Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis

Summary: Baseline serum PINP value was significantly and independently associated with the increased bone mineral density (≥ 3%) in both total hip and femoral necks by 12 months of romosozumab treatment in patients with treatment-naive postmenopausal osteoporosis. Purpose: Some patients fail to obtain a sufficiently increased hip bone mineral density (BMD) by romosozumab (ROMO) treatment. This study aimed to investigate the prognostic factor for increased hip BMD with ROMO in patients with treatment-naive postmenopausal osteoporosis. Methods: This prospective, observational, and multicenter study included patients (n = 63: mean age, 72.6 years; T-scores of the lumbar spine [LS], − 3.3; total hip [TH], − 2.6; femoral neck [FN], − 3.3; serum type I procollagen N-terminal propeptide [PINP], 68.5 µg/L) treated by ROMO for 12 months. BMD and serum bone turnover markers were evaluated at each time point. A responder analysis was performed to assess the patient percentage, and both univariate and multivariate analyses were performed to investigate the factors associated with clinically significant increased BMD (≥ 3%) in both TH and FN. Results: Percentage changes of BMD from baseline in the LS, TH, and FN areas were 17.5%, 4.9%, and 4.3%, respectively. In LS, 96.8% of patients achieved ≥ 6% increased LS-BMD, although 57.1% could not achieve ≥ 3% increased BMD in either TH or FN. Multiple regression analysis revealed that only the baseline PINP value was significantly and independently associated with ≥ 3% increased BMD in both TH and FN (p = 0.019, 95% confidence interval = 1.006–1.054). The optimal cut-off PINP value was 53.7 µg/L with 54.3% sensitivity and 92.3% specificity (area under the curve = 0.752). Conclusions: In a real-world setting, baseline PINP value was associated with the increased BMD of TH and FN by ROMO treatment in treatment-naive patients.This version of the article has been accepted for publication, after peer review (when applicable) and is subject to Springer Nature’s AM terms of use, but is not the Version of Record and does not reflect post-acceptance improvements, or any corrections. The Version of Record is available online at: https://doi.org/10.1007/s00198-022-06642-1Kashii M., Kamatani T., Nagayama Y., et al. Baseline serum PINP level is associated with the increase in hip bone mineral density seen with Romosozumab treatment in previously untreated women with osteoporosis. Osteoporosis International 34, 563 (2023

Juvenile Muscular Atrophy of the Proximal Upper Extremity as So-Called Proximal-Type Hirayama Disease: Case Report and Review of the Literature

Hirayama disease is a distinct type of cervical myelopathy characterized by juvenile onset of unilateral muscular atrophy of a distal upper extremity. We report herein a case with Hirayama disease-like juvenile muscular atrophy involving proximal muscles in the upper extremities. In this case, in the flexion position of the neck, cervical magnetic resonance imaging revealed that the spinal cord was compressed by expansion of the posterior extradural space with forward displacement of the dura matter. These neuroimaging results are identical to those of Hirayama disease. However, the involved muscles in this case were the proximal muscles, unlike Hirayama disease. Five previous cases have displayed this rare subtype of Hirayama disease. The cause of the unique phenotype may be abnormal cervical column alignment, with upper cervical kyphosis producing a higher apex of the vertebral level in a cervical flexion position, resulting in mid-cervical segmental myelopathy

Electron microscopic features of a brain tumor induced in hamster by BK virus, a human papova virus.

In order to locate the target cells for malignant transformation by BK virus (a human papova virus) in hamster brain, electron microscopic observation of tumor originally induced in hamster brain by BK virus was performed. With light microscopy, the BK virus-induced tumor (Vn 17) bore a close resemblance to human malignant ependymoma. Under the electron microscope, numerous microvilli and few cilia were visible on the surface of the tumor cells. These tumor cells were joined to each other by desmosomes. Gap junctions were not observed. Multilayered cuboidal cells were observed around the lumen and blood vessels in the tumor. With regard to fine structure, three types of Vn 17 cells were recognized; ependymal like cells, tanycytes with prominent cell processes, and undifferentiated cells with few cytoplasmic organelles. There was no basal lamina between the ependymal cells and the connective tissue stroma. The Vn 17 cells showed some similarity to the ultrastructural features of the epemdymal cells of newborn rabbits, suggesting that the target cells for Vn 17 may be cells related to ependyma. Malignant transformation of the cells would be initiated in the early stages after BK virus inoculation into the brain of newborn hamsters.</p

Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis

Background: The risk of osteoporosis in patients with rheumatoid arthritis (RA) is frequently overlooked, and investigating a simple indicator in routine care may be beneficial to motivate osteoporosis examination. The aim of this retrospective, case-controlled study was to identify the correlation between serum albumin concentrations and the prevalence of osteoporosis in postmenopausal patients with RA. Methods: This study enrolled 197 patients who underwent dual-energy X-ray absorptiometry of lumbar spine (LS) and proximal femur without osteoporosis treatment [mean age, 67.5 years; disease duration, 12.8 years; Disease Activity Score assessing 28 joints with C-reactive protein, 2.0; prednisolone dose, 4.9 mg/day (usage, 42.6%); and LS T-score, −1.9]. Patients were classified into 2 groups: osteoporosis, defined as ≥ 1 part bone mineral density T-score ≤ −2.5 or history of fragility fracture of the vertebra or proximal femur (121 patients), and non-osteoporosis (76 patients). Groups were then matched by propensity score using clinical backgrounds affecting bone metabolism. Results: In non-matched model, serum albumin concentration was significantly associated with osteoporosis-related factors such as aging, inflammation, physical disability, and glucocorticoid dose. Multivariate logistic regression revealed that serum albumin concentration was independently and significantly associated with osteoporosis risk (odds ratio = 0.22, 95% confidence interval = 0.08, 0.61, p = 0.0033). After propensity score matching, 57 patients for each group showed that in addition to the LS and femoral neck T-scores (p < 0.001), serum albumin concentrations (p = 0.01) remained lower in the osteoporosis group compared to non-osteoporosis group. Receiver operating characteristic curve analysis in non-matched model revealed that when cut-off value of serum albumin concentration for indicating osteoporosis was set at 4.2 g/dl, the area under the curve was 0.69, sensitivity 0.74, and specificity 0.58. Conclusions: Low serum albumin concentration was significantly and independently associated with the prevalence of osteoporosis, which may be considered as one of the osteoporosis-related factors in postmenopausal patients with RA.Nagayama Y., Ebina K., Tsuboi H., et al. Low serum albumin concentration is associated with increased risk of osteoporosis in postmenopausal patients with rheumatoid arthritis. Journal of Orthopaedic Science 27, 1283 (2022); https://doi.org/10.1016/j.jos.2021.08.018

A new therapeutic strategy with istradefylline for postural deformities in Parkinson’s disease

Aim of the study. Postural deformities are common in Parkinson’s disease (PD) patients. Several treatment options have been reported, but responses to these treatments appear unpredictable. Istradefylline is a novel drug for PD. Cases of PD patients whose postural deformities were improved after withdrawal of dopamine agonists and initiation of istradefylline are presented. Materials and Methods. Four consecutive patients with postural deformities including antecollis, Pisa syndrome, and camptocormia were recruited and treated with istradefylline in combination with withdrawal of dopamine agonists, which are possible causes of postural deformities. Results. The dopamine agonists were discontinued an average of 26 months after the development of the postural deformities, and istradefylline was initiated an average of 1.3 months after dopamine agonist withdrawal. Three patients with preserved paraspinal muscle volume showed good responses to the treatment regimen at least two months after dopamine agonist withdrawal. Conclusions and clinical Implications. Postural deformities caused by dopamine agonists generally improve less than two weeks after dopamine agonist withdrawal. Given the response time in the present study, the response was unlikely to be caused solely by dopamine agonist withdrawal. Istradefylline can be a potential therapeutic option; however, appropriate selection of patients for treatment with istradefylline is warranted

Impact of non-motor fluctuations on QOL in patients with Parkinson’s disease

IntroductionLong-term levodopa treatment in patients with Parkinson’s disease (PwPD) often causes motor fluctuations, which are known to affect their quality of life (QOL). These motor fluctuations may be accompanied by fluctuations in non-motor symptoms. There is no consensus on how non-motor fluctuations affect QOL.MethodsThis was a single-center, retrospective study and included 375 patients with Parkinson’s disease (PwPD) who visited the neurology outpatient department of Fukuoka University Hospital between July 2015 and June 2018. All patients were evaluated for age, sex, disease duration, body weight, and motor symptoms by the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale part III, depression scale by the Zung self-rating depression scale, apathy scale, and cognitive function by the Japanese version of The Montreal Cognitive Assessment. A nine-item wearing-off questionnaire (WOQ-9) was used to assess the motor and non-motor fluctuations. QOL in PwPD was investigated using the eight-item Parkinson’s Disease Questionnaire (PDQ-8).ResultsIn total, 375 PwPD were enrolled and classified into three groups according to the presence or absence of motor and non-motor fluctuations. The first group included 98 (26.1%) patients with non-motor fluctuations (NFL group), the second group included 128 (34.1%) patients who presented with only motor fluctuations (MFL group), and the third group included 149 (39.7%) patients without fluctuations in motor or non-motor symptoms (NoFL group). Among them, the PDQ-8 SUM and SI were significantly higher in the NFL group than in the other groups (p &lt; 0.005), implying that the NFL group had the poorest QOL among groups. Next, multivariable analysis showed that even one non-motor fluctuation was an independent factor that worsened QOL (p &lt; 0.001).ConclusionThis study showed that PwPD with non-motor fluctuation had a lower QOL than those with no or only motor fluctuation. Moreover, the data showed that PDQ-8 scores were significantly reduced even with only one non-motor fluctuation

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17)

Frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17) is an autosomal dominant neurodegenerative disorder, which has three cardinal features: behavioral and personality changes, cognitive impairment, and motor symptoms. FTDP-17 was defined during the International Consensus Conference in Ann Arbor, Michigan, in 1996. The prevalence and incidence remain unknown but FTDP-17 is an extremely rare condition. It is caused by mutations in the tau gene, which encodes a microtubule-binding protein. Over 100 families with 38 different mutations in the tau gene have been identified worldwide. The phenotype of FTDP-17 varies not only between families carrying different mutations but also between and within families carrying the same mutations. The pathogenetic mechanisms underlying the disorder are thought to be related to the altered proportion of tau isoforms or to the ability of tau to bind microtubules and to promote microtubule assembly. Definitive diagnosis of FTDP-17 requires a combination of characteristic clinical and pathological features and molecular genetic analysis. Genetic counseling should be offered to affected and at-risk individuals; for most subtypes, penetrance is incomplete. Currently, treatment for FTDP-17 is only symptomatic and supportive. The prognosis and rate of the disease's progression vary considerably among individual patients and genetic kindreds, ranging from life expectancies of several months to several years, and, in exceptional cases, as long as two decades