Corticosteroid induced avascular necrosis and COVID-19: The drug dilemma

The severe and life-threatening nature of the COVID-19 infection, the ARDS (acute respiratory distress syndrome) as well as the cytokine storm induced by the infection, commands lifesaving high doses of steroid therapy. As in all pharmacological therapies adverse effects are present. One such adverse effect which is being reported is corticosteroid induced avascular necrosis of the femoral head/ osteonecrosis of the femoral head. It must be noted that AVN principally affects the femoral head and most commonly the anterolateral aspect thereof as it is the crux of weight bearing. Corticosteroids induce fat mobilization and this thus innately enhances the likelihood of fat emboli developing from the liver to occlude minor blood vessels in the femur, this thereby compromises the microvascular environment. Superadded to this the steroid therapy disrupts calcium metabolism and homeostasis which induces hypertrophy in the intramedullary fat cells, Gaucher cells and inflammatory cells; whilst increasing the activity of osteoclasts, thus increasing bone resorption and decreasing calcium uptake and deposition; ultimately leading to an insufficiency in the trabecular and cortical bone. This insufficiency thus equates to an increased intraosseous pressure which impedes intramedullary circulation and results in avascular necrosis. It is evident that avascular necrosis is directly caused by high dose steroid therapy, however the case reports have very clearly indicated that the rapid onset of AVN post recovery from the COVID-19 infection cannot be solely attributed to steroid therapy and that another benefactor induced by the COVID-19 infection is at play. It is thus vital for treating physicians to take cognisance of this adverse effect post recovery and therefore should ensure that prophylactic bisphosphonate therapy is initiated timeously and congruently.

Mesenchymal stromal cells for osteonecrosis

Osteonecrosis (ON) is an acquired debilitating skeletal disorder, which is caused by a multitude of traumatic and non-traumatic etiological factors. Vascular damage, mechanical stress and increased intraosseous pressure have been discussed as contributors to ON. The optimal treatment of ON remains to be determined, since the current gold standard, core decompression, is insufficiently effective. Specific properties of mesenchymal stromal cells (MSCs) provide the rationale for their assessment in advanced stages of ON: Osteoinductive potential has been demonstrated and MSC preparations of suitable quality for use as medicinal products have been developed. Here we review the scant information on the use of allogeneic or autologous MSCs in advanced ON as well as potentially supportive data from pre-clinical studies with autologous bone marrow mononuclear cells (auto BM-MNCs), which have been studied quite extensively and the presumed therapeutic effect of which was attributed to the rare MSCs contained in these cell products. Outcomes in clinical trials with MSCs and auto-BM-MNCs remain preliminary and non-definitive, at best promising, with respect to their pharmacological effect. Clearly, though, the application of any of these cell therapies was technically feasible and safe in that it was associated with low complication rates. The heterogeneity of cell type and source, study protocols, cell manufacturing, cell properties, cell doses and surgical techniques might contribute to inconsistent results.

Sensitization of cutaneous primary afferents in bone cancer revealed by in vivo calcium imaging

Cancer-induced bone pain (CIBP) is a complex condition comprising components of inflammatory and neuropathic processes, but changes in the physiological response profiles of bone-innervating afferents remain poorly understood. We used a combination of retrograde labelling and in vivo calcium imaging of bone marrow-innervating DRG neurons to determine the contribution of these cells in the establishment and maintenance of CIBP. We found a majority of femoral bone afferent cell bodies in L3 DRG that also express the sodium channel subtype Nav1.8 - a marker of nociceptive neurons- and lack expression of parvalbumin - a marker for proprioceptive primary afferents. Surprisingly, the response properties of bone marrow afferents to both increased intraosseous pressure and acid were unchanged by the presence of cancer. On the other hand, we found increased excitability and polymodality of cutaneous afferents innervating the ipsilateral paw in cancer bearing animals, as well as a behavioral phenotype that suggests changes at the level of the DRG contribute to secondary hypersensitivity.

Degenerative knee osteoarthritis animal model and changes in intraosseous pressure during pathological processes

Background Degenerative knee osteoarthritis (KOA) is a common clinical disease which affecting patients' quality of life. However, there is currently no standard animal model for KOA research. The purpose of this study was to find a reasonable age range of animal model for the studying of KOA pathological process, and to investigate Intraosseous pressure (IOP) in the process during different degeneration stages of KOA. Methods Male Dunkin-Hartley guinea pigs were selected and divided into groups of 3, 6, 9, 12, 18 months old by age, 10 in each group. All knees underwent imaging examination including X-ray, Micro CT and MRI. Observed the imaging findings with the use of Kellgren-Lawrence (K-L) classification and knee osteoarthritis MRI scores. Measured the IOP of distal femur and proximal tibia in each group, and observed the differences of bilateral tibiofemoral articular cartilage in histological and immunohistochemistry, staining results were evaluated by using Mankin’s score. Using one-way ANOVA and T-test were used to compare the differences indicators between groups. Results With the increase of age, changes in X-ray, Micro-CT and MRI imaging findings and pathological staining results of articular cartilage in all stages were consistent with the changing of degenerative KOA process. The IOP of distal femur and proximal tibia increased gradually with age, and reached its peak in 12-month age group, and then gradually decreased, there was a statistically significant difference of IOP between each group (femur side: F=8.261, P=0.000; tibial side: F=8.469, P=0.000). The IOP of the distal femur was slightly higher than that of proximal tibia, but the difference was not statistically significant (P>0.05). Conclusions Dunkin-Hartley guinea pig can be used as an animal model to study different pathological stages of KOA. And there might be a correlation between the changes of IOP and the pathological progress of articular cartilage and subchondral bone in distal femur and proximal tibia.

Degenerative knee osteoarthritis animal model and changes in intraosseous pressure during pathological processes

Background Degenerative knee osteoarthritis (KOA) is a common clinical disease which affecting patients' quality of life. However, there is currently no standard animal model for KOA research. The purpose of this study was to find a reasonable age range of animal model for the studying of KOA pathological process, and to investigate Intraosseous pressure (IOP) in the process during different degeneration stages of KOA. Methods Male Dunkin-Hartley guinea pigs were selected and divided into groups of 3, 6, 9, 12, 18 months old by age, 10 in each group. All knees underwent imaging examination including X-ray, Micro CT and MRI. Observed the imaging findings with the use of Kellgren-Lawrence (K-L) classification and knee osteoarthritis MRI scores. Measured the IOP of distal femur and proximal tibia in each group, and observed the differences of bilateral tibiofemoral articular cartilage in histological and immunohistochemistry, staining results were evaluated by using Mankin’s score. Using one-way ANOVA and T-test were used to compare the differences indicators between groups. Results With the increase of age, changes in X-ray, Micro-CT and MRI imaging findings and pathological staining results of articular cartilage in all stages were consistent with the changing of degenerative KOA process. The IOP of distal femur and proximal tibia increased gradually with age, and reached its peak in 12-month age group, and then gradually decreased, there was a statistically significant difference of IOP between each group (femur side: F=8.261, P=0.000; tibial side: F=8.469, P=0.000). The IOP of the distal femur was slightly higher than that of proximal tibia, but the difference was not statistically significant (P>0.05). Conclusions Dunkin-Hartley guinea pig can be used as an animal model to study different pathological stages of KOA. And there might be a correlation between the changes of IOP and the pathological progress of articular cartilage and subchondral bone in distal femur and proximal tibia.

Effect of cementing on pulmonary arterial pressure in vertebroplasty: A comparison of two techniques

Background: Increase in intraosseous pressure and displacement of bone marrow contents leading to fat embolism and hypotension during cement injection in vertebroplasty (VP). We aimed to compare the effect of low and high viscosity cements during VP on pulmonary arterial pressure (PAP) with different cannula. Materials and Methods: Fifty-two patients having multilevel VP due to osteoporotic vertebral compression fractures were randomly treated either by a high viscosity cement (group A, n = 27 patients) and 2.8 mm cannula or a low viscosity cement (group B, n = 25 patients) injected through 4.2 mm cannula. PAP was measured by standard echocardiography and blood d-dimer values were recorded preoperatively, 24 h and third day after operation. Results: Mean age was 69 (62–87) years in group A and 70 (64–88) years in group B, and sex and comorbidities were similar. Average number of augmented levels was 5.4 in group A and 5.7 in group B. Preoperative mean PAP was 33 mm/Hg in group A, elevated to 41 mm/Hg on first day, and decreased to 36 mm/Hg on third day. The mean PAP in group B was 35 mm/Hg preoperatively, 51 mm/Hg on first day and 46 mm/Hg on third day ( p < 0.05). The average blood d-dimer values in group A increased from 2.1 µg/mL to 2.3 µg/mL and in group B from 2.2 µg/mL to 4.2 µg/mL. Conclusion: The finding of this study showed that high viscosity cement injected through a narrower cannula results in lesser PAP increase and d-dimer levels when compared to low viscosity cement injected through a wider cannula. Higher PAP and d-dimer level may show possible thromboembolism. This finding may give spine surgeons to reconsider their choice of cement type and cannula size.

The Effectiveness of Calcaneal Drilling for Treatment of Resistance Cases of Plantar Heel Pain

Background: Plantar heel pain is a clinical syndrome characterized by pain and tenderness beneath the heel which is typically worse in the morning and improves after the first few steps in the day. It is a common and frequently disabling clinical complaint that may be caused by a broad spectrum of osseous or soft tissue disorders. Objective: To evaluate the effectiveness of an operation of multiple drilling of calcaneum for resistant plantar heel pain syndrome. Methods: During the period from November 2012 to August 2016, 17 patients (17heels) were enrolled in a cohort clinical study at the orthopedic unit in AL-Sheikh Zayed and Al-Wassity Hospitals. Result: Drilling of the calcaneum is a simple procedure achieving 70.6% cure in resistant ases with few complications provided good patient selection was done. Conclusion: Abnormalities in the intraosseous pressure within the calcaneum are a possible cause of plantar heel pain in some patients who failed to respond to conservative treatment