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Introduction/aims: VCP multisystem proteinopathy 1 (MSP1), encompassing inclusion body myopathy (IBM), Paget's disease of bone (PDB) and frontotemporal dementia (FTD) (IBMPFD), features progressive muscle weakness, fatty infiltration, and disorganized bone structure in Pagetic bones. The aim of this study is to utilize dual-energy x-ray absorptiometry (DXA) parameters to examine it as a biomarker of muscle and bone disease in MSP1., Methods: DXA scans were obtained in 28 patients to assess body composition parameters (bone mineral density [BMD], T-score, total fat, and lean mass) across different groups: total VCP disease (n = 19), including myopathy without Paget's ("myopathy"; n = 12) and myopathy with Paget's ("Paget"; n = 7), and unaffected first-degree relatives serving as controls (n = 6)., Results: In the VCP disease group, significant declines in left hip BMD and Z-scores were noted versus the control group (p ≤ .03). The VCP disease group showed decreased whole body lean mass % (p = .04), and increased total body fat % (p = .04) compared to controls. Subgroup comparisons indicated osteopenia in 33.3% and osteoporosis in 8.3% of the myopathy group, with 14.3% exhibiting osteopenia in the Paget group. Moreover, the Paget group displayed higher lumbar L1-L4 T-score values than the myopathy group., Discussion: In MSP1, DXA revealed reduced bone and lean mass, and increased fat mass. These DXA insights could aid in monitoring disease progression of muscle loss and secondary osteopenia/osteoporosis in MSP1, providing value both clinically and in clinical research., (© 2024 The Authors. Muscle & Nerve published by Wiley Periodicals LLC.)

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., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Introduction: Paget's disease of bone (PDB) frequently presents at an advanced stage with irreversible skeletal damage. Clinical outcomes might be improved by earlier diagnosis and prophylactic treatment., Methods: We randomised 222 individuals at increased risk of PDB because of pathogenic SQSTM1 variants to receive 5 mg zoledronic acid (ZA) or placebo. The primary outcome was new bone lesions assessed by radionuclide bone scan. Secondary outcomes included change in existing lesions, biochemical markers of bone turnover and skeletal events related to PDB., Results: The median duration of follow-up was 84 months (range 0-127) and 180 participants (81%) completed the study. At baseline, 9 (8.1%) of the ZA group had PDB lesions vs 12 (10.8%) of the placebo group. Two of the placebo group developed new lesions versus none in the ZA group (OR 0.41, 95% CI 0.00 to 3.43, p=0.25). Eight of the placebo group had a poor outcome (lesions which were new, unchanged or progressing) compared with none of the ZA group (OR 0.08, 95% CI 0.00 to 0.42, p=0.003). At the study end, 1 participant in the ZA group had lesions compared with 11 in the placebo group. Biochemical markers of bone turnover were significantly reduced in the ZA group. One participant allocated to placebo required rescue therapy with ZA because of symptomatic disease. The number and severity of adverse events did not differ between groups., Conclusions: Genetic testing for pathogenic SQSTM1 variants coupled with intervention with ZA is well tolerated and has favourable effects on the progression of early PDB., Trial Registration Number: ISRCTN11616770., Competing Interests: Competing interests: DS reports receiving honoraria from GE Healthcare outside the submitted work; OC reports receiving lecture fees from Nordic Pharma and financial support for attending conferences from Abbvie, outside the submitted work; GH reports funding from the Royal Osteoporosis Society to her institution and honoraria from Amgen and UCB outside the submitted work; JT reports funding to his institution from the Wellcome trust and Medical Research Council, outside the submitted work and that he is chair of the Royal Osteoporosis Society Research and Innovation grant assessment panel; SYM report receiving lecture fees from Janssen Pharmaceuticals outside the submitted work; RC reports funding to her institution from Kyowa Kirin and Amgen outside the submitted work; WDF reports funding to his institution from Novartis, Takeda, NPS Pharma, Sanofi, Amolyt and Entera-Bio Pharma outside the submitted work and donation of assay materials and evaluation kits from Abbot Diagnostics outside the submitted work; NG reports receiving honoraria from Amgen, UCB, Lilly and Gedeon Richter and support from UCB for attending conferences outside the submitted work; MJS reports funding to his institution from Amgen and Allergen outside the submitted work and funding from the National Health and Medical Research Council of Australia to his institution outside the submitted work; MKK reports funding to his institution from the Medical Research Futures Fund; GM is a member of the Scientific Advisory Board of Osteoporosis Australia; SHR reports funding to his institution from Kyowa Kirin, UCB, the Paget’s Association and the Royal Osteoporosis Society outside the submitted work. The other authors have no interests to declare., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY. Published by BMJ.)

The differential diagnosis for an isolated lytic mastoid lesion is broad, encompassing various conditions requiring careful consideration. These include granulomatous disorders such as Langerhans cell histiocytosis and sarcoidosis, neoplastic processes like multiple myeloma, leukemia, lymphoma, and metastases, primary bone diseases such as Paget's disease, fibrous dysplasia, and osteitis fibrosa cystica, as well as infectious causes like osteomyelitis. In this report, we present a patient with otalgia and an isolated lytic mastoid lesion., (© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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., Competing Interests: Disclosure: The Disclosure of Potential Conflicts of Interest forms are provided with the online version of the article (http://links.lww.com/JBJSCC/C155)., (Copyright © 2023 by The Journal of Bone and Joint Surgery, Incorporated.)

Background: Patients who have Paget's Disease more frequently require total hip arthroplasty (THA) and total knee arthroplasty (TKA) than matched controls. However, controversy remains regarding their outcome. We aimed to evaluate the literature regarding outcomes following THA and TKA in patients who have Paget's Disease., Methods: MEDLINE, EMBASE and Cochrane databases were searched for all articles evaluating outcomes following THA and TKA in patients who have Paget's Disease. Quality of included studies was assessed using the Newcastle-Ottawa Scale., Results: A total of 19 articles (published between 1976 and 2022) were included, comprising 58,695 patients (48,766 controls and 10,018 patients who have Pagets Disease), from 209 potentially relevant titles. Patients with Paget's Disease have a pooled mortality of 32.5% at a mean of 7.8 years (range, 0.1 to 20) following THA and 31.0% at a mean of 8.5 years (range, 2 to 20) following TKA, with a pooled revision rate of 4.4% at 7.2 years (range, 0 to 20) following THA and 2.2% at 7.4 years (range, 2 to 20) following TKA. Renal and respiratory complications, as well as heterotopic ossification and surgical-site infection were the most common post-operative complications., Conclusion: There is marked heterogeneity in outcome reporting of studies assessing arthroplasty in patients who have Paget's Disease, with studies of low to moderate quality. Patients with Paget's Disease undergoing THA and TKA appear to have similar implant longevity as their unaffected counterparts. However, they appear to have an increased risk of medical and surgical complications and may have a higher mortality risk from their procedure., (Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: European and Australian studies have reported a decrease in the prevalence, incidence and clinical severity of Paget's disease of bone (PDB). There are no studies on the current clinical characteristics of PDB in Quebec, Canada., Aims: The purpose of this study was to describe the characteristics of unrelated patients with PDB diagnosed after the year 2000 in our region and to compare them to a historical cohort diagnosed before 2000., Methods: In this retrospective descriptive cohort study, socio-demographic data and clinical characteristics for the contemporary cohort were collected from electronic medical records of patients with PDB followed at our university hospital. For the historical cohort, the same data were collected from the research files of PDB participants in our research program. Inclusion criteria were: age > 18 years, having PDB diagnosed by a rheumatologist, and being followed in our hospital. Exclusion criteria were: having a relative with PDB participating in this study. Variables were reported as mean, standard deviation, frequency and percentage. Chi-square tests were used to compare categorical variables. Continuous values were compared with Wilcoxon-Mann-Whitney tests. Unadjusted p-values and adjusted p-values with the Bonferroni correction method were calculated. A p-value <0.05 was considered statistically significant., Results: Among the 195 patients with PDB in the contemporary cohort, 53.3 % were men, 60.5 % had monostotic involvement, 14.2 % were symptomatic at diagnosis. In comparison to the historical cohort of 173 patients, patients in the contemporary cohort were older at diagnosis (68.7  10.7 vs. 58.5  10.1; p < 0.0001) and had less family history of PDB (13.8 % vs. 33.6 %; p = 0.0024). They also had lower total alkaline phosphatase levels at diagnosis (118.0 (85.0-184.0)) vs. 184.0 (115.0-312.0)); p = 0.0006), a lower pagetic bone number (1.0 (1.0-3.0) vs. 2.0 (1.0-5.0); p < 0.0001), lower pagetic bone fractures (6.7 % vs. 36.7 %; p = 0.0078) and lower bone deformities (13.0 % vs. 54.0 %; p < 0.0001). There was no significant difference for pagetic bone pain (52.0 % vs. 52.6 %; p = 1.0000), percentage of patients who had orthopedic surgery related to PDB complications (8.8 % vs. 28.6 %; p = 1.0000), secondary osteoarthritis (43.0 % vs. 51.6 %; p = 1.0000), and hearing impairment (51.9 % vs. 61.1 %; p = 0.1000)., Conclusion: The contemporary cohort is characterized by an older age at diagnosis, a majority of monostotic disease and fewer complications of PDB. This decline in clinical severity of PDB in Quebec is consistent with studies reported in other countries., Competing Interests: Declaration of competing interest Jacques P. Brown has received research support from Mereo BioPharma, Radius Health, and Servier; has served as a consultant for Amgen, Gilead, Paladin, Pfizer, Servier and Ultragenyx; and has served on speakers' bureau for Amgen, all outside the scope of this manuscript. Laetitia Michou has received honoraria for a conference from Roche, Janssen, Abbvie, Amgen; has served as consultant on Advisory Boards of Pfizer, Roche, Amgen, outside the scope of this paper. The other authors have no competing interest to disclose in relation to this article., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Introduction: Paget's disease of bone (PDB) is a focal bone disorder caused by a marked dysregulation of osteoblasts and osteoclasts in basic multicellular units, leading to abnormal and disorganized deposition of collagen fibers (the so-called 'woven bone'). Therefore, pagetic bones are increased in size, and at increased risk for bone pain, deformities, fractures, osteoarthritis, and, more rarely, neoplastic degeneration., Areas Covered: In this review, we revise the available information concerning the pharmacological treatment of PDB., Expert Opinion: PDB progresses slowly within the affected skeletal sites and, if untreated, often leads to bone overgrowth, with bone pain, deformity, and a likely increased risk of complications. Thus, the primary goal of treatment is the restoration of a normal bone turnover, in order to relieve bone pain or other symptoms and possibly prevent the complications. PDB long remained a poorly treatable disorder until the discovery of antiresorptive agents such as calcitonin first and bisphosphonates (BPs) later. With the recent development of potent intravenous BPs like zoledronate, allowing a better control of disease activity over the long term with a single infusion, has contributed to a marked improvement of the clinical management of this invalidating disorder.

If Paget's disease can undermine Alzheimer's disease, there is the possibility of an association between Alzheimer's disease and Paget's disease. We report the observation of an 81-year-old hypertensive patient with Alzheimer's disease, who presented with an isolated increase in alkaline phosphatase, which led to the discovery of Paget's disease. The physician must therefore be careful to distinguish between genuine Alzheimer's disease and a neurological complication of Paget's disease.

Paget's disease (PDB) is a chronic osteopathy more common in male, Caucasic, European population, after the age of 50 years, that can lead to bone deformities. A challenging surgical solution for affected hip with severe hip osteoarthritis is total hip replacement (THA). We describe a case of THA in a 71-year-old patient with PDB and we present a literature review. In particular we find out that more studies comparing cementless THA with cemented one are necessary, in order to understand if one implant is better than the other.

Paget's disease is a metabolic bone disorder affecting the elderly and characterized by bone resorption followed by compensatory bone formation. Radiography is the imaging modality of choice for the diagnosis whereas bone scintigraphy helps stage the extent of the disease and assess response to treatment. MRI and CT are important imaging methods in the assessment of complications and surgical planning. Osteolytic lesions of Paget's first phase present with well-defined margins on radiographs, most commonly in the femur, pelvis, and skull. Cortical thickening, trabecular coarsening, bone marrow sclerosis, and deformities of long bones are present in the mixed- and late-sclerotic phases., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Dermatomyositis is associated with malignancies and is known to have systemic involvement. However, associations with bone diseases have not been well described in the current literature. This article describes the second reported case of the co-existence of dermatomyositis and Paget's disease of bone (PDB), but this is the first report to describe such co-existence in a specific subtype of dermatomyositis-hypomyopathic dermatomyositis. Our patient was a 51 year old woman who presented with prolonged fever, myalgia, morning stiffness, and rashes pathognomonic of dermatomyositis. There was no muscle weakness clinically, although muscle enzymes were increased and electromyogram revealed myopathic changes. Further imaging showed the incidental finding of a T11 vertebral bone lesion, of which biopsy confirmed the diagnosis of PDB. Our report illustrates the diagnostic approach to bone lesions in patients with dermatomyositis and takes a closer look at the pathophysiology and management implications of the co-occurrence of these two rare diseases., (© Japan College of Rheumatology 2021. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Inclusion Body Myopathy, Paget's Disease of Bone, with Frontotemporal Dementia is a progressive autosomal dominant disease that affects the ubiquitin-proteasome complex, that is caused by variants in the Valosin Containing Protein (VCP) gene. We report the first case of concurrent pathogenic variants in both MYBPC3 and VCP that led to earlier onset of congestive heart failure with features of dilated cardiomyopathy. Cardiomyopathy has previously been associated with VCP inclusion body myopathy mostly at an advanced stage of the disease. Due to acute onset of cardiomyopathy in a previous asymptomatic individual, a cardiomyopathy gene panel was obtained which revealed an additional c.177&#95;187del variant of the MYBPC3 gene. We report a first case of concurrent pathogenic variants in both c.177&#95;187del gene of MYBPC3 and p.R155C VCP that led to earlier onset and a more severe form of the cardiomyopathy., (Copyright © 2022. Published by Elsevier Masson SAS.)

Dual-energy X-ray absorptiometry (DXA) is the method of choice for assessing bone mineral density (BMD). Unfortunately, the performance and interpretation of DXA can be challenging and errors are common. In fact, it has been reported that up to 90% of BMD reports contain at least 1 error. Errors can be the result of technique or interpretative in nature or both and can result in inappropriate diagnosis and management. In this article, we review the various types of pitfalls frequently encountered by physicians interpreting DXA studies. Being aware of these pitfalls will help readers recognize and avoid them when encountered in clinical practice.

We present the case of a 65-year-old man with brown tumors due to secondary hyperparathyroidism. Magnetic resonance imaging of the pelvis showed multiple lesions with expansive bone appearance. Additionally, prostate cancer was diagnosed during this time. For this reason, differential diagnosis was performed through biopsy of the right iliac bone lesion. Brown tumors are caused by osteoclastic activity and fibroblast proliferation; the differential diagnosis of these bone lesions includes giant tumors, metastases, Paget's disease, and paraneoplastic syndrome with high levels of parathyroid hormone-related peptide (PTHrP). This case report describes the coexistence of two pathologies that could explain these images. In this report, we present a case of a 65-year-old man with brown tumors due to secondary hyperparathyroidism and prostate cancer. In this setting, histologic confirmation is recommended.

Hereditary spastic paraplegia (HSP) is a neurodegenerative disorder clinically characterized by slowly progressing spastic paraparesis. We herein report a 50-year-old Japanese woman who presented with slowly progressing spastic paraplegia and a history of Paget's disease of bone (PDB). Genetic testing revealed a mutation of the Valosin-containing protein (VCP) gene (p.Arg155Cys; c.436C>T). This mutation has not been reported to cause HSP with PDB.

Introduction: Paget bone disease (PBD) is characterized by a disorder in the bone remodeling activity at sites of involvement. This can produce dramatic alterations of local bone architecture and causes most of the complications. We aimed to focus on the characteristics of complications of PDB among hospitalized patients., Material and Methods: A retrospective study was conducted, on PBD patients hospitalized in two rheumatology centers from 1994 to 2019. Characteristics of the PBD complications were studied., Results: Sixty-nine patients were collected with a sex ratio of 0.76 and a mean age of 75.4±6.4 years [43-101]. The diagnosis of PBD was established in the average age of 64.2±11.5 years. The primary reason for consultation was pain (78.3%). The PBD was localized in the pelvis (58%), lower limb (42%), spine (36.2%), skull (23.2%) and upper limb (5.8%). It was polyostotic in 44.9% of cases. Dosage of ALP was 324 [68-8390]. The PDB complication rate was 52.2% and it decreased over time. The main complication was osteoarthritis (23.2%), followed by deafness (17.4%), fracture (15.9%), hydrocephalus (7.2%), neurological disease (7.2%) and osteosarcoma (1.4%). The presence of complications was significantly associated with the polyostotic form (p=0.01), the skull localization (p=0.04), an increased ALP (p=0.02)., Conclusion: According to our study, the incidence rate of PBD among hospitalized cases is higher among elderly women and decreases over time. Complications related to PDB are frequent (52%). It concerns patients with a polyostotic form, skull localization and high ALP., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

A 60-year-old man presented to our hospital with complaints of pain and deformity on his right thigh for the past 2 days following a history of accidental slip and fall. Radiological investigations suggested a pathological type 2 Seinsheimer subtrochanteric fracture of the right femur with a 'bone within bone' appearance, which posed a diagnostic dilemma as this radiological appearance is seen in a spectrum of conditions. Radiographic skeletal survey failed to identify a similar appearance elsewhere in the body. Laboratory investigations pointed in favour of bone mineral disease, and histopathological examination of the bone narrowed it down to Paget's disease. The fracture was fixed with a contralateral distal femur locking compression plate. The fracture site failed to show signs of union until 6 months postsurgery and hence the patient was advised for grafting procedure. The patient deferred surgery and remains without major complications until 18 months of follow-up., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Context: Nephrolithiasis (NL) and primary hyperparathyroidism (HPTH) are metabolic complications of Paget disease of bone (PDB), but recent data regarding their prevalence in PDB patients are lacking., Objectives: Study 1: To compare the prevalence of primary HPTH and NL in 708 patients with PDB and in 1803 controls. Study 2: To evaluate the prevalence of NL-metabolic risk factors in 97 patients with PDB and NL, 219 PDB patients without NL, 364 NL patients without PDB, and 219 controls, all of them without HPTH., Design: Cross-sectional multicentric study., Setting: Italian referral centers for metabolic bone disorders., Participants: Patients with PDB from the Associazione Italiana malati di osteodistrofia di Paget registry. Participants in the Olivetti Heart and the Siena Osteoporosis studies., Main Outcome Measures: HPTH; NL; NL-metabolic risk factors., Results: Patients with PDB showed higher prevalence of primary HPTH and NL compared with controls (P < 0.01). The NL recurrence occurs more frequently in patients with polyostotic PDB. About one-half of patients with PDB but without NL showed 1 or more NL-related metabolic risk factors. The hyperoxaluria (HyperOx) prevalence was higher in patients with PDB and NL compared with patients with NL but without PDB and in patients with PDB without NL compared with controls (P = 0.01). Patients with PDB and HyperOx showed a longer lapse of time from the last aminobisphosphonate treatment., Conclusions: NL and HPTH are frequent metabolic complication of PDB. The NL occurrence should be evaluated in patients with PDB, particularly in those with polyostotic disease and/or after aminobisphosphonate treatment to apply an adequate prevention strategy., (© Endocrine Society 2020. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Paget bone disease is a chronic benign bone disease characterized by excessive and abnormal bone remodeling. The scintigraphic and bone SPECT/CT hybrid imaging appearances of the affected bone(s) depend on the stage of the disease. We report the case of a patient newly diagnosed with prostate cancer who was found to have multiple osseous metastases, with coexisting Paget disease in the left hemipelvis diagnosed because of typical scintigraphic and SPECT/CT appearance. Ga-prostate-specific membrane antigen PET/CT was also performed for initial staging. Pagetoid bones showed increased prostate-specific membrane antigen uptake like skeletal metastases.

Paget disease of bone is a benign disorder characterized by focal areas of increased bone turnover in one or more skeletal sites. It usually affects older adults, and men are at a higher risk than women. Any bone may be affected, but the disease has a high preference for the pelvis, spine, skull, and long bones. Pain is the most common symptom, and presentation of the disease may depend on which bones are affected, the extent of involvement, and the presence of complications. Paget disease of bone may be asymptomatic, and suspicion arises from incidental findings of elevated serum alkaline phosphatase levels on routine blood work or abnormalities on imaging tests performed for an unrelated cause. Evidence-based guidelines recommend the use of plain radiography and serum alkaline phosphatase testing for initial diagnosis and radionuclide scans for delineation of the extent of disease. Treatment with nitrogen-containing bisphosphonates is recommended in active disease or when risk of complications is possible. Complications of the disease include arthritis, gait changes, hearing loss, nerve compression syndromes, and osteosarcoma. Total serum alkaline phosphatase is the suggested marker for assessing treatment response when high bone turnover occurs, and it should be measured at three to six months to evaluate initial response. Early diagnosis of Paget disease of bone remains key to its management because patients generally have a good prognosis if treatment is initiated before major complications arise. The primary care physician may need to consult with a specialist for confirmation of diagnosis and initiation of treatment.

Air-bone gaps (ABGs) are commonly found in patients with conductive or mixed hearing loss generally due to outer- and/or middle-ear diseases such as otitis externa, tympanic membrane perforation, interruption or fixation of the ossicular chain, and chronic suppurative otitis media. ABGs can also be found in correlation with inner-ear disorders, such as endolymphatic hydrops, enlarged vestibular aqueduct syndrome, semicircular canal dehiscence, gusher syndrome, cochlear dehiscence, and Paget disease's as well cerebral vascular anomalies including dural arteriovenous fistula. The typical clinical presentation of inner-ear conditions or cerebral vascular anomalies causing ABGs includes audiological and vestibular symptoms like vertigo, oscillopsia, dizziness, imbalance, spinning sensation, pulsatile or continuous tinnitus, hyperacusis, autophony, auricular fullness, Tullio's phenomenon, and Hennebert's sign. Establishing a definitive diagnosis of the underlying condition in patients presenting with an ABG is often challenging to do and, in many patients, the condition may remain undefined. Results from an accurate clinical, audiological, and vestibular evaluation can be suggestive for the underlying condition; however, radiological assessment by computed tomography and/or magnetic resonance imaging is mandatory to confirm any diagnostic suspicion. In this review, we describe and discuss the most recent updates available regarding the clinical presentation and diagnostic workup of inner-ear conditions that may present together with ABGs.

Objective: Paget's disease of the bone (PDB) is a focal bone disorder characterized by excessive resorption and deposition of pathologic bone. It can involve the skull and cause neurologic dysfunction. Hydrocephalus occurring as a complication has also been reported. However, owing to its rarity, the optimal treatment has not yet been determined., Methods: We report the case of a 60-year-old woman with a diagnosis of PDB who had presented with symptomatic hydrocephalus and was successfully treated with ventriculoperitoneal shunt insertion. We also performed a systematic review of the Scopus and PubMed databases for case reports and series documenting patients with PDB complicated by hydrocephalus and discussed the clinical features and therapeutic strategies used., Results: We found 28 cases of PDB complicated by hydrocephalus in reported studies, including the present case. The median age was 67 years (range, 48-85 years; interquartile range, 7 years), with a female sex predilection. The most common neurologic manifestations were cognitive impairment, gait unsteadiness, urinary incontinence, hearing loss, and headache. Surgery had been performed in 73% of the 28 cases. The most common operation was insertion of a ventriculoperitoneal shunt (63.2%). Cerebrospinal fluid diversion resulted in significant or complete neurologic recovery in 78.9% of the 28 patients. Posterior fossa decompression was performed in 15.8% of operative cases but did not significantly alter the clinical course., Conclusion: Patients with hydrocephalus occurring as a complication of PDB will most commonly present with cognitive impairment, gait unsteadiness, and urinary incontinence. Surgery plays an important role in the treatment, with CSF diversion procedures resulting in significant neurologic recovery in most cases., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Context: Intravenous aminobisphosphonates (N-BPs) can induce an acute phase reaction (APR) in up to 40% to 70% of first infusions, causing discomfort and often requiring intervention with analgesics or antipyretics., Objective: Our aim was to explore the risk factors of APR in a large sample of patients with Paget's disease of bone (PDB) and to assess the possible preventive effects of vitamin D administration., Methods: An observational analysis was performed in 330 patients with PDB at the time of N-BP infusion. Then, an interventional study was performed in 66 patients with active, untreated PDB to evaluate if vitamin D administration (oral cholecalciferol 50 000 IU/weekly for 8 weeks before infusion) may prevent APR., Results: In a retrospective study, APR occurred in 47.6% and 18.3% of naive or previously treated patients, respectively. Its prevalence progressively increased in relation to the severity of vitamin D deficiency, reaching 80.0% in patients with 25-hydroxyvitamin D (25OHD) levels below 10 ng/mL (relative risk (RR) = 3.7; 95% confidence interval (CI) 2.8-4.7, P < .0001), even in cases previously treated with N-BPs. Moreover, APR occurred more frequently in patients who experienced a previous APR (RR = 2.8; 95% CI 1.5-5.2; P < .001) or in carriers of SQSTM1 mutation (RR = 2.3; 95% CI 1.3-4.2; P = .005). In the interventional study, vitamin D supplementation prevented APR in most cases, equivalent to a RR of 0.31 (95% CI 0.14-0.67; P < .005) with respect to prevalence rates of the observational cohort. A similar trend was observed concerning the occurrence of hypocalcemia., Conclusions: The achievement of adequate 25OHD levels is recommended before N-BP infusion in order to minimize the risk of APR or hypocalcemia in PDB., (© Endocrine Society 2019. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Paget's disease of bone (PDB) is characterised by increased and disorganised bone remodelling affecting one or more skeletal sites. Complications include bone pain, deformity, deafness and pathological fractures. Mutations in sequestosome-1 ( SQSTM1 ) are strongly associated with the development of PDB. Bisphosphonate therapy can improve bone pain in PDB, but there is no evidence that treatment alters the natural history of PDB or prevents complications. The Zoledronate in the Prevention of Paget's disease trial (ZiPP) will determine if prophylactic therapy with the bisphosphonate zoledronic acid (ZA) can delay or prevent the development of PDB in people who carry SQSTM1 mutations., Methods and Analysis: People with a family history of PDB aged >30 years who test positive for SQSTM1 mutations are eligible to take part. At the baseline visit, participants will be screened for the presence of bone lesions by radionuclide bone scan. Biochemical markers of bone turnover will be measured and questionnaires completed to assess pain, health-related quality of life (HRQoL), anxiety and depression. Participants will be randomised to receive a single intravenous infusion of 5 mg ZA or placebo and followed up annually for between 4 and 8 years at which point baseline assessments will be repeated. The primary endpoint will be new bone lesions assessed by radionuclide bone scan. Secondary endpoints will include changes in biochemical markers of bone turnover, pain, HRQoL, anxiety, depression and PDB-related skeletal events., Ethics and Dissemination: The study was approved by the Fife and Forth Valley Research Ethics Committee on 22 December 2008 (08/S0501/84). Following completion of the trial, a manuscript will be submitted to a peer-reviewed journal. The results of this trial will inform clinical practice by determining if early intervention with ZA in presymptomatic individuals with SQSTM1 mutations can prevent or slow the development of bone lesions with an adverse event profile that is acceptable., Trial Registration Number: ISRCTN11616770., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. Published by BMJ.)

Incidental findings on PET CT studies are common. The distribution of Ga-DOTATATE is dependent on cell surface expression of somatostatin receptors, which may be pathologic or physiologic. Osteoporosis circumscripta is the early lytic phase of Paget disease associated with well-defined osteopenia, most commonly seen within the skull on imaging. The appearance has been well demonstrated on Tc HDP/MDP bone scans. Here, we present the case of a 76-year-old man with a small bowel carcinoid tumor who underwent staging imaging with Ga-DOTATATE PET CT with the incidental finding of osteoporosis circumscripta.

BACKGROUND Paget disease is a primary bone disease with adjacent joint involvement that commonly presents with degenerative arthritis. Rheumatoid arthritis (RA) is mainly an articular disease with symmetric synovitis of the peripheral joints and usually does not involve the lumbar spine. The coexistence of Rheumatoid Arthritis and Paget disease of bone is infrequently reported in the literature. CASE REPORT A 74-year-old African-American man was referred for the investigation of symmetrical polyarthritis, left upper arm joint deformity, and low back pain. X-ray imaging of the hands demonstrated bilateral erosions and deformities of the carpal bones, and the left arm showed mixed lytic and sclerotic bone lesions. Laboratory tests showed high levels of rheumatoid factor and alkaline phosphatase. Analysis of the synovial fluid from the left knee was consistent with inflammatory joint disease. CONCLUSIONS The purpose of this article is to present the diagnostic challenges associated with the rare coexistence of Rheumatoid Arthritis and Paget disease of bone in the same patient. The correct diagnosis of both diseases has important consequences in preventing treatment delay.

Paget's disease of bone (PDB) is a chronic skeletal disorder that can affect one or several bones in individuals older than 55 y of age. PDB-like changes have been reported in archaeological remains as old as Roman, although accurate diagnosis and natural history of the disease is lacking. Six skeletons from a collection of 130 excavated at Norton Priory in the North West of England, which dates to medieval times, show atypical and extensive pathological changes resembling contemporary PDB affecting as many as 75% of individual skeletons. Disease prevalence in the remaining collection is high, at least 16% of adults, with age at death estimations as low as 35 y. Despite these atypical features, paleoproteomic analysis identified sequestosome 1 (SQSTM1) or p62, a protein central to the pathological milieu of PDB, as one of the few noncollagenous human sequences preserved in skeletal samples. Targeted proteomic analysis detected >60% of the ancient p62 primary sequence, with Western blotting indicating p62 abnormalities, including in dentition. Direct sequencing of ancient DNA excluded contemporary PDB-associated SQSTM1 mutations. Our observations indicate that the ancient p62 protein is likely modified within its C-terminal ubiquitin-associated domain. Ancient miRNAs were remarkably preserved in an osteosarcoma from a skeleton with extensive disease, with miR-16 expression consistent with that reported in contemporary PDB-associated bone tumors. Our work displays the use of proteomics to inform diagnosis of ancient diseases such as atypical PDB, which has unusual features presumably potentiated by yet-unidentified environmental or genetic factors., Competing Interests: The authors declare no conflict of interest., (Copyright © 2019 the Author(s). Published by PNAS.)

Introduction and Objectives: Paget's disease of bone (PDB) may lead to hearing loss. The present study was conducted with the aim of measuring, characterizing and determining the risk factors for hearing loss in a group of subjects with PDB., Methods: An observational, transversal, case-control study was conducted, a cohort of 76 subjects diagnosed with PDB in the case group and a control group of 134 subjects were included. Clinical, demographic and audiometric data were analysed., Results: The comparative analysis between the subjects in the PDB group and the control group found that the case group showed higher hearing thresholds (39,51dB) compared with the control group (37.28dB) (P=.069) and presented a greater rate of conductive hearing loss (22.76%) than the control group (12.05%) (P=.0062). The study of risk factors for hearing loss found that skull involvement in bone scintigraphy, age and high blood pressure were risk factors for higher impairment in PDB., Conclusions: The subjects with PDB showed more profound and a higher proportion of conductive hearing loss than the control group. The patients with PDB and skull involvement presented a more severe hearing loss compared with the subjects without skull involvement. Skull involvement and age were found to be risk factors for hearing loss., (Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.)

We present the case of a 75-year-old man with a rapidly progressive cervical myelopathy on a background of a 3-year history of neck pain and a severely degenerative cervical spine. The patient developed progressive myelopathy over a six-month period and suffered from worsening kyphosis. Suspicion of an underlying oncological process prompted transfer to our tertiary referral unit. Biopsy was consistent for Paget's disease, an extremely rare diagnosis of the cervical spine. Magnetic resonance imaging revealed cord compression between C4 and C6 with associated cord signal change indicative of myelopathy. A three-level corpectomy and posterior instrumented fusion was performed. There was significant blood loss (3.5l) intraoperatively, consistent with a diagnosis of Paget's disease of the bone. Cell salvage was used, as was neuromonitoring for both the anterior and posterior part of the procedure. Postoperatively, neurological function improved slightly and the patient required community neurorehabilitation to allow independent living.

Purpose: Scanty data about glucose metabolism and hypertension have been reported in Paget's disease of bone (PDB) to be related with increased cardiovascular mortality. The aim of the present study was to evaluate glucose and blood pressure levels in PDB, looking for their association with disease severity., Methods: We performed an observational cross-sectional study in 54 patients with PDB and 54 age, sex and BMI-matched controls. Glucose and blood pressure levels and parameters of bone and mineral metabolism were assessed., Results: Patients with PDB showed increased glucose levels (6.3 ± 1.7 vs 5.3 ± 1.4 mmol/l, p < 0.001) and prevalence of impaired fasting glucose (14.8%, 5.3-24.3 vs 1.9%, 0-5.4, p < 0.02) as well as enhanced systolic blood pressure (145.9 ± 21.3 vs 132.9 ± 18.9 mmHg, p < 0.005), pulse pressure (69.6 ± 20.0 vs 56.0 ± 16.9 mmHg, p < 0.01) and prevalence of isolated systolic hypertension (46.3%, 33.0-59.6 vs 16.7%, 6.7-26.6, p < 0.003) in comparison to controls. Moreover, we found a positive association of (1) glucose levels with ionized calcium and bone alkaline phosphatase; (2) both systolic and pulse pressure with total and bone alkaline phosphatase (p < 0.05). By multiple linear regression analysis (R 2  = 0.26; p < 0.05) serum ionized calcium correlated with glucose levels (β = 0.44; p < 0.04), after adjusting for age and BMI., Conclusions: Our study shows increased fasting glucose, systolic and pulse pressure levels as well as enhanced prevalence of impaired fasting glucose and isolated systolic hypertension in PDB, potentially accounting for increased cardiovascular mortality. Furthermore, our findings suggest high serum calcium and/or increased bone alkaline phosphatase as a link between PDB and cardio-metabolic disorders.

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Background: We present a rare case of Paget's disease (PD) with involvement of the lumbar spine over a period of 19 years. We discuss the diagnostic process to rule out alternative diagnoses and medical and surgical treatment strategies., Case Description: A 58-year-old man first diagnosed with PD in 1998 with solid involvement of the 4th lumbar vertebra has been undergoing periodic examinations over a period of 18 years. Since then, the patient has been treated conservatively with bisphosphonates. When conservative treatment options have been exhausted, surgery was indicated due to a progressively reduced ability to walk. Surgery with undercutting decompression via laminotomy was performed. PD was confirmed by biopsy. Bisphosphonate treatment was continued pre- and postoperatively. Follow-up examinations showed an improvement in clinical outcome measures., Conclusions: Conservative treatment remains the gold standard for PD with spinal involvement. This patient had been asymptomatic on bisphosphonate therapy for almost 17 years, but presented with new onset back pain. In such cases, fracture and rare conversion into sarcoma must be ruled out, and biopsy should be performed even in the absence of signs of malignancy. Currently, there are no clear treatment recommendations available in the literature regarding cases of PD with expansive growth and involvement of the spinal canal causing neurologic deficits. Furthermore, laminectomy has been shown to cause complications in up to 27% of cases with the risk of early postoperative death. In contrast, extended laminotomy and undercutting decompression should be considered.

Paget's disease of bone (PDB) is an age-related metabolic bone disorder, characterised by focally increased and disorganised bone remodelling initiated by abnormal and hyperactive osteoclasts. The germline P392L mutation of SQSTM1 (encoding p62) is a strong genetic risk factor for PDB in humans, and the equivalent mutation in mice (P394L) causes a PDB-like disorder. However, it is unclear why pagetic lesions become more common with age. Here, we assessed the effect of the p62 P394L mutation on osteoclastogenesis and bone morphometry in relation to ageing, the natural history of lesion progression in p62 P394L mice and the effect of zoledronic acid (ZA) on lesion development. p62 P394L+/+ osteoclast precursors had increased sensitivity to RANKL (also known as TNFSF11) compared with wild-type (WT) cells, and the sensitivity further increased in both genotypes with ageing. Osteoclastogenesis from 12-month-old p62 P394L+/+ mice was twofold greater than that from 3-month-old p62 P394L+/+ mice ( P <0.001) and three-fold greater than that from age-matched WT littermates. The p62 P394L+/+ mice lost 33% more trabecular bone volume in the long bones by 12 months compared with WT mice ( P <0.01), and developed pagetic-like lesions in the long bones which progressed with ageing. ZA prevented the development of pagetic-like lesions, and increased trabecular bone volume tenfold compared with vehicle by 12 months of age ( P <0.01). This demonstrates that ageing has a pro-osteoclastogenic effect, which is further enhanced by the p62 P394L mutation, providing an explanation for the increased penetrance of bone lesions with age in this model. Lesions are prevented by ZA, providing a rationale for early intervention in humans., Competing Interests: Competing interestsS.H.R. has received honoraria to his institution from Novartis, is in receipt of research grants from Eli Lilly and UCB, and was an investigator in clinical trials sponsored by Abbvie, Ultragenyx, Amgen, Gilead and Eli Lilly. The other authors have no competing interests to declare., (© 2018. Published by The Company of Biologists Ltd.)

The interleukin (IL)-6 biological system plays a key role in the pathogenesis of Paget disease (PD) of bone and pathological bone pain. Bone pain, particularly in the lower back region, is the most frequent symptom in patients with PD. This case-control study aimed to evaluate the relationship between the IL-6 system and low back pain (LBP) in patients with PD. We evaluated 85 patients with PD, with the disease localized in the lumbar spine, pelvis, and/or sacrum, and classified them based on the presence or absence of LBP, before and after aminobisphosphonate treatment. We also examined 32 healthy controls without LBP. Before treatment, IL-6 levels in patients with PD were higher than those in the controls, without difference between patients with or without LBP. Patients with PD with LBP (35/85) showed higher IL-6-soluble receptor (sIL-6R) and lower soluble glycoprotein (sgp) 130 levels compared with both patients with PD without LBP and controls (sIL-6R: 46.9 ± 7.4 vs 35.4 ± 8.6 vs 29.9 ± 4.2 ng/mL; sgp130: 307.2 ± 35.4 vs 341.4 ± 41.4 vs 417.1 ± 58.5 ng/mL, respectively). Paget disease remission, 6 months after treatment, is associated with LBP improvement. This phenomenon is associated with reduced sIL-6R levels and increased sgp130 levels in patients with PD with LBP at the baseline. Considering the biological properties of IL-6, sIL-6R, and sgp130, the results of the study suggest that the perception of LBP in patients with PD could be linked to an enhanced transmission of IL-6 signal in the specialized neural system activated by nociceptors.

Mutations of the human VCP gene, which encodes the V: alosin C: ontaining P: rotein (synonyms: p97, TER ATPase), are associated with various multi-systemic protein aggregation diseases. We report on a patient with progressive myopathy and incipient cognitive deficits. A diagnostic muscle biopsy revealed an inclusion body myopathy with protein aggregates. Magnetic resonance imaging and F18-positron-emission-tomography disclosed a fronto-temporal atrophy and glucose hypometabolism of the frontal and temporal lobes, respectively. Based on the clinical findings, a genetic analysis was performed which revealed a heterozygous c.277C>T (p.Arg93Cys) mutation of the VCP gene, thus confirming the diagnosis of IBMPFD (I: nclusion B: ody M: yopathie with P: aget Disease of the Bones and F: ronto-temporal D: ementia)., Competing Interests: D. Mengel, D. Librizzi, B. Schoser, D. Gläser, C.S. Clemen, R. Dodel und R. Schröder geben an, dass kein Interessenkonflikt in Bezug auf den Inhalt des Artikels besteht., (© Georg Thieme Verlag KG Stuttgart · New York.)

Background: Osteonecrosis of the jaw (ONJ) is a serious complication of both radiation and antiresorptive therapies. This study aimed to determine how many patients have been treated for medication-related osteonecrosis of the jaws (MRONJ) and osteoradionecrosis (ORN), and whether the number of diagnoses has decreased over time with improved awareness and preventative measures., Methods: Medical records at the Royal Brisbane and Women's Hospital, Gold Coast University Hospital and Robina Hospital were reviewed to identify patients diagnosed with MRONJ and ORN between January 2003 and May 2017. Data on patient demographics, year of admission and primary disease were analysed., Results: Two hundred and thirty-eight patients were diagnosed with ONJ, of which 74.4% were ORN and 25.6% were MRONJ. Tongue (24.6%), floor of mouth (17.3%) and tonsillar (15.1%) squamous cell carcinomas were the most common primary diseases associated with ORN, with a strong male predominance (80%). Of patients diagnosed with MRONJ, 52.5% were taking low-dose antiresorptives for osteoporosis (44.2%), rheumatoid arthritis (4.6%) or Paget's disease (3.3%), while 47.5% were oncology patients receiving high-dose antiresorptives., Conclusions: The number of patients diagnosed with MRONJ and ORN has trended upwards since 2003. ORN affected three times more patients than MRONJ, and patients on low-dose antiresorptives accounted for over half of the MRONJ cases., (© 2018 Australian Dental Association.)

Paget's disease of bone is the second most common metabolic bone disease after osteoporosis. Its pathogenesis is not yet clearly understood. Geographic distribution and epidemiological variations suggest a role of genetic and environmental factors in its pathophysiology. The frequency of the Paget's disease of bone increases with age. Its discovery can be fortuitous. Prognosis mainly depends on the occurrence of complications involving bones and joints, neurological, cardiovascular or metabolic systems. Treatment of symptomatic forms currently relies on bisphosphonates that have transformed its prognosis., (Copyright © 2017 Société Nationale Française de Médecine Interne (SNFMI). Published by Elsevier SAS. All rights reserved.)

Purpose of Review: Several bone disorders affecting the skeleton often are manifest in the maxillofacial region. This review presents the most common bone disorders in children and their dental-oral manifestations: fibrous dysplasia, Paget's disease, osteogenesis imperfecta, renal osteodystrophy, hypophosphatasia, and osteoporosis. The specific intraoral characteristics will reviewed in detail., Recent Findings: Recent studies confirmed the close relationship between the mandible and the maxilla with the most prevalent systemic bone disorders in children. This review will help practitioners to integrate the oral health into the systemic health and improve the multidisciplinary approach of pediatric patients between medicine and dentistry.