Unveiling the clinical spectrum of relapsing polychondritis: insights into its pathogenesis, novel monogenic causes, and therapeutic strategies.

Relapsing polychondritis is a rare multisystem disease involving cartilaginous and proteoglycan-rich structures. The diagnosis of this disease is mainly suggested by the presence of flares of inflammation of the cartilage, particularly in the ears, nose or respiratory tract, and more rarely, in the presence of other manifestations. The spectrum of clinical presentations may vary from intermittent episodes of painful and often disfiguring auricular and nasal chondritis to an occasional organ or even life-threatening manifestations such as lower airway collapse. There is a lack of awareness about this disease is mainly due to its rarity. In 2020, VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, a novel autoinflammatory syndrome, was described. VEXAS syndrome is attributed to somatic mutations in methionine-41 of UBA1, the major E1 enzyme that initiates ubiquitylation. This new disease entity connects seemingly unrelated conditions: systemic inflammatory syndromes (relapsing chondritis, Sweet's syndrome, and neutrophilic dermatosis) and hematologic disorders (myelodysplastic syndrome or multiple myeloma). Therefore, this article reviews the current literature on both disease entities.

Ultrasound ability in early diagnosis of metatarsal stress fractures.

Stress fractures are common in young and active individuals, associated with aggressive or repetitive physical activity and their early detection is fundamental to optimise patient care, decrease complications and avoid unnecessary exams. Currently, magnetic resonance imaging is the standard of care for detecting these lesions. Recently, ultrasound has been getting an increasing interest for the detection of stress fractures. In this article, we describe a clinical case that involved a second metatarsal stress fracture diagnosed by ultrasound and review the literature regarding the use of ultrasound in the diagnosis of stress fractures, particularly of the metatarsals.

Genetic, Immunological, Dietary, Gut Microbiota, and Environmental Determinants of Osteoporosis in the Course of Celiac Disease: Which Factor Plays the First Violin in This Orchestra?

Celiac disease (CD) is a chronic small intestinal immune-mediated enteropathy precipitated by exposure to dietary gluten in genetically predisposed individuals. The worldwide prevalence of CD is estimated to be 0.7-1.4% of the general population. Etiopathology of this disease is multifactorial, with genetic determinants being a major contributing player to CD susceptibility. Its manifestation embraces different organs, including the musculoskeletal apparat. Patients with CD have increased risk of bone disorders. According to data, bone disorders - osteopenia and osteoporosis - can affect up to 70% of patients with CD at diagnosis, and it decreases after the initiation of a gluten-free diet. Gluten consumption in patients with CD triggers an inflammatory reaction followed by tissue damage, and both; local and systemic inflammation can increase the risk of bone mass deterioration. Other theory assumes shortages of vitamin D and an impaired calcium absorption mechanism leading to secondary hyperparathyroidism. Taking into account the increasing prevalence of CD and osteoporosis, we broadly discuss genetic, immunological, dietary, gut microbiota, and environmental factors that could increase the risk of osteoporosis in CD. Furthermore, we discuss lifestyle and pharmacological preventing and treatment measures.

Association between knee magnetic resonance imaging markers and knee symptoms over 6-9 years in young adults.

OBJECTIVES: To describe associations between MRI markers with knee symptoms in young adults. METHODS: Knee symptoms were assessed using the WOMAC scale during the Childhood Determinants of Adult Health Knee Cartilage study (CDAH-knee; 2008-2010) and at the 6- to 9-year follow-up (CDAH-3; 2014-2019). Knee MRI scans obtained at baseline were assessed for morphological markers (cartilage volume, cartilage thickness, subchondral bone area) and structural abnormalities [cartilage defects and bone marrow lesions (BMLs)]. Univariable and multivariable (age, sex, BMI adjusted) zero-inflated Poisson (ZIP) regression models were used for analysis. RESULTS: The participants' mean age in CDAH-knee and CDAH-3 were 34.95 (s.d. 2.72) and 43.27 (s.d. 3.28) years, with 49% and 48% females, respectively. Cross-sectionally, there was a weak but significant negative association between medial femorotibial compartment (MFTC) [ratio of the mean (RoM) 0.99971084 (95% CI 0.9995525, 0.99986921), P < 0.001], lateral femorotibial compartment (LFTC) [RoM 0.99982602 (95% CI 0.99969915, 0.9999529), P = 0.007] and patellar cartilage volume [RoM 0.99981722 (95% CI 0.99965326, 0.9999811), P = 0.029] with knee symptoms. Similarly, there was a negative association between patellar cartilage volume [RoM 0.99975523 (95% CI 0.99961427, 0.99989621), P = 0.014], MFTC cartilage thickness [RoM 0.72090775 (95% CI 0.59481806, 0.87372596), P = 0.001] and knee symptoms assessed after 6-9 years. The total bone area was negatively associated with knee symptoms at baseline [RoM 0.9210485 (95% CI 0.8939677, 0.9489496), P < 0.001] and 6-9 years [RoM 0.9588811 (95% CI 0.9313379, 0.9872388), P = 0.005]. The cartilage defects and BMLs were associated with greater knee symptoms at baseline and 6-9 years. CONCLUSION: BMLs and cartilage defects were positively associated with knee symptoms, whereas cartilage volume and thickness at MFTC and total bone area were weakly and negatively associated with knee symptoms. These results suggest that the quantitative and semiquantitative MRI markers can be explored as a marker of clinical progression of OA in young adults.

Two Pathological Fractures in a Patient with Chronic Abnormalities in Serum Markers Following Two Liver Transplantations: A Case Report and Literature Review.

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.

Bone Dysregulation in Acute Kidney Injury.

Acute kidney injury (AKI) is a highly prevalent condition with multiple acute and chronic consequences. Survivors of AKI are at risk of AKI-to-chronic kidney disease (CKD) transition, which carries significant morbidity and mortality. One retrospective analysis showed increased risk of bone fracture post-AKI in humans, which was independent of CKD development. While there are several theoretical reasons for late disturbances of bone health post-AKI, no definitive data are available to date. An important question is whether there are bone sequelae from AKI that are independent of CKD, meaning bone disease prior to the onset, or in the absence of CKD - a form of "post-AKI osteopathy." While preclinical studies examining bone health after acute stressors have focused mostly on sepsis models, multiple experimental AKI models are readily available for longitudinal bone health interrogation. Future research should be tailored to define whether AKI is a risk factor, independent of CKD, for bone disease and if present, the time course and type of bone disease. This review summarizes a fraction of the existing data to provide some guidance in future research efforts.

Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement.

BACKGROUND CONTEXT: Patients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions. PURPOSE: In this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments. STUDY DESIGN: Retrospective cohort study. PATIENT SAMPLE: In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included. OUTCOME MEASURES: The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations. METHODS: Data were collected through manual chart review. Hosmer and Lemeshow's purposeful regression method was used to identify risk factors for complications and reoperations. RESULTS: The median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04-1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79-9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30-36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19-5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37-0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript. CONCLUSION: The goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial.

European Achondroplasia Forum guiding principles for the detection and management of foramen magnum stenosis.

Foramen magnum stenosis is a serious, and potentially life-threatening complication of achondroplasia. The foramen magnum is smaller in infants with achondroplasia, compared with the general population, and both restricted growth in the first 2 years and premature closure of skull plate synchondroses can contribute to narrowing. Narrowing of the foramen magnum can lead to compression of the brainstem and spinal cord, and result in sleep apnoea and sudden death. There is a lack of clarity in the literature on the timing of regular monitoring for foramen magnum stenosis, which assessments should be carried out and when regular screening should be ceased. The European Achondroplasia Forum (EAF) is a group of clinicians and patient advocates, representative of the achondroplasia community. Members of the EAF Steering Committee were invited to submit suggestions for guiding principles for the detection and management of foramen magnum stenosis, which were collated and discussed at an open workshop. Each principle was scrutinised for content and wording, and anonymous voting held to pass the principle and vote on the level of agreement. A total of six guiding principles were developed which incorporate routine clinical monitoring of infants and young children, timing of routine MRI screening, referral of suspected foramen magnum stenosis to a neurosurgeon, the combination of assessments to inform the decision to decompress the foramen magnum, joint decision making to proceed with decompression, and management of older children in whom previously undetected foramen magnum stenosis is identified. All principles achieved the ≥ 75% majority needed to pass (range 89-100%), with high levels of agreement (range 7.6-8.9). By developing guiding principles for the detection and management of foramen magnum stenosis, the EAF aim to enable infants and young children to receive optimal monitoring for this potentially life-threatening complication.

Bilateral Rhinogenous Optic Neuropathy Caused by the Regrowth of a Large Sphenoid Sinus Mucocele.

A 59-year-old man, who had a history of left blind at 36 years old, suddenly lost right visual acuity. Magnetic resonance imaging revealed a large left sphenoid sinus cyst, which protruded intracranially. The cyst was fenestrated by endoscopic sinus surgery, but his right vision did not recover. Ten cases of bilateral rhinogenous optic neuropathy caused by mucocele have been reported, and the cause was sphenoid sinus in 9 cases. Postoperative visual acuity in these cases was poor, especially in slow progressive cases, because it was diagnosed as an unknown cause, and surgery was delayed. Rhinogenous optic neuropathy caused by mucocele should be differentiated from bilateral visual impairment of unknown cause. The authors highlight the importance of early diagnosis of sphenoid sinus mucocele and fully informing patients about the future risk of bilateral visual impairment, even if they are asymptomatic or have been treated.

Variable Bone Phenotypes in Patients with Pseudohypoparathyroidism.

PURPOSE OF REVIEW: Pseudohypoparathyroidism (PHP) is a disorder caused by mutations and/or epigenetic changes at the complex GNAS locus. It is characterized by hypocalcemia, hyperphosphatemia, and an elevated parathyroid hormone concentration secondary to the resistance of target tissues to the biological actions of parathyroid hormone. PHP is divided into several subtypes with different yet overlapping phenotypes. Research on the bone status in patients with PHP is sparse and has yielded inconsistent results. This review was performed to summarize the current knowledge on the bone phenotypes and possible mechanisms of PHP. RECENT FINDINGS: Patients with PHP exhibit highly variable bone phenotypes and increased concentrations of bone turnover markers. Long-standing elevation of the parathyroid hormone concentration may lead to hyperparathyroid bone diseases, including rickets and osteitis fibrosa. Compared with normal controls, patients with PHP may exhibit similar, increased, or decreased bone mineral density. Higher bone mineral density has been found in patients with PHP type 1A than in normal controls, whereas decreased bone mass, osteosclerosis, and osteitis fibrosa cystica have been reported in patients with PHP type 1B, indicating more variable bone phenotypes in PHP type 1B. Bone tissues show partial sensitivity to parathyroid hormone in patients with PHP, leading to heterogeneous reactions to parathyroid hormone in different individuals and even in different regions of bone tissues in the same individual. Regions rich in cancellous bone are more sensitive and show more obvious improvement after therapy. Active vitamin D and calcium can significantly improve abnormal bone metabolism in patients with PHP.

Fully constrained acetabular liner vs. dual mobility hip joint in the surgical treatment of metastatic bone disease of the hip: study protocol for a randomized, open-label, two-arm, non-inferiority trial evaluating the post-operative hip dislocation rate.

BACKGROUND: Patients receiving total hip arthroplasty (THA) due to metastatic bone disease of the hip (MBD) are at an increased risk of post-operative joint dislocation compared to other populations. Different joint solutions have been developed with the purpose of reducing the dislocation risk compared to regular THAs. One of these solutions, the constrained liner (CL), has been used increasingly at our department in recent years. This design, however, is prone to polyethylene wear and higher revision rates. An alternative is the dual mobility cup (DM), which has been shown to reduce the risk of dislocation in other high-risk populations. Few studies have investigated DM for THA due to MBD, and no studies have directly compared these two treatments in this population. We therefore decided to conduct a trial to investigate whether DM is non-inferior to CL regarding the post-operative joint dislocation risk in patients receiving THA due to MBD. MATERIALS AND METHODS: This study is a single-center, randomized, open-label, two-arm, non-inferiority trial. We will include 146 patients with MBD of the hip who are planned for THA at the Department of Orthopedic Surgery, Rigshospitalet. Patients with previous osteosynthesis or endoprosthetic surgery of the afflicted hip, or who are planned to receive partial pelvic reconstruction or total femoral replacement, will be excluded. Patients will be stratified by whether subtrochanteric bone resection will be performed and allocated to either CL or DM in a 1:1 ratio. The primary outcome is the 6 months post-operative joint dislocation rate. Secondary outcomes include overall survival, implant survival, the rate of other surgical- and post-operative complications, and quality of life and functional outcome scores. DISCUSSION: This study is designed to investigate whether DM is non-inferior to CL regarding the risk of post-operative dislocation in patients receiving THA due to MBD. To our knowledge, this trial is the first of its kind. Knowledge gained from this trial will help guide surgeons in choosing a joint solution that minimizes the risk of dislocation and, ultimately, reduces the need for repeat surgeries in this patient population. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT05461313. Registered on July 15 2022. This trial is reported according to the items in the WHO Trial Registration Data Set (Version 1.3.1).

Long-term outcomes of ilio-sacral screws in minimally invasive bipolar fusionless technique for neuromuscular scoliosis: a retrospective study in 167 patients.

INTRODUCTION: Pelvic fixation in patients with neuromuscular scoliosis is difficult, due to their fragile general condition and poor bone quality. Many techniques have been described, associated with high rates of mechanical complications. The objective of this work was to evaluate the mechanical complications and long-term radiological results of ilio-sacral screw pelvic fixation. MATERIALS AND METHODS: 167 consecutive patients with neuromuscular scoliosis who underwent minimally invasive bipolar fixation with ilio-sacral screw pelvic fixation were retrospectively reviewed. The instrumentation consisted in a bilateral sliding rods construct extended from T1 to the sacrum, anchored proximally by double-hook claws and distally by ilio-sacral screws through a minimally invasive approach. Mechanical complications and radiographic measurements (angle of the major coronal curve, pelvic obliquity, lumbar lordosis) were evaluated preoperatively, postoperatively, and at the last follow-up. RESULTS: Mean operative age was 12 ± 3 years, and follow-up 6.4 years (3.0-10.4 years). Pelvic obliquity decreased from 20° preoperatively to 5° (77% correction) at last follow-up, Angle of the major coronal curve from 75° to 36° (52% correction), and lumbar lordosis from 28° to 38°. 16 mechanical complications in nine patients occurred: screw prominence (n = 1), connector failure (n = 4), screw malposition (n = 11). Unplanned surgery was required in seven cases, two were managed during rod lengthening, seven did not require treatment. CONCLUSION: In this series of neuromuscular patients operated by ilio-sacral screws as pelvic fixation, the results were stable with a mean follow-up of more than 6 years and the complication rate was reduced comparatively to the literature.

Posterior shoulder dislocation with associated reverse Hill-Sachs lesion: clinical outcome 10 years after joint-preserving surgery.

INTRODUCTION: Posterior shoulder dislocation in association with reverse Hill-Sachs lesion is a rather rare injury. Few studies reporting results after joint-preserving surgery in these cases are available. This current study presents the clinical outcomes 10 years postoperatively. MATERIALS AND METHODS: In a prospective case series, we operatively treated 12 consecutive patients (all males) after posterior shoulder dislocation with associated reverse Hill-Sachs lesion using joint-preserving techniques. Patients received surgery in a single center between January 2008 and December 2011. The joint-preserving surgical procedure was chosen depending on the defect size and bone quality. The following outcome-measures were analyzed: Constant-Score, DASH-Score, ROWE-Score, and SF-12. Results 1, 5, and 10 years postoperatively were compared. RESULTS: Out of 12 patients, ten patients (83.3%) were followed-up with a mean follow-up interval of 10.7 years (range 9.3-12.8). The mean patient age at the time of the last follow-up was 51 years (32-66). The outcome scores at the final follow-up were: Constant 92.5 (range 70.0-100), DASH 3.2 (0.0-10.8), ROWE 91.0 (85.0-100), and SF-12 87.8 (77.5-98.3). Clinical results had improved from 1 to 5 years postoperatively and showed a tendency for even further improvement after 10 years. CONCLUSIONS: Joint-preserving surgical therapy of posterior shoulder dislocation provides excellent results when the morphology of the reverse Hill-Sachs lesion is respected in surgical decision-making. TRIAL REGISTRATION: 223/2012BO2, 02 August 2010.

Three different techniques for pelvic fixation in the management of neuromuscular scoliosis in nonambulatory spastic cerebral palsy: A comparative study of Galveston Rod, iliac screw, and sacroiliac screw.

OBJECTIVE: This study aimed to compare the clinical and radiographic results of three different pelvic fixation techniques, i.e., Galveston Rod, Iliac Screw, and Sacroiliac Screw, in managing neuromuscular scoliosis in nonambulatory children with spastic cerebral palsy (CP). METHODS: This retrospective study included nonambulatory children aged < 18 years with neuromuscular scoliosis secondary to CP, undergoing a spinal fusion and pelvic fixation by either Galveston rod, iliac screw, or sacroiliac screw techniques. The primary outcome variable was to determine the stability of the major curve angle and pelvic obliquity over timeline intervals for each pelvic fixation tech nique. The two radiographic parameters were measured at five timeline intervals and were compared to define stability among the groups. RESULTS: One hundred and one patients (54 females [53%]) with spastic nonambulatory CP met the inclusion criteria; the mean age at sur gery was 13.5±3.1 years. Mean follow-up intervals were first-year (12.9±1.5) and second-year (25.8±2.5). Forty-one patients had minimum five-year (81.5±23 months) postoperative follow-up. Groups were based on pelvic fixation techniques: 25 patients with the Galveston rod, 24 with the iliac screw, and 52 with the sacroiliac screw. Of the 41 patients with a minimum five-year follow-up, 10 had the Galveston rod, 11 had an iliac screw, and 20 had sacroiliac screw fixation. Gross Motor Function Classification System level, medical comorbidities, intra thecal baclofen pump, and vitamin D level were compared with each pelvic fixation technique (P > .05). Major curve angle parameters were measured at the five timelines as 70.5°±21.1°, 15.7°±13°, 15.7°±12°, 17.5°±12.7°, and 15.1°±9.6°, and pelvic obliquity as 14.8°±10.4°, 4.9°±4.2°, 5.7°±4.6°, 5°±4.4°, and 7.2°±4.4°, respectively. After the surgery, corrected major curve angle and pelvic obliquity showed no sta tistically significant difference between pelvic fixation techniques (P > .05) and remained stable over timeline intervals (P > .05). Fifteen patients had complications requiring additional surgery. The iliac screw group (nine patients) had the highest rate of complications. CONCLUSION: All three pelvic fixation techniques can provide equivalent correction for major curve angle and pelvic obliquity in managing neuromuscular scoliosis in nonambulatory CP children. Pelvic obliquity after surgery may remain stable regardless of pelvic fixation type. A higher rate of postoperative complication can be encountered with the iliac screw. LEVEL OF EVIDENCE: Level III, Retrospective Study.

Mechanistic insights into CKD-MBD-related vascular calcification and its clinical implications.

Chronic Kidney Disease (CKD) is linked to a rising prevalence of morbidity and mortality primarily from cardiovascular complications and is considered a high or very high-risk associated cardiovascular state. These poor outcomes are associated with CKD-mineral and bone disorders (CKD-MBD) in CKD patients, which are manifested by vascular calcification. Patients with chronic renal illness have not only accelerated intimal and medial calcification, but heart valves, and possibly the myocardium get also calcified, as well as the uncommon state of calcific uremic arteriolopathy (calciphylaxis). So the CKD-MBD associated vascular calcification might be a key mediator for an array of cardiovascular sequelae. Various routes link vascular calcification with CKD including the involvement of non-traditional risk factors but still, mechanisms are incompletely understood, and focused treatments have been slow to emerge. Major events and factors in vascular calcification involve the conversion of vascular smooth muscles cells into chondrocyte-like cells. Further dysregulation of calcium, phosphate, parathyroid hormone (PTH), Vitamin D hormonal system, phosphorous, and imbalance of promoters and inhibitors (Fetuin-A and Vitamin K dependent matrix Gla protein) plays the important role in promoting CKD-MBD associated vascular calcification. Fibroblast growth factor-23 (FGF-23), Sclerostin, and Klotho are thought to be the emerging factors involved in the CKD-MBD leading to vascular calcification process and cardiovascular mortality. This review summarizes the brief pathological basis of vascular calcification in CKD, current and emerging approaches including the vast arrangement of contributors and inhibitors for the early identification and treatment.

Mineral Bone Disorders in Kidney Disease Patients: The Ever-Current Topic.

Chronic kidney disease (CKD) is a complex and multifactorial disease, and one of the most prevalent worldwide. Chronic kidney disease-mineral bone disorders (CKD-MBD) with biochemical and hormonal alterations are part of the complications associated with the progression of CKD. Pathophysiology of CKD-MBD focused on abnormalities in serum levels of several biomarkers (such as FGF-23, klotho, phosphate, calcium, vitamin D, and PTH) which are discussed in this review. We therefore examine the prognostic association between CKD-MBD and the increased risk for cardiovascular events, mortality, and CKD progression to end-stage kidney disease (ESKD). Lastly, we present specific treatments acting on CKD to prevent and treat the complications associated with secondary hyperparathyroidism (SHPT): control of hyperphosphatemia (with dietary restriction, intestinal phosphate binders, and adequate dialysis), the use of calcimimetic agents, vitamin D, and analogues, and the use of bisphosphonates or denosumab in patients with osteoporosis.

Autosomal recessive LRP1-related syndrome featuring cardiopulmonary dysfunction, bone dysmorphology, and corneal clouding.

We provide the first study of two siblings with a novel autosomal recessive LRP1-related syndrome identified by rapid genome sequencing and overlapping multiple genetic models. The patients presented with respiratory distress, congenital heart defects, hypotonia, dysmorphology, and unique findings, including corneal clouding and ascites. Both siblings had compound heterozygous damaging variants, c.11420G > C (p.Cys3807Ser) and c.12407T > G (p.Val4136Gly) in LRP1, in which segregation analysis helped dismiss additional variants of interest. LRP1 analysis using multiple human/mouse data sets reveals a correlation to patient phenotypes of Peters plus syndrome with additional severe cardiomyopathy and blood vessel development complications linked to neural crest cells.

[Research Progress of Non-coding RNAs in the Regulation of Multiple Myeloma Bone Disease--Review].

Multiple myeloma bone disease is the most common complication of multiple myeloma, which mutually promotes the progression of multiple myeloma, severely affects patients' survival quality and prognosis. Recently, many studies revealed that non-coding RNAs play an important role in the imbalance of bone remodeling by regulating gene expression and participating in various signaling pathways. Additionally, most bone lesions fail to heal even when myeloma patients are in complete remission due to the sustained suppression of osteoblast activity, while non-coding RNAs may become a novel research field and clinical intervention targets. In this review, the latest research advances of non-coding RNAs which affect the occurrence and progress of multiple myeloma bone disease are summarized briefly.

MicroRNA and Diabetic Bone Disease.

PURPOSE OF REVIEW: The incidence of diabetes is increasing worldwide. Diabetes mellitus is characterized by hyperglycemia, which in the long-term damages the function of many organs including the eyes, the vasculature, the nervous system, and the kidneys, thereby imposing an important cause of morbidity for affected individuals. More recently, increased bone fragility was also noted in patients with diabetes. While patients with type 1 diabetes mellitus (T1DM) have low bone mass and a 6-fold risk for hip fractures, patients with type 2 diabetes mellitus (T2DM) have an increased bone mass, yet still display a 2-fold elevated risk for hip fractures. Although the underlying mechanisms are just beginning to be unraveled, it is clear that diagnostic tools are lacking to identify patients at risk for fracture, especially in the case of T2DM, in which classical tools to diagnose osteoporosis such as dual X-ray absorptiometry have limitations. Thus, new biomarkers are urgently needed to help identify patients with diabetes who are at risk to fracture. RECENT FINDINGS: Previously, microRNAs have received great attention not only for being involved in the pathogenesis of various chronic diseases, including osteoporosis, but also for their value as biomarkers. Here, we summarize the current knowledge on microRNAs and their role in diabetic bone disease and highlight recent studies on miRNAs as biomarkers to predict bone fragility in T1DM and T2DM. Finally, we discuss future directions and challenges for their use as prognostic markers.

Diabetic Bone Disease and Diabetic Myopathy: Manifestations of the Impaired Muscle-Bone Unit in Type 1 Diabetes.

Type 1 diabetes is associated with complications affecting muscle and bone, with diabetic bone disease and diabetic myopathy becoming increasingly reported in the past few decades. This review is aimed at succinctly reviewing the literature on the current knowledge regarding these increasingly identified and possibly interconnected complications on the musculoskeletal system. Furthermore, this review summarizes several nonmechanical factors that could be mediating the development and progression of premature musculoskeletal decline in this population and discusses preventative measures to reduce the burden of diabetes on the musculoskeletal system.