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Frontiers in Endocrinology 2023Osteosclerotic metaphyseal dysplasia (OSMD, OMIM 615198) is an extremely rare autosomal recessive osteopetrosis disorder resulting in a distinctive pattern of...
BACKGROUND
Osteosclerotic metaphyseal dysplasia (OSMD, OMIM 615198) is an extremely rare autosomal recessive osteopetrosis disorder resulting in a distinctive pattern of osteosclerosis of the metaphyseal margins of long tubular bones. To date, only thirteen cases have been reported (eight molecularly confirmed). Five homozygous sequence variants in the leucine-rich repeat kinase 1 () gene have been identified to cause OSMD. We present two male siblings with OSMD with a novel variant.
CASES
The index case, now aged 6 years, was referred aged 9 months when diffuse sclerosis of the ribs and vertebral bodies, suggestive of osteopetrosis, was incidentally identified on a chest radiograph for suspected lower respiratory tract infection. Parents were consanguineous and of Pakistani origin. Further evaluation revealed developmental delay, nystagmus with bilateral optic nerve hypoplasia and severe visual impairment. Skeletal survey confirmed typical changes of OSMD, with widespread diffuse sclerosis and Erlenmeyer flask deformity of long bones. His older sibling, now aged 12 years, was 7 years at the time of referral and had similar clinical course and skeletal findings. Additionally, he had a chronic progressive osteonecrosis of the left mandible that required debridement, debulking and long-term antibiotics. Skeletal survey revealed findings similar to his sibling. Neither sibling had significant skeletal fractures or seizures. Unlike most previous reports suggesting sparing of the skull and lack of visual impairment, our patients had evidence of osteosclerosis of the cranium. Genetic screening for the common autosomal recessive and dominant pathogenic variants of osteopetrosis was negative. Whole Exome Sequencing (WES) followed by Sanger sequencing, identified a novel homozygous c.2506C>T p. (Gln836Ter) nonsense variant predicted to result in premature truncation of LRRK1 transcript.
CONCLUSION
Our cases confirm the autosomal recessive inheritance and expand the spectrum of genotype and phenotype of OSMD reported in the literature. Increasing reports of variants in this phenotype raise the question of whether should be included in targeted osteopetrosis panels. Bone histology in previous cases has shown this to be an osteoclast rich form of osteopetrosis raising the possibility that haematopoietic stem cell transplantation may be an appropriate treatment modality.
Topics: Humans; Male; Mutation; Optic Nerve; Osteopetrosis; Osteosclerosis; Protein Serine-Threonine Kinases; Ribs; Sclerosis; Vision Disorders; Child
PubMed: 37920250
DOI: 10.3389/fendo.2023.1258340 -
JCEM Case Reports Jul 2023A 21-year-old woman presented with polyuria, fragility fractures, and a history of recurrent renal calculi, which was also present in her maternal aunt. Examination...
A 21-year-old woman presented with polyuria, fragility fractures, and a history of recurrent renal calculi, which was also present in her maternal aunt. Examination revealed an oval palpable mass in the neck. Biochemistry revealed a grossly elevated serum calcium, PTH, and serum alkaline phosphatase with low serum phosphorous, suggestive of primary hyperparathyroidism. Ultrasonography of the neck and parathyroid scintigraphy localized a large lesion arising from the right posterior and inferior aspect of the thyroid gland, suggesting a parathyroid tumor. Parathyroid carcinoma was suspected based on the severe clinical manifestations. A computed tomography scan of the abdomen revealed cysts in the kidneys, bilateral medullary nephrocalcinosis, left ectopic-pelvic kidney, and lytic lesions in the iliac bone. The patient underwent a right inferior parathyroidectomy with normalization of serum calcium postoperatively. Histopathologic examination revealed a parathyroid adenoma, which was contrary to the expectation. Whole exome sequencing in the index case revealed a novel 99-bp heterozygous insertion, likely pathogenic variant in the exon 2 of CDC73 gene causing hyperparathyroidism jaw tumor syndrome. Here, we report a rare case of hyperparathyroidism jaw tumor syndrome that presented with severe hypercalcemia, renal cysts, and an ectopic-pelvic kidney without jaw tumor or uterine abnormalities.
PubMed: 37909004
DOI: 10.1210/jcemcr/luad098 -
Dentistry Journal Sep 2023Zygomatic implants are used for the rehabilitation of the upper jaw of patients with severe and moderate bone atrophy. Possible post-surgical complications include soft...
Zygomatic implants are used for the rehabilitation of the upper jaw of patients with severe and moderate bone atrophy. Possible post-surgical complications include soft tissue dehiscence, sinusitis, and prosthodontic fractures, and maintaining an accurate control is crucial. Additionally, zygomatic implants have a unique peri-implant anatomy, making traditional periodontal parameters unsuitable. The present paper aims to provide guidelines for the maintenance and interception of complications in patients rehabilitated with these kinds of implants. The proposed protocol includes: 1. intra/extraoral and temporo-mandibular joint examination; 2. soft tissue and transmucosal path observation with magnifiers; 3. peri-implant health indices and digital stimulation of tissues; 4. examination of prosthodontic devices; and 5. photographic recording. These steps facilitate the comprehensive evaluation and monitoring of clinical conditions of zygomatic-supported rehabilitations, including dehiscence and occlusal wear during follow-up appointments.
PubMed: 37886911
DOI: 10.3390/dj11100226 -
NIHR Open Research 2022Recent studies show that adults with intellectual disabilities (ID) have high incidence of major osteoporotic fracture, especially hip fracture. In those ≥ 50 years,...
BACKGROUND
Recent studies show that adults with intellectual disabilities (ID) have high incidence of major osteoporotic fracture, especially hip fracture. In those ≥ 50 years, women and men with ID have an approximately two and four times higher rate of hip fracture than women and men without ID. Increased awareness of osteoporotic fracture risk in ID may lead to wider use of antiresorptive drugs (bisphosphonates and denosumab) in this population. We aimed to compare, between people with and without ID, the incidence of 1) major side effects, namely medication related osteoporosis of the jaw (ONJ) and oesophagitis; 2) oral pathology, which can be a risk factor for ONJ.
METHODS
Exploratory study investigating safety of first line osteoporosis medication within the population of a previous study comparing fracture incidence in people with and without ID in the GOLD database of the Clinical Practice Research Datalink 1998-2017.
RESULTS
The percentage of people on antiresorptive drugs was identical in the ID and non ID group (1.4%). The number of individuals who developed ONJ and oesophagitis during the study was too low to allow an accurate estimate of incidence of the events and a comparison between the two groups. The incidence of any oral pathology was 119.31 vs 64.68/10000 person year in the ID vs non ID group.
CONCLUSIONS
Medication related ONJ and oesophagitis are rare in people with and without ID. There is no reason based on our findings to use antiresorptives differently in people with ID as in the rest of the population. However, the potential for side effects of antiresorptives will inherently increase with wider use of these drugs. Given the higher incidence of oral pathology in people with ID, which could put them at higher risk of ONJ, precautions should be taken to prevent this complication by attention to oral health.
PubMed: 37881308
DOI: 10.3310/nihropenres.13352.1 -
The American Journal of Case Reports Oct 2023BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related...
BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.
Topics: Female; Humans; Middle Aged; Diphosphonates; Alendronate; Osteoporosis, Postmenopausal; Bone Density Conservation Agents; Mandibular Fractures; Osteoporosis; Fractures, Spontaneous; Femoral Fractures; Osteomyelitis
PubMed: 37867315
DOI: 10.12659/AJCR.941144 -
Journal of Cranio-maxillo-facial... Nov 2023This study aimed to compare open and closed treatment for unilateral mandibular condyle neck and base fractures by final three-dimensional (3D) condylar position at 6...
This study aimed to compare open and closed treatment for unilateral mandibular condyle neck and base fractures by final three-dimensional (3D) condylar position at 6 months follow-up. 3D position was associated with mandibular functioning and pain. A total of 21 patients received open (n = 11) or closed (n = 10) treatment. 3D positions were assessed on cone-beam computed tomography scans. Volume differences, root mean square, translations, and rotations were obtained related to the pursued anatomical position and compared between treatment groups by the Mann-Whitney U test. The 3D position parameters were associated with the maximum interincisal opening (MIO), mixing ability test (MAT), Mandibular Function Impairment Questionnaire (MFIQ), and pain based on Spearman correlation coefficients (r). Translation in the medial-lateral direction was smaller after open treatment (P = 0.014). 3D position was not associated with the MAT; however, worse position was associated with a smaller MIO. A larger pitch rotation was associated with a worse MFIQ (r = 0.499, P = 0.025). Volume reduction of the affected condyle was associated with more pain (r = -0.503, P = 0.020). In conclusion, after unilateral condylar fractures, worse 3D position is associated with a smaller mouth opening and worse patient-reported outcomes. This is independent of the chosen treatment, despite a better anatomical reduction after open treatment.
Topics: Humans; Mandibular Condyle; Mandibular Fractures; Treatment Outcome; Mandible; Pain; Fracture Fixation, Internal
PubMed: 37852888
DOI: 10.1016/j.jcms.2023.09.013 -
The Saudi Dental Journal Sep 2023Digitalized workflow eliminates the need for the tray, impression materials, its decontamination, packaging and shipping, pouring with plaster, cast fabrication,...
Digitalized workflow eliminates the need for the tray, impression materials, its decontamination, packaging and shipping, pouring with plaster, cast fabrication, mounting in an articulator, reducing storage spaces, and the risks of any loss or fracture of the plaster model is overcome by archiving on the computer. This clinical investigation aimed to evaluate the effectiveness of the fully digitalized rehabilitation [implant-supported prosthesis] method in partially edentulous patients and with TMD, using advanced software. Twelve patients requiring implant-supported prosthesis in the mandibular molar area with Temporomandibular disorders [TMD] were selected. The fully digitalized rehabilitation method with advanced software was used for rehabilitation. For each subject, Optical impressions, CBCT scan, and Digital recording of jaw movement data. Guided implant surgery and digitalized prosthetic rehabilitation; were performed. The effectiveness of the digitalized workflow was assessed by evaluating the changes in the joint symptoms before and after the end of the treatment, changes in the electromyographic tracings, the precision of the prosthetic artefact, assessed through the amount of chair adjustment operating time and the number of retouching/ modifications to be carried out before the completion of the work. The results showed that the mean operative time required in 12 patients was 9.42 min, significantly less than the time recorded in previous studies when the medium mean was 16.00 min. The mean number of touch-ups [adjustments] was less than 3, most of which were on the interproximal surfaces. There were no significant changes recorded in the electromyography tracings. There were also no changes in joint symptoms. It was found that this way of working was entirely reliable and significantly reduced operating times and the number of appointments. Digital flow is beneficial ei dysfunctional patients, not about improvements in temporomandibular symptoms but in times of operability and prosthetic retouching.
PubMed: 37817790
DOI: 10.1016/j.sdentj.2023.05.024 -
Journal of Translational Medicine Sep 2023Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It... (Review)
Review
Osteoporosis is a systemic bone disease characterized by low bone mass, microarchitectural deterioration, increased bone fragility, and fracture susceptibility. It commonly occurs in older people, especially postmenopausal women. As global ageing increases, osteoporosis has become a global burden. There are a number of medications available for the treatment of osteoporosis, categorized as anabolic and anti-resorptive. Unfortunately, there is no drugs which have dual influence on bone, while all drugs have limitations and adverse events. Some serious adverse events include jaw osteonecrosis and atypical femoral fracture. Recently, a novel medication has appeared that challenges this pattern. Romosozumab is a novel drug monoclonal antibody to sclerostin encoded by the SOST gene. It has been used in Japan since 2019 and has achieved promising results in treating osteoporosis. However, it is also accompanied by some controversy. While it promotes rapid bone growth, it may cause serious adverse events such as cardiovascular diseases. There has been scepticism about the drug since its inception. Therefore, the present review comprehensively covered romosozumab from its inception to its clinical application, from animal studies to human studies, and from safety to cost. We hope to provide a better understanding of romosozumab for its clinical application.
Topics: Animals; Female; Humans; Aged; Osteoporosis; Antibodies, Monoclonal; Aging; Bone Development
PubMed: 37759285
DOI: 10.1186/s12967-023-04563-z -
MedRxiv : the Preprint Server For... Sep 2023Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict...
PURPOSE
Osteoradionecrosis of the jaw (ORN) can manifest in varying severity. The aim of this study is to identify ORN risk factors and develop a novel classification to depict the severity of ORN.
METHODS
Consecutive head-and-neck cancer (HNC) patients treated with curative-intent IMRT (≥ 45Gy) in 2011-2018 were included. Occurrence of ORN was identified from in-house prospective dental and clinical databases and charts. Multivariable logistic regression model was used to identify risk factors and stratify patients into high-risk and low-risk groups. A novel ORN classification system was developed to depict ORN severity by modifying existing systems and incorporating expert opinion. The performance of the novel system was compared to fifteen existing systems for their ability to identify and predict serious ORN event (jaw fracture or requiring jaw resection).
RESULTS
ORN was identified in 219 out of 2732 (8%) consecutive HNC patients. Factors associated with high-risk of ORN were: oral-cavity or oropharyngeal primaries, received IMRT dose ≥60Gy, current/ex-smokers, and/or stage III-IV periodontal disease. The ORN rate for high-risk vs low-risk patients was 12.7% vs 3.1% (p<0.001) with an area-under-the-receiver-operating-curve (AUC) of 0.71. Existing ORN systems overclassified serious ORN events and failed to recognize maxillary ORN. A novel ORN classification system, RadORN, was proposed based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. This system detected serious ORN events in 5.7% of patients and statistically outperformed existing systems.
CONCLUSION
We identified risk factors for ORN, and proposed a novel ORN classification system based on vertical extent of bone necrosis and presence/absence of exposed bone/fistula. It outperformed existing systems in depicting the seriousness of ORN, and may facilitate clinical care and clinical trials.
PubMed: 37745576
DOI: 10.1101/2023.09.12.23295454 -
Dental and Medical Problems 2023In the context of dental prostheses, splinting multiple implants together may improve their stability. The approach may be especially favorable when performing immediate...
BACKGROUND
In the context of dental prostheses, splinting multiple implants together may improve their stability. The approach may be especially favorable when performing immediate loading procedures, increasing the implant osseointegration rate, and reducing the risk of implant and prosthetic failure. The instantaneous loading technique (ILT) involves creating a metal framework to splint the implants by intraorally welding them pair-by-pair, using purposefully created abutments.
OBJECTIVES
The aim of the study was to investigate the prosthetic success when using ILT to rehabilitate partially edentulous patients through immediately loaded prostheses.
MATERIAL AND METHODS
Clinical records of patients treated with ILT were retrospectively assessed, and the prosthetic success rate was analyzed in terms of fractures, chipping, unscrewing, screw fracture rate, and mucositis. Furthermore, the implant success rates were evaluated by measuring marginal bone loss (MBL).
RESULTS
A total of 55 patients (20 males and 35 females with a mean age of 59.8 ±9.4 years), corresponding to 66 prostheses, were included. A total of 160 implants were placed. At the last follow-up (39.6 ±28.4 months), 1 patient (1.8%; 1 prosthesis (1.5%)) showed the fracture of the prosthesis material. Peri-implantitis affected 4 implants (2.5%), and 4 more implants (2.5%) showed radiolucency, affecting 5 patients (9.1%). Two other patients (3.6%) suffered from mucositis. The implant success rate, according to the Albrektsson and Zarb criteria, was 94.4%. No implants were lost. The mean MBL values at the implant level, the prosthesis level and the patient level were 0.28 ±0.56 mm, 0.30 ±0.51 mm and 0.33 ±0.54 mm, respectively.
CONCLUSIONS
The instantaneous loading technique appears to be a viable approach to rehabilitating partially edentulous patients through immediate loading.
Topics: Male; Female; Humans; Middle Aged; Aged; Dental Implants; Retrospective Studies; Mucositis; Jaw, Edentulous; Mouth, Edentulous; Fractures, Bone; Dental Prosthesis, Implant-Supported; Dentures
PubMed: 37706658
DOI: 10.17219/dmp/154981