Improved biomechanics in experimental chronic rotator cuff repair after shockwaves is not reflected by bone microarchitecture

Purpose The aim of this study was to investigate the effect of extracorporeal shockwave therapy (ESWT) on bone microstructure as well as the bone-tendon-interface and the musculo-tendinous transition zone to explain the previously shown improved biomechanics in a degenerative rotator cuff tear animal model. This study hypothesized that biomechanical improvements related to ESWT are a result of improved bone microstructure and muscle tendon properties. Methods In this controlled laboratory study unilateral supraspinatus (SSP) tendon detachment was performed in 48 male Sprague-Dawley rats. After a degeneration period of three weeks, SSP tendon was reconstructed transosseously. Rats were randomly assigned into three groups (n = 16 per group): control (noSW); intraoperative shockwave treatment (IntraSW); intra- and postoperative shockwave treatment (IntraPostSW). Eight weeks after SSP repair, all rats were sacrificed and underwent bone microstructure analysis as well as histological and immunohistochemical analyses. Results With exception of cortical porosity at the tendon area, bone microstructure analyses revealed no significant differences between the three study groups regarding cortical and trabecular bone parameters. Cortical Porosity at the Tendon Area was lowest in the IntraPostSW (p≤0.05) group. Histological analyses showed well-regenerated muscle and tendon structures in all groups. Immunohistochemistry detected augmented angiogenesis at the musculo-tendinous transition zone in both shockwave groups indicated by CD31 positive stained blood vessels. Conclusion In conclusion, bone microarchitecture changes are not responsible for previously described improved biomechanical results after shockwave treatment in rotator cuff repair in rodents. Immunohistochemical analysis showed neovascularization at the musculo-tendinous transition zone within ESWT-treated animals. Further studies focusing on neovascularization at the musculo-tendinous transition zone are necessary to explain the enhanced biomechanical and functional properties observed previously. Clinical relevance In patients treated with a double-row SSP tendon repair, an improvement in healing through ESWT, especially in this area, could prevent a failure of the medial row, which is considered a constantly observed tear pattern.

First osteohistological and histotaphonomic approach of Equus occidentalis Leidy, 1865 (Mammalia, Equidae) from the late Pleistocene of Rancho La Brea (California, USA)

Rancho La Brea (California, USA) is the most emblematic Quaternary fossiliferous locality in the world, since both the high number and diversity of the specimens recovered and their excellent preservational quality. In the last decades, paleobiological and paleoecological knowledge of the different groups of mammals from this site has increased notably; however, some aspects have not yet been inquired or there is little information. In this work we provide information on one of the most abundant mammals of this site, the equid Equus occidentalis, based on the study, from osteohistological and histotaphonomic perspectives, of thin sections of different limb bones. On the one hand, from an osteohistological viewpoint, we observe that the distribution and characterization of bone tissues in the different skeletal elements are, in general lines, similar to that mentioned for other extant and extinct equids. Cyclical growth marks allowed us to propose preliminary skeletochronological interpretations. On the other hand, from a taphonomic viewpoint, we note that all the samples reflect an excellent preservation of the bone microstructure, slightly altered by different pre- and post-burial processes. The variations recorded evidence different taphonomic history and preservation conditions among pits. This is the first study including fossil material from Rancho La Brea exclusively based on the analysis of the bone microstructure features.

Evaluation of the effect of vitamin D3 on mandibular condyles in an ovariectomized mouse model: a micro-CT study

Background This study aimed to investigate the effect of ovariectomy and vitamin D3 on bone microstructure; this effect was examined in three regions of interest at one femoral and two mandibular sampling sites bone in an ovariectomized mouse model. Methods Thirty-six week-old female mice were randomly divided into three groups: 10 subjects were given oral cholecalciferol (vitamin D3) daily for 6 weeks after undergoing bilateral ovariectomy (D3 group), while 10 ovariectomized subjects (OVX) and 10 subjects who underwent a sham operation (SHAM) received peanut oil daily during the investigation. After extermination, the left hemimandible and femur were removed and scanned by micro-CT. The bone micromorphology parameters were analyzed and the BMD was calculated. Results The bone volume fraction (BV/TV) was significantly lower in the trabecular bone of the mandibular condyle in the OVX group than in the SHAM and D3 groups. Also there was a significant difference between the SHAM and D3 groups. The specific bone surface (BS/BV) was significantly higher in the OVX and D3 groups than in the SHAM group. Trabecular thickness (Tb.Th) was significantly higher in the SHAM group, and the trabecular bone pattern factor (Tb.Pf) was significantly higher in the OVX group than in the other two groups. Bone mineral density (BMD) of the femur and the mandible was significantly lower in the OVX group than in the SHAM and D3 groups. Conclusions Our results show that ovariectomy causes a significantly weaker bone microstructure in the mandibular condyle, where the protective effect of vitamin D3 resulted in a partial resorption.

Bone Microstructure Changes due to Once-/Twice-Weekly Teriparatide Administration: A Report of Five Cases Using High-Resolution Peripheral Quantitative Computed Tomography

This study was conducted with the aim of presenting cases in which high-resolution peripheral quantitative computed tomography (HR-pQCT) was used to investigate changes in bone microstructure due to once-weekly/twice-weekly administration of teriparatide (TPTD). Of osteoporosis patients who participated in a non-inferiority trial (TWICE study: once-weekly vs twice-weekly TPTD) with lumbar bone mineral density (BMD) as the primary endpoint, five cases scanned by HR-pQCT before TPTD administration were analyzed. Two cases were given once-weekly TPTD, three were given twice-weekly TPD, and HR-pQCT was repeated after 48 weeks. A sufficient anabolic effect of once-weekly/twice-weekly TPTD on the trabecular and cortical bone at the tibia was obtained. In addition, the average change in cortical porosity (Ct.Po) was only 0.3% in the tibia and 0.2% in the radius. These findings indicate that once-weekly and twice-weekly TPTD can be expected to improve bone microstructure, and the increase in Ct.Po may be suppressed.

Chondroitin Sulfate Alleviates Diabetic Osteoporosis and Repairs Bone Microstructure via Anti-Oxidation, Anti-Inflammation, and Regulating Bone Metabolism

Diabetic osteoporosis (DOP) belongs to secondary osteoporosis caused by diabetes; it has the characteristics of high morbidity and high disability. In the present study, we constructed a type 1 diabetic rat model and administered chondroitin sulfate (200 mg/kg) for 10 weeks to observe the preventive effect of chondroitin sulfate on the bone loss of diabetic rats. The results showed that chondroitin sulfate can reduce blood glucose and relieve symptoms of diabetic rats; in addition, it can significantly increase the bone mineral density, improve bone microstructure, and reduce bone marrow adipocyte number in diabetic rats; after 10 weeks of chondroitin sulfate administration, the SOD activity level was upregulated, as well as CAT levels, indicating that chondroitin sulfate can alleviate oxidative stress in diabetic rats. Chondroitin sulfate was also found to reduce the level of serum inflammatory cytokines (TNF-α, IL-1, IL-6, and MCP-1) and alleviate the inflammation in diabetic rats; bone metabolism marker detection results showed that chondroitin sulfate can reduce bone turnover in diabetic rats (decreased RANKL, CTX-1, ALP, and TRACP 5b levels were observed after 10 weeks of chondroitin sulfate administration). At the same time, the bone OPG and RUNX 2 expression levels were higher after chondroitin sulfate treatment, the bone RANKL expression was lowered, and the OPG/RANKL ratio was upregulated. All of the above indicated that chondroitin sulfate could prevent STZ-induced DOP and repair bone microstructure; the main mechanism was through anti-oxidation, anti-inflammatory, and regulating bone metabolism. Chondroitin sulfate could be used to develop anti-DOP functional foods and diet interventions for diabetes.

Study and Prediction of Bone Strength of Osteoporosis Model Based on Synchrotron Radiation

Background: As the gold standard for clinical osteoporosis diagnosis, bone mineral density has significant limitations in bone strength assessment and fracture risk prediction. The purpose of this study is to explore a new osteoporotic bone quality evaluation criteria from both diagnosis site selection and bone strength prediction. Methods: Ovariectomized rats with different intensity swimming therapy were investigated in this study. The lumbar vertebrae and femurs of all the rats were scanned by synchrotron radiation computed tomography. Bone microstructure analysis and finite element analysis were combined to obtain bone microstructure parameters and estimated bone strength. And the sensitivity of different skeletal sites to therapy was explored. An elastic network regression model was established to predict bone strength by integrating additional bone microstructure characteristics besides bone mass.Results: Histomorphometry analysis showed that swimming therapy could reduce the risk of osteoporosis of lumbar vertebrae and femur and suggested that the femur might be a more suitable site for osteoporosis diagnosis and efficacy evaluation than the lumbar vertebrae. The average coefficient of determination and average root mean squared error of our predictive model were 0.774 and 0.110. Bland-Altman analysis showed that our model could be a good alternative to the finite element method. Conclusions: The present study developed a machine learning model for prediction of bone strength of osteoporosis model based on synchrotron x-ray imaging and demonstrated that different skeletal sites had different sensitivity to therapy, which is of great significance for the early diagnosis of osteoporosis, the prevention of fractures and the monitoring of therapy.

The Negative Impacts of Acromegaly on Bone Microstructure Not Fully Reversible

PurposeThis study aimed to evaluate the bone turnover markers and bone microarchitecture parameters derived from high-resolution peripheral quantitative computed tomography (HR-pQCT) in active and controlled acromegaly patients.MethodsThis cross-sectional study involved 55 acromegaly patients from a tertiary hospital (23 males and 32 females, aged 45.0 ± 11.6 years). Firstly, growth hormone (GH), insulin-like growth factor-1 (IGF-1), and markers for bone turnover were assessed. Next, we derived peripheral bone microstructure parameters and volumetric bone mineral density (vBMD) through HR-pQCT. These parameters were compared between acromegaly patients and 110 healthy controls, as well as between 27 active and 28 controlled acromegaly patients. Moreover, the relationship between GH/IGF-1 and bone microstructure parameters was analyzed through multiple linear regression.ResultsAs compared with healthy controls, acromegaly patients exhibited elevated cortical vBMD, reduced trabecular vBMD, and increased trabecular inhomogeneity in the distal radius and tibia. While controlled acromegaly patients had slower bone turnover, they did not necessarily have better bone microstructure relative to active patients in intergroup comparison. Nevertheless, multiple regression indicated that higher IGF-1 was associated with lower tibial stiffness and failure load. Additionally, males with higher IGF-1 typically had larger trabecular separation, lower trabecular number, and larger cortical pores in the radius. Moreover, patients with elevated GH typically had more porous cortical bone in the radius and fewer trabeculae in the tibia. However, the compromised bone strength in active patients was partially compensated by increased bone thickness. Furthermore, no significant linkage was observed between elevated GH/IGF-1 and the most important HR-pQCT parameters such as trabecular volumetric bone density.ConclusionAcromegaly adversely affected bone quality, even in controlled patients. As the deterioration in bone microstructure due to prolonged GH/IGF-1 exposure was not fully reversible, clinicians should be aware of the bone fragility of acromegaly patients even after they had achieved biochemical remission.

Validation and Optimization of Proximal Femurs Microstructure Analysis Using High Field and Ultra-High Field MRI

Trabecular bone could be assessed non-invasively using MRI. However, MRI does not yet provide resolutions lower than trabecular thickness and a comparative analysis between different MRI sequences at different field strengths and X-ray microtomography (μCT) is still missing. In this study, we compared bone microstructure parameters and bone mineral density (BMD) computed using various MRI approaches, i.e., turbo spin echo (TSE) and gradient recalled echo (GRE) images used at different magnetic fields, i.e., 7T and 3T. The corresponding parameters computed from μCT images and BMD derived from dual-energy X-ray absorptiometry (DXA) were used as the ground truth. The correlation between morphological parameters, BMD and fracture load assessed by mechanical compression tests was evaluated. Histomorphometric parameters showed a good agreement between 7T TSE and μCT, with 8% error for trabecular thickness with no significative statistical difference and a good intraclass correlation coefficient (ICC > 0.5) for all the extrapolated parameters. No correlation was found between DXA-BMD and all morphological parameters, except for trabecular interconnectivity (R2 > 0.69). Good correlation (p-value < 0.05) was found between failure load and trabecular interconnectivity (R2 > 0.79). These results suggest that MRI could be of interest for bone microstructure assessment. Moreover, the combination of morphological parameters and BMD could provide a more comprehensive view of bone quality.