Radiographical bony lesions after discontinuation of immunosuppressant therapy: bone involvement in sarcoidosis.

We describe a patient who had failed renal transplant after 13 years, eventually requiring a graft nephrectomy and discontinuation of immunosuppressive therapy, including antithymocyte globulin, tacrolimus and mycophenolate while on steroid avoidance protocol. Within a few months of complete discontinuation of the immunosuppressive medications, she developed lower back pain associated with numbness in her right anterolateral thigh. The radiological imaging demonstrated multiple bony lesions throughout her axial and appendicular skeleton with normal pulmonary findings. A computerised tomography-guided bone biopsy from the left iliac crest revealed fragments of bone with granulomatous inflammation, thus making the diagnosis of extrapulmonary sarcoidosis. Initiating treatment with prednisone resulted in near-complete resolution of symptoms. Long-term immunosuppressive therapy is administered to all renal transplant recipients to help prevent acute rejection and loss of renal allograft. This case highlights that immunosuppressants can conceal the presence of underlying conditions in transplant patients.

The effect of immunomodulatory drugs on bone metabolism of patients with multiple myeloma.

INTRODUCTION: Immunomodulatory drugs (IMiDs) are widely used in the management of newly diagnosed and relapsed/refractory multiple myeloma patients. These agents show their potential effect on myeloma bone disease (MBD), including inhibition of osteoclasts activity and effects on osteoblasts differentiation. It is unclear whether these effects are direct, which may have an impact on bone formation markers when combined with proteasome inhibitors. AREAS COVERED: This review summarizes the available evidence on the role of IMiDs in microenvironment regulation and their potential effects on bone metabolism. The literature search methodology consisted of searching PubMed for basic and clinical trials using medical subject terms. Included articles were screened and evaluated by the coauthors of this review. EXPERT OPINION: As a therapeutic option, IMiDs directly affect preosteoblast/osteoclast differentiation. The combination of proteasome inhibitors may counteract the short-term up-regulation of osteogenic activity markers, and therefore intravenous zoledronic acid is recommended, however, obtaining a more significant myeloma response will have a long-term positive impact on myeloma bone disease.

Advances in the pathogenesis of multiple myeloma bone disease. / å¤šå‘æ€§éª¨é«“ç˜¤éª¨ç— å‘ç— æœºåˆ¶çš„ç ”ç©¶è¿›å±•.

Multiple myeloma (MM) is a clonal proliferative malignant tumor of plasma cells in bone marrow. With the aging of population in China, the incidence of MM is on the rise. Multiple myeloma bone disease (MBD) is one of the common clinical manifestations of MM, and 80%-90% of MM patients are accompanied by osteolytic lesions at the time of their first visit to the clinic. MBD not only increases the disability rate of patients, but also severely reduces the physical function of patients due to skeletal lesions and bone-related events. Currently available drugs for treating of MBD are ineffective and associated with side effects. Therefore, it is important to find new therapeutic approaches for the treatment of MBD. It is generally believed that the increased osteoclast activity and suppressed osteoblast function are the main pathologic mechanisms for MBD. However, more and more studies have suggested that soluble molecules in the bone marrow microenvironment, including cytokines, extracellular bodies, and metabolites, play an important role in the development of MBD. Therefore, exploring the occurrence and potential molecular mechanisms for MBD from multiple perspectives, and identifying the predictive biomarkers and potential therapeutic targets are of significance for the clinical treatment of MBD.

Pediatric focal calvarial lesions: an illustrated review.

Focal skull lesions in children can be diagnostically challenging with a wide variety of potential etiologies. Understanding the diverse pathologies and recognizing their associated clinical and imaging characteristics is crucial for accurate diagnosis and appropriate treatment planning. We review pertinent anatomy of the scalp and calvarium and review different pathologies that can present with focal skull lesions in pediatric patients. These include neoplastic, non-neoplastic tumor-like, congenital, post traumatic, and vascular-associated etiologies. We review the key clinical and imaging features associated with these pathologies and present teaching points to help make the correct diagnosis. It is important for radiologists to be aware of the common and rare etiologies of skull lesions as well as the clinical and imaging characteristics which can be used to develop an accurate differential to ensure a timely diagnosis and initiate appropriate management.

Opiate use after total hip arthroplasty for metastatic bone disease.

OBJECTIVES: To investigate post-operative opioid use following a total hip arthroplasty (THA) in metastatic bone disease (MBD) patients and identify factors associated with post-operative opioid use at 6 weeks and 90 days. BACKGROUND: MBD commonly affects the hip, and surgical intervention including THA may be indicated for pain relief or to improve function. Following THA, patients are often prescribed short courses of opioids for post-operative pain relief. No study has evaluated opiate use following THA in patients for MBD. METHODS: This was a retrospective review of patients using opioids preoperatively who underwent primary THA for MBD at two institutions between 2009 and 2022. Preoperative and post-operative opioid usages, respectively, at 6 weeks and 90 days were quantified through calculating daily morphine milligram equivalents (MMEs) and compared using the sign test. Factors associated with post-operative opioid use at 6 weeks and 90 days were compared using χ2 test or Fisher's exact test as appropriate. RESULTS: Nineteen THA and 11 THA with complex acetabular reconstruction were included. At 6 weeks, 26 (86.7 percent) patients were utilizing opiates, and at 90 days, 23 (76.7 percent) patients were utilizing opiates. There was a statistically significant difference between median daily preoperative MME compared to daily MME at 90 days (p < 0.001). The only statistically significant association with opioid use at 90 days was opioid use at 6 weeks. CONCLUSION: To our knowledge, this is the first paper evaluating post-operative opioid use following primary THA in MBD patients. After THA in the setting of MBD, patients exhibit decreased post-operative opioid use. Future studies with larger cohorts should be conducted to characterize post-operative opioid use following joint arthroplasty in MBD patients.

[Constitutional diseases of bone: clinical flags]. / Quand penser à une maladie osseuse constitutionnelle ?

Constitutional diseases of bone form a heterogeneous group of rare diseases of varied phenotypic presentations with a vast genetic heterogeneity. Detected mostly in childhood, they may also be diagnosed in adulthood. Medical history, clinical examination as well as biological and radiological investigations may lead to the diagnosis, which should be confirmed genetically. Joint limitations, early osteoarthritis, hip dysplasia, bone deformity, enthesopathies, bone fragility or a small height can be warning signs of a constitutional disease of bone. Establishing the diagnosis is crucial to enable optimal medical management with a specialized multidisciplinary team.

Les maladies osseuses constitutionnelles constituent un groupe hétérogène de maladies rares de présentations phénotypiques variées et d'une grande hétérogénéité génétique. Le plus souvent détectées dans l'enfance, elles peuvent également être diagnostiquées à l'âge adulte. L'anamnèse, l'examen clinique et les bilans biologiques et radiologiques permettent d'orienter le diagnostic, qui devra être confirmé par une analyse génétique. Les limitations articulaires, l'arthrose précoce, les dysplasies de hanches, les déformations osseuses, les enthésopathies ou la fragilité osseuse ainsi qu'une petite taille sont des signes d'alerte pour rechercher une maladie osseuse constitutionnelle. Établir le diagnostic est crucial pour permettre une prise en charge optimale, multidisciplinaire et spécialisée.

Effect of aluminum accumulation on bone and cardiovascular risk in the current era.

BACKGROUND: The prevalence of aluminum (Al) intoxication has declined over the past 3 decades. However, different groups still report on the diagnosis of Al in bone. Prolonged and low-intensity exposures to Al may not be captured by serum Al measurements, preventing its proper diagnosis. We hypothesize that bone Al accumulation may be related to bone and cardiovascular events in the current Era. AIMS: To detect the diagnosis of bone Al accumulation; to explore bone and cardiovascular consequences of Al accumulation. METHODS: This is a sub-analysis of The Brazilian Registry of Bone Biopsy, a prospective, multicentre cohort, with a mean follow-up of 3.4 years, including patients with CKD undergoing bone biopsy; bone fracture and major cardiovascular events (MACE) were adjudicated; Al accumulation was identified by solochrome-azurine staining; history of previous Al accumulation was registered based on information provided by the nephrologist who performed the bone biopsy; bone histomorphometry parameters, clinical data, and general biochemistry were registered. RESULTS: 275 individuals were considered; 96 (35%) patients have diagnosed with bone Al accumulation and were younger [50 (41-56) vs. 55 (43-61) years; p = 0.026], had lower body mass index [23.5 (21.6-25.5) vs. 24.3 (22.1-27.8) kg/m2; p = 0.017], higher dialysis vintage [108 (48-183) vs. 71 (28-132) months; p = 0.002], presented pruritus [23 (24%) vs. 20 (11%); p = 0.005], tendon rupture [7 (7%) vs. 3 (2%); p = 0.03) and bone pain [2 (0-3) vs. 0 (0-3) units; p = 0.02]. Logistic regression reveals that prior bone Al accumulation [OR: 4.517 (CI: 1.176-17.353); p = 0.03] and dialysis vintage [OR: 1.003 (CI: 1.000-1.007); p = 0.046] as independent determinants of bone Al accumulation; minor perturbations in dynamic bone parameters and no differences in bone fractures rate were noted; MACE was more prevalent in patients with bone Al accumulation [21 (34%) vs. 23 (18%) events; p = 0.016]. Cox regression shows the actual/prior diagnosis of bone Al accumulation and diabetes mellitus as independent predictors for MACE: [HR = 3.129 (CI: 1.439-6.804; p = 0.004) and HR = 2.785 (CI: 1.120-6.928; p = 0.028]. CONCLUSIONS: An elevated proportion of patients have bone Al accumulation, associated with a greater prevalence of bone pain, tendon rupture, and pruritus; bone Al accumulation was associated with minor perturbations in renal osteodystrophy; actual/prior diagnosis of bone Al accumulation and diabetes mellitus were independent predictors for MACE.

Occlusive wound closure prevents prolonged wound discharge-A randomised controlled trial in patients undergoing tumour resection and endoprosthetic reconstruction of the proximal femur because of metastatic bone disease.

Prolonged wound discharge is a common postoperative complication of orthopaedic procedures and a risk factor for implant-related infection. Occlusive wound closure methods have previously been suggested to reduce or even prevent this complication. We performed a randomised controlled trial on 70 patients who underwent surgical treatment for metastatic bone disease involving the proximal femur at our centre between January 2017 and August 2018. At conclusion of the tumour resection and endoprosthetic reconstruction procedure, patients were randomised to either occlusive wound closure (n = 35), using the Dermabond Prineo-22 skin closure system, or routine wound closure with conventional skin staples (n = 35). Skin closure with occlusive wound closure resulted in a lesser degree (P < .0001) and shorter duration of postoperative wound discharge (HR 2.89 [95% CI 1.6-5.05], P < .0018). Compared with staples, surgical wounds were already dry after a mean of 3.5 days [95% CI 3.2-3.9] versus 6.1 days [95% CI 4.8-7.3] (P < .0001). Prolonged wound discharge for 7 days or more was observed in 23% of patients (n = 8) in the Staples-group but was entirely absent in the occlusive wound closure group (P < .003). This study provides strong evidence that occlusive wound closure reduces frequency, degree, and duration of wound discharge in a patient population at particularly high risk for this complication.

Patellar development after patella instability and early reduction in growing rabbits.

BACKGROUND: Patella-shaped disorder has been considered as a predisposing factor for patella instability. But the influence of early patella reduction for patellar development remains unclear. This study aimed to evaluate whether early operation in patella instability could improve patella morphology in growing rabbits. METHODS: Fifty rabbits (1-month-old) were included in the study. The control group underwent no surgical procedures. The two experimental groups (reduction group and non-reduced group), underwent medial soft tissue restraint release surgery. The reduction group, rabbits underwent the medial soft tissue sutura surgery in order to stabilize the patella 2 months after release surgery. The non-reduced group, rabbits did not undergo suture surgery. Computed Tomography (CT) scans analysis in two experimental endpoints (2, 5 months after release surgery) were selected to evaluate the transverse diameter, thickness, Wiberg index and Wiberg angle. Gross observation was conducted to assess morphological changes of the patella. RESULTS: CT scans showed significant difference in the mean transverse diameter, Wiberg angle between the two experimental groups and the control group 2 months after release surgery. 5 months after release surgery, the indices of patella were found no statistically difference in the reduction group versus the control group. However, the transverse diameter, Wiberg angle in the non-reduced group were significantly differences than that in the reduction group (P < 0.05). Gross observation showed a flattened articular surface of the patella in the non-reduced group. CONCLUSIONS: The results indicated that patella instability may lead to patella-shaped disorder, showing a flattened morphology. Early patella reduction can improve the patella morphology in growing rabbits.

The use of bone-modifying agents in multiple myeloma.

Multiple myeloma is a hematological neoplasm characterized by abnormal proliferation of plasma cells in the bone marrow and is usually associated with increased bone pain and skeletal-related events such as pathological fracture and/or spinal cord compression. Myeloma bone disease results in changes in the bone-marrow microenvironment evidenced by increased osteoclastic activity and/or decreased osteoblastic activity, which negatively affect quality of life. Treatment of myeloma bone disease includes bisphosphonates or denosumab (bone-modifying agents). These agents do not induce the formation of new bone or repair existing bone damage, but they can decrease bone pain and the risk of pathological fracture. While these agents improve quality of life, it is not known whether they improve overall survival. This review focuses on different classes of bone-modifying agents, their mechanisms of action, time of initiation, duration of therapy, and potential survival benefits.

Concomitant coracoid base fracture and acromioclavicular joint disruption: A series of patients treated with a clavicle hook plate and review of the literature.

INTRODUCTION: Concomitant acromioclavicular joint (ACJ) disruptions with coracoid base fractures are rare high energy injuries. The management of these injuries can be challenging. The aim of this study is to assess the functional and radiographic outcomes of a retrospective case series of patients presenting with concomitant ACJ and coracoid base injuries managed with a clavicle hook plate with subsequent hardware removal at a later stage. METHODS: Six patients were identified for inclusion in the study. Radiographic and clinical data were available which allowed for collection of demographic information as well as classification of the fractures. Telephone consultation with patients allowed for collection of functional scores which included the Oxford shoulder score (OSS), QuickDASH (Q-DASH), Euroqol-5 Dimension (EQ-5D) and the SF-12 score. RESULTS: All patients were male with a mean age of 39.8 years and a median follow-up period of 34 months. All patients underwent a successful operative procedure with a median time to union of 3.75 months. Good functional outcomes were reported by all patients: mean OSS 45.0, mean Q-DASH 4.8, mean EQ-VAS 82.8 and encouraging SF-12 scores (mean PCS 56.0, mean MCS 56.4). CONCLUSION: The use of a lateral clavicle hook plate can achieve good healing and functional outcomes when managing patients with acromioclavicular joint disruptions associated with a coracoid base fracture.

[Receptor Activator of Nuclear Factor κB Ligand-Receptor Activator of Nuclear Factor κB Signaling Pathway in Myeloma Bone Disease].

Multiple myeloma is an incurable malignant disease characterized by proliferation of clonal plasma cells in the bone marrow.About 90% of the patients with multiple myeloma develop myeloma bone disease(MBD),which seriously affects the quality of life and prognosis of the patients.Traditional therapies for MBD include bisphosphonates,radiotherapy,and surgery.The recent studies have confirmed that the receptor activator of nuclear factor κB ligand (RANKL)-receptor activator of nuclear factor κB(RANK) signaling pathway plays a key role in MBD,providing a new therapeutic target for MBD.This review summarized the role of RANKL-RANK signaling pathway in the pathogenesis of MBD and the advance in the targeted therapy.

Adynamic bone disease: Revisited.

The bone and mineral disorders form an integral part of the management of a chronic kidney disease (CKD) patient. Amongst various types of bone pathologies in chronic kidney disease-mineral bone disorder (CKD-MBD), the prevalence of adynamic bone disease (ABD) is increasing. The present review discusses the updated pathophysiology, risk factors, and management of this disorder.

The spectrum of manifestations of primary hyperparathyroidism in children and adolescents.

INTRODUCTION: Primary hyperparathyroidism (PHPT) is a rare disease in children and adolescents. Early recognition of this disease is important to prevent significant morbidity and mortality. MATERIAL AND METHODS: We included 10 consecutive patients with PHPT aged 14 to 19 years of age and followed-up prospectively upto one year after parathyroidectomy. RESULTS: Our cohort included 6 females and 4 males. The mean age of the patients was 16.7 ±1.8 years. The symptoms at presentation were musculoskeletal pain (90%), bone deformity (50%), fracture (30%), proximal myopathy (40%), renal stones (50%), reflux symptoms (40%), and pancreatitis (30%). The mean serum calcium was 3.1 ±0.5 mmol/l, mean serum inorganic phosphorus was 0.9 ±0.3 mmol/l and median serum alkaline phosphatase (ALP) was 1911.5 IU/l (IQR: 522.7-5702.3). The median serum intact parathyroid hormone was 133.5 pmol/l (IQR: 69.5 -178.7) while serum 25(OH)D was 47.7 nmol/l (IQR: 23.7-72.7). Hypercalciuria was observed in 7 patients. Hungry bone syndrome was observed in 4 (40%) patients after surgery. Typical parathyroid adenoma was found in 9 (90%) patients while one patient had atypical adenoma with high mitotic index. After one year of surgery, all patients had significant improvement in clinical and biochemical parameters with persistence of residual bone deformities. CONCLUSIONS: Our study showed the spectrum of manifestations of PHPT in children and adolescents and outcomes of parathyroidectomy till one year. Long-term follow-up studies with bigger cohorts are required to understand the true nature of the disease in children and adolescents.

Radiological outcome of bone disease in multiple myeloma patients pre- and post therapy: A single center experience.

OBJECTIVES: To find any correlation between the clinical response as per International Working Myeloma Group (IWMG) response criteria and the radiological response at the end of treatment. METHODS: A retrospective cohort study was conducted, total of 39 patients whom diagnosed with multiple myeloma (MM) between January 2010 and December 2018 and fulfilled the study criteria were included. RESULTS: The high sensitivity and specificity of positron emission tomography/computed tomography (PET/CT) in detecting osteolytic myeloma lesions in the bones was strongly emphasized in our study. Follow up PET/CT, we found that while 17 patients showed complete remission in PET/CT, and 14 of these of patients demonstrated a complete clinical response at end of therapy assessment. CONCLUSION: Although we did not find a statistically significant correlation between the response versus metabolic activity and the number of bone/bone marrow lesions, however, our study was limited by the absence of clear criteria for defining disease response in PET/CT in MM patients. Further prospective analysis would be needed to establish a defined criterion.

Bone lesions of Langerhans cell histiocytosis triggered by trauma in children.

BACKGROUND: Bone lesions of Langerhans cell histiocytosis (LCH) may be triggered by trauma. METHODS: The characteristics of pediatric patients in the JLSG-02 study cohort who developed a bone lesion at the trauma site at diagnosis of LCH were analyzed retrospectively. RESULTS: Of the 261 pediatric patients with LCH, 12 (4.6%), of median age 4.9 years, had trauma-triggered bone LCH lesions at diagnosis, making them significantly older than the remaining patients (P = 0.006). Trauma sites included the craniofacial regions in 10 patients and the lumbar spine and pelvis in one patient each. At the time of trauma, six patients had a bump at the site, whereas none had extradural hematomas or bone fractures. The median time from trauma to onset was 4 weeks. Of these 12 patients, three had isolated bone (IB) disease; four had multifocal bone (MFB) disease, including the bone lesion at the trauma site; and five had multisystem disease, including four with lesions in neighboring tissue and one with polyuria (posterior pituitary lesion) more than 1 year before the trauma-triggered bone lesion. Treatment responses were good in all 12 patients and none died, but relapses were observed in two patients, one each with IB and MFB disease. CONCLUSIONS: About 5% of pediatric patients with LCH developed new trauma-triggered bone lesions at a relatively old age. These lesions can manifest as IB, or, in patients with underlying LCH diseases, as MFB or multisystem. Good clinical outcomes were observed in these patients.