Multicentric carpotarsal osteolysis syndrome with variants of MAFB gene: a case report and literature review.

BACKGROUND: Multicentric carpotarsal osteolysis (MCTO) is a rare genetic disorder characterized by the progressive loss of bone in the hands, feet, and other skeletal structures. It presents with symptoms that may resemble those of juvenile idiopathic arthritis, making diagnosis challenging for clinicians. The identification of MAF BZIP Transcription Factor B (MAFB) mutations as significant contributors to MCTO represents a major breakthrough in our understanding of the pathogenesis of this rare skeletal disorder. CASE PRESENTATION: Our objective was to present the phenotype, treatment, and outcome of a patient with a variant of MAFB-induced MCTO to broaden the range of clinical features associated with MCTO and share our clinical experience for improved diagnosis and treatment. In our case, early MRI examination of the bones and whole exome sequencing enabled an early and accurate MCTO diagnosis, and timely Denosumab administration resulted in no deterioration. CONCLUSION: This suggests that MRI examination and whole exome sequencing should be considered when MCTO is suspected, and Denosumab might be an option in the treatment of MCTO.

Heterotopic ossification, osteolysis and implant failure following cervical total disc replacement with the M6-C™ artificial disc.

INTRODUCTION: A recent study reported a 34% mid-term revision rate after M6-C™ cervical total disc replacement (CTDR) for wear-related osteolysis. Here, we aim to investigate the prevalence, risk factors, and radiographic characteristics of periprosthetic bony changes and implant failure of the M6-C™ artificial disc. METHODS: We retrospectively analysed radiographic (conventional X-ray, CT scan) and clinical outcomes (EQ-5D-5L, Neck Disability Index (NDI), and Visual Analog Scale (VAS) for neck and arm pain) data collected during routine follow-up of patients who underwent CTDR with the M6-C™ between 2011 and 2015. RESULTS: In total, 85 patients underwent CTDR with the M6-C™. Follow-up data were available for 43 patients (54% female, mean age 44 years) with 50 implants and a mean follow-up of 8.1 years (6.5-11 years). Implant failure with the presence of severe osteolysis was identified in 5 (12%) patients who were all male (p = 0.016) and implanted at the C5/6 level (p = 0.11). All failed implants required revision surgery. The overall prevalence of osteolysis was 44% (22/50 implants) and 34% (17/50 implants) for significant heterotopic ossification. Patients with high-grade osteolysis showed higher VAS arm pain (p = 0.05) and lower EQ-5D-VAS health VAS (p = 0.03). CONCLUSION: We report a lower reoperation rate for failed M6-C™ implants than previously published, but confirmed that osteolysis and heterotopic ossification are common following CTDR with the M6-C™ and may be asymptomatic. Therefore, we strongly recommend ongoing clinical and radiographic monitoring after CTDR with the M6-C™, particularly for male patients implanted at the C5/6 level.

Comparison of osteolysis around 3 different cement restrictors in total hip arthroplasty.

BACKGROUND AND AIM: Several studies reported osteolysis around polyethylene glycol/polybutylene terephthalate (PEG/PBT) based femoral cement restrictors. Our goal was to evaluate and compare osteolysis around 3 different plug designs: the slow biodegradable PEG/PBT cement restrictor; the fast biodegradable gelatin cement restrictor; and the non-biodegradable polyethylene plug. PATIENTS AND METHODS: In a retrospective multicentre cohort study chart data were extracted of patients who received a total hip arthroplasty between 2008 and 2012. A total of 961 hips were included. Cortical ratio between inner and outer cortices at the centre of the plug was measured on routine postoperative follow-up moments. Median follow up of all 3 hospitals was 3.5 years (1.4-7.3). The primary outcome was evidence of osteolysis (i.e. the difference in cortical ratio [CR]) on anteroposterior (AP) radiographs at final follow-up. RESULTS: Progressive osteolysis was found around the PEG/PBT cement restrictor represented by a significantly increasing cortical ratio (ΔCR 0.067 (95% CI, 0.063-0.071). Distance from tip prosthesis to plug and size of the plug were found to be independent factors in predicting increased cortical ratio. CONCLUSIONS: Our multicentre cohort shows increase of cortical ratio around the PEG/PBT cement restrictor which progresses over time. Physicians should be aware of this fact and are advised to intensify follow-up of patients who received this cement restrictor.

From breast cancer cell homing to the onset of early bone metastasis: The role of bone (re)modeling in early lesion formation.

Breast cancer often metastasizes to bone, causing osteolytic lesions. Structural and biophysical changes are rarely studied yet are hypothesized to influence metastasis. We developed a mouse model of early bone metastasis and multimodal imaging to quantify cancer cell homing, bone (re)modeling, and onset of metastasis. Using tissue clearing and three-dimensional (3D) light sheet fluorescence microscopy, we located enhanced green fluorescent protein-positive cancer cells and small clusters in intact bones and quantified their size and spatial distribution. We detected early bone lesions using in vivo microcomputed tomography (microCT)-based time-lapse morphometry and revealed altered bone (re)modeling in the absence of detectable lesions. With a new microCT image analysis tool, we tracked the growth of early lesions over time. We showed that cancer cells home in all bone compartments, while osteolytic lesions are only detected in the metaphysis, a region of high (re)modeling. Our study suggests that higher rates of (re)modeling act as a driver of lesion formation during early metastasis.

Medication-related osteonecrosis of the lower jaw without osteolysis on computed tomography images.

INTRODUCTION: Surgery is the standard treatment for medication-related osteonecrosis of the jaw (MRONJ). This study reviewed patients with mandibular MRONJ who underwent surgical treatment, and in particular the characteristics of non-osteolytic MRONJ with no evidence of osteolysis on CT were described. MATERIALS AND METHODS: We conducted a retrospective study of patients with mandibular MRONJ who underwent surgery between January 2016 and September 2022. Various clinical and imaging factors regarding treatment outcomes were investigated and analyzed. Additionally, the disease course of non-osteolytic MRONJ was examined in detail. RESULTS: This study included 55 patients (66 surgeries) with a mean age of 74.7. The primary disease was osteoporosis (24 patients) and malignancy (31 patients); the type of antiresorptive agent was bisphosphonate (BP) in 21 patients and denosumab (DMB) in 26. BP was initially administered; however, it was changed to DMB in eight patients. Preoperatively, the cumulative cure rates for all 66 surgeries were 72.8% at 1 year and 77.3% at 2 years. Cure rates were significantly lower in patients with malignancy, those without osteolysis, and those who underwent sequestrum removal or marginal mandibulectomy than those with osteoporosis, osteolysis, and segmental mandibulectomy. Non-osteolytic MRONJ was observed in eight patients, all with malignancy and receiving high-dose DMB. Only two patients were cured after the initial surgery, and most patients ultimately underwent segmental mandibulectomy. CONCLUSIONS: Surgical treatment yielded good treatment outcomes in most patients with mandibular MRONJ; however, the cure rate was lower in patients with malignancy who showed no osteolysis on CT images.

Corrosion of a Fassier-Duval Telescopic Nail Causing Pain and Osteolysis: A Case Report.

CASE: A 15-year-old girl known with osteogenesis imperfecta presented with left femoral pain. She had been treated with multiple Fassier-Duval intramedullary nails, which were still in situ. Radiographic imaging demonstrated focal osteolysis and periosteal reaction at the telescopic junction of the rod in the distal femur. She underwent implant removal. Intraoperative sampling demonstrating acute sterile inflammation and presence of brownish colored particles consistent with metal debris and osteolysis. Explant analysis confirmed corrosion of the stainless-steel telescopic nail as the underlying cause. CONCLUSION: Osteolysis and periosteal reaction because of corrosion should be considered in conjunction with other more common causes of pain, such as fracture or infection, in patients treated with telescopic intramedullary nails.

Osteolysis After Augmented Scapholunate Ligament Reconstruction: A Report of 3 Cases.

CASE: Augmented scapholunate ligament reconstruction using polyether ether ketone anchors and ultra-high molecular weight polyethylene synthetic tape has the theoretical advantage of improved stability, avoidance of K-wire fixation, and the potential for earlier mobilization. We present 3 cases of scaphoid and lunate osteolysis/fragmentation, operative and histologic findings at reoperation, and the sequelae of this technique. CONCLUSION: If planning to use suture anchors and synthetic tapes in small carpal bones, we recommend advising patients about the risk of osteolysis and monitoring closely patients who complain of pain with motion after surgery.

A Unique Case of Familial Expansile Osteolysis: Findings on 99mTc-MDP Bone Scan.

ABSTRACT: Familial expansile osteolysis is an exceedingly rare autosomal dominant bone dysplasia, which can have overlapping features with Paget disease and expansile skeletal hyperphosphatasia. We present a novel case of familial expansile osteolysis evaluated on 99mTc-MDP bone scan with correlative radiographs and CT.

The ceramic coated implant (CCI). Evolution total ankle replacements: a retrospective analysis of 40 ankles with 8 years follow-up.

Diminutive data is available on the outcome of several previously used total ankle replacement implants. The purpose of this study was to investigate the medium-term functional and radiological outcome and implant survival of the CCI Evolution implant. Consecutive series of 40 ankles operated in our hospital with primary TAR using the CCI Evolution implant in 2010-2013 were available for follow-up. The prospective clinical and radiographic data including the Kofoed score, subjective satisfaction and standard radiographs were collected preoperatively and at fixed time-points postoperatively. A CT was obtained in cases where osteolysis or loosening were suspected. The improvement of the Kofoed score and subjective satisfaction were statistically significant (p<0.0001). The implant survival was 97% (95% confidence interval (CI) 81%-100 %) at 5 years, and 81 % (95% confidence interval (CI) 60 %-92%) at 8 years. There were altogether 25 (64%) complications. Overall revision rate was 28% and failure rate 13%. The CCI implant outcome was not acceptable. The malposition of prosthetic components, subsidence, and peri-implant osteolysis were recorded often. Although the patient reported outcome measures improved, mostly due to positive changes in pain severity, overall revision and failure rates were high and comparable with previous findings of the CCI implant.

Clinical, radiographic and molecular characterization of two unrelated families with multicentric osteolysis, nodulosis, and arthropathy.

BACKGROUND: Multicentric osteolysis nodulosis and arthropathy (MONA) is a rare autosomal recessive disorder characterized by marked progressive bone loss and joint destruction resulting in skeletal deformities. MONA is caused by MMP2 deficiency. Here we report clinical and molecular analyses of four patients in two families from Pakistan and Finland. METHODS: Clinical analyses including radiography were completed and blood samples were collected. The extracted DNA was subjected to whole-exome analysis or target gene sequencing. Segregation analyses were performed in the nuclear pedigree. Pathogenicity prediction scores for the selected variants and conservation analyses of affected amino acids were observed. RESULTS: The phenotype in the four affected individuals was consistent with multicentric osteolysis or MONA, as the patients had multiple affected joints, osteolysis of hands and feet, immobility of knee joint and progressive bone loss. Long-term follow up of the patients revealed the progression of the disease. We found a novel MMP2 c.1336 + 2T > G homozygous splice donor variant segregating with the phenotype in the Pakistani family while a MMP2 missense variant c.1188 C > A, p.(Ser396Arg) was homozygous in both Finnish patients. In-silico analysis predicted that the splicing variant may eventually introduce a premature stop codon in MMP2. Molecular modeling for the p.(Ser396Arg) variant suggested that the change may disturb MMP2 collagen-binding region. CONCLUSION: Our findings expand the genetic spectrum of Multicentric osteolysis nodulosis and arthropathy. We also suggest that the age of onset of this disorder may vary from childhood up to late adolescence and that a significant degree of intrafamilial variability may be present.

Medication-related osteonecrosis of the jaw without osteolysis on computed tomography: a retrospective and observational study.

Medication-related osteonecrosis of the jaw (MRONJ) is a refractory osteonecrosis caused by antiresorptive agents such as bisphosphonate and denosumab (DMB). In MRONJ surgery, computed tomography (CT) is generally used to determine the extent of bone resection. However, in some recent MRONJ cases, no abnormal findings were detected on CT. Therefore, we aimed to clarify the characteristics of MRONJ without osteolysis. This retrospective and observational study included 18 patients diagnosed with MRONJ between October 2020 and October 2022 at Department of Dentistry and Oral Surgery, Kansai Medical University Medical Center. In four of 18 patients with MRONJ, no abnormal findings such as osteolysis, separation of sequestrum, and periosteal reaction were observed on CT images at the first visit. All four patients with non-osteolytic MRONJ had malignant tumors and received high-dose DMB, and in the four patients there were no preceding dental infections such as apical lesions or periodontal disease and the trigger of MRONJ was unknown. Surgery was performed in three of the four patients. The extent of bone resection was determined using magnetic resonance imaging and intraoperative gross findings. In the future, it is necessary to establish a method for diagnosing non osteolytic MRONJ and determining the extent of bone resection.

A report of 5 Indian families with multicentric carpotarsal osteolysis syndrome.

Multicentric carpotarsal osteolysis syndrome (MCTO) is a rare autosomal dominant skeletal dysplasia characterised by swelling and restriction of movement in the wrist and ankle joints, as well as osteolysis of the carpal and tarsal bones, that can be misdiagnosed as juvenile idiopathic arthritis. We describe five Indian families with heterozygous nonrecurrent missense pathogenic variants in exon 1 of MAF bZIP transcription factor B (MAFB).

Prominent osteolysis in the maxilla: case report of an odontogenic fibroma mimicking a cyst.

BACKGROUND: Odontogenic fibroma (OF) is a rare benign odontogenic tumor of ectomesenchymal origin, mostly affecting the tooth-bearing portions of the jaws in middle-aged patients. Whilst small lesions tend to be clinically asymptomatic, varying unspecific clinical symptoms occur with an increase in size and may mimic odontogenic or other maxillofacial bone tumors, cysts, or fibro-osseous lesions of the jaws. CASE PRESENTATION: A 31-year-old female patient presented with a hard, non-fluctuating protrusion in the vestibule of the upper right maxilla. It was visualized on cone beam computed tomography (CBCT) as space-occupying osteolysis with the displacement of the floor and facial wall of the maxillary sinus, mimicking a cyst-like lesion. The tissue was surgically removed and identified as an OF in the histopathological examination. One year after the surgery, restitution of regular sinus anatomy and physiological intraoral findings were observed. CONCLUSIONS: This case report emphasizes that rare entities, like the maxillary OF presented, often demonstrate nonspecific clinical and radiological findings. Nevertheless, clinicians need to consider rare entities as possible differential diagnoses and plan the treatment accordingly. Histopathological examination is essential to conclude the diagnosis. OF rarely recur after proper enucleation.

An unusual manifestation in a pediatric patient with MAFB mutation: Sacroiliitis in multicentric carpotarsal osteolysis syndrome.

Multicentric carpotarsal osteolysis (MCTO) syndrome, is typically characterized by progressive bone resorption in especially carpal and tarsal bones, in addition to abnormal facial appearance and proteinuria. This disorder is caused by monoallelic pathogenic MAFB mutations, which result in excessive osteoclastogenesis via aberrant receptor activator of nuclear factor kappa-B ligand activation. Most cases are sporadic with de-novo mutations, and it is still unclear why carpal and tarsal bones are predominantly affected. The early phases of MCTO resemble juvenile idiopathic arthritis (JIA) with ankle and wrist swelling and pain, even with inflammatory changes in magnetic resonance imaging. Herein we report a pediatric patient, previously treated with antirheumatic drugs, and eventually diagnosed with MCTO. This case was a descriptive case with exophthalmos, significant proteinuria, and total loss of carpal and tarsal bones at the time of genetic diagnosis. Similar to the literature, our case had typical radiological findings despite methotrexate and anti-tumor necrosis factor-alpha treatment. However, while arthritis affecting joints other than wrists and ankles has not been reported so far in the literature, our case had bilateral sacroiliitis which completely resolved after adalimumab treatment. We cannot be sure if sacroiliitis was incidental or occurred as a component of the disease, nonetheless, we think that sharing our experience may lead to easy and early recognition of MCTO, with more knowledge on rare manifestations of MCTO, and thus we may be able to clarify the benefits of denosumab, which is the most promising agent in early phases of the disease.

Satisfactory clinical and radiographic outcomes following revision total hip arthroplasty by direct anterior approach using primary femoral stems at 2-8 years of follow-up.

INTRODUCTION: To report clinical and radiographic outcomes of revision total hip arthroplasty (THA) through the direct anterior approach (DAA) using primary stems. MATERIALS AND METHODS: The authors assessed a consecutive series of revision THAs operated by DAA using primary (cemented and uncemented) stems between 1/1/2010 and 30/06/2017. The initial cohort comprised 47 patients (50 hips), aged 65 ± 10 years with BMI of 25 ± 4 kg/m2. Clinical assessment included modified Harris Hip Score (mHHS) and satisfaction with surgery. Radiographic assessment included radiolucent lines > 2 mm, bone remodelling, cortical hypertrophy, pedestal formation, and osteolysis. Linear regression analyses were performed. RESULTS: Of the 50 hips (47 patients) in the initial cohort, intraoperative complications that did not require re-revision occurred in 5 hips. At a follow-up of > 2 years: 5 hips (10%) were lost to follow-up and 3 hips (6%) required stem re-revision, leaving a final cohort of 42 hips (40 patients). Postoperative complications that did not require re-revision occurred in 4 hips (8%). At 4.3 ± 1.6 years, post-revision mHHS was 89 ± 14 (range 47-100) and 38 patients were satisfied or very satisfied with revision surgery. Bone remodelling was observed in 8 hips (16%), cortical hypertrophy in 6 hips (12%), grade I heterotopic ossification in 7 hips (14%), and grade II in 1 hip (2%). There were no cases of radiolucent lines, pedestal formation, or osteolysis. Regression analyses revealed that post-revision mHHS was not associated with any variable. CONCLUSIONS: Revision THA performed through the DAA using primary stems grants satisfactory clinical and radiographic outcomes at a minimum follow-up of two years.

Talar component subsidence correlates with periprosthetic osteolysis after total ankle arthroplasty.

PURPOSE: This study aimed to investigate the relationship between periprosthetic osteolysis around the talar component and the amount of talar component subsidence after total ankle arthroplasty (TAA). METHODS: This study included forty patients who underwent TAA with a mean follow-up of 67.5 ± 17.0 months. The patients were divided into two groups based on the amount of osteolysis around the talar component, as measured by computed tomography at the latest clinic visit: none to 2 mm (N group, n = 20) and greater than or equal to 2 mm (O group, n = 20). The average amount of talar component subsidence, clinical outcomes, and complications were compared between the two groups. In the O group, the correlation between osteolysis and talar component subsidence was evaluated. RESULTS: The average talar component subsidence was significantly different between the N (0.22 ± 0.94 mm) and O groups (2.12 ± 2.28 mm). Five out of 20 ankles in the O group required revision surgery owing to talar component subsidence. The Japanese Society for Surgery of the Foot scores in the N and O groups were significantly different: 93.5 ± 7.7 and 85.3 ± 15.4, respectively. In the O group, we found that osteolysis tended to develop on the lateral side, and the amount of osteolysis was positively correlated with the talar component subsidence (r = 0.59, P = .007). CONCLUSION: In the O group, a positive correlation between osteolysis and talar component subsidence was found, and five patients required revision surgery.

Forte ceramic-on-delta ceramic cementless total hip arthroplasty: an 8- to 15-year follow-up study.

INTRODUCTION: Forte ceramic head on delta ceramic liner articulation showed satisfactory midterm results without ceramic-related complication. We aimed to investigate the clinical and radiological outcomes of cementless total hip arthroplasty (THA) with forte ceramic head on delta ceramic liner articulation. MATERIALS AND METHODS: Overall, 107 patients (57 men, 50 women; 138 hips) who underwent cementless THA with forte ceramic head on delta ceramic liner articulation were enrolled. The mean follow-up duration was 11.6 years. For the clinical assessments, Harris hip score (HHS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), presence of thigh pain, and presence of squeaking were evaluated. Radiographs were assessed to search for osteolysis, stem subsidence, loosening of implants. Kaplan-Meier survival curves were evaluated. RESULTS: The mean HHS and WOMAC improved from 57.1 and 28.1 preoperatively to 81.4 and 13.1 at the final follow-up, respectively. Nine revisions (6.5%) were performed; 5 hips for stem loosening, 1 hip for ceramic liner fracture, 2 hips for periprosthetic fracture, and 1 hip for progressive osteolysis around cup and stem. Thirty-two patients (37 hips) complained squeaking, in which 4 cases (2.9%) were identified as ceramic-related noises. After a mean follow-up period of 11.6 years, 91% (95% CI 87.8-94.2) were free from revision of both femoral and acetabular components due to any reason. CONCLUSIONS: Cementless THA with forte ceramic-on-delta ceramic articulation showed acceptable clinical and radiological results. Serial surveillance of these patients should be performed due to the possibility of cerami- related complications such as squeaking, osteolysis, and ceramic liner fracture.