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Stem Cell Research Sep 2023A TNFRSF11B (TNF Receptor Superfamily Member 11b) gene encodes a soluble decoy receptor, osteoprotegerin (OPG), which has a key role in repressing osteoclast...
A TNFRSF11B (TNF Receptor Superfamily Member 11b) gene encodes a soluble decoy receptor, osteoprotegerin (OPG), which has a key role in repressing osteoclast differentiation. In this report, we generated a biallelic knock-out hiPSC line for the TNFRSF11B gene via CRISPR/Cas9. When TNFRSF11B Knock-out hiPSCs were differentiated into mesenchymal progenitor cells (MPCs), the expression level of OPG was significantly decreased compared to normal hiPSC-derived MPCs. This knock-out hiPSCs will provide a chance to study Paget disease of bone 5 (juvenile Paget disease).
Topics: Humans; Osteoprotegerin; Induced Pluripotent Stem Cells; CRISPR-Cas Systems; Osteitis Deformans
PubMed: 37481965
DOI: 10.1016/j.scr.2023.103167 -
Neuromuscular Disorders : NMD Jan 2024Valosin-containing protein (VCP) pathogenic variants are the most common cause of multisystem proteinopathy presenting with inclusion body myopathy, amyotrophic lateral...
Valosin-containing protein (VCP) pathogenic variants are the most common cause of multisystem proteinopathy presenting with inclusion body myopathy, amyotrophic lateral sclerosis/frontotemporal dementia, and Paget disease of bone in isolation or in combination. We report a patient manifesting with adolescent-onset myopathy caused by a novel heterozygous VCP variant (c.467G > T, p.Gly156Val). The myopathy manifested asymmetrically in lower limbs and extended to proximal, axial, and upper limb muscles, with loss of ambulation at age 35. Creatine kinase value was normal. Alkaline phosphatase was elevated. Electromyography detected mixed low amplitude, short duration and high amplitude, long duration motor unit potentials. Muscle biopsy showed features of inclusion body myopathy, which in combination with newly diagnosed Paget disease of bone, supported the VCP variant pathogenicity. In conclusion, VCP-multisystem proteinopathy is not only a disease of adulthood but can have a pediatric onset and should be considered in differential diagnosis of neuromuscular weakness in the pediatric population.
Topics: Adolescent; Adult; Child; Humans; Cell Cycle Proteins; Muscular Diseases; Mutation; Myositis, Inclusion Body; Osteitis Deformans; Proteostasis Deficiencies; Valosin Containing Protein
PubMed: 38159460
DOI: 10.1016/j.nmd.2023.11.014 -
Endocrine Mar 2024The aims of the current study were to describe clinical and biochemical features of patients with Paget disease of bone (PDB) followed at our medical center, and to...
PURPOSE
The aims of the current study were to describe clinical and biochemical features of patients with Paget disease of bone (PDB) followed at our medical center, and to examine the long-term effectiveness of zoledronate.
METHODS
Retrospective cohort study included consecutive patients≥18 years with a diagnosis of PDB, followed in the Rabin Medical Center (RMC) Institute of Endocrinology from 1973 to 2023. The cohort comprised two groups: patients treated/not treated with zoledronic acid (ZOL/NZOL). The primary outcome was the percentage of patients who achieved a biochemical therapeutic response.
RESULTS
Overall, 101 patients with PDB were included, 68 in the ZOL group and 33 in the NZOL group. The mean age was 65.2 ± 10.0 years, and 47% were female. Notably, 77% exhibited monostotic involvement, and only 3% had experienced fractures attributed to PDB. Mean ALP level at diagnosis was 160 ± 70.6 U/L. The median follow-up duration was 17 years since PDB diagnosis, comparable between the groups. Primary outcome was more prevalent in the ZOL compared to the NZOL group [42 patients (88%) VS 11 patients (52%) respectively, P = 0.004]. At the end of follow-up, mean ALP levels in the NZOL group were significantly higher than the levels in the ZOL group irrespective of the number of infusions received.
CONCLUSION
The majority of patients with PDB experience a mild disease course, marked by monostotic involvement and a low prevalence of fractures. Zoledronic acid effectively manages PDB, providing sustained biochemical response. The necessity for multiple zoledronic acid injections remains questionable, often implemented due to osteoporosis.
PubMed: 38555314
DOI: 10.1007/s12020-024-03791-7 -
Malaria Journal Jan 2024Sri Lanka after eliminating malaria in 2012, is in the prevention of re-establishment (POR) phase. Being a tropical country with high malariogenic potential, maintaining...
BACKGROUND
Sri Lanka after eliminating malaria in 2012, is in the prevention of re-establishment (POR) phase. Being a tropical country with high malariogenic potential, maintaining vigilance is important. All malaria cases are investigated epidemiologically and followed up by integrated drug efficacy surveillance (iDES). Occasionally, that alone is not adequate to differentiate Plasmodium falciparum reinfections from recrudescences. This study evaluated the World Health Organization and Medicines for Malaria Venture (MMV) recommended genotyping protocol for the merozoite surface proteins (msp1, msp2) and the glutamate-rich protein (glurp) to discriminate P. falciparum recrudescence from reinfection in POR phase.
METHODS
All P. falciparum patients detected from April 2014 to December 2019 were included in this study. Patients were treated and followed up by iDES up to 28 days and were advised to get tested if they develop fever at any time over the following year. Basic socio-demographic information including history of travel was obtained. Details of the malariogenic potential and reactive entomological and parasitological surveillance carried out by the Anti Malaria Campaign to exclude the possibility of local transmission were also collected. The msp1, msp2, and glurp genotyping was performed for initial and any recurrent infections. Classification of recurrent infections as recrudescence or reinfection was done based on epidemiological findings and was compared with the genotyping outcome.
RESULTS
Among 106 P. falciparum patients, six had recurrent infections. All the initial infections were imported, with a history of travel to malaria endemic countries. In all instances, the reactive entomological and parasitological surveillance had no evidence for local transmission. Five recurrences occurred within 28 days of follow-up and were classified as recrudescence. They have not travelled to malaria endemic countries between the initial and recurrent infections. The other had a recurrent infection after 105 days. It was assumed a reinfection, as he had travelled to the same malaria endemic country in between the two malaria attacks. Genotyping confirmed the recrudescence and the reinfection.
CONCLUSIONS
The msp1, msp2 and glurp genotyping method accurately differentiated reinfections from recrudescence. Since reinfection without a history of travel to a malaria endemic country would mean local transmission, combining genotyping outcome with epidemiological findings will assist classifying malaria cases without any ambiguity.
Topics: Male; Humans; Merozoite Surface Protein 1; Plasmodium falciparum; Reinfection; Protozoan Proteins; Antigens, Protozoan; Genotype; Glutamic Acid; Sri Lanka; Genetic Variation; Malaria, Falciparum; Recurrence; Osteitis Deformans; Myositis, Inclusion Body; Muscular Dystrophies, Limb-Girdle; Frontotemporal Dementia
PubMed: 38281044
DOI: 10.1186/s12936-024-04858-6 -
Scientific Reports Mar 2024Multisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of...
Multisystem Proteinopathy 1 (MSP1) disease is a rare genetic disorder caused by mutations in the Valosin-Containing Protein (VCP) gene with clinical features of inclusion body myopathy (IBM), frontotemporal dementia (FTD), and Paget's disease of bone (PDB). We performed bone scan imaging in twelve patients (6 females, 6 males) with confirmed VCP gene mutation six (50%) of which has myopathy alone, four (33%) with both PDB and myopathy, and two (15%) were presymptomatic carriers. We aim to characterize the PDB in diagnosed individuals, and potentially identify PDB in the myopathy and presymptomatic groups. Interestingly, two patients with previously undiagnosed PDB had positive diagnostic findings on the bone scan and subsequent radiograph imaging. Among the individuals with PDB, increased radiotracer uptake of the affected bones were of typical distribution as seen in conventional PDB and those reported in other MSP1 cohorts which are the thoracic spine and ribs (75%), pelvis (75%), shoulder (75%) and calvarium (15%). Overall, we show that technetium-99m bone scans done at regular intervals are a sensitive screening tool in patients with MSP1 associated VCP variants at risk for PDB. However, diagnostic confirmation should be coupled with clinical history, biochemical analysis, and skeletal radiographs to facilitate early treatment and prevention complications, acknowledging its limited specificity.
Topics: Male; Female; Humans; Frontotemporal Dementia; Valosin Containing Protein; Cell Cycle Proteins; Osteitis Deformans; Merozoite Surface Protein 1; Tomography, X-Ray Computed; Mutation; Myositis, Inclusion Body; Muscular Dystrophies, Limb-Girdle
PubMed: 38467645
DOI: 10.1038/s41598-024-54526-7 -
Clinical Nuclear Medicine Dec 2023Familial expansile osteolysis is an exceedingly rare autosomal dominant bone dysplasia, which can have overlapping features with Paget disease and expansile skeletal...
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.
Topics: Humans; Technetium Tc 99m Medronate; Tomography, X-Ray Computed; Osteolysis; Osteitis Deformans
PubMed: 37934705
DOI: 10.1097/RLU.0000000000004902 -
JBJS Case Connector Jul 2023Paget osteosarcoma is a rare but serious complication of Paget disease requiring immediate management before further malignant transformation. This case report examines...
Paget osteosarcoma is a rare but serious complication of Paget disease requiring immediate management before further malignant transformation. This case report examines the progression of a previously reported case of Paget disease with atypical pseudotumor manifestation, mimicking osteosarcoma over a 21-year time lapse. After presenting with substantial pain and elevated alkaline phosphatase levels, imaging proved extensive bony expansion of the lesion with high-grade trabecular and cortical thickening and extraosseous soft-tissue extension, prompting the need for biopsy to rule out Paget sarcoma. The atypical features of the pseudotumor's development helps distinguish key radiographic and clinical criteria for malignant development.
Topics: Humans; Osteosarcoma; Sarcoma; Adenocarcinoma; Osteitis Deformans; Bone Neoplasms
PubMed: 37523479
DOI: 10.2106/JBJS.CC.22.00694 -
Calcified Tissue International May 2024In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of...
In this case report, we describe an uncommon case of neuroendocrine cancer of unknown origin began with cauda equina syndrome in a patient affected by Paget disease of bone (PDB). A 76-year-old man with diagnosis of PDB, without history of pain or bone deformity, developed sudden severe low back pain. Bone alkaline phosphatase was increased and MRI and whole-body scintigraphy confirmed the localization of the disease at the third vertebra of the lumbar spine. Treatment with Neridronic Acid was started, but after only 2 weeks of therapy anuria and bowel occlusion occurred together with lower limb weakness and walking impairment. Cauda equina syndrome consequent to spinal stenosis at the level of L2-L3 was diagnosed after admission to Emergency Department and the patient underwent neurosurgery for spinal medulla decompression. The histologic results showed a complete subversion of bone structure in neoplastic tissue, consistent with metastatic neuroendocrine carcinoma of unknown origin. In conclusion, low back pain in the elderly may require deep investigation to individuate rare diseases. In asymptomatic patients with apparently stable PDB, the sudden appearance of pain or neurologic symptoms may alert the clinician for the possibility of other superimposing diseases, like bone metastases.
Topics: Humans; Aged; Male; Osteitis Deformans; Bone Neoplasms; Neuroendocrine Tumors; Cauda Equina Syndrome; Low Back Pain; Lumbar Vertebrae; Carcinoma, Neuroendocrine
PubMed: 38506956
DOI: 10.1007/s00223-024-01195-3 -
AIDS (London, England) May 2024Paget's disease of bone (PDB) has rarely been reported in people with HIV (PWH). We describe the prevalence and characteristics of patients with PDB in the French...
Paget's disease of bone (PDB) has rarely been reported in people with HIV (PWH). We describe the prevalence and characteristics of patients with PDB in the French multicenter Dat'AIDS cohort. Among 49 698 PWH actively followed in 2022, 9 had a diagnosis of PDB. The overall prevalence of PDB was 0.02% [95% confidence interval (CI) 0.01-0.03]. The prevalence of PDB in PWH is very low and does not appear to differ from the non-HIV population.
Topics: Humans; Osteitis Deformans; HIV Infections; Adenocarcinoma
PubMed: 38578964
DOI: 10.1097/QAD.0000000000003874 -
Zhonghua Nei Ke Za Zhi Aug 2023
Topics: Humans; Sequestosome-1 Protein; Osteitis Deformans; Mutation; Proteins; Bone and Bones
PubMed: 37528043
DOI: 10.3760/cma.j.cn112138-20220901-00648