Bone Osteonecrosis Research Articles

Three cases of uncommon medication‐associated osteonecrosis of temporal bone

AbstractIntroductionMedication‐related osteonecrosis of the temporal bone is rare and has been reported to be associated with the use of anti‐resorptive and biologic agents. Here, we present the first case of tyrosine‐kinase inhibitor‐related external auditory canal (EAC) osteonecrosis as well as two cases related to anti‐resorptive therapies.MethodsA retrospective case series.ResultsCase one: an 84‐year‐old female presented with chronic otitis externa and osteonecrosis of EACs bilaterally. She had a history of osteoporosis treated with denosumab and risedronic acid. She successfully underwent left EAC reconstruction using an inferiorly‐based pedicle periosteal flap while the right ear canal was managed conservatively. Case two: a 69‐year‐old male presented with osteonecrosis of the right EAC. He had a history of osteoporosis treated with alendronic acid and zoledronic acid. His osteonecrosis is conservatively managed with local debridement and antibiotic application. Case three: a 60‐year‐old male presented with osteonecrosis of the right inferior EAC. He had a history of chronic myelogenous leukemia treated with a tyrosine‐kinase inhibitor, imatinib. After failing conservative therapy, he underwent right ear canal reconstruction using a periosteal vascular pedicle flap without complication and experienced complete resolution to his symptoms.ConclusionAnti‐resorptive agents and/or tyrosine kinase inhibitors may lead to dysregulation of bone remodeling and result in rare cases of temporal bone osteonecrosis. When a local debridement and antibiotic therapy fail, definitive surgical excision of necrotic bone with subsequent reconstruction of the EAC may offer patients a possible resolution in symptoms.

Heat Generation during Minimally Invasive First Metatarsal Osteotomy: A Cadaveric Study

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Bunions are one of the most common pathologies treated by orthopedic foot and ankle surgeons. The usage of minimally invasive and percutaneous surgical techniques continues to rise due to evidence of less pain, improved functional outcomes and low recurrence rates. Still, concern regarding heat generation during these procedures, osteonecrosis of bone, and nonunion persists. Literature suggests cool irrigation is superior to room temperature irrigation, but the question remains if irrigation is needed at all. This study evaluates the heat generation during percutaneous bunion surgery and analyzes the use of cooled irrigation compared to no irrigation at all. This study tested the hypothesis that cool irrigation would lead to overall lower heat generation compared to no irrigation at all. Methods: 5 matched paired cadavers (10 legs) were used to simulate MIS first metatarsal distal transverse osteotomy for all trials. Prior to osteotomy, 4 temperature probes were inserted as to the border where the Shannon burr would travel along the osteotomy site (Image 1). Probes were secured by suture and temperature was recorded using K-type thermocouples. All trials were completed using a pulse technique of 20 seconds on, 5 seconds off with a Shannon Burr and fluoroscopic guidance. Trials were complete with continuous cold irrigation (N=5) and without any irrigation at all (N=4). Temperatures were evaluated at baseline, during burring, and after burring to assess total heat generation and dissipation. A two-tailed t-test was used to analyze differences in heat generation and dissipation between procedures completed with irrigation and without irrigation (P < 0.05). Results: 5 cadavers with a mean age of 86.2 were evaluated (10 total simulations, 9 analyzed). Cadavers underwent 1 trial with irrigation, and 1 without on opposite feet. 88.9% of patients showed heat generation below the level of bone necrosis (50 oC). One trial with irrigation temperature rose to 79.1oC. Matching specimen without irrigation had probe failure and no temperature was obtained. Average burr time was 51.2±2.4 seconds with irrigation, and 35±0.5 seconds without. Irrigation was associated with a significant increase in burr time (P=0.002). Average temperature change was 13.62±11.9 and 0.7±0.5 during burring, 7.1±1.8 and 5.8±0.3 after burring in procedures with and without irrigation, respectively. No significant difference was detected between heat generation in irrigated vs non-irrigated procedures (P = 0.371, 0.548). Conclusion: This study found that in a cadaveric model the use of cooled irrigation, compared to no irrigation, did not lead to a significant difference in the heat generation during MIS first metatarsal distal transverse osteotomy. However, 1 out of the 9 samples used in this study showed a heat generation above 50 oC. Additionally, to our surprise the use of irrigation led to a significant increase in burring time. This may be useful information for a surgeon when considering the usage of cooled irrigation to reduce the potential risk of osteonecrosis when performing a MIS first metatarsal distal transverse osteotomy.

Wnt/β-Catenin Signaling in Craniomaxillofacial Osteocytes.

There is a growing appreciation within the scientific community that cells exhibit regional variation. Whether the variation is attributable to differences in embryonic origin or anatomical location and mechanical loading has not been elucidated; what is clear, however, is that adult cells carry positional information that ultimately affects their functions. The purpose of this review is to highlight the functions of osteocytes in the craniomaxillofacial (CMF) skeleton as opposed to elsewhere in the body, and in doing so gain mechanistic insights into genetic conditions and chemically-induced diseases that particularly affect this region of our anatomy. In the CMF skeleton, elevated Wnt/β-catenin signaling affects not only bone mass and volume, but also mineralization of the canalicular network and osteocyte lacunae. Aberrant elevation in the Wnt/β-catenin pathway can also produce micropetrosis and osteonecrosis of CMF bone, presumably due to a disruption in the signaling network that connects osteocytes to one another, and to osteoblasts on the bone surface.

Thermal Management of Bone Drilling Based on Rotating Heat Pipe

Bone drilling is a common surgical operation, which often causes an increase in bone temperature. A temperature above 47 °C for 60 s is the critical temperature that can be allowed in bone drilling because of thermal bone osteonecrosis. Therefore, thermal management in bone drilling by a rotating heat pipe was proposed in this study. A new rotating heat pipe drill was designed, and its heat transfer mechanism and thermal management performance was investigated at occasions with different input heat flux and rotational speed. Results show that boiling and convection heat transfer occurred in the evaporator and film condensation appears in the condenser. The thermal resistance decreases with the increase of the rotational speed at the range from 1200 to 2000 rpm and it decreases as the input heat flux rises from 5000 to 10,000 W/m2 and increases at 20,000 W/m2. The temperature on the drill tip was found to be 46.9 °C with an input heat flux of 8000 W/m2 and a rotational speed of 2000 rpm. The new designed rotating heat pipe drill showed a good prospect for application to bone drilling operations.

ALCOHOL ABUSE AS AN UNDERESTIMATED CAUSE OF NON-TRAUMATIC OSTEONECROSIS OF THE FEMORAL HEAD (DESCRIPTION OF CLINICAL CASES)

Osteonecrosis of the femoral head is a severe degenerative-dystrophic disease, which is characterized by the destruction of the bone substance in the head in the most vulnerable (loaded) parts. Due to a rapid progression in the absence of proper surgical treatment, osteonecrosis of the femoral head, as a rule, results in disability. There is a wide range of causes that cause the development of osteonecrosis. According to the authors, alcohol abuse should be attributed to the underestimated causal factors of this pathology. The article presents two clinical observations which convincingly demonstrate the role of alcohol abuse as a cause of osteonecrosis. In a 44-year-old man prolonged alcohol abuse led to a progressive (within a year) advance of osteonecrosis in the heads of both femurs, and in a 26-year-old woman, along with a short-term intake of glucocorticoids, it contributed to the formation of multifocal non-traumatic osteonecrosis with damage to the pelvic, right knee, shoulder joints. The authors explain underestimated role of alcohol abuse as a causal factor of osteonecrosis as follows. Firstly, patients, as a rule, try not to display their addiction, and therefore, unlike other predictors of developing femoral bone osteonecrosis (injuries, serious somatic diseases, taking glucocorticoids), this fact is not reflected in medical documentation. Secondly, patients with idiopathic forms of osteonecrosis often do not have an "assigned" doctor who could dynamically follow up the patient and, consequently, monitor more carefully his condition and risk factors for osteonecrosis. When consulting such a patient, a subspecialist, as a rule, sets himself the task first of all to exclude "his disease", which makes the patient vulnerable in terms of finding out the causes of osteonecrosis. These clinical cases demonstrate the need to take into account alcohol abuse as a significant causal factor in the development of osteonecrosis.

Bisphosphonates in Dentistry – State of the Art

Abstract Bisphosphonates remain the most used and most effective drugs for the treatment of systemic bone diseases followed by bone resorption. Although their side effects in a form of alveolar bone osteonecrosis have been reported, bisphosphonates have a potential of being used in the treatment of the most common oral diseases followed by alveolar bone resorption such as peri-implantitis, periapical lesions, and periodontitis. The aim of this article was to review the most recent research regarding the use of bisphosphonates in the field of dentistry. The results of studies indicate that bisphosphonate use in the treatment of peri-implantitis, periapical lesions, and periodontitis can reduce alveolar bone resorption and contribute to bone preservation. However, the most beneficial way of their application in the treatment of these oral diseases remain to be determined.

ROLE OF DASHMOOLADI MAJJA SNEHA (THERAPEUTIC ENEMA) IN AVASCULAR NECROSIS: A CASE STUDY

Introduction:Avascular necrosis is also known as aseptic, osteonecrosis and ischaemic necrosis of bone. There are a multitude of risk factors but over 80% of cases are attributed to glucocorticoid treatment or alcohol excess. Avascular Necrosis of femoral head is the most common type of necrosis, because the artery supplying to neck of femur is very narrow which easily gets injured. In modern medicine there is no specic treatment rather than surgery. In Ayurveda avascular necrosis can be correlated with Asthimajjagatvata. Aim: To assess the efcacy of Dashmooladi Majja Sneha in the management of avascular necrosis. The objective of the treatment includes the preservation of structure and function of hip joint with symptomatic relief. Materials & Methods:The present case study is upon a 32 year old, diagnosed case of avascular necrosis of femoral head with complaints of pain in bilateral sacroiliac joint since one and half years which was associated with difculty in doing normal daily activities such as walking, sitting, squatting along with change in the gait, at the Panchakarma OPD of Govt. Ayurvedic hospital Bhopal. The patient of idiopathic AVN of femoral head was treated with Dashmooladi Majja Sneha, Brihatvata Chintamani Rasa, Amritaristha, Panchtikta Ghrita Guggulu and Shastik Shali Pind Swedan have done as per the classical method for 30 days. Assessment was done after treatment and follow up after 15 days for 2months. Observations: The Ayurvedic therapies and oral medicines yielded complete symptomatic relief from pain, general debility and improvement in the gait. Conclusion: On the basis of the results obtained it can be concluded that Dashmooladi Majja Sneha, Shastik Shali Pind Swedan and some oral medicines can be used as an effective treatment in the management of Avascular Necrosis.

Radiological evaluation of avascular necrosis of bone with clinical correlation

Osteonecrosis of bone is a progressive disease affecting the areas with precarious blood supply like head of the femur, head of the humerus, Scaphoid, Talus, Navicular, Condyles of long bones etc. Causes are mostly unknown and few are related to Corticosteroids, Trauma, Alcoholism, and hematological disorders. In the present study, 45 symptomatic patients were evaluated for osteonecrosis using X Ray, CT Scan and MRI in a tertiary care hospital. The age of incidence, gender variability, laterality, involvement of the different bones were studied. The sensitivity of various imaging modalities according to the disease stages was also noted. In majority of the cases the cause was unknown and the head of the femur came out to be the most involved site. MRI was found to be the most sensitive imaging modality followed by CT and X ray. The common findings detected by X ray and CT were Sclerosis, Subchondral lucency, Altered morphology and associated degenerative changes. Bone marrow edema was the most common finding detected by MRI in very early stage. Joint effusion, Double line sign, subchondral collapse, degenerative changes of the joint were other significant findings. T1 hyposensitivity was the main finding in the osteonecrosis of Scaphoid, Navicular and Talus with no enhancement post contrast.

Oral and radiographic manifestations brought on by Sickle Cell Anemia - Clinical Case Report

Sickle cell anemia is a hereditary, monogenic blood disease characterized by chronic hemolytic anemia and vasoconstricting phenomena leading to acute painful crises and chronic and progressive tissue damage. It is the most common disease among hemoglobinopathies in Brazil and worldwide. The disease originated in Africa and was brought to the Americas by the forced immigration of slaves. Sickle cell patients have clinical conditions that can be intensified during dental treatment by precipitating vasoconstrictive seizures. In this clinical case, paleness was detected in the buccal buccal and the tongue despapilada. In the intra-oral radiographic examinations, areas suggestive of bone sclerosis and radiolucent areas between the root apices were found. Maxillary protrusion due to medullary expansion was found in lateral cephaladiography. In scintigraphy and magnetic resonance imaging, areas corresponding to bone infarcts and osteonecrosis were found. The dental surgeon performs an important function, being able to diagnose the oral manifestations through clinical and/or radiographic examination. By acting preventively, we can reduce the complications and improve the quality of lives of these patients.

Hip bone osteonecrosis with intraosseous pneumatosis after abdominal aortic aneurysm repair: a case of emphysematous osteomyelitis

Intraosseous pneumatosis is a rare and often fatal condition characterised by air accumulation in the bone that may be brought about by infection, trauma (surgical or otherwise), degenerative disease or neoplastic processes. Here, we present a case of pelvic emphysematous osteomyelitis following repair of an infected abdominal aortic aneurysm.A 56-year-old Saudi male, known to have diabetes and hypertension, presented to the emergency department complaining of intermittent abdominal pain over the right lower quadrant. The patient was later diagnosed intraoperatively with an infected abdominal aortic aneurysm and treated appropriately. During multiple follow-up imaging studies, the patient was noted to have multiple intra-abdominal fluid collections, as well as intraosseous pneumatosis in the pelvis and right femur. 3 months later, intervention was again required due to patient deterioration and possible aortic graft leakage. Graft abscess was diagnosed and managed.We present a case of an infected abdominal aortic aneurysm that eventually led to emphysematous osteomyelitis of the pelvis. This case report sheds light on intraosseous pneumatosis and emphysematous osteomyelitis, which is characterised by the former, in addition to signs of an underlying infection or abscess formation.

Deficiency of the SMOC2 matricellular protein impairs bone healing and produces age-dependent bone loss

Secreted extracellular matrix components which regulate craniofacial development could be reactivated and play roles in adult wound healing. We report a patient with a loss-of-function of the secreted matricellular protein SMOC2 (SPARC related modular calcium binding 2) presenting severe oligodontia, microdontia, tooth root deficiencies, alveolar bone hypoplasia, and a range of skeletal malformations. Turning to a mouse model, Smoc2-GFP reporter expression indicates SMOC2 dynamically marks a range of dental and bone progenitors. While germline Smoc2 homozygous mutants are viable, tooth number anomalies, reduced tooth size, altered enamel prism patterning, and spontaneous age-induced periodontal bone and root loss are observed in this mouse model. Whole-genome RNA-sequencing analysis of embryonic day (E) 14.5 cap stage molars revealed reductions in early expressed enamel matrix components (Odontogenic ameloblast-associated protein) and dentin dysplasia targets (Dentin matrix acidic phosphoprotein 1). We tested if like other matricellular proteins SMOC2 was required for regenerative repair. We found that the Smoc2-GFP reporter was reactivated in adjacent periodontal tissues 4 days after tooth avulsion injury. Following maxillary tooth injury, Smoc2−/− mutants had increased osteoclast activity and bone resorption surrounding the extracted molar. Interestingly, a 10-day treatment with the cyclooxygenase 2 (COX2) inhibitor ibuprofen (30 mg/kg body weight) blocked tooth injury-induced bone loss in Smoc2−/− mutants, reducing matrix metalloprotease (Mmp)9. Collectively, our results indicate that endogenous SMOC2 blocks injury-induced jaw bone osteonecrosis and offsets age-induced periodontal decay.

Expert consensus on prevention and treatment strategies for osteonecrosis of femoral head during the prevention and control of novel coronavirus pneumonia (2020)

Novel coronavirus pneumonia is a new type of respiratory infectious disease that has rapidly spread in many countries or regions around the world. The World Health Organization (WHO) named it "coronavirus disease 2019 (COVID-19)". Glucocorticoids (GC) have certain application value in patients with COVID-19, but they need to be used with caution and strict indications and dosage. Application of large doses of GC can also cause osteonecrosis of femoral head (ONFH). On the basis of the latest literature and evidence-based medical evidence on the fight against COVID-19 epidemic and steroid ONFH diagnosis and treatment, the Bone Circulation and Osteonecrosis Professional Committee, Shockwave Medical Specialty Committee of Chinese Research Hospital Association organized Chinese bone necrosis related experts to jointly write this consensus, focusing on the prevention strategy and the protective management measures in the ONFH diagnosis and treatment process during the prevention and control of COVID-19, which can provide reference for hospitals at all levels to carry out early prevention and treatment of ONFH.

Clinical profile of osteonecrosis in systemic lupus erythematosus - Experience from a tertiary care centre in South India.

Introduction:Osteonecrosis or Avascular necrosis of bone (AVN) is a well recognized complication of systemic lupus erythematosus (SLE) leading to significant morbidity.Methods:We did a cross sectional descriptive study in cohort of SLE patients, on regular follow-up at our Rheumatology OPD over a period of 5 years from 2012 to 2017.Results:Of the total 415 SLE, 5.1% (n = 21) patients were diagnosed to have osteonecrosis. The mean age was 32.8 ± 7.6 years. Male: female were 1:4.2. Mean time interval between the onset of SLE and diagnosis of osteonecrosis was 4.1 ± 2.7 years. Pain (100%) was the most common presenting symptom followed by limping gait (42.8%). Most common site affected by osteonecrosis was femoral head (80.9%) (n = 17). 14.3% (n = 3) had multifocal involvement. The most common systemic involvement was musculoskeletal system (80.9%). In total 28.5% had secondary antiphospholipid syndrome. Mean SLEDAI-2K at the time of diagnosis of osteonecrosis was 5.3 ± 2.9. Hypertension 19%, hypothyroidism 9.5%, osteoporosis 24%, and chronic HCV infection 4.7% were the associated comorbidities. The most common stage by imaging at diagnosis was stage IV (38%), followed by 24% stage V, 19% stage III and 9.5% stage II and 9.5% stage VI. Medical management include bisphosphonates (100%), statins (90.4%) and anticoagulant therapy (28.5%), while 9.5% received core decompression surgery and 14.3% underwent total hip replacement. The mean daily dose of prednisolone at diagnosis of osteonecrosis was 8.5mg (range 5–20mg).Conclusion:This study described the prevalence and epidemiology of osteonecrosis in our cohort of SLE patients.

Adult Tarsal Scaphoiditis: Management

Adult tarsal scaphoiditis or Mueller Weiss disease is a rare condition characterized by collapse of lateral half of the navicular bone. It is a spontaneous adult onset osteonecrosis of navicular bone with unclear etiology. Mueller Weiss disease is not sequelae to childhood onset Kohler's disease. Middle-aged women complain of midfoot and hindfoot pain. A detailed clinical and plain weight-bearing radiograph of foot is often diagnostic. The condition is graded using Maceira classification based on the deformity on lateral radiographs. Numerous surgical options are described for the management but no gold standard. We are presenting three patients, one with bilateral feet involvement, all in Maceira stage III deformity treated with double arthrodesis (talonavicular-cuneiform and calacaneocuboid) and autologous bone grafting achieving solid fusion and good functional outcome. How to cite this article: Simon R, Sukesh AN, Jose DP. Adult Tarsal Scaphoiditis: Management. J Foot Ankle Surg (Asia Pacific) 2020;7(1):21–23.

Experimental periodontitis in Msx2 mutant mice induces alveolar bone necrosis.

Msx2 homeoprotein is a key transcription factor of dental and periodontal tissue formation and is involved in many molecular pathways controlling mineralized tissue homeostasis such as Wnt/sclerostin pathway. This study evaluated the effect of Msx2-null mutation during experimental periodontitis in mice. Experimental periodontitis was induced for 30 days in wild-type and Msx2 knock-in Swiss mice using Porphyromonas gingivalis infected ligatures. In knock-in mice, Msx2 gene was replaced by n-LacZ gene encoding β-galactosidase. Periodontal tissue response was assessed by histomorphometry, tartrate-resistant acid phosphatase histoenzymology, β-galactosidase, sclerostin immunochemistry, and terminal deoxynucleotidyl transferase-mediated dUTP nickend labeling assay. Expression of Msx2 gene expression was also evaluated in human gingival biopsies using RT-qPCR. During experimental periodontitis, osteonecrosis area and osteoclast number were significantly elevated in knock-in mice compared with wild-type mice. Epithelial downgrowth and bone loss was similar. Sclerostin expression in osteocytes appeared to be reduced during periodontitis in knock-in mice. Msx2 expression was detected in healthy and inflamed human gingival tissues. These data indicated that Msx2 pathway influenced periodontal tissue response to experimental periodontitis and appeared to be a protective factor against alveolar bone osteonecrosis. As shown in other inflammatory processes such as atherothrombosis, genes initially characterized in early development could also play an important role in human periodontal pathogenesis.

III–3 Low-Intensity Pulsed Ultrasound (LIPUS) for the Treatment of Massive Osteonecrosis Following Carbon Ion Radiotherapy for Malignant Bone Tumor

Objective: Carbon ion radiotherapy (CIR) can be applied for unresectable malignant bone tumors, especially arising from the pelvis and spine. The most serious adverse effect of CIR is a massive osteonecrosis of healthy bone surrounding the tumor. We applied LIPUS therapy in 2 cases and report here their clinical courses. Materials and Methods: Two cases with the pelvic sarcoma were treated by CIR. Thirteen year-old-male had a metastasis of osteosarcoma at the acetabulum. Seventy three year-old-male had a chondrosarcoma in the pubis, acetabulum and iliac bone. Results: Malignant tumors were controlled by CIR only and at present, we find no evidence of disease. Both cases complained of severe hip pain after CIR due to osteonecrosis of the acetabulum. Their pains were well improved at 1 month after LIPUS therapy. Destruction of the hip joint was not observed at the final follow-up. Discussion: Until now, positive effect of LIPUS have been reported on osteonecrosis of knee, hip joint and jaw bone. However, there have been, to our knowledge, no report on applying LIPUS for these difficult conditions. LIPUS therapy seems beneficial for pain relief and bone regeneration for massive osteonecrosis after CIR.

Lunate bone osteonecrosis in hemodialysis patient with rheumatoid arthritis: case report

Kienbock's disease is the osteonecrosis of lunate bone. Patients usually present with unilateral localized dorsal wrist swelling and pain that increase with movement. Direct radiographic and other imaging methods are used for diagnosis. Cautious evaluation of the radiological findings is substantial, because the management of the disease depends on radiological stage. Here, we present a 46-year-old woman with rheumatoid arthritis who admitted to the outpatient clinic of our hospital, because of pain, swelling and limitation of movement in the left wrist. We want to draw attention Kienbock's disease in patient with rheumatoid arthritis.

The biomechanical changes of load distribution with longitudinal tears of meniscal horns on knee joint: a finite element analysis

BackgroundMeniscal horns are important structures of meniscus, and longitudinal tears of these places could significantly change the load distribution among the knee joint. Few studies concerned the stress concentrated on bones, which may induce the osteonecrosis of subchondral bone. The goal of this study was to construct a finite element (FE) model with high fidelity of the knee joint and evaluate the biomechanical changes of load distribution of components after longitudinal tears of the horns of meniscus.MethodsComputed tomography and magnetic resonance images were used to develop the FE model, and two different kinds of simulations, the vertical and the anterior load, mimicking the static stance and slight flexion simulations, were applied after longitudinal tears of the horns of meniscus.ResultsSignificantly elevated peak compressive and shear stress was observed on the menisci, cartilages, and subchondral bones, and enlarged meniscus extrusion was noticed. Between all the four types of longitudinal tears investigated in this study, longitudinal tears at the posterior horn of the medial meniscus were found to be the most significant.ConclusionsThese findings showed that longitudinal tears of the meniscal horns lead to increased magnitude and changed distribution of stress and indicated the important role of posterior horn of medial meniscus. This may contribute to the mechanism between meniscal tears and spontaneous subchondral bone osteonecrosis.

Characterization of Solitary Lesions in the Extremities on Whole-Body Bone Scan in Patients With Known Cancer: Contribution of Single-Photon Emission Computed Tomography/Computed Tomography.

Background: Solitary lesions in the extremities showing 99mTc-methylene diphosphate (MDP) uptake are often encountered on whole-body bone scan (WBS), and proper interpretation of this diagnostic method is important for patients with known cancer. The purpose of this study was to summarize the characteristics of solitary lesions in the extremities of patients with known cancer and to evaluate the diagnostic accuracy of single-photon emission computed tomography/computed tomography (SPECT/CT) in differentiating bone metastases from benign bone lesions.Methods: This study was a retrospective review of 86 patients (54 males and 32 females; mean age, 57.88 ± 10.97 years; range, 31–81 years) with known cancer who underwent WBS and showed solitary lesions with 99mTc-MDP uptake in the extremities and then underwent SPECT/CT for further diagnosis. SPECT/CT images were independently interpreted by two experienced nuclear medicine physicians. The diagnostic accuracy of SPECT/CT in differentiating malignant from benign solitary lesions in the extremities was evaluated. Inter-reviewer agreement was assessed by using weighted k statistics. The standard diagnostic criterion was based on biopsy or radiologic follow-up over at least 12 months.Results: In total, 23 bone metastases and 63 (73.26%) benign lesions were diagnosed. The majority (16/23, 69.57%) of bone metastases were found in the diaphyses. The most common benign bone disease was a benign bone tumor (31.75%, 20/63). The majority (13/20, 65%) of benign bone tumors were enchondromas. In the proximal and distal extremities, the most common disease was degeneration (27.11%, 16/59), followed by benign bone tumors and osteonecrosis of the femoral head (ONFH) (22.03%, 13/59). In the diaphyses of the extremities, bone metastasis was the most common disease, accounting for 64% (16/25) of the findings. For the SPECT/CT analysis, the accuracy was 94.19% (81/86) for reviewer 1 and 95.34% (82/86) for reviewer 2. The weighted kappa score for inter-reviewer agreement was 0.813.Conclusion: When solitary disease of the extremities is detected by WBS in patients with known cancer, benign lesions may be more common than malignant lesions. SPECT/CT resulted in not only fewer equivocal lesions but also in higher diagnostic accuracy.

Highlights of This Issue

Raja and colleagues explored changes in levels of ctDNA in advanced/metastatic NSCLC and UC patients receiving the anti-PD-L1 monoclonal antibody durvalumab. Reduction in ctDNA levels at 6 weeks was associated with RECIST responses, PFS and OS, and often preceded RECIST response. Thus, early changes in ctDNA may predict long-term benefit from immunotherapy and enable treatment decisions, particularly in indications in which assessing radiographic responses may be difficult.Mesothelioma is an aggressive cancer with limited treatment options and often with resistance to immunotherapy. To overcome resistance to previous treatments, Tallón de Lara and colleagues showed that the synergy of gemcitabine and immune checkpoint inhibitors (ICI) outperformed single treatment in a preclinical mouse model of mesothelioma. Two patients with mesothelioma, who did not respond to the single treatments, responded to the combination when given. Interestingly, dexamethasone, widely used in the clinics to treat side effects, dampened the response in the preclinical model. This study gives a new rationale to combine ICI and gemcitabine in mesothelioma patientsPatients with leukemia can develop bone defects (osteonecrosis) in hip bones, which can lead to joint collapse. A new treatment involves drilling a track in the affected bone (decompression surgery), aspirating marrow cells from the pelvis and implanting them into the bone defect. To visualize the cells, the authors treated patients with an iron supplement 1 to 2 days before the surgery. The cells in the bone marrow took up the iron. When iron-loaded cells were then harvested from the bone marrow and transplanted in the bone defect, they could be detect with MR imaging. This new stem cell imaging approach may help to better understand and optimize stem cell therapies.TRC105 is a neutralizing antibody targeting the TGF-β coreceptor endoglin and is currently being tested in clinical trials as antiangiogenic therapy. TRC105 prevents binding of BMP-9 to endoglin, which controls (tumor) angiogenesis. Paauwe and colleagues show that endoglin also is expressed on cancer-associated fibroblasts (CAFs) and reveal a role for this receptor in CAF invasion. TRC105 treatment reduced invasive capacity of CAFs in vitro and metastatic spread of CRC in vivo. This underlines the potential of TRC105 to be more than a “classic anti-angiogenic drug,” targeting both endothelium and CAF, thereby limiting metastatic spread on multiple levels.