonates are reported to reduce formation of new bone. Reduced bone formation has been suggested to lead to accumulation of microfractures and contribute to rare side effects in cortical bone such as atypical femur fractures. However, most studies are limited to trabecular bone. In this study, the cortical bone remodeling in human iliac bone specimens of 65 non-treated and 24 alendronate-treated osteoporotic women was investigated using a new histomorphometric classification of intracortical pores. The study showed that only 12.4 ± 11% of the cortical pore area reflected quiescent pores/osteons in alendronate-treated patients versus 8.5 ± 5% in placebo, highlighting that new cortical remodeling events remain to be activated. The percent and size of eroded pores (events in resorption-reversal phase) remained unchanged, but their contribution to total pore area was 1.4-fold higher in alendronate versus placebo treated patients (66 ± 22% vs 48 ± 22%, p < 0.001). On the other hand, the mixed eroded-formative pores (events with mixed resorption-reversal-formation phases) was 2-fold lower in alendronate versus placebo treated patients (19 ± 14% vs 39 ± 23% of total pore area, p < 0.001), and formative pores (event in formation phase) was 2.2-fold lower in alendronate versus placebo treated patients (2.1 ± 2.4% vs 4.6 ± 3.6%, p < 0.01), and their contribution to total pore area was 2.4-fold lower (1.3 ± 2.1% vs 3.1 ± 4.4%, p < 0.05). Importantly, these differences between alendronate and placebo treated patients were significant in patients after 3 years of treatment, not after 2 years of treatment. Collectively, the results support that cortical remodeling events activated during alendronate treatment has a prolonged reversal-resorption phase with a delayed transition to formation, becoming increasingly evident after 3-years of treatment. A potential contributor to atypical femur fractures associated with long-term bisphosphonate treatment.
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Alendronato , Remodelación Ósea , Alendronato/farmacología , Alendronato/uso terapéutico , Densidad Ósea , Huesos , Hueso Cortical , Difosfonatos/farmacología , Difosfonatos/uso terapéutico , Femenino , HumanosRESUMEN
INTRODUCTION: Recent technological advances with dual-energy quantitative computed tomography (DEQCT) allow to combine two images of different level of energy to obtain simulated mono-energetic images at 60 keV (SIM60KeV-QCT) with improved image contrast in clinical practice. This study includes three topics: (1) compare bone mineral content (BMC), areal and volumetric bone mineral density (aBMD, vBMD) obtained with SIM60KeV-QCT, single-energy QCT (SEQCT), and dual X-ray absorptiometry (DXA); (2) compare ash density and weight with respective vBMD and BMC assessed on SIM60KeV-QCT, SEQCT, and DXA; and (3) compare the influence of reconstruction kernels on the accuracy of vBMD and BMC using ash density and ash weight as the reference values. METHODS: DXA, SEQCT, and DEQCT acquisitions were performed ex vivo on 42 human femurs. Standard kernel (SK) and bone kernel (BK) were applied to each stack of images. Ten diaphyses and 10 femoral necks were cut, scanned, and reconstructed using the techniques described above. Finally, the bone specimens were calcined to obtain the ash weight. RESULTS: QCT analysis (SEQCT, SIM60KeV-QCT) underestimated BMC value compared to DXA. For femoral necks, all QCT analyses provided an unbiased estimate of ash weight but underestimated ash density regardless of the kernel used. For femoral diaphysis, SEQCT BK, SIM60KeV-QCT BK, and SK underestimated ash weight but not ash density. CONCLUSION: BMC and vBMD quantifications with the SIM60KeV-QCT gave similar results as the SEQCT. Further studies are needed to optimize the use of SIM60KeV-QCT in clinical situations. SK should be used given the effect of kernels on QCT assessment.
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Densidad Ósea , Fémur , Absorciometría de Fotón/métodos , Fémur/diagnóstico por imagen , Cuello Femoral/diagnóstico por imagen , Humanos , Minerales , Tomografía Computarizada por Rayos X/métodosRESUMEN
Bisphosphonates are widely used anti-osteoporotic drugs targeting osteoclasts. They strongly inhibit bone resorption, but also strongly reduce bone formation. This reduced formation is commonly ascribed to the mechanism maintaining the resorption/formation balance during remodeling. The present study provides evidence for an additional mechanism where bisphosphonates actually impair the onset of bone formation after resorption. The evidence is based on morphometric parameters recently developed to assess the activities reversing resorption to formation. Herein, we compare these parameters in cancellous bone of alendronate- and placebo-treated postmenopausal osteoporotic patients. Alendronate increases the prevalence of eroded surfaces characterized by reversal cells/osteoprogenitors at low cell density and remote from active bone surfaces. This indicates deficient cell expansion on eroded surfaces - an event that is indispensable to start formation. Furthermore, alendronate decreases the coverage of these eroded surfaces by remodeling compartment canopies, a putative source of reversal cells/osteoprogenitors. Finally, alendronate strongly decreases the activation frequency of bone formation, and decreases more the formative compared to the eroded surfaces. All these parameters correlate with each other. These observations lead to a model where bisphosphonates hamper the osteoprogenitor recruitment required to initiate bone formation. This effect results in a larger eroded surface, thereby explaining the well-known paradox that bisphosphonates strongly inhibit bone resorption without strongly decreasing eroded surfaces. The possible mechanism for hampered osteoprogenitor recruitment is discussed: bisphosphonates may decrease the release of osteogenic factors by the osteoclasts, and/or bisphosphonates released by osteoclasts may act directly on neighboring osteoprogenitor cells as reported in preclinical studies.
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Resorción Ósea , Difosfonatos , Alendronato/farmacología , Remodelación Ósea , Resorción Ósea/inducido químicamente , Resorción Ósea/tratamiento farmacológico , Difosfonatos/farmacología , Humanos , Osteoclastos , OsteogénesisRESUMEN
BACKGROUND: Dual X-ray absorptiometry body composition measurements are widely used for clinical and research settings. It is well known that measurements vary across instruments, needing caution for longitudinal monitoring or multicentric studies. This study was to quantify intra- and inter-center variability of bone mineral content, bone mineral density, fat and lean body composition measurements between Hologic Discovery models in order to calculate the corrective factors to be applied for multicenter research projects. MATERIALS AND METHODS: A whole body phantom composed of materials representing the thickness and percentage of bone, lean and fat mass in the human physiological range was analyzed ten times in three different centers using dual energy X-ray absorptiometry scanners (Two Hologic Discovery QDR A and one QDR W). In addition, we used a morphometric vertebral phantom to monitor stability and a three steps block phantom to check accuracy. RESULTS: We found a good long-term stability and accuracy for the three devices. Intra-center coefficients of variation were within the range of the manufacturer acceptable values (bone mineral density: 1.40%, bone mineral content: 1%, area: 1.50%, fat mass: 0.89%, lean mass: 0.76%, total mass: 0.12%). Whereas the inter-center coefficient of variation exceeded 8% (bone mineral density: 8.18%, bone mineral content: 3.03%, area: 8.63%: fat mass: 3,92%, lean mass: 7.89%, total mass: 2.85%). CONCLUSION: Our study showed that the discrepancies across centers remain a major concern, particularly with regard to body composition results. Our study highlight the need of cross calibration between densitometers and proposes corrective factors evaluated from a whole body phantom to lead multicentric studies adjustment.
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Composición Corporal , Densidad Ósea , Absorciometría de Fotón , Huesos , Humanos , Fantasmas de ImagenRESUMEN
PURPOSE: Beside areal bone mineral density (aBMD), evaluation of fragility fracture risk mostly relies on global microarchitecture. However, microarchitecture is not a uniform network. Therefore, this study aimed to compare local structural weakness to global microarchitecture on whole vertebral bodies and to evaluate how local and global microarchitecture was associated with bone biomechanics. METHODS: From 21 human L3 vertebrae, aBMD was measured using absorptiometry. Parameters of global microarchitecture were measured using HR-pQCT: trabecular bone volume fraction (Tb.BV/TVglobal), trabecular number, structure model index and connectivity density (Conn.D). Local minimal values of aBMD and Tb.BV/TV were identified in the total (Tt) or trabecular (Tb) area of each vertebral body. "Two dimensional (2D) local structural weakness" was defined as Tt.BMDmin, Tt.BV/TVmin and Tb.BV/TVmin. Mechanical testing was performed in 3 phases: 1/ initial compression until mild vertebral fracture, 2/ unloaded relaxation, and 3/ second compression until failure. RESULTS: Initial and post-fracture mechanics were significantly correlated with bone mass, global and local microarchitecture. Tt.BMDmin, Tt.BV/TVmin, Tb.BV/TVmin, and initial and post-fracture mechanics remained significantly correlated after adjustment for aBMD or Tb.BV/TVglobal (p < 0.001 to 0.038). The combination of the most relevant parameter of bone mass, global and local microarchitecture associated with failure load and stiffness demonstrated that global microarchitecture explained initial and post-fracture stiffness, while local structural weakness explained initial and post-fracture failure load (p < 0.001). CONCLUSION: Local and global microarchitecture was associated with different features of vertebral bone biomechanics, with global microarchitecture controlling stiffness and 2D local structural weakness controlling strength. Therefore, determining both localized low density and impaired global microarchitecture could have major impact on vertebral fracture risk prediction.
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BACKGROUND AND OBJECTIVES: Histomorphometric analysis of a transiliac bone biopsy is the gold standard for the diagnosis of renal osteodystrophy (ROD). This procedure is costly, invasive and usually performed with a trephine with an internal diameter of 7.5 mm. Our objective was to evaluate the accuracy of ROD diagnosis on halved histological bone sections to determine if they are comparable to the standard 7.5 mm samples. DESIGN: We included 68 bone biopsies performed in CKD patients for diagnostic purposes with a 7.5 mm diameter trephine. Quantitative histomorphometric analysis of the whole bone samples was performed including assessment of bone mineralization, turnover and volume. Each histological section (representing the whole 7.5 mm diameter biopsy) was then divided lengthwise in two hemisections (representing the 3.5 mm diameter biopsy). Histomorphometric analysis was repeated this time on the two hemibiopsies for each sample, blinded from initial results. Diagnoses were classified as osteitis fibrosa, adynamic bone disease, mixed uremic bone disease, osteomalacia or other. Correlations between the whole sample and the hemibiopsies for each parameter were studied. Concordance between the various bone parameters and final ROD diagnosis obtained from the whole section versus the two hemi sections was evaluated. RESULTS: Highly significant correlations were found between parameters measured on the whole section and the corresponding hemisections, with r coefficient of 0.98 for osteoid surface and thickness and bone formation rate, 0.97 for osteoclast surface, and 0.96 for bone volume (p < 0.001). Final diagnosis was in full accordance between the whole biopsy and the two corresponding hemi-biopsies in 91% of cases. CONCLUSIONS: Accurate diagnosis of ROD type was obtained by evaluation of bone surface areas of 3 mm diameter. These data suggest that small invasive bone biopsies might provide accurate ROD diagnostics while decreasing both invasiveness and cost of the procedure.
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Enfermedades Óseas , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica , Osteomalacia , Biopsia , Trastorno Mineral y Óseo Asociado a la Enfermedad Renal Crónica/diagnóstico , Humanos , Ilion/diagnóstico por imagenRESUMEN
In January 2019, high mortalities were reported among African Penguins (Spheniscus demersus) in a breeding colony on Halifax Island, Namibia, Africa. Analysis of samples by reverse transcription quantitative PCR indicated the presence of highly pathogenic avian influenza (HPAI) subtype H5N8. Sequence analysis of the hemagglutinin and neuraminidase genes confirmed the presence of the virus in the birds and its high similarity to HPAI subtype H5N8 identified in South Africa in 2017. There have been no previous reports of HPAI H5N8 in Namibia.
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Brotes de Enfermedades/veterinaria , Subtipo H5N8 del Virus de la Influenza A/genética , Gripe Aviar/virología , Spheniscidae/virología , Animales , Gripe Aviar/epidemiología , Gripe Aviar/patología , Namibia/epidemiologíaRESUMEN
Sclerostin, a protein produced by osteocytes, inhibits bone formation. Administration of sclerostin antibody results in increased bone formation in multiple animal models. Romosozumab, a humanized sclerostin antibody, has a dual effect on bone, transiently increasing serum biochemical markers of bone formation and decreasing serum markers of bone resorption, leading to increased BMD and reduction in fracture risk in humans. We aimed to evaluate the effects of romosozumab on bone tissue. In a subset of 107 postmenopausal women with osteoporosis in the multicenter, international, randomized, double-blind, placebo-controlled Fracture Study in Postmenopausal Women with Osteoporosis (FRAME), transiliac bone biopsies were performed either after 2 (n = 34) or 12 (n = 73) months of treatment with 210 mg once monthly of romosozumab or placebo to evaluate histomorphometry and microcomputed tomography-based microarchitectural endpoints. After 2 months, compared with either baseline values assessed after a quadruple fluorochrome labeling or placebo, significant increases (P < 0.05 to P < 0.001) in dynamic parameters of formation (median MS/BS: romosozumab 1.51% and 5.64%; placebo 1.60% and 2.31% at baseline and month 2, respectively) were associated with a significant decrease compared with placebo in parameters of resorption in cancellous (median ES/BS: placebo 3.4%, romosozumab 1.8%; P = 0.022) and endocortical (median ES/BS: placebo 6.3%, romosozumab 1.6%; P = 0.003) bone. At 12 months, cancellous bone formation was significantly lower (P < 0.05 to P < 0.001) in romosozumab versus placebo and the lower values for resorption endpoints seen at month 2 persisted (P < 0.001), signaling a decrease in bone turnover (P = 0.006). No significant change was observed in periosteal and endocortical bone. This resulted in an increase in bone mass and trabecular thickness with improved trabecular connectivity, without significant modification of cortical porosity at month 12. In conclusion, romosozumab produced an early and transient increase in bone formation, but a persistent decrease in bone resorption. Antiresorptive action eventually resulted in decreased bone turnover. This effect resulted in significant increases in bone mass and improved microarchitecture. © 2019 American Society for Bone and Mineral Research.
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Anticuerpos Monoclonales/uso terapéutico , Conservadores de la Densidad Ósea/uso terapéutico , Huesos/diagnóstico por imagen , Huesos/patología , Osteogénesis , Osteoporosis Posmenopáusica/diagnóstico por imagen , Osteoporosis Posmenopáusica/tratamiento farmacológico , Microtomografía por Rayos X , Anciano , Anticuerpos Monoclonales/farmacología , Biopsia , Conservadores de la Densidad Ósea/farmacología , Resorción Ósea/diagnóstico por imagen , Resorción Ósea/tratamiento farmacológico , Huesos/efectos de los fármacos , Femenino , Humanos , Osteogénesis/efectos de los fármacosRESUMEN
Denosumab, a RANKL inhibitor, reduced the risk of vertebral, hip, and nonvertebral fractures in the Fracture REduction Evaluation of Denosumab in Osteoporosis every 6 Months (FREEDOM) trial of postmenopausal women with osteoporosis compared with placebo. Previous bone histomorphometric analysis in FREEDOM showed decreased bone resorption and turnover in cancellous bone after 2 and 3 years. The purpose of the present study was to evaluate the effects of denosumab compared with placebo in the cortical compartment from transiliac bone biopsies obtained during FREEDOM. A total of 112 specimens were evaluable for cortical histomorphometry, including 67 obtained at month 24 (37 placebo, 30 denosumab) and 45 at month 36 (25 placebo, 20 denosumab). Eroded surface, osteoclast surface, erosion depth, and wall thickness were measured on the endocortical surface. Cortical thickness and cortical porosity were also measured. Dynamic parameters of bone formation were assessed for endocortical, periosteal, and intracortical envelopes. Endocortical osteoclast surface, eroded surface, and mean and maximum erosion depth were significantly lower in the denosumab group versus placebo at months 24 and 36 (p < 0.0001 to p = 0.04). Endocortical wall thickness and intracortical measures (cortical porosity and cortical thickness) were not different between the two groups. Dynamic parameters were low with tetracycline labels in cortical bone observed in 13 (43%) and 10 (50%) of denosumab biopsies at months 24 and 36, respectively, reflecting a marked decrease in bone turnover. In conclusion, our data reveal the mechanism of action of denosumab on cortical bone: inhibition of osteoclastic resorption and reduced activation of new remodeling sites. In addition, reduced endocortical erosion depth with no change of wall thickness may contribute to increased bone strength by reducing the bone loss and fragility associated with deep resorption cavities and may likely contribute to the greater BMD gain with denosumab than with other antiresorptive agents. © 2018 The Authors. Journal of Bone and Mineral Research Published by Wiley Periodicals Inc.
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Remodelación Ósea/efectos de los fármacos , Hueso Cortical , Denosumab/administración & dosificación , Ilion , Osteoclastos , Osteoporosis , Fracturas Osteoporóticas , Anciano , Anciano de 80 o más Años , Hueso Cortical/metabolismo , Hueso Cortical/patología , Método Doble Ciego , Femenino , Humanos , Ilion/metabolismo , Ilion/patología , Persona de Mediana Edad , Osteoclastos/metabolismo , Osteoclastos/patología , Osteoporosis/tratamiento farmacológico , Osteoporosis/metabolismo , Osteoporosis/patología , Fracturas Osteoporóticas/metabolismo , Fracturas Osteoporóticas/patología , Fracturas Osteoporóticas/prevención & controlRESUMEN
Osteophytes have been suggested to influence the bone mechanical properties. The aim of this study was to compare the microcrack density in osteophytes with that in the other parts of the osteoarthritic femoral neck (FN). The presence of microcracks was investigated in the ultra-distal FN and in the osteophytes in samples obtained during hip arthroplasty in 24 postmenopausal women aged 67 ± 10 years. Furthermore, the 3D microarchitecture and the collagen crosslinks contents were assessed by high-resolution peripheral quantitative computed tomography and high-performance liquid chromatography, respectively. Osteophytes were present in the 24 FN, mainly at the level of the inferior quadrant. Microcracks were present in all FN with an average of 2.8 per sample. All observed microcracks were linear. The microcrack density (Cr.N/BV; #/mm2) was significantly higher in cancellous than in cortical bone (p = 0.004), whereas the microcrack length (Cr.Le, µm) was significantly greater in cortical bone (p = 0.04). The collagen crosslinks ratio pyridinoline/deoxypyridinoline was significantly and negatively correlated with Cr.N/BV in the posterior (r' = - 0.68, p = 0.01) and inferior (r' = - 0.53, p = 0.05) quadrants. Microcracks were observed in seven osteophytes in seven patients. When microcracks were present in the osteophyte area, Cr.N/BV was also significantly higher in the whole FN and in the quadrant of the osteophyte compared to the cases without microcrack in the osteophyte (p < 0.03). In conclusion, in FN from hip osteoarthritis microcracks are present in all FNs but in only 23% of the osteophytes. The microcrack formation was greater and their progression was smaller in the cancellous bone than in the cortex. The spatial distribution of microcracks varied according to the proximity of the osteophyte, and suggests that osteophyte may influence microcrack formation related to changes in local bone quality.
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Cuello Femoral/patología , Osteoartritis de la Cadera/patología , Osteofito/patología , Anciano , Femenino , Humanos , Persona de Mediana EdadRESUMEN
PURPOSE: Using a cementless femoral stem in total hip arthroplasty (THA), optimal filling of the proximal femoral metaphyseal volume (PFMV) and restoration of the extramedullary proximal femoral (PF) parameters (i.e., femoral offset (FO), neck length (FNL), and head height (FHH)) constitute key goals for optimal hip biomechanics, functional outcome, and THA survivorship. However, almost 30% of mismatch between the PF anatomy and implant geometry of the most widely implanted non-modular cementless femoral stem has been demonstrated in a computed tomography scan (CT scan) study. Therefore, this anatomic study aimed to evaluate the relationship between the intra- and extramedullary PF parameters using tridimensional CT scan reconstructions. METHODS: One hundred fifty-one CT scans of adult healthy hips were obtained from 151 male Caucasian patients (mean age = 66 ± 11 years) undergoing lower limb CT scan arteriography. Tridimensional PF reconstructions and parameter measurements were performed using a corrected PF coronal plane-defined by the femoral neck and diaphyseal canal longitudinal axes-to avoid influence of PF helitorsion and femoral neck version on extramedullary PF parameters. RESULTS: Independently of the femoral neck-shaft angle, the PFMV was significantly and positively correlated with the FO, FNL, and FHH (r = 0.407 to 0.420; p < 0.0001). CONCLUSION: This study emphasized that the tridimensional PF geometry measurement in the corrected coronal plane of the femoral neck can be useful to determine and optimize the design of a non-modular cementless femoral stem. Particularly, continuous homothetic size progression of the intra- and extramedullary PF parameters should be achieved to assure stem fixation and restore anatomic hip biomechanics.
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Artroplastia de Reemplazo de Cadera/instrumentación , Fémur/diagnóstico por imagen , Prótesis de Cadera/estadística & datos numéricos , Imagenología Tridimensional/métodos , Diseño de Prótesis/métodos , Tomografía Computarizada por Rayos X/métodos , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Cadera/métodos , Fémur/cirugía , Articulación de la Cadera/cirugía , Humanos , Masculino , Persona de Mediana Edad , Estudios RetrospectivosRESUMEN
The femoral neck (FN) has been previously characterized by thinner cortices in osteoporotic fracture (HF) when compared to hip osteoarthritis (HOA). The purposes of this study were to complete the previous investigations on FNs from HF and HOA by analyzing the complexity of the cortical structure and to approach the intrinsic properties of cortical bone by assessing the collagen crosslink contents. FN samples were obtained during arthroplasty in 35 postmenopausal women (HF; n = 17; mean age 79 ± 2 years; HOA; n = 18; mean age 66 ± 2 years). The cortical fractal dimension (Ct.FD) and lacunarity (Ct.Lac) derived from high-resolution peripheral quantitative tomography (isotropic voxel size: 82 µm) images of FN by using Ctan software and Fraclac running in ImageJ were analyzed. The collagen crosslinks content [pyridinoline, deoxypyridinoline, pentosidine (PEN)] were assessed in cortical bone. Ct.FD was significantly lower (p < 0.0001) in HF than HOA reflecting a decreased complexity and was correlated to the age and BMD. In two sub-groups, BMD- and age-matched, respectively, Ct.FD remained significantly lower in HF than HOA (p < 0.001). Ct.Lac was not different between HF and HOA. PEN content was two times higher in HF than HOA (p < 0.0001) independently of age. In conclusion, FN with HF was characterized by a less complex cortical texture and higher PEN content than HOA. In addition to the decreased bone mass and BMD previously reported, these modifications contribute to the lower bone quality in HF than HOA in postmenopausal women.
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Colágeno/metabolismo , Cuello Femoral/metabolismo , Osteoporosis Posmenopáusica/metabolismo , Posmenopausia/metabolismo , Anciano , Anciano de 80 o más Años , Densidad Ósea , Femenino , Humanos , Masculino , Fracturas de la Columna Vertebral/fisiopatologíaRESUMEN
OBJECTIVES: The aim of the study was to evaluate the mandible cortical bone changes in patients with oral squamous cell carcinoma (OSCC). PATIENTS AND METHODS: Twenty patients who underwent some mandibular bone removal as part of the treatment of OSCC had bone samples collected in two parts: in the proximity of the tumor (BPT) and in the surgical margin (BEP). Cortical microarchitecture was analyzed trough micro-computed tomography, together with texture analysis, followed by microcrack evaluation in histological sections and gene expression of RANK, RANKL, OPG, and sclerostin by quantitative polymerase chain reaction. RESULTS: Bone surface was higher in BPT (0.005 ± 0.002 vs 0.004 ± 0.002, p = 0.01) compared with BEP. In BPT, the subset of patients without bone invasion presented higher anisotropy (0.83 ± 0.07) compared with the ones with bone invasion (0.70 ± 0.14) (p = 0.04). RANK, RANKL, OPG, and sclerostin were found to be downregulated in the majority of cases in both parts. There were significant correlations between the parameters of microarchitecture and gene expression analysis (p < 0.001 to p < 0.05), most of them related with OPG levels. CONCLUSION: The cortex in the mandible in the proximity of the tumor reveals more bone surface than the bone in the surgical margin, and the tumor invasion causes a decrease in anisotropy. RANK, RANKL, OPG, and sclerostin are downregulated in mandible, in both parts analyzed. Correlation tests revealed the association between cortical thickness, bone surface, anisotropy, porosity, bone mineral density, and OPG levels. CLINICAL RELEVANCE: The mandible cortical bone microarchitecture changes in the proximity of the squamous cell carcinoma lesion.
Asunto(s)
Carcinoma de Células Escamosas/patología , Mandíbula/patología , Neoplasias de la Boca/patología , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Biomarcadores de Tumor/metabolismo , Proteínas Morfogenéticas Óseas/metabolismo , Carcinoma de Células Escamosas/diagnóstico por imagen , Carcinoma de Células Escamosas/cirugía , Regulación hacia Abajo , Femenino , Marcadores Genéticos , Humanos , Masculino , Mandíbula/diagnóstico por imagen , Mandíbula/cirugía , Márgenes de Escisión , Persona de Mediana Edad , Neoplasias de la Boca/diagnóstico por imagen , Neoplasias de la Boca/cirugía , Osteoprotegerina/metabolismo , Estudios Prospectivos , Ligando RANK/metabolismo , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptor Activador del Factor Nuclear kappa-B/metabolismo , Microtomografía por Rayos XRESUMEN
Type 2 diabetes mellitus (T2DM) is associated with skeletal complications, including an increased risk of fractures. Reduced blood supply and bone strength may contribute to this skeletal fragility. We hypothesized that long-term administration of Exenatide, a glucagon-like peptide-1 receptor agonist, would improve bone architecture and strength of T2DM mice by increasing blood flow to bone, thereby stimulating bone formation. In this study, we used a model of obesity and severe T2DM, the leptin receptor-deficient db/db mouse to assess alterations in bone quality and hindlimb blood flow and to examine the beneficial effects of 4 weeks administration of Exenatide. As expected, diabetic mice showed marked alterations in bone structure, remodeling and strength, and basal vascular tone compared with lean mice. Exenatide treatment improved trabecular bone mass and architecture by increasing bone formation rate, but only in diabetic mice. Although there was no effect on hindlimb perfusion at the end of this treatment, Exenatide administration acutely increased tibial blood flow. While Exenatide treatment did not restore the impaired bone strength, intrinsic properties of the matrix, such as collagen maturity, were improved. The effects of Exenatide on in vitro bone formation were further investigated in primary osteoblasts cultured under high-glucose conditions, showing that Exenatide reversed the impairment in bone formation induced by glucose. In conclusion, Exenatide improves trabecular bone mass by increasing bone formation and could protect against the development of skeletal complications associated with T2DM.
RESUMEN
Climate change and fisheries are transforming the oceans, but we lack a complete understanding of their ecological impact [1-3]. Environmental degradation can cause maladaptive habitat selection, inducing ecological traps with profound consequences for biodiversity [4-6]. However, whether ecological traps operate in marine systems is unclear [7]. Large marine vertebrates may be vulnerable to ecological traps [6], but their broad-scale movements and complex life histories obscure the population-level consequences of habitat selection [8, 9]. We satellite tracked postnatal dispersal in African penguins (Spheniscus demersus) from eight sites across their breeding range to test whether they have become ecologically trapped in the degraded Benguela ecosystem. Bayesian state-space and habitat models show that penguins traversed thousands of square kilometers to areas of low sea surface temperatures (14.5°C-17.5°C) and high chlorophyll-a (â¼11 mg m-3). These were once reliable cues for prey-rich waters, but climate change and industrial fishing have depleted forage fish stocks in this system [10, 11]. Juvenile penguin survival is low in populations selecting degraded areas, and Bayesian projection models suggest that breeding numbers are â¼50% lower than if non-impacted habitats were used, revealing the extent and effect of a marine ecological trap for the first time. These cascading impacts of localized forage fish depletion-unobserved in studies on adults-were only elucidated via broad-scale movement and demographic data on juveniles. Our results support suspending fishing when prey biomass drops below critical thresholds [12, 13] and suggest that mitigation of marine ecological traps will require matching conservation action to the scale of ecological processes [14].