Joost J. A. de Jong

High-resolution in vivo imaging of bone and joints: a window to microarchitecture

Imaging is essential to the evaluation of bone and joint diseases, and the digital era has contributed to an exponential increase in the number of publications on noninvasive analytical techniques for the quantification of changes to bone and joints that occur in health and in disease. One such technique is high-resolution peripheral quantitative CT (HR-pQCT), which has introduced a new dimension in the imaging of bone and joints by providing images that are both 3D and at high resolution (82 μm isotropic voxel size), with a low level of radiation exposure (3–5 μSv). HR-pQCT enables the analysis of cortical and trabecular properties separately and to apply micro-finite element analysis for calculating bone biomechanical competence in vivo at the distal sites of the skeleton (distal radius and distal tibia). Moreover, HR-pQCT makes possible the in vivo assessment of the spatial distribution, dimensions and delineation of cortical bone erosions, osteophytes, periarticular cortical and trabecular microarchitecture, and 3D joint-space volume of the finger joints and wrists. HR-pQCT is, therefore, a technique with a high potential for improving our understanding of bone and joint diseases at the microarchitectural level.

NSAIDs and fracture healing

Purpose of reviewPublished data raise concerns about the use of nonselective NSAIDs and selective cyclo-oxygenase (COX)-2 inhibitors as anti-inflammatory or analgesic drugs in patients after a recent fracture or who are undergoing (uncemented) arthroplasty or osteotomy. However, clinical reports on the effect of COX-2 inhibition on fracture healing in humans have been variable and inconclusive. This review gives an overview of the published data and an advice when to avoid NSAIDs. Recent findingsProstaglandins play an important role as mediators of inflammation and COX are required for their production. Inflammation is an essential step in the fracture healing process in which prostaglandin production by COX-2 is involved. Data from animal studies suggest that NSAIDs, which inhibit COX-2, can impair fracture healing due to the inhibition of the endochondral ossification pathway. Animal data suggest that the effects of COX-2 inhibitors are dependent on the timing, duration, and dose, and that these effects are reversible. SummaryThese animal data, together with the view of limited scientifically robust clinical evidence in humans, indicate that physicians consider only short-term administration of COX-2 inhibitors or other drugs in the pain management of patients who are in the phase of fracture or other bone defect healing. COX-2-inhibitors should be considered a potential risk factor for fracture healing, and therefore to be avoided in patients at risk for delayed fracture healing.

Definition for Rheumatoid Arthritis Erosions Imaged with High Resolution Peripheral Quantitative Computed Tomography and Interreader Reliability for Detection and Measurement

Objective. High-resolution peripheral quantitative computed tomography (HR-pQCT) sensitively detects erosions in rheumatoid arthritis (RA); however, nonpathological cortical bone disruptions are potentially misclassified as erosive. Our objectives were to set and test a definition for pathologic cortical bone disruptions in RA and to standardize reference landmarks for measuring erosion size. Methods. HR-pQCT images of metacarpophalangeal joints of RA and control subjects were used in an iterative process to achieve consensus on the definition and reference landmarks. Independent readers (n = 11) applied the definition to score 58 joints and measure pathologic erosions in 2 perpendicular multiplanar reformations for their maximum width and depth. Interreader reliability for erosion detection and variability in measurements between readers [root mean square coefficient of variation (RMSCV), intraclass correlation (ICC)] were calculated. Results. Pathologic erosions were defined as cortical breaks extending over a minimum of 2 consecutive slices in perpendicular planes, with underlying trabecular bone loss and a nonlinear shape. Interreader agreement for classifying pathologic erosions was 90.2%, whereas variability for width and depth erosion assessment was observed (RMSCV perpendicular width 12.3%, axial width 20.6%, perpendicular depth 24.0%, axial depth 22.2%; ICC perpendicular width 0.206, axial width 0.665, axial depth 0.871, perpendicular depth 0.783). Mean erosion width was 1.84 mm (range 0.16–8.90) and mean depth was 1.86 mm (range 0.30–8.00). Conclusion. We propose a new definition for erosions visualized with HR-pQCT imaging. Interreader reliability for erosion detection is good, but further refinement of selection of landmarks for erosion size measurement, or automated volumetric methods, will be pursued.

Bone stiffness and failure load are related with clinical parameters in men with chronic obstructive pulmonary disease

Osteoporosis is frequently seen in patients with chronic obstructive pulmonary disease (COPD). Because research on bone structure and bone strength in COPD patients is limited, the objectives of this pilot study were as follows: (1) to compare bone structure, stiffness, and failure load, measured at the peripheral skeleton, between men with and without COPD after stratification for areal bone mineral density (aBMD); and (2) to relate clinical parameters with bone stiffness and failure load in men with COPD. We included 30 men with COPD (normal aBMD, n = 18; osteoporosis, n = 12) and 17 men without COPD (normal aBMD, n = 9; osteoporosis, n = 8). We assessed pack‐years of smoking, body mass index (BMI), fat free mass index (FFMI), pulmonary function (forced expiratory volume in 1 second [FEV1], FEV1/forced vital capacity [FVC], diffusion capacity for carbon monoxide [DLCO], and transfer coefficient for carbon monoxide [KCO]), and extent of emphysema. Bone structure of the distal radius and tibia was assessed by high‐resolution peripheral quantitative computed tomography (HR‐pQCT), and bone stiffness and failure load of the distal radius and tibia were estimated from micro finite element analysis (µFEA). After stratification for aBMD and COPD, men with osteoporosis showed abnormal bone structure (p < 0.01), lower bone stiffness (p < 0.01), and lower failure load (p < 0.01) compared with men with normal aBMD, and men with COPD had comparable bone structure, stiffness, and failure load compared with men without COPD. In men with COPD, lower FFMI was related with lower bone stiffness, and failure load of the radius and tibia and lower DLCO and KCO were related with lower bone stiffness and failure load of the tibia after normalization with respect to femoral neck aBMD. Thus, this pilot study could not detect differences in bone structure, stiffness, and failure load between men with and without COPD after stratification for aBMD. FFMI and gas transfer capacity of the lung were significantly related with bone stiffness and failure load in men with COPD after normalization with respect to femoral neck aBMD.

Fracture repair in the distal radius in postmenopausal women:a follow-up 2 years postfracture using HRpQCT

Fracture healing is characterized by an intense increase in modeling and remodeling of bone, which allows removal of the cast after a stable distal radius fracture within 3 to 5 weeks. However, at that time, bone strength has not recovered yet. We studied the changes in bone mineral density (BMD), microarchitecture, and bone stiffness after a distal radius fracture during a 2‐year follow‐up in comparison to the contralateral side and the association between the 2‐year stiffness and baseline BMD, microarchitecture, and early changes in these parameters. The fractured side of 14 postmenopausal women (mean age 64 ± 8 years) with a conservatively treated distal radius fracture was scanned by high‐resolution peripheral quantitative computed tomography (HRpQCT) at 1 to 2, 3 to 4, 6 to 8, and 12 weeks and 2 years postfracture. The same region contralaterally was scanned as well at the 2‐year visit. BMD, microarchitecture, and stiffness parameters were determined and the fracture side was compared with the contralateral side using a linear mixed‐effect model. Spearmans correlation was used to correlate the 2‐year bone stiffness with baseline BMD, microarchitecture, and early 3‐month changes in these parameters. Two years postfracture, cortical and trabecular thickness and torsional and bending stiffness were significantly higher at the fractured side compared with the nonfractured side (21%, 55%, 31%, and 29%, respectively, p < 0.05), whereas BMD was similar. Two‐year torsional and bending stiffness correlated significantly with baseline BMD and cortical perimeter (|rho| ≥ 0.63, p < 0.016) but not with early changes in bone parameters. Using HRpQCT, this study illustrates that fracture healing is not completed by the time the cast is removed. We showed that from 6 weeks to 2 years postfracture, large changes occur in BMD, microarchitecture, and biomechanical parameters at the fractured side, which were fully recovered after 2 years in comparison to the nonfractured contralateral side. Interestingly, higher 2‐year torsional and bending stiffness were associated with lower BMD and higher cortical perimeter at baseline.

Synthesis and characterization of a new vertebroplasty cement based on gold-containing PMMA microspheres

There are a number of drawbacks to incorporating large concentrations of barium sulfate (BaSO4) as the radiopacifier in PMMA-based bone cements for percutaneous vertebroplasty. These include adverse effects on injectability, viscosity profile, setting time, mechanical properties of the cement and bone resorption. We have synthesized a novel cement that is designed to address some of these drawbacks. Its powder includes PMMA microspheres in which gold particles are embedded and its monomer is the same as that used in commercial cements for vertebroplasty. In comparison to one such commercial cement brand, VertaPlex™, the new cement has longer doughing time, longer injection time, higher compressive strength, higher compressive modulus, and is superior in terms of cytotoxicity. For augmentation of fractured fresh-frozen cadaveric vertebral bodies (T6-L5) using simulated vertebroplasty, results for compressive strength and compressive stiffness of the construct and the percentage of the volume of the vertebral body filled by the cement were comparable for the two cements although the radiopacity of the new cement was significantly lower than that for VertaPlex™. The present results indicate that the new cement warrants further study.

Distal radius plate of CFR-PEEK has minimal effect compared to titanium plates on bone parameters in high-resolution peripheral quantitative computed tomography: a pilot study

BackgroundCarbon-fiber-reinforced poly-ether-ether-ketone (CFR-PEEK) has superior radiolucency compared to other orthopedic implant materials, e.g. titanium or stainless steel, thus allowing metal-artifact-free postoperative monitoring by computed tomography (CT). Recently, high-resolution peripheral quantitative CT (HRpQCT) proved to be a promising technique to monitor the recovery of volumetric bone mineral density (vBMD), micro-architecture and biomechanical parameters in stable conservatively treated distal radius fractures. When using HRpQCT to monitor unstable distal radius fractures that require volar distal radius plating for fixation, radiolucent CFR-PEEK plates may be a better alternative to currently used titanium plates to allow for reliable assessment. In this pilot study, we assessed the effect of a volar distal radius plate made from CFR-PEEK on bone parameters obtained from HRpQCT in comparison to two titanium plates.MethodsPlates were instrumented in separate cadaveric human fore-arms (n = 3). After instrumentation and after removal of the plates duplicate HRpQCT scans were made of the region covered by the plate. HRpQCT images were visually checked for artifacts. vBMD, micro-architectural and biomechanical parameters were calculated, and compared between the uninstrumented and instrumented radii.ResultsNo visible image artifacts were observed in the CFR-PEEK plate instrumented radius, and errors in bone parameters ranged from −3.2 to 2.6%. In the radii instrumented with the titanium plates, severe image artifacts were observed and errors in bone parameters ranged between −30.2 and 67.0%.ConclusionsWe recommend using CFR-PEEK plates in longitudinal in vivo studies that monitor the healing process of unstable distal radius fractures treated operatively by plating or bone graft ingrowth.

Effect of a cast on short-term reproducibility and bone parameters obtained from HR-pQCT measurements at the distal end of the radius

BACKGROUND High-resolution peripheral quantitative computed tomography (HR-pQCT) is a promising tool to assess the fracture-healing process at the microscale in vivo. Since casts are often used during fracture treatment, they might affect the assessment of bone density, microarchitectural, and biomechanical parameters and the short-term reproducibility of those parameters, e.g., as a result of beam-hardening. The aim of this study was to assess the effect of a plaster-of-Paris and/or fiberglass cast on bone parameters and on the short-term reproducibility of the HR-pQCT measurements of those parameters. METHODS The effects of a cast on HR-pQCT-derived bone parameters were evaluated by comparing HR-pQCT scans of fifteen human cadaveric distal radial specimens from one male and fourteen female donors (median age, eighty-four years [range, sixty-two to ninety years] at the time of death) in three conditions: with a plaster-of-Paris cast, with a fiberglass cast, or without a cast. Short-term reproducibility was assessed using duplicate scans of the distal end of the radius in sixteen healthy volunteers without a fracture (nine men and seven women with a median age of twenty-six years; range, twenty-two to thirty-nine years) while wearing and not wearing a fiberglass cast. RESULTS Compared with measurements made with no cast, the plaster-of-Paris cast introduced a systematic error in the bone parameters ranging from -2.6% in trabecular separation to -9.8% in cortical thickness. Bone parameters were affected only marginally by fiberglass, with errors between -0.6% and -1.6% in trabecular separation and cortical thickness, respectively. Short-term reproducibility with a fiberglass cast was similar to that with no cast: approximately 1% for bone density parameters, 4% to 5% for microarchitectural parameters, and 3% to 4% for biomechanical parameters. CONCLUSIONS A plaster-of-Paris cast has a considerable effect on HR-pQCT measurements. A fiberglass cast only marginally affects the bone parameters, and the short-term reproducibility of HR-pQCT measurements in patients with a fiberglass cast is comparable with that in patients without a cast. In studies on fracture-healing using HR-pQCT, a fiberglass cast is desirable if immobilization is indicated. The use of a plaster-of-Paris cast should be avoided if possible; however, if not avoidable, corrections after the scan are desirable to adjust for the error introduced in the bone parameters.

Modelo de degeneração do disco intervertebral por punção da cauda de ratos Wistar: avaliação histológica e radiográfica

RESUMO Objetivo: descrever a caracterização histológica e radiográfica do método de indução da degeneração do disco intervertebral da cauda de ratos Wistar induzida por meio de punção. Métodos: ratos Wistar machos adultos foram anestesiados, radiografados e submetidos à punção dos discos intervertebrais localizados entre a sexta e a sétima e a oitava e nona vértebras coccígeas. Para a punção foi utilizada agulha de 20G, que foi introduzida até o ânulo fibroso, e foi realizada dupla rotação de 360°, mantendo-se a mesma posição durante 30 segundos antes da retirada. O disco intermediário aos segmentos lesados (7-8) não foi puncionado e foi utilizado como controle. Foi selecionado o período pós-lesão de 30 dias (n=9) para sacrifício e análise dos discos intervertebrais. ABSTRACT Objective: to report the induction of intervertebral disc degeneration of the rat caudal spine by needle puncture and its radiographic and histologic characterization. Methods: adult male Wistar rats were anesthetized, submitted to the X-Ray and then to the needle puncture (20G) of intervertebral disc between the sixth and seventh (proximal segment) and the eighth and ninth (distal segment) coccygeal vertebrae. Radiographies were taken 30 days after lesion for analysis of intervertebral disc height. The intermediate disc (78) to injured segments was not punctured and was considered as control. All segments were removed, fixed and demineralized, processed and stained with Hematoxylin-Eosin for histological evaluation. Results: RESUMEN Objetivo: describir la caracterización histológica y radiográfica del método de inducción de la degeneración del disco intervertebral de la cola de ratas Wistar, inducida por medio de la punción. Métodos: ratas Wistar machos adultos fueron anestesiados, radiografiados y sometidos a la punción de los discos intervertebrales localizados, entre la sexta y la séptima; y la octava y novena vértebras coccígeas. Para la punción, fue utilizada una aguja de 20G, que fue introducida hasta el ánulo fibroso, y fue realizada una dupla rotación de 360°, manteniendo esta posición durante 30 segundos, previamente a la retirada. El disco intermediario a los segmentos lesionados (7-8) no fue puncionado y fue considerado como control. Fue seleccionado el periodo post-lesión de 30 días (n=9) para sacrificio y análisis deOBJETIVO: describir la caracterizacion histologica y radiografica del metodo de induccion de la degeneracion del disco intervertebral de la cola de ratas Wistar, inducida por medio de la puncion. METODOS: ratas Wistar machos adultos fueron anestesiados, radiografiados y sometidos a la puncion de los discos intervertebrales localizados, entre la sexta y la septima; y la octava y novena vertebras coccigeas. Para la puncion, fue utilizada una aguja de 20G, que fue introducida hasta el anulo fibroso, y fue realizada una dupla rotacion de 360o, manteniendo esta posicion durante 30 segundos, previamente a la retirada. El disco intermediario a los segmentos lesionados (7-8) no fue puncionado y fue considerado como control. Fue seleccionado el periodo post-lesion de 30 dias (n=9) para sacrificio y analisis de los discos intervertebrales. Los animales fueron radiografiados 30 dias despues de la lesion para analisis de la altura del disco intervertebral. Los segmentos de la cola fueron removidos, fijados y desmineralizados, procesados y coloreados con hematoxilina-eosina para evaluacion histologica. RESULTADOS: el analisis radiografico mostro una reduccion significativa de la altura de los discos lesionados en relacion al control. La evaluacion histologica mostro alteraciones en el nucleo pulposo y el anulo fibroso de los discos lesionados en relacion al control. No fueron observadas diferencias en la intensidad de la lesion entre los discos proximal y distal. CONCLUSIONES: la degeneracion del disco intervertebral de la cola de ratas Wistar inducida por medio de puncion mostro ser un metodo reproducible para el estudio de la degeneracion del disco intervertebral. Ese modelo mostro validez para la evaluacion experimental de nuevas intervenciones terapeuticas en los procesos de la degeneracion del disco intervertebral.

Evaluation of interference fit and bone damage of an uncemented femoral knee implant

Background: During implantation of an uncemented femoral knee implant, press‐fit interference fit provides the primary stability. It is assumed that during implantation a combination of elastic and plastic deformation and abrasion of the bone will occur, but little is known about what happens at the bone‐implant interface and how much press‐fit interference fit is eventually achieved. Methods: Five cadaveric femora were prepared and implantation was performed by an experienced surgeon. Micro‐CT‐ and conventional CT‐scans were obtained pre‐ and post‐implantation for geometrical measurements and to measure bone mineral density. Additionally, the position of the implant with respect to the bone was determined by optical scanning of the reconstructions. By measuring the differences in surface geometry, assessments were made of the cutting error, the actual interference fit, the amount of bone damage, and the effective interference fit. Findings: Our analysis showed an average cutting error of 0.67 mm (SD 0.17 mm), which pointed mostly towards bone under‐resections. We found an average actual AP interference fit of 1.48 mm (SD 0.27 mm), which was close to the nominal value of 1.5 mm. Interpretation: We observed combinations of bone damage and elastic deformation in all bone specimens, which showed a trend to be related with bone density. Higher bone density tended to lead to lower bone damage and higher elastic deformation. The results of the current study indicate different factors that interact while implanting an uncemented femoral knee component. This knowledge can be used to fine‐tune design criteria of femoral components to achieve adequate primary stability for all patients. HighlightsInterference fit and bone damage was assessed using micro‐CT scan of distal femurs.Average actual interference fit was close to the nominal interference fit.It was revealed that damage goes beyond the bone‐implant interface.Bone density was the most effective factor to achieve high interference fit.Bone particles can penetrate into the inter‐trabecular spaces.