Real-time assessment of bone metabolism in small animal models for osteoarthritis using multi pinhole-SPECT/CT.

OBJECTIVE: Destructive techniques such as histology and biochemical assays are still regarded the gold standard to study the effects of novel therapies or etiologic aspects of osteoarthritis in small animal models. These techniques are time-consuming and require many animals. Multi-pinhole single photon emission computed tomography (MPH-SPECT) is a relatively novel, high resolution imaging technique which enables assessment of biological processes in real-time and thus it might provide a good substitute for destructive assessment techniques. DESIGN: For this study, we assessed mono-iodoacetate (MIA) induced osteoarthritic knees in 18 rats. The animals were scanned using MPH-SPECT/CT and a diphosphonate labelled with 99m-technetium as the radioactive tracer to monitor subchondral bone turnover (bone-scan) at 2 (n = 18), 14 (n = 12) and 42 (n = 6) days after injection of MIA. At each time-point six animals were sacrificed and also assessed with high-resolution micro-computed tomography (µCT) and histology. RESULTS: At 2 days after injection of MIA, the MPH-SPECT/CT already showed elevated bone turnover in the affected knee, whereas with histology and µCT we could not detect clear alterations at all this time-point. The increase in bone turnover induced by MIA was elevated further at 14 and 42 days after injection. At this time alterations on histology and µCT scanning also became visible. CONCLUSIONS: MPH-SPECT/CT proved to be a highly sensitive assessment technique for experimental osteoarthritis in small animal models, detecting real-time changes in bone turnover at a very early time point, which might make it a valuable technique to measure the direct effect of interventional strategies on osteoarthritis.

Hip and groin pain in male field hockey players: Prevalence, incidence and associations with patient reported outcome scores and hip muscle strength.

OBJECTIVES: Investigate point prevalence (second half season 2018-2019) and incidence (season 2017-2018 and first half season 2018-2019) of non-time-loss and time-loss hip/groin pain in male field hockey players. Secondary aims were to study associations between: current/previous hip/groin pain and hip muscle strength, patient reported outcome measures (PROM) and hip muscle strength, and previous hip/groin pain and PROMs. Additionally we studied normal values for the PROMs (Hip and Groin Outcome Score (HAGOS)). DESIGN: Cross-sectional study. SETTING: Testing at field hockey clubs. PARTICIPANTS: 100 male field hockey players (elite, sub-elite and amateur). MAIN OUTCOME MEASURES: Point prevalence and incidence of hip/groin pain, strength: eccentric adduction and abduction, adductor squeeze, HAGOS. RESULTS: Hip/groin pain point prevalence was 17% (time-loss: 6%) and incidence was 36% (time-loss: 12%). Presence of current or previous hip/groin and lower HAGOS-values were not associated with lower hip muscle strength. Previous hip/groin pain was associated with a significant lower HAGOS-values in all domains, except for the 'participation in physical activities' domain. CONCLUSIONS: Hip/groin pain is common in field hockey. One fifth of players have hip/groin pain and one third had pain in the previous season. Previous hip/groin pain was associated with worse ongoing patient reported outcomes in most domains.

CT arthrography of the human knee to measure cartilage quality with low radiation dose.

OBJECTIVE: Recently, CT arthrography (CTa) was introduced as a non-destructive technique to quantitatively measure cartilage quality in human knees. This study investigated whether this is also possible using lower radiation dose CT protocols. Furthermore, we studied the ability of (lower radiation) CTa to distinguish between local sulphated glycosaminoglycan (sGAG) content differences. DESIGN: Of ten human cadaveric knee joints, six CT scans using different radiation doses (81.33-8.13 mGy) were acquired after intra-articular ioxaglate injection. The capability of CTa to measure overall cartilage quality was determined in seven anatomical regions of interest (ROIs), using equilibrium partitioning of an ionic contrast agent using (EPIC)-microCT (µCT) as reference standard for sGAG content. To test the capability of CTa to spatially distinguish between local differences in sGAG content, we calculated the percentage of pixels incorrectly predicted as having high or low sGAG content by the different CTa protocols. RESULTS: Low radiation dose CTa correlated well with EPIC-µCT in large ROIs (R = 0.78; R(2) = 0.61; P < 0.0001). CTa can also distinguish between high and low sGAG content within a single slice. However, the percentage of incorrectly predicted quality pixels increases (from 35% to 41%) when less radiation is used. This makes is hard or even impossible to differentiate between spatial differences in sGAG content in the lowest radiation scans. CONCLUSIONS: CTa acquired using low radiation exposure, comparable to a regular knee CT, is able to measure overall cartilage quality. Spatial sGAG distribution can also be determined using CTa, however for this purpose a higher radiation dose is necessary. Nevertheless, radiation dose reduction makes CTa suitable for quantitative analysis of cartilage in clinical research.

Clinically applied CT arthrography to measure the sulphated glycosaminoglycan content of cartilage.

OBJECTIVE: Similar to delayed gadolinium enhanced MRI of cartilage, it might be possible to image cartilage quality using CT arthrography (CTa). This study assessed the potential of CTa as a clinically applicable tool to evaluate cartilage quality in terms of sulphated glycosaminoglycan content (sGAG) and structural composition of the extra-cellular matrix (ECM). METHODS: Eleven human cadaveric knee joints were scanned on a clinical CT scanner. Of each knee joint, a regular non-contrast CT (ncCT) and an ioxaglate injected CTa scan were performed. Mean X-ray attenuation of both scans was compared to identify contrast influx in seven anatomical regions of interest (ROIs). All ROIs were rescanned with contrast-enhanced µCT, which served as the reference standard for sGAG content. Mean X-ray attenuation from both ncCT and CTa were correlated with µCT results and analyzed with linear regression. Additionally, residual values from the linear fit between ncCT and µCT were used as a covariate measure to identify the influence of structural composition of cartilage ECM on contrast diffusion into cartilage in CTa scans. RESULTS: CTa resulted in higher X-ray attenuation in cartilage compared to ncCT scans for all anatomical regions. Furthermore, CTa correlated excellent with reference µCT values (sGAG) (R=0.86; R(2)=0.73; P<0.0001). When corrected for structural composition of cartilage ECM, this correlation improved substantially (R=0.95; R(2)=0.90; P<0.0001). CONCLUSIONS: Contrast diffusion into articular cartilage detected with CTa correlates with sGAG content and to a lesser extent with structural composition of cartilage ECM. CTa may be clinically applicable to quantitatively measure the quality of articular cartilage.

In vivo imaging of cartilage degeneration using microCT-arthrography.

OBJECTIVE: In vivo imaging of cartilage degeneration in small animal models is nowadays practically impossible. In the present study, we investigated the use of micro-computed tomography (microCT) in combination with a negatively charged ionic iodine dimer (ioxaglate) for in vivo assessment of cartilage degeneration in a small animal model. METHODS: Cartilage degeneration was induced in the right knee of rats by injection of mono-iodoacetate (MIA). We imaged the rat knees with ioxaglate enhanced microCT-arthrography at 4, 16 and 44 days after MIA injection. Subsequently, microCT-arthrographic findings were evaluated and compared with quantitative histology of the patellar cartilage. RESULTS: In vivo microCT-arthrography clearly detected cartilage degeneration in the rat knee-joints, in which the ioxaglate diffused into the degenerated cartilage layer. Higher microCT-attenuation values and smaller total volumes of the cartilage layer were detected at longer time periods after MIA injection, which is quantitatively confirmed by histology. CONCLUSION: In vivo microCT-arthrography is a valuable tool for detection of minor cartilage alterations and distinguishes different stages of cartilage degeneration in a small animal model. Since microCT, at the same time, also visualizes osteophyte formation and changes in the underlying subchondral bone structures, the technique will be very useful for longitudinal overall assessment of the development of (osteo)arthritis and to study interventions in small animal models.

Imaging of experimental osteoarthritis in small animal models.

Normally, tissue alterations in small animal models for osteoarthritis (OA) are assessed by time-consuming and destructive histology or biochemical assays. Some high resolution imaging modalities are used for longitudinal monitoring of the OA disease process in vivo. microCT is one of these imaging modalities, which is known for superb high-resolution imaging of bone architecture alterations. A major drawback of microCT is that it has low soft-tissue contrast, which makes direct imaging of cartilage impossible. The use of microCT in combination with negatively charged radiopaque contrast agents enables imaging of cartilage degeneration. We demonstrate the possibility of microCT to image cartilage degeneration as a consequence of experimental OA, by the use contrast enhanced microCT in vivo in a rat model for OA. Furthermore, for the assessment of alterations in molecular processes involved in OA we used the recently developed technique of multi pinhole SPECT. This enables us to assess molecular processes involved in experimental OA in a rat at sub-millimeter level. Here we show quantification of subchondral bone turnover in an OA rat knee. These new techniques demonstrate the possibilities of quantitative experimental OA assessment in small animal models such as mice and rats and might enable substitution of the conventional destructive methods.

Bilateral vanishing hips, coincidence or systemic disease? A case report and overview of current literature.

Rapidly progressive hip disease (RDHD) is a rare condition of the hip joint, causing destruction of the femoral head. The pathogenesis is unknown. The disease is self-limiting, there is no treatment to stop the disease. Hip arthroplasty is a successful way to relieve pain and restore function. We present a case where both hips were involved and analysed. A favourable result was obtained by bilateral total hip arthroplasty.

[Knee joint distraction: a solution for young patients with osteoarthritis of the knee?] / Kniedistractie: een oplossing voor jonge patiënten met knieartrose?

The current treatment for patients with end-stage generalised osteoarthritis of the knee is total knee replacement. In a recent paper in Plos One the authors examined an alternative approach, namely knee joint distraction. On the basis of a model, they claim that this treatment can postpone total knee replacement for about 20 years. This would reduce the costs for the healthcare services and improve quality of life for these patients. Although these claims seem promising, the model is only based on extrapolations of short-term results of small cohort studies. Furthermore, concerns about potential complications, e.g. osteomyelitis following pin-tract infections, are not mentioned. Further high quality studies in knee joint distraction are needed to prove its long-term efficacy and safety before this procedure can be implemented in standard clinical care.

Pathophysiology of peri-articular bone changes in osteoarthritis.

Osteoarthritis (OA) is a disease that involves the entire joint, but its pathophysiology is not well described. Alterations in peri-articular bone are an integral part of the OA disease process and different aspects of bone changes have been described in different patient (sub)groups and animal models. In this review we will discuss the osteoarthritis pathophysiology from the perspective of periarticular bone changes, which can be considered at three hierarchical levels: the bone (or joint) shape, the subchondral bone architecture and its cellular and molecular phenotype. In this review we try to provide an overview of the current knowledge of peri-articular bone changes in OA and what it could possibly imply for the initiation of OA and its progression. This article is part of a Special Issue entitled "Osteoarthritis".

Unfocused extracorporeal shock waves induce anabolic effects in rat bone.

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 control tibiae. Histological analysis showed intramedullary soft-tissue damage and de novo bone with active osteoblasts and osteoid in the bone marrow of the legs treated with extracorporeal shock waves. Microcrack analysis showed no differences between the treated and control legs. CONCLUSIONS: This study shows that a single treatment with extracorporeal shock waves induces anabolic effects in both cancellous and cortical bone, leading to improved biomechanical properties. Furthermore, treatment with extracorporeal shock waves results in transient damage to the bone marrow, which might be related to the anabolic effects. After further examination and optimization, unfocused extracorporeal shock waves might enable local treatment of skeletal sites susceptible to fracture.