Local compression of the sciatic nerve by a vascular malformation as a rare cause of sciatica: A case report and review of literature.

Background: Sciatica is typically caused by disc herniations or spinal stenosis. Extraspinal compression of the sciatic nerve is less frequent. Case Description: We report a rare case of sciatica with compression of the sciatic nerve by a low-flow vascular malformation in a 24-year-old female patient. The special feature of this case was sciatica along the S1 dermatome, which only occurred in the sitting position and inclination because of compression of the sciatic nerve between the vascular malformation and the lesser trochanter. Spinal imaging showed no abnormal findings. Surgery was performed interdisciplinary and included neurosurgery, vascular surgery, and trauma surgery. After surgery, the patient became symptom-free. Conclusion: Rare and extraspinal causes of local compression of the sciatic nerve should be considered, especially in cases of lacking spinal imaging correlation and untypical clinical presentation. Interdisciplinary surgical cooperation is of special value in cases of rare entities and uncommon locations.

Results of a monocentric field study: value of histology compared to sonication method and conventional tissue culture in the diagnosis of periprosthetic joint infection (PJI).

BACKGROUND: To confirm the diagnosis of periprosthetic joint infection (PJI), the Infectious Diseases Society of America (IDSA) and the International Consensus Meeting (ICM) have defined criteria that include histology as a minor criterion and the sonication method only as an additional criterion. The aim of this monocentric, retrospective study was to investigate the value of histology and whether sonication leads to a more accurate diagnosis. MATERIALS AND METHODS: All revision surgeries for knee and hip arthroplasty between 2017 and 2020 were included. With regard to microbiological diagnostic, conventional culture of periprosthetic biopsies and sonication of explant material were performed. In addition, histology and non-specific inflammatory markers (CRP, leukocytes) were recorded. RESULTS: A total of 78 patients with PJI and 62 aseptic controls were included. From both microbiological methods (conventional culture / sonication), Staphyloccus (S.) epidermidis and S. aureus were detected most frequently. However, compared to the conventional microbiology, a higher sensitivity was calculated for sonication, albeit with a lower specificity in relation to a PJI. In two logistic regression models for the significance of all diagnostic parameters in PJI, the AUC was 0.92 and 0.96 with histology in particular making the decisive contribution in both models (p < 0. 001, both models). CONCLUSION: Since histology showed the highest accuracy in the current study, its importance in the PJI criteria should be reevaluated. Sonication shows a high sensitivity for germ detection with a lower specificity and should only be used in combination with the conventional culture for microbiolgical diagnostics.

Accuracy of polyp characterization by artificial intelligence and endoscopists: a prospective, non-randomized study in a tertiary endoscopy center.

Background and study aims Artificial intelligence (AI) in gastrointestinal endoscopy is developing very fast. Computer-aided detection of polyps and computer-aided diagnosis (CADx) for polyp characterization are available now. This study was performed to evaluate the diagnostic performance of a new commercially available CADx system in clinical practice. Patients and methods This prospective, non-randomized study was performed at a tertiary academic endoscopy center from March to August 2022. We included patients receiving a colonoscopy. Polypectomy had to be performed in all polyps. Every patient was examined concurrently by an endoscopist and AI using two opposing screens. The AI system, overseen by a second observer, was not visible to the endoscopist. The primary outcome was accuracy of the AI classifying the polyps into "neoplastic" and "non-neoplastic." The secondary outcome was accuracy of the classification by the endoscopists. Sessile serrated lesions were classified as neoplastic. Results We included 156 patients (mean age 65; 57 women) with 262 polyps ≤10 mm. Eighty-four were hyperplastic polyps (32.1%), 158 adenomas (60.3%), seven sessile serrated lesions (2.7%) and 13 other entities (normal/inflammatory colonmucosa, lymphoidic polyp) (4.9%) on histological diagnosis. Sensitivity, specificity and accuracy of AI were 89.70% (95% confidence interval [CI]: 84.02%-93.88%), 75.26% (95% CI: 65.46%-83.46%) and 84.35% (95% CI:79.38%-88.53%), respectively. Sensitivity, specificity and accuracy for less experienced endoscopists (2-5 years of endoscopy) were 95.56% (95% CI: 84.85%-99.46%), 61.54% (95% CI: 40.57%-79.77%) and 83.10% (95% CI: 72.34%-90.95%) and for experienced endoscopists 90.83% (95% CI: 84.19%-95.33%), 71.83% (95% CI: 59.90%-81.87%) and 83.77% (95% CI: 77.76%-88.70%), respectively. Conclusion Accuracy for polyp characterization by a new commercially available AI system is high, but does not fulfill the criteria for a "resect-and-discard" strategy.

Prolonged Survival in Peritoneal Metastatic Appendiceal Carcinoma Patients Treated With Combined Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy.

INTRODUCTION: Primary treatment for peritoneal dissemination of appendiceal cancer is the combination of cytoreductive surgery and hyperthermic intraperitoneal chemotherapy. The endpoints were overall survival and evaluation of prognostic factors. METHODS: Clinicopathological and treatment-related factors were obtained from a prospective database. A total of 84 patients, 55 (65%) primary and 29 (35%) recurrent malignant appendiceal carcinomas with synchronous and metachronous peritoneal metastases, underwent multimodal treatment between 2011 and 2021. The endpoints of the study were overall survival and evaluation of prognostic factors. RESULTS: The median follow-up was 4.8 y; the mean age was 54.5 y (range 25-77), with a sex distribution of 69% female and 31% male. The mean peritoneal cancer index was 11.3. The proportion of mucinous, intestinal-type, signet ring cell, and goblet cell carcinoma was 56%, 23%, 11%, and 10%, respectively. The 5-y survival rate of the whole cohort was 56.7%. In primary and recurrent diseases, the overall median survival was 8.4 and 4.9 y. Significantly improved survival was detected after complete cytoreduction resection (hazard ratio [HR] for CCR-2 versus CCR-0: 9.388, 95% confidence interval [CI] 3.026-29.124, P = 0.001) and initial local operation with undelayed admission to the center (HR 0.262, 95% CI 0.089-0.773; P = 0.015). The five independent factors in Kaplan-Meier analysis and univariable Cox regression analysis associated with significant adverse survival were cancer antigen (CA) 19-9 over 37 IU/mL, signet ring cell and intestinal-type histology, positive nodal status, grading, and peritoneal cancer index >20. Neoadjuvant chemotherapy administration did not impact survival (HR 1.220, 95% CI 0.612-2.432, P = 0.571). CONCLUSIONS: With multimodal treatment, prolonged survival is attainable in stage IV primary and recurrent appendiceal carcinoma with peritoneal dissemination. Direct referral to specialized centers after confirmation of peritoneal metastasis is recommended because prompt definitive treatment may significantly improve survival.

Inhibition of CXCR4 Enhances the Efficacy of Radiotherapy in Metastatic Prostate Cancer Models.

Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 inhibition also reduced lymph node metastasis from primary PCa. Notably, CXCR4 inhibition promoted the normalization of bone metastatic PCa vasculature and reduced tissue hypoxia. In conclusion, the SDF1α/CXCR4 axis is a potential therapeutic target in metastatic PCa patients treated with RT.

Ten-year single-center experience with treatment of primary diffuse malignant peritoneal mesothelioma (DMPM) by cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

PURPOSE: This single-center study evaluated cytoreductive surgery (CRS) combined with hyperthermic intraperitoneal chemotherapy (HIPEC) for diffuse malignant peritoneal mesothelioma (DMPM). METHODS: Prospectively collected data from a single institution data registry was retrospectively investigated. Eighty-four patients with primary malignant peritoneal mesothelioma underwent CRS and HIPEC with cisplatin and doxorubicin either for 60 min or 90 min of duration from 2011 to 2021. The primary endpoint was overall survival. The secondary endpoint was the evaluation of prognostic factors for overall survival. The tertiary endpoint was to assess the effect of neoadjuvant chemotherapy on survival. RESULTS: The median follow-up was 5.0 years (95%-CI 4.6-5.5). The median age was 59.2 years (IQR: 47-66). Eighty-two patients (97.6%) had epithelioid tumors. The median peritoneal cancer index was 18.0 (IQR: 13-27). Sixty-six patients (78.6%) had complete or near-complete cytoreduction (CCR 0 or CCR 1). Seventy patients (83.3%) received HIPEC for 60 min and 14 patients (16.7%) received it for 90 min. Twenty-two patients (26.2%) had grade 3 to 4 complications. Acute kidney injury (AKI) stage I-III occurred in 30 (35.7%) patients. Three patients (3.6%) died perioperatively. The overall median survival was 38.4 months (95%-CI 23.6-54.3), and the 5-year survival rate was 42%. Survival was independently associated with age, female gender, and thrombocytosis. Preoperative chemotherapy did not emerge as an adverse prognostic factor. CONCLUSION: In well-selected patients with DMPM, prolonged survival is achievable with CRS and HIPEC in specialized centers.

The histopathological synovitis score is influenced by biopsy location in patients with knee osteoarthritis.

INTRODUCTION: Osteoarthritis (OA) and rheumatoid arthritis (RA) represent the most common forms of arthritis, which are mainly caused by mechanical and inflammatory components, respectively. Determination of synovial inflammation in synovial biopsies via the histopathological Krenn score may be crucial for correct diagnosis and treatment. Specifically, it remains unclear whether synovitis scores differ among multiple biopsy locations within a single joint. MATERIALS AND METHODS: Eighty synovial samples were taken from four standardized regions of the knee in 20 patients (ten primary OA, ten secondary OA) undergoing total knee arthroplasty (TKA) or total synovectomy. The Krenn synovitis score (grade 0-9) was determined in a blinded manner by two expert pathologists in all biopsies. Next to the inter-rater reliability, we evaluated the agreement of the determined scores among the four biopsy locations within each knee. RESULTS: The inter-rater reliability between the two pathologists was very high (Cohen's kappa = 0.712; r = 0.946; ICC = 0.972). The mean synovitis score was significantly higher in knees with secondary than in primary OA (p = 0.026). Importantly, we found clear differences between the scores of the four different biopsy locations within the individual knee joints, with an average deviation of 10.6%. These deviations were comparable in knees with primary and secondary OA (p = 0.64). CONCLUSIONS: While we confirmed the synovitis score as a reliable and reproducible parameter to assess the histopathological synovitis grade in the knee, the considerable variability within the joint indicates that multiple synovial biopsies from different regions should be obtained to enable reliable results of the synovitis score.

Malignant Struma Ovarii Τreated With Cytoreductive Surgery (CRS) and Hyperthermic Intraperitoneal Chemotherapy (HIPEC).

BACKGROUND/AIM: Malignant struma ovarii is an extremely rare tumor entity among ovarian tumors. In the presence of ascites and peritoneal metastases, the preoperative appearance may resemble the most common epithelial ovarian carcinoma (EOC) and accordingly, the surgical therapy may be identical if a preoperative histology diagnosis is not possible. The objective of this case report is to present a patient with histopathologically confirmed malignant struma ovarii who underwent cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (CRS and HIPEC) with the aim of complete tumor resection. CASE REPORT: This study reports on a patient with preoperatively proven peritoneal metastasis of an 18 cm ovarian tumor with large struma ovarii and papillary thyroid carcinoma within the struma, who was treated with CRS and HIPEC after neoadjuvant chemotherapy. CONCLUSION: This disease has a significantly better prognosis than EOC, however, HIPEC could provide an additional effect in examining the presence of peritoneal metastasis.

Microdont Developing Outside the Alveolar Process and Within Oral Diffuse and Plexiform Neurofibroma in Neurofibromatosis Type 1.

BACKGROUND/AIM: Numerical aberrations of permanent dentition and dystopic tooth eruption are part of the phenotype of the tumor predisposition syndrome neurofibromatosis type 1 (NF1). In these cases, surplus tooth germs usually develop in the alveolar processes of the jaw. This report attests to the dystopic development of a dysplastic supernumerary tooth in NF1 arising outside the jaw. CASE REPORT: The 8-year-old male patient developed a microdont outside the bone and above the occlusal plane of the retained maxillary right second molar. The supernumerary tooth was completely embedded in oral soft tissue. Hyperplastic oral soft tissue in the molar region and microdont were excised. Specimen of the mucosa surrounding the teeth was interspersed with diffuse and plexiform neurofibroma. The retained upper right first molar emerged spontaneously within a few months after surgery. The upper right second molar did not change position. CONCLUSION: Odontogenesis can take place within tumorous oral mucosa in NF1. Surgical removal of the tumorous mucous membrane facilitates tooth eruption in some cases.

Neurofibromatosis Type 1 With Cherubism-like Phenotype, Multiple Osteolytic Bone Lesions of Lower Extremities, and Alagille-syndrome: Case Report With Literature Survey.

BACKGROUND/AIM: Neurofibromatosis type 1 (NF) is an autosomal dominant hereditary disease. The cardinal clinical findings include characteristic skeletal alterations. Difficulties in diagnosis and therapy can arise if an individual has further illnesses. CASE REPORT: This is a case report of a 16-year-old patient affected by NF1. She also suffered from Alagille syndrome and the consequences of fetal alcohol exposure. The patient's facial phenotype showed findings that could be assigned to one or more of the known diseases. The patient was referred for treating a cherubism-like recurrent central giant cell granuloma (CGCG) of the jaw. The patient developed bilateral, multilocular non-ossifying fibromas (NOF) of the long bones of the lower extremity. Treatment of the skeletal lesions consisted of local curettage. While NOF regressed after surgery, the CGCG of the jaw remained largely unchanged. Extensive genetic tests confirmed a previously unknown germline mutation in the JAG1 gene, the germline mutation of the NF1 gene, and the somatic mutation in the NF1 gene in the diffuse plexiform neurofibroma, but not in the CGCG. CONCLUSION: Assigning facial findings to a defined syndrome is ambiguous in many cases and especially difficult in patients who have multiple diseases that can affect the facial phenotype. Surgical therapy should be adapted to the individual findings.

Compound Heterozygous Frameshift Mutations in MESD Cause a Lethal Syndrome Suggestive of Osteogenesis Imperfecta Type XX.

Multiple genes are known to be associated with osteogenesis imperfecta (OI), a phenotypically and genetically heterogenous bone disorder, marked predominantly by low bone mineral density and increased risk of fractures. Recently, mutations affecting MESD, which encodes for a chaperone required for trafficking of the low-density lipoprotein receptors LRP5 and LRP6 in the endoplasmic reticulum, were described to cause autosomal-recessive OI XX in homozygous children. In the present study, whole-exome sequencing of three stillbirths in one family was performed to evaluate the presence of a hereditary disorder. To further characterize the skeletal phenotype, fetal autopsy, bone histology, and quantitative backscattered electron imaging (qBEI) were performed, and the results were compared with those from an age-matched control with regular skeletal phenotype. In each of the affected individuals, compound heterozygous mutations in MESD exon 2 and exon 3 were detected. Based on the skeletal phenotype, which was characterized by multiple intrauterine fractures and severe skeletal deformity, OI XX was diagnosed in these individuals. Histological evaluation of MESD specimens revealed an impaired osseous development with an altered osteocyte morphology and reduced canalicular connectivity. Moreover, analysis of bone mineral density distribution by qBEI indicated an impaired and more heterogeneous matrix mineralization in individuals with MESD mutations than in controls. In contrast to the previously reported phenotypes of individuals with OI XX, the more severe phenotype in the present study is likely explained by a mutation in exon 2, located within the chaperone domain of MESD, that leads to a complete loss of function, which indicates the relevance of MESD in early skeletal development. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR)..

Globally altered epigenetic landscape and delayed osteogenic differentiation in H3.3-G34W-mutant giant cell tumor of bone.

The neoplastic stromal cells of giant cell tumor of bone (GCTB) carry a mutation in H3F3A, leading to a mutant histone variant, H3.3-G34W, as a sole recurrent genetic alteration. We show that in patient-derived stromal cells H3.3-G34W is incorporated into the chromatin and associates with massive epigenetic alterations on the DNA methylation, chromatin accessibility and histone modification level, that can be partially recapitulated in an orthogonal cell line system by the introduction of H3.3-G34W. These epigenetic alterations affect mainly heterochromatic and bivalent regions and provide possible explanations for the genomic instability, as well as the osteolytic phenotype of GCTB. The mutation occurs in differentiating mesenchymal stem cells and associates with an impaired osteogenic differentiation. We propose that the observed epigenetic alterations reflect distinct differentiation stages of H3.3 WT and H3.3 MUT stromal cells and add to H3.3-G34W-associated changes.

Ablation Precision and Thermal Effects of a Picosecond Infrared Laser (PIRL) on Roots of Human Teeth: A Pilot Study Ex Vivo.

BACKGROUND/AIM: Picosecond infrared laser (PIRL) was investigated regarding its possible therapeutic application in cutting dental roots. MATERIALS AND METHODS: Extracted human teeth were processed in the root area by laser ablations followed by histological evaluation. Dentin adjacent to the cutting surface was evaluated morphometrically. RESULTS: PIRL produced clearly defined cutting boundaries in dental roots. At the bottom of the cavity, the ablation surface became slightly concave. Heat development in this scantly hydrated tissue was considerable. We attributed the excess heating effects to heat accumulation due to multiple pulse overlap across a limited scan range imposed by tooth geometries. CONCLUSION: Defined areas of the tooth root may be treated using the PIRL. For clinical translation, it would be necessary to improve beam delivery to facilitate beam steering for the intended oral application (e.g. by using a fiber) and identify optimal repetition rates/scan speeds combined with cooling techniques to minimize accumulated heat within ablation cavities.

Lingual Mandibular Bone Depression.

BACKGROUND/AIM: In the area of the jaw angle, osteolytic lesions can occur, the differential diagnosis of which can be difficult and require very different therapeutic measures. One of these lesions is lingual mandibular bone depression (LMBD). The aim of this study was to present the characteristics of the lesion in a group of LMBD patients and to differentiate it from other lesions. PATIENTS AND METHODS: Radiological images of 21 patients with LMBD were examined. RESULTS: The majority of LMBDs were located in the jaw angle. On cross-sectional images, the lesion could be distinguished from salivary tissue (n=2). One case of LMBD had an impact on the course of the fracture line in the mandibular trauma. CONCLUSION: LMBD is a developmental disorder of the mandible and only rarely of pathological importance. Imaging the lesion with cross-sectional images is preferable to using plain X-ray projections. In some cases, surgical exploration is essential for diagnosis.

Case Report: Molecular Identification of Larval Taenia martis Infection in the Pouch of Douglas.

Taenia martis is a tapeworm dwelling in the intestine of mustelids and a rare zoonotic cysticercosis pathogen in its larval stage. The metacestode is morphologically very similar to more prevalent cysticercosis parasites, such as the larvae of Taenia solium and Taenia crassiceps, and may be indistinguishable from other metacestodes on histological sections. However, the epidemiology of human T. martis infections is different, and for prognosis, prevention, and detection of natural parasite reservoirs, the species should be identified. We here report the molecular identification of a T. martis larva located in the pouch of Douglas in a female German patient who underwent surgery for endometriosis. This case represents the fifth human infection described worldwide; all previous cases were also in European women, involving the eye, brain, and the peritoneum.

Can necrotic bone be objectively identified in chronic fracture related infections? - First clinical experience with an intraoperative fluorescence imaging technique.

INTRODUCTION: Adequate debridement of necrotic bone is of paramount importance for eradication of infection in chronic osteomyelitis. Currently, no tools are available to detect the exact amount of necrotic bone in order to optimize surgical resection. The aim of the present study was to evaluate the feasibility of an intraoperative illumination method (VELscope®) and the correlation between intraoperative and pathohistological findings in surgically treated chronic fracture related infection patients. METHODS: Ten consecutive patients with chronic fracture related infections of the lower extremity were included into this prospectively performed case series. All patients had to be treated surgically for fracture related infections requiring bony debridement. An intraoperative illumination method (VELscope®) was used to intraoperatively differentiate between viable and necrotic bone. Tissue samples from the identified viable and necrotic bone areas were histopathologically examined and compared to intraoperative findings. RESULTS: In all included patients, the intraoperative illumination was deemed helpful to differentiate between necrotic and viable bone tissues during bony debridement. The histopathological examination of the samples showed good correlation of the intraoperative illumination findings with histopathological signs of necrosis for areas deemed dead and histopathological signs of intact bone for areas deemed vital during illumination. CONCLUSION: The fluorescence-assisted, intraoperative detection of necrotic and viable bone using the VELscope® is an easy-to-use procedure that can help surgeons to optimize intraoperative bone resection in chronic fracture related infections by unmasking viable from necrotic bone tissue. This may help to improve resection techniques and eventually treatment outcome in patients in the future.

Radiological and Histopathological Features of Internal Tooth Resorption.

BACKGROUND: Internal root resorption is an endodontic disease characterized by progressive resorption of dentin from the inside of the pulp chamber. It is a comparatively rare finding in the permanent dentition, and the underlying pathology is not fully understood. CASE REPORT: A 45-year-old patient was referred to our Department for the evaluation of the lower right canine and the upper left wisdom tooth. Pulp sensitivity tests, cone-beam tomography, and magnetic resonance imaging were used to determine the extent of lesions of the affected teeth. The teeth were subsequently extracted due the extent of the lesions. The same was the case for the upper right canine, which developed a severe internal resorption 10 months later. Micro-computed tomography of the extracted teeth revealed that all lesions had a well-defined border with no evidence of sclerosis or hypomineralization. Pulp stones were evident inside the pulp chamber. Ground sectioning of the upper right canine revealed pulp necrosis and an acute infection that had gradually moved in the apical direction. Large multi-nucleated resorbing cells were found on the dentin surface. Importantly, the apical half of the pulp exhibited comparatively normal tissue without substantial inflammatory changes. Decalcified histology of the upper left wisdom tooth demonstrated a completely different histopathological appearance characterized by chronically inflamed granulation tissue with pseudoepitheliomatous hyperplasia and massive bacterial colonization. CONCLUSION: Our analyses demonstrate that internal root resorption is a multifaceted dental disease with considerable variability in the rate of the underlying inflammatory changes. Oral surgeons should take this into consideration when evaluating the need for extraction of teeth with internal root resorption.

Osteoidosis leads to altered differentiation and function of osteoclasts.

In patients with osteomalacia, a defect in bone mineralization leads to changed characteristics of the bone surface. Considering that the properties of the surrounding matrix influence function and differentiation of cells, we aimed to investigate the effect of osteoidosis on differentiation and function of osteoclasts. Based on osteomalacic bone biopsies, a model for osteoidosis in vitro (OIV) was established. Peripheral blood mononuclear cells were differentiated to osteoclasts on mineralized surfaces (MS) as internal control and on OIV. We observed a significantly reduced number of osteoclasts and surface resorption on OIV. Atomic force microscopy revealed a significant effect of the altered degree of mineralization on surface mechanics and an unmasking of collagen fibres on the surface. Indeed, coating of MS with RGD peptides mimicked the resorption phenotype observed in OIV, suggesting that the altered differentiation of osteoclasts on OIV might be associated with an interaction of the cells with amino acid sequences of unmasked extracellular matrix proteins containing RGD sequences. Transcriptome analysis uncovered a strong significant up-regulation of transmembrane glycoprotein TROP2 in osteoclastic cultures on OIV. TROP2 expression on OIV was also confirmed on the protein level and found on the bone surface of patients with osteomalacia. Taken together, our results show a direct influence of the mineralization state of the extracellular matrix surface on differentiation and function of osteoclasts on this surface which may be important for the pathophysiology of osteomalacia and other bone disorders with changed ratio of osteoid to bone.

Adult Osteosclerotic Metaphyseal Dysplasia With Progressive Osteonecrosis of the Jaws and Abnormal Bone Resorption Pattern Due to a LRRK1 Splice Site Mutation.

Osteosclerotic metaphyseal dysplasia (OSMD) is a rare autosomal recessive sclerosing skeletal dysplasia. We report on a 34-year-old patient with sandwich vertebrae, platyspondyly, osteosclerosis of the tubular bones, pathologic fractures, and anemia. In the third decade, he developed osteonecrosis of the jaws, which was progressive in spite of repeated surgical treatment over a period of 11 years. An iliac crest bone biopsy revealed the presence of hypermineralized cartilage remnants, large multinucleated osteoclasts with abnormal morphology, and inadequate bone resorption typical for osteoclast-rich osteopetrosis. After exclusion of mutations in TCIRG1 and CLCN7 we performed trio-based exome sequencing. The novel homozygous splice-site mutation c.261G>A in the gene LRRK1 was found and co-segregated with the phenotype in the family. cDNA sequencing showed nearly complete skipping of exon 3 leading to a frameshift (p.Ala34Profs*33). Osteoclasts differentiated from the patient's peripheral blood monocytes were extremely large. Instead of resorption pits these cells were only capable of superficial erosion. Phosphorylation of L-plastin at position Ser5 was strongly reduced in patient-derived osteoclasts showing a loss of function of the mutated LRRK1 kinase protein. Our analysis indicates a strong overlap of LRRK1-related OSMD with other forms of intermediate osteopetrosis, but an exceptional abnormality of osteoclast resorption. Like in other osteoclast pathologies an increased risk for progressive osteonecrosis of the jaws should be considered in OSMD, an intermediate form of osteopetrosis. © 2020 The Authors. Journal of Bone and Mineral Research published by American Society for Bone and Mineral Research.