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Cureus Feb 2024Idiopathic osteosclerosis (IO) is described as a localized radiopacity of unknown etiology. Also known as dense bone islands, enostoses, bone scar, or focal periapical...
Idiopathic osteosclerosis (IO) is described as a localized radiopacity of unknown etiology. Also known as dense bone islands, enostoses, bone scar, or focal periapical osteopetrosis, it is generally clinically asymptomatic and appears round, elliptical, or irregular in shape on a radiograph. The internal structure is usually homogenous. It should be distinguished from condensing osteitis and other alveolar bone-related radiopacities. This condition may cause changes in tooth position or interfere with orthodontic treatment. Two cases of IO involving the maxilla and mandible are highlighted. Both patients were females and presented with complaints of malocclusion and desired orthodontic correction. One case was detected incidentally on routine radiographic examination of the patient. In contrast, the other case presented as an expansile lesion lingual to the left mandibular first molar and second premolar. Radiographically, both lesions appeared as well-defined radiopaque masses with no surrounding radiolucent rim; the maxillary lesion was irregular in shape, while the mandibular lesion was elliptical. Both patients underwent orthodontic treatment without any adverse sequelae. The clinical and radiographic findings are discussed to facilitate the diagnosis of radiopacities of jaws. Usually asymptomatic and of no clinical significance, IO may occasionally induce root resorption, traumatic occlusion, traumatic/pathologic migration of teeth, and inhibit eruption of teeth. Though orthodontic tooth movement through areas of IO can be undertaken, the rate of tooth movement may be slower due to higher trabecular bone density. Lower force levels are warranted to avoid adverse effects like root resorption and bone hyalinization.
PubMed: 38435170
DOI: 10.7759/cureus.53426 -
Journal of Molecular Medicine (Berlin,... Apr 2024Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and... (Review)
Review
Current knowledge of bone-derived factor osteocalcin: its role in the management and treatment of diabetes mellitus, osteoporosis, osteopetrosis and inflammatory joint diseases.
Osteocalcin (OC) is the most abundant non-collagenous and osteoblast-secreted protein in bone. It consists of two forms such as carboxylated OC (cOC) and undercarboxylated OC (ucOC). While cOC promotes bone mineralization and increases bone strength, ucOC is regarded an endocrinologically active form that may have several functions in multiple end organs and tissues. Total OC (tOC) includes both of these forms (cOC and ucOC) and is considered a marker of bone turnover in clinical settings. Most of the data on OC is limited to preclinical studies and therefore may not accurately reflect the situation in clinical conditions. For the stated reason, the aim of this review was not only to summarize current knowledge of all forms of OC and characterize its role in diabetes mellitus, osteoporosis, osteopetrosis, inflammatory joint diseases, but also to provide new interpretations of its involvement in the management and treatment of aforementioned diseases. In this context, special emphasis was placed on available clinical trials. Significantly lower levels of tOC and ucOC could be associated with the risk of type 2 diabetes mellitus. On the contrary, tOC level does not seem to be a good indicator of high bone turnover status in postmenopausal osteoporosis, osteoarthritis and rheumatoid arthritis. The associations between several pharmacological drugs used to treat all disorders mentioned above and OC levels have also been provided. From this perspective, OC may serve as a medium through which certain medications can influence glucose metabolism, body weight, adiponectin secretion, and synovial inflammation.
Topics: Humans; Diabetes Mellitus, Type 2; Osteocalcin; Osteopetrosis; Osteoporosis; Joint Diseases; Biomarkers
PubMed: 38363329
DOI: 10.1007/s00109-024-02418-8 -
Cureus Jan 2024Osteopetrosis is an uncommon and inherited disorder. Some disease-specific characteristics, such as diffuse osteosclerosis and a high incidence of fractures, may...
Osteopetrosis is an uncommon and inherited disorder. Some disease-specific characteristics, such as diffuse osteosclerosis and a high incidence of fractures, may potentially affect postoperative rehabilitation. This report presents a case of successful rehabilitation early after total hip arthroplasty for osteopetrosis. A 56-year-old Japanese man, who was diagnosed with osteopetrosis at the age of 11, underwent total hip arthroplasty in the right hip. Full weight-bearing was allowed on the day after the operation; the postoperative rehabilitation program was proceeded based on a standard program as done after total hip arthroplasty for osteoarthritis. A shoe lift in the left leg was used in supervised walking training to correct the imbalanced alignment due to leg length discrepancy. The patient could walk independently with a cane 17 days after the operation. Three weeks after the operation, the patient demonstrated comfortable and maximal walking speed of 1.11 and 1.34 m/s, respectively, and maximal hip abductor muscle strength of 3.96 kgf・m, both of which were better than those before the operation. There were no adverse events during the postoperative rehabilitation course. These findings suggest the safety and efficacy of standard rehabilitation programs after total hip arthroplasty even in individuals with osteopetrosis. In addition, it may be important to consider the whole-body condition in the rehabilitation of individuals with osteopetrosis.
PubMed: 38357069
DOI: 10.7759/cureus.52293 -
Nature Communications Feb 2024Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts,...
Osteoclasts are over-activated as we age, which results in bone loss. Src deficiency in mice leads to severe osteopetrosis due to a functional defect in osteoclasts, indicating that Src function is essential in osteoclasts. G-protein-coupled receptors (GPCRs) are the targets for ∼35% of approved drugs but it is still unclear how GPCRs regulate Src kinase activity. Here, we reveal that GPR54 activation by its natural ligand Kisspeptin-10 (Kp-10) causes Dusp18 to dephosphorylate Src at Tyr 416. Mechanistically, Gpr54 recruits both active Src and the Dusp18 phosphatase at its proline/arginine-rich motif in its C terminus. We show that Kp-10 binding to Gpr54 leads to the up-regulation of Dusp18. Kiss1, Gpr54 and Dusp18 knockout mice all exhibit osteoclast hyperactivation and bone loss, and Kp-10 abrogated bone loss by suppressing osteoclast activity in vivo. Therefore, Kp-10/Gpr54 is a promising therapeutic target to abrogate bone resorption by Dusp18-mediated Src dephosphorylation.
Topics: Animals; Mice; Osteoclasts; Kisspeptins; Receptors, G-Protein-Coupled; src-Family Kinases; Mice, Knockout; Bone Resorption; Receptors, Kisspeptin-1
PubMed: 38346942
DOI: 10.1038/s41467-024-44852-9 -
Stem Cell Research Apr 2024Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from...
Infantile Malignant Osteopetrosis (IMO) is a rare, severe autosomal recessive form of osteopetrosis. Here, the peripheral blood mononuclear cells (PBMCs) extracted from a patient with IMO carrying a compound heterozygous mutation in T cell immune regulator 1, ATPase H + transporting V0 subunit a3 (TCIRG1) gene (c.242delC; c.1114C > T) were successfully reprogrammed using Sendai virus encoding the four Yamanaka factors. The generated hiPSCs, IMO-hiPSCs, displayed typical embryonic stem cell-like morphology and were verified by expression of pluripotency markers such as OCT4, SOX2, NANOG, TRA-1-60 and SSEA4, as well as in vivo and in vitro differentiation into derivatives of three germ layers.
Topics: Humans; Induced Pluripotent Stem Cells; Osteopetrosis; Leukocytes, Mononuclear; Mutation; Genes, Homeobox; Cell Differentiation; Vacuolar Proton-Translocating ATPases
PubMed: 38335662
DOI: 10.1016/j.scr.2024.103330 -
Canadian Journal of Surgery. Journal... 2024Large-diameter head (LDH) total hip arthroplasty (THA) with a monobloc acetabular component improves hip stability. However, obtaining initial press-fit stability is...
Total hip arthroplasty with monobloc press-fit acetabular components and large-diameter bearings for atypical acetabula is safe: a consecutive case series of 125 hips with mean follow-up of 9 years.
BACKGROUND
Large-diameter head (LDH) total hip arthroplasty (THA) with a monobloc acetabular component improves hip stability. However, obtaining initial press-fit stability is quite challenging in atypical acetabula. The purpose of this study was to assess primary and secondary fixation of monobloc cups in atypical acetabula.
METHODS
In this consecutive case series, the local arthroplasty database was used to retrospectively identify patients with secondary osteoarthritis who underwent primary hip replacement with press-fit only LDH monobloc acetabular components between 2005 and 2018 and who had a minimum of 2 years of follow-up. Radiographic evaluation was performed at last follow-up, and patient-reported outcome measures (PROMs) were assessed with the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), the Forgotten Joint Score (FJS), and the Patient's Joint Perception (PJP) question.
RESULTS
One hundred and six LDH THAs and 19 hip resurfacings were included in the study. Preoperative diagnoses included hip dysplasia (36.8%), Legg-Calve-Perthes disease (32.0%), osteoarthritis with acetabular deficiency (17.6%), periacetabular osteotomy (8.0%), arthrodesis (4.0%), and osteopetrosis (1.6%). After a mean follow-up of 9.2 years, no aseptic loosening of the acetabular component was recorded nor observed on radiologic review. There were 13 (10.4%) revisions unrelated to the acetabular component fixation. The mean WOMAC and FJS scores were 9.2 and 80.9, respectively. In response to the PJP question, 49.4% of the patients perceived their hip as natural, 19.1% as an artificial joint with no restriction, 31.5% as an artificial joint with restriction, and none as a non-functional joint.
CONCLUSION
Primary press-fit fixation of monobloc acetabular components with LDH implanted in atypical acetabula led to secondary fixation in all cases with low revision and complication rates and great functional outcomes. With careful surgical technique and experience, systematic use of supplemental screw fixation is not essential in THA with atypical acetabula.
Topics: Humans; Arthroplasty, Replacement, Hip; Acetabulum; Follow-Up Studies; Retrospective Studies; Reoperation; Osteoarthritis; Hip Prosthesis; Treatment Outcome
PubMed: 38320777
DOI: 10.1503/cjs.014022 -
Global Pediatric Health 2024Carbonic anhydrase II deficiency is an extremely rare inborn error of metabolism that constitutes a triad osteopetrosis, renal tubular acidosis and intracerebral...
Carbonic anhydrase II deficiency is an extremely rare inborn error of metabolism that constitutes a triad osteopetrosis, renal tubular acidosis and intracerebral calcification. Unlike other subtypes of osteopetrosis, the presence of developmental delay and relative infrequency of skeletal fractures may not be a typical signs of symptoms indolent trajectory. This case report demonstrates a 11-year-old boy who had a bilateral midshaft tibial fracture despite low mechanism of injury. He was found to have severe respiratory distress with hypokalemia shortly after arriving to the emergency department venous blood gas (VBG) showed moderate metabolic acidosis. Potassium was corrected but he persistently had low potassium level despite frequent corrections. He was then started on sodium bicarbonate boluses. Whole exome sequencing (WES) was sent, and result was consistent with autosomal recessive osteopetrosis type III with renal tubular acidosis (RTA) evident by pathologic variant on gene confirming the diagnosis of carbonic anhydrase II (CA II) deficiency consistent with the unique Arabic mutation. Conversely, low mechanism of fracture injury in the context of severe form of fracture type should raise the concern of (CA II) deficiency especially in a pediatric patient who show no signs of developmental of cognitive delay.
PubMed: 38328522
DOI: 10.1177/2333794X241230873 -
Journal of Cell Science Feb 2024Microglia, professional phagocytic cells of the brain, rely upon the appropriate activation of lysosomes to execute their immune and clearance functions. Lysosomal...
Microglia, professional phagocytic cells of the brain, rely upon the appropriate activation of lysosomes to execute their immune and clearance functions. Lysosomal activity is, in turn, modulated by a complex network of over 200 membrane and accessory proteins that relay extracellular cues to these key degradation centers. The ClC-7 chloride (Cl-)-proton (H+) antiporter (also known as CLCN7) is localized to the endolysosomal compartments and mutations in CLCN7 lead to osteopetrosis and neurodegeneration. Although the functions of ClC-7 have been extensively investigated in osteoclasts and neurons, its role in microglia in vivo remains largely unexamined. Here, we show that microglia and embryonic macrophages in zebrafish clcn7 mutants cannot effectively process extracellular debris in the form of apoptotic cells and β-amyloid. Despite these functional defects, microglia develop normally in clcn7 mutants and display normal expression of endosomal and lysosomal markers. We also find that mutants for ostm1, which encodes the β-subunit of ClC-7, have a phenotype that is strikingly similar to that of clcn7 mutants. Together, our observations uncover a previously unappreciated role of ClC-7 in microglia and contribute to the understanding of the neurodegenerative phenotypes that accompany mutations in this channel.
Topics: Animals; Microglia; Membrane Proteins; Chlorides; Zebrafish; Protons; Phagocytes; Chloride Channels
PubMed: 38294065
DOI: 10.1242/jcs.261616 -
Radiology Case Reports Apr 2024Osteopetrosis is a heterogenous group of inheritable disorders which manifests as increased bone density and brittleness. The most common and mildest variant typically...
Osteopetrosis is a heterogenous group of inheritable disorders which manifests as increased bone density and brittleness. The most common and mildest variant typically presents in adulthood with bone pain and pathologic fractures, including spondylolysis. We present the case of an otherwise healthy, active 17-year-old male with a history of osteopetrosis and 1 year of chronic back pain, found to have multilevel (L1-L4) spondylolysis in the setting of severe diffuse bony sclerosis consistent with osteopetrosis. While single-level spondylolysis is an uncommon complication of osteopetrosis, multilevel spondylolysis in the pediatric population is extremely rare and the genetics of prior cases studies have not been reported. Spondylolysis should be considered as one of the types of fractures that may occur in patients with osteopetrosis.
PubMed: 38292800
DOI: 10.1016/j.radcr.2024.01.017 -
Case Reports in Ophthalmology 2024Osteopetrosis is a rare heritable disorder characterized by increased bone density resulting from osteoclast dysfunction. Major complications include bone fracture,...
INTRODUCTION
Osteopetrosis is a rare heritable disorder characterized by increased bone density resulting from osteoclast dysfunction. Major complications include bone fracture, osteomyelitis, anemia, and cranial nerve compression. Optic atrophy can occur due to compression of the optic nerve. Although osteomyelitis of the jaw is a common complication, it rarely occurs in the maxilla. Here, we report a case of a 74-year-old female with osteopetrosis who developed maxillary osteomyelitis, leading to orbital inflammation.
CASE PRESENTATION
She was referred to our clinic for 2 months of ptosis and swelling of the left eyelid and temporal region. Previous imaging revealed a left intraorbital occupying lesion, but a biopsy of the temporal subcutaneous tissue did not provide a definitive diagnosis. After 7 months, she presented with severe temporal swelling and purulent discharge. Upon examination, maxillary osteomyelitis resulting from caries of the upper jaw was observed. Treatment with oral antibiotics, drainage of the temporal skin fistula, and regular cleaning of the maxillary drainage improved her symptoms.
CONCLUSION
This is a rare case of maxillary osteomyelitis associated with osteopetrosis, causing orbital inflammation.
PubMed: 38288029
DOI: 10.1159/000536140