-
Zhonghua Kou Qiang Yi Xue Za Zhi =... Aug 2023Tooth replacement disorders are characterized by retention of deciduous teeth and abnormalities in permanent teeth eruption. Hereditary disorders with multiple teeth...
Tooth replacement disorders are characterized by retention of deciduous teeth and abnormalities in permanent teeth eruption. Hereditary disorders with multiple teeth involved include cleidocranial dysplasia, osteopetrosis and Gardner syndrome. These rare diseases have great difficulty in treatment with various principles reported. This article focused on clinical manifestations and early treatment principles of these hereditary disorders, as well as the important role of dentists in early diagnosis of these diseases.
PubMed: 37550037
DOI: 10.3760/cma.j.cn112144-20230403-00131 -
International Journal of Surgery Case... Dec 2023Osteopetrosis is a rare genetic disorder characterized by increased bone density. This condition is clinically manifested with a brittle intramedullary structure and...
INTRODUCTION
Osteopetrosis is a rare genetic disorder characterized by increased bone density. This condition is clinically manifested with a brittle intramedullary structure and reduced bone toughness, increasing the risk of fracture. A limited case has been reported on the management of physeal fracture in patients with osteopetrosis. The objective of this study is to report a rare osteopetrosis patient who sustains Salter-Harris II at the distal tibia with its long-term follow-up along with its literature review.
PRESENTATION OF CASE
We report a case of a four-year-old boy with an established a diagnosis of osteopetrosis brought by the parents to the emergency department after sustaining a fall while playing in the playground. Radiological examination revealed a Salter-Harris type II distal tibial fracture. The patient underwent closed reduction and fixation using the cannulated screw. 18-month postoperative patients have an uneventful healing.
DISCUSSION
Osteopetrosis is caused by impaired osteoclast function and differentiation, leading to impaired in remodelling. Salter-Harris type II distal tibial fracture can be treated by either closed reduction or open reduction. A closed reduction was performed successfully with cannulated screw in his patient.
CONCLUSION
There is a delayed union of fracture in osteopetrosis patient. This will increase the risk of displacement which will eventually resulted in growth disturbance. Delayed weight bearing and stable fixation is highly recommended.
PubMed: 38007865
DOI: 10.1016/j.ijscr.2023.109090 -
Special Care in Dentistry : Official... 2023We report a rare case of late diagnosis of malignant osteopetrosis in a 36-year-old male patient due to multiple intraoral sinus tracts and trismus.
AIMS
We report a rare case of late diagnosis of malignant osteopetrosis in a 36-year-old male patient due to multiple intraoral sinus tracts and trismus.
CASE REPORT
The patient reported a history of facial scars that could not be attributed to the older external fistulas that were present and various complicated dental extractions since infancy. In addition, the patient had not been previously diagnosed with any other significant diseases other than blindness since infancy. Computed tomography revealed a marble-like sclerotic pattern of all cranial bones, a thickened parietal bone, and a narrowing of the encephalic space and the optic canal. Further laboratory and imaging studies revealed complete sclerosed bone of the chest and pelvis, anemia, reticulocitosis, extramedular hematopoiesis, altered dehydrogenasis lactate, and acid phosphatasis. An interdisciplinary treatment was initiated with medical and dental care monitoring. The patient is still receiving attention after 4 years of follow-up.
CONCLUSIONS
The outcome of this case represents the daily challenges faced by interdisciplinary care providers and reveals pearls and pitfalls that can serve as a reference for professional practice in such cases.
PubMed: 36316790
DOI: 10.1111/scd.12798 -
Calcified Tissue International Apr 2024Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption caused by heterozygous missense mutations in the chloride...
Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption caused by heterozygous missense mutations in the chloride channel 7 (CLCN7). Adenylate cyclase, which catalyzes the formation of cAMP, is critical for lysosomal acidification in osteoclasts. We found reduced cAMP levels in ADO2 osteoclasts compared to wild-type (WT) osteoclasts, leading us to examine whether regulating cAMP would improve ADO2 osteoclast activity. Although forskolin, a known activator of adenylate cyclase and cAMP levels, negatively affected osteoclast number, it led to an overall increase in ADO2 and WT osteoclast resorption activity in vitro. Next, we examined cAMP hydrolysis by the phosphodiesterase 4 (PDE4) proteins in ADO2 versus WT osteoclasts. QPCR analysis revealed higher expression of the three major PDE4 subtypes (4a, 4b, 4d) in ADO2 osteoclasts compared in WT, consistent with reduced cAMP levels in ADO2 osteoclasts. In addition, we found that the PDE4 antagonists, rolipram and roflumilast, stimulated ADO2 and WT osteoclast formation in a dose-dependent manner. Importantly, roflumilast and rolipram displayed a concentration-dependent increase in osteoclast resorption activity which was greater in ADO2 than WT osteoclasts. Moreover, treatment with roflumilast rescued cAMP levels in ADO2 OCLs. The key findings from our studies demonstrate that osteoclasts from ADO2 mice exhibit reduced cAMP levels and PDE4 inhibition rescues cAMP levels and ADO2 osteoclast activity dysfunction in vitro. The mechanism of action of PDE4 inhibitors and their ability to reduce the high bone mass of ADO2 mice in vivo are currently under investigation. Importantly, these studies advance the understanding of the mechanisms underlying the ADO2 osteoclast dysfunction which is critical for the development of therapeutic approaches to treat clinically affected ADO2 patients.
Topics: Humans; Mice; Animals; Rolipram; Phosphodiesterase 4 Inhibitors; Osteoclasts; Adenylyl Cyclases; Bone Resorption; Chloride Channels; Aminopyridines; Benzamides; Cyclopropanes
PubMed: 38483547
DOI: 10.1007/s00223-024-01191-7 -
Journal of Biomechanical Engineering Feb 2024Sensitivity coefficients are used to understand how errors in subject-specific musculoskeletal model parameters influence model predictions. Previous sensitivity studies...
Sensitivity coefficients are used to understand how errors in subject-specific musculoskeletal model parameters influence model predictions. Previous sensitivity studies in the lower limb calculated sensitivity using perturbations that do not fully represent the diversity of the population. Hence, the present study performs sensitivity analysis in the upper limb using a large synthetic dataset to capture greater physiological diversity. The large dataset (n = 401 synthetic subjects) was created by adjusting maximum isometric force, optimal fiber length, pennation angle, and bone mass to induce atrophy, hypertrophy, osteoporosis, and osteopetrosis in two upper limb musculoskeletal models. Simulations of three isometric and two isokinetic upper limb tasks were performed using each synthetic subject to predict muscle activations. Sensitivity coefficients were calculated using three different methods (two point, linear regression, and sensitivity functions) to understand how changes in Hill-type parameters influenced predicted muscle activations. The sensitivity coefficient methods were then compared by evaluating how well the coefficients accounted for measurement uncertainty. This was done by using the sensitivity coefficients to predict the range of muscle activations given known errors in measuring musculoskeletal parameters from medical imaging. Sensitivity functions were found to best account for measurement uncertainty. Simulated muscle activations were most sensitive to optimal fiber length and maximum isometric force during upper limb tasks. Importantly, the level of sensitivity was muscle and task dependent. These findings provide a foundation for how large synthetic datasets can be applied to capture physiologically diverse populations and understand how model parameters influence predictions.
Topics: Humans; Models, Biological; Musculoskeletal System; Muscles; Upper Extremity; Lower Extremity; Muscle, Skeletal; Isometric Contraction
PubMed: 37978046
DOI: 10.1115/1.4064056 -
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 -
Calcified Tissue International Apr 2024Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption that usually results from heterozygous missense mutations...
Autosomal Dominant Osteopetrosis type II (ADO2) is a rare bone disease of impaired osteoclastic bone resorption that usually results from heterozygous missense mutations in the chloride channel 7 (CLCN7) gene. We previously created mouse models of ADO2 (p.G213R) with one of the most common mutations (G215R) as found in humans and demonstrated that this mutation in mice phenocopies the human disease of ADO2. Previous studies have shown that roflumilast (RF), a selective phosphodiesterase 4 (PDE4) inhibitor that regulates the cAMP pathway, can increase osteoclast activity. We also observed that RF increased bone resorption in both wild-type and ADO2 heterozygous osteoclasts in vitro, suggesting it might rescue bone phenotypes in ADO2 mice. To test this hypothesis, we administered RF-treated diets (0, 20 and 100 mg/kg) to 8-week-old ADO2 mice for 6 months. We evaluated bone mineral density and bone micro-architecture using longitudinal in-vivo DXA and micro-CT at baseline, and 6-, 12-, 18-, and 24-week post-baseline time points. Additionally, we analyzed serum bone biomarkers (CTX, TRAP, and P1NP) at baseline, 12-, and 24-week post-baseline. Our findings revealed that RF treatment did not improve aBMD (whole body, femur, and spine) and trabecular BV/TV (distal femur) in ADO2 mice compared to the control group treated with a normal diet. Furthermore, we did not observe any significant changes in serum levels of bone biomarkers due to RF treatment in these mice. Overall, our results indicate that RF does not rescue the osteopetrotic bone phenotypes in ADO2 heterozygous mice.
Topics: Humans; Animals; Mice; Phosphodiesterase 4 Inhibitors; Phenotype; Biomarkers; Osteoclasts; Bone Resorption; Osteopetrosis; Chloride Channels; Aminopyridines; Benzamides; Cyclopropanes
PubMed: 38300304
DOI: 10.1007/s00223-023-01180-2 -
Pediatric Health, Medicine and... 2023Leukoerythroblastosis is rarely encountered in clinical practice and is characterized by the presence of leukocytosis and erythroid and myeloid blast cells in peripheral...
Leukoerythroblastosis is rarely encountered in clinical practice and is characterized by the presence of leukocytosis and erythroid and myeloid blast cells in peripheral blood. The most common causes of leukoerythroblastosis in early childhood are viral infection, juvenile myelomonocytic leukemia, and osteopetrosis. To the best of our knowledge, leukoerythroblastic reactions associated with hemolysis have not been previously reported in newborns. Here, we report a 24-hour-old female term newborn diagnosed with a leukoerythroblastic reaction, severe anemia, and neonatal hyperbilirubinemia secondary to Rh incompatibility based on presentation, laboratory determination, and peripheral morphology. A high index of clinical suspicion is required to avoid life-threatening complications among health professionals in the neonatal care unit.
PubMed: 37872980
DOI: 10.2147/PHMT.S430828 -
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 -
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