Growth Rate and Bone Hydroxyproline Concentration in Turkeys Fed with a Silage-Composed Diet Modified with Different Diet Cation–Anion Differences (DCADs)

Our goal was to determine the responses of body weight (BW) and bone hydroxyproline (Hyp) concentration in turkeys fed a corn silage (CS) diet with different values of dietary cation–anion differences (DCADs). The turkeys (n = 90) were divided into five groups and fed as follows: group A (control)—standard diet (SD) (60%) plus CS (40%); group B—SD (60%), CS (40%) plus 240 g of CaCl2 per 100 kg of diet; group C—SD (60%), CS (40%) plus 480 g of CaCl2 per 100 kg of diet; group D—SD (60%), CS (40%) plus 240 g of NaHCO3 per 100 kg of diet; group E—SD (60%), CS (40%) plus 480 g NaHCO3 per 100 kg of diet. The addition of a lesser amount of CaCl2 lowered the DCAD, which ranged between 52.5 ± 4.19 and 91.14 ± 3.14 mEq/kg DM. An increased content of CaCl2 led to high negative values of DCAD. NaHCO3 supplemented in both doses resulted in a significant elevation of DCAD. Compared to each experimental group, feeding birds with a diet supplemented only with CS resulted in a lower BW. Addition of CaCl2 or NaHCO3 to the diet improved BW, but only CaCl2 addition enhanced the bone Hyp amount. In conclusion, we suggest that an anionic diet with low DCAD can prevent bone abnormalities in large turkeys, especially in the final course of production.

Spondyloocular Syndrome: A Novel XYLT2 Variant with Description of the Neonatal Phenotype

Spondyloocular syndrome (SOS) is a skeletal disorder caused by pathogenic variants in XYLT2 gene encoding a xylotransferase involved in the biosynthesis of proteoglycans. This condition, with autosomal recessive inheritance, has a high phenotypic variability. It is characterized by bone abnormalities (osteoporosis, fractures), eye and cardiac defects, hearing impairment, and varying degrees of developmental delay. Until now only 20 mutated individuals have been reported worldwide. Here, we describe two siblings from consanguineous healthy parents in which a novel homozygous frameshift variant c.1586dup p(Thr530Hisfs*) in the XYLT2 gene was detected by exome sequencing (ES). The first patient (9 years) presented short stature with skeletal defects, long face, hearing loss and cataract. The second patient, evaluated at a few days of life, showed macrosomia, diffuse hypertrichosis on the back, overabundant skin in the retronucal area, flattened facial profile with drooping cheeks, elongated eyelid rims, wide and flattened nasal bridge and turned down corners of the mouth. During the prenatal period, high nuchal translucency and intestinal hyperechogenicity were observed at ultrasound. In conclusion, these two siblings with a novel pathogenic variant in XYLT2 further expand the clinical and mutational spectrum of SOS.

DCIR and its ligand asialo-biantennary N-glycan regulate DC function and osteoclastogenesis

Dendritic cell immunoreceptor (DCIR) is a C-type lectin receptor with a carbohydrate recognition domain and an immunoreceptor tyrosine-based inhibitory motif. Previously, we showed that Dcir−/− mice spontaneously develop autoimmune enthesitis and sialadenitis, and also develop metabolic bone abnormalities. However, the ligands for DCIR functionality remain to be elucidated. Here we showed that DCIR is expressed on osteoclasts and DCs and binds to an asialo-biantennary N-glycan(s) (NA2) on bone cells and myeloid cells. Osteoclastogenesis was enhanced in Dcir−/− cells, and NA2 inhibited osteoclastogenesis. Neuraminidase treatment, which exposes excess NA2 by removing the terminal sialic acid of N-glycans, suppressed osteoclastogenesis and DC function. Neuraminidase treatment of mice ameliorated collagen-induced arthritis and experimental autoimmune encephalomyelitis in a DCIR-dependent manner, due to suppression of antigen presentation by DCs. These results suggest that DCIR activity is regulated by the modification of the terminal sialylation of biantennary N-glycans, and this interaction is important for the control of both autoimmune and bone metabolic diseases.

Jaw involvement in Gaucher disease: a not-so-uncommon feature of a rare disease

Gaucher disease is an inborn error of metabolism resulting from the deficiency of the enzyme glucocerebrosidase and consequent accumulation of glucocerebroside within the lysosomes of macrophages. The clinical presentation is very diverse, depending on the age of onset and the severity of the disease, and results from the progressive infiltration of lipid-laden cells in various organs. Common manifestations of Gaucher disease include enlarged liver and/or spleen (hepatosplenomegaly), bone marrow disease (pancytopenia) and bone abnormalities, which are extremely variable and can affect multiple skeletal sites. While bone involvement of long bones and vertebrae is a well-recognised feature of Gaucher disease, jawbone involvement is less commonly noted. Here, we describe a case of a 63-year-old patient with type 1 Gaucher disease with a history of long-term use of bisphosphonates and who had presented with dental pain, with subsequent investigations confirming the radiological features of jaw involvement in Gaucher disease, including periodontal disease.

Radiographs of 366 removed limb lengthening nails reveal differences in bone abnormalities between different nail types

Aims Limb lengthening nails have largely replaced external fixation in limb lengthening and reconstructive surgery. However, the adverse events and high prevalence of radiological changes recently noted with the STRYDE lengthening nail have raised concerns about the use of internal lengthening nails. The aim of this study was to compare the prevalence of radiological bone abnormalities between STRYDE, PRECICE, and FITBONE nails prior to nail removal. Methods This was a retrospective case series from three centres. Patients were included if they had either of the three limb lengthening nails (STYDE, PRECICE, or FITBONE) removed. Standard orthogonal radiographs immediately prior to nail removal were examined for bone abnormalities at the junction of the telescoping nail parts. Results In total, 306 patients (168 male, 138 female) had 366 limb lengthening nails removed. The mean time from nail insertion to radiological evaluation was 434 days (36 to 3,015). Overall, 77% of STRYDE nails (20/26) had bone abnormalities at the interface compared with only 2% of FITBONE (4/242) and 1% of PRECICE nails (1/98; p < 0.001). Focal osteolysis in conjunction with periosteal reaction at the telescoping interface was only observed in STRYDE nails. Conclusion Bone abnormalities at the interface of telescoping nail parts were seen in the majority of STRYDE nails, but only very rarely with FITBONE or PRECICE nails. We conclude that the low prevalence of radiological changes at the junctional interface of 242 FITBONE and 98 PRECICE nails at the time of nail removal does not warrant clinical concerns.

Current Understanding of Osteoimmunology in Certain Osteoimmune Diseases

The skeletal system and immune system seem to be two independent systems. However, there in fact are extensive and multiple crosstalk between them. The concept of osteoimmunology was created to describe those interdisciplinary events, but it has been constantly updated over time. In this review, we summarize the interactions between the skeletal and immune systems in the co-development of the two systems and the progress of certain typical bone abnormalities and bone regeneration on the cellular and molecular levels according to the mainstream novel study. At the end of the review, we also highlighted the possibility of extending the research scope of osteoimmunology to other systemic diseases. In conclusion, we propose that osteoimmunology is a promising perspective to uncover the mechanism of related diseases; meanwhile, a study from the point of view of osteoimmunology may also provide innovative ideas and resolutions to achieve the balance of internal homeostasis.

A Japanese single-center experience of the efficacy and safety of enzyme replacement therapy in childhood-onset hypophosphatasia

BackgroundHypophosphatasia (HPP) is a rare inherited metabolic disorder caused by mutations in the ALPL gene, which encodes tissue nonspecific alkaline phosphatase. The phenotype of HPP is widely diverse from the perinatal severe form to the adult mild form. The former represents the most severe form and was earlier associated with high mortality due to impaired development of the lungs and severe hypomineralization of the bones. Enzyme replacement therapy (ERT) using asfotase alfa was approved in 2015 in Japan for treating patients with HPP and has improved their pulmonary function and life prognosis. There are several practical and ethical challenges related to using orphan drugs for a rare disorder in a publicly funded healthcare system. Sharing experiences about their application is essential towards formulating guidelines to assist clinicians with decisions about their initiation and withdrawal. We report the details of ERT experience in ten cases of childhood-onset HPP in nine families from January 2015 to November 2019 (median [interquartile range] age 11.0 years [7.6–12.5] years; 60% male). This is the largest study of a single-center cohort describing the clinical course of HPP patients treated with ERT in Asia. ResultsOne case of perinatal lethal form of HPP, two cases of perinatal benign form, six cases of childhood form, and one case of odontohypophophatasia were observed. The most common symptom at onset was bone abnormalities. All patients had low serum ALP levels as compared to the age-matched reference range before the commencement of ERT. All HPP patients responded to ERT without serious adverse effects. Genetic analysis showed that eight out of ten patients had compound heterozygosity; two patients had only one heterozygous variant. In this study, two patients had a heterozygous variant of ALPL and responded to ERT, although the variants did not have the dominant-negative effect. ConclusionsERT may be effective in patients with symptoms of HPP even with only one pathogenic variant of ALPL without dominant-negative effect. Early diagnosis based on symptoms such as bone abnormalities or low serum alkaline phosphatase levels might be essential for early treatment and can contribute to better prognosis.

Association Between Transtibial Meniscus Root Repair and Rate of Meniscal Healing and Extrusion on Postoperative Magnetic Resonance Imaging: A Prospective Multicenter Study

Background: Prospective studies evaluating second-look imaging of meniscus root repair using a transtibial pull-out technique are limited; therefore, optimal surgical indications and the technique for meniscus root repair remain uncertain. Hypothesis: It was hypothesized that there would be a high rate of healing, improvement in meniscal extrusion, and prevention of articular cartilage degeneration and subchondral bone abnormalities after meniscus root repair. Study Design: Case series; Level of evidence, 4. Methods: Consecutive patients undergoing transtibial root repair were prospectively enrolled at 2 orthopaedic centers between March 2017 and January 2019. Pre- and postoperative magnetic resonance imaging (MRI) scans were reviewed by a musculoskeletal radiologist in a blinded fashion for meniscal healing, quantification of extrusion, articular cartilage grade, subchondral bone changes, and coronary/meniscotibial ligament abnormalities. Given persistent extrusion observed on postoperative MRI scans, an additional 10 patients gave consent and were enrolled for immediate (before weightbearing) postoperative MRI scans. Results: A total of 45 patients (16 male, 29 female; mean ± standard deviation age, 42.3 ± 12.9 years; body mass index, 31.6) were prospectively enrolled in the study; there were 47 meniscus root repairs: 29 medial and 18 lateral (2 with both). Postoperative MRI was obtained at an average of 6.3 months (range, 5.1-8 months); 98% of meniscal repairs had evidence of healing. Mean extrusion increased significantly, from 1.9 ± 1.5 mm preoperatively to 2.6 ± 1.4 mm postoperatively ( P = .03). There was no significant progression of chondromalacia grade, subchondral edema, insufficiency fracture, subchondral cysts, or subchondral collapse. In the additional 10-patient cohort, the mean preoperative extrusion (1.6 ± 1.2 mm) was not significantly different from that immediately postoperatively (2.0 ± 1.0 mm; P = .23). Conclusion: Prospective MRI analysis of transtibial meniscus root repair confirmed a high rate of meniscal healing and no observable progression of cartilage degeneration or subchondral bone abnormalities at the short-term follow-up. However, meniscal extrusion worsened in the first 6 months after surgery. Registration: NCT03037242 ( ClinicalTrials.gov identifier).

Congenital Syphilis in Neonate: A Single Center Study for 10 Years

Purpose: Syphilis infections are becoming more prevalent in the Republic of Korea, and inadequately treated syphilis can lead to congenital syphilis (CS) in newborns. This study aimed to analyze the clinical manifestations of syphilis in mothers and newborns and to make suggestions to improve disease prognosis. Methods: This single-center study was performed between August 2009 and August 2019 and included 29 newborns with CS. We retrospectively evaluated the clinical features, rapid plasma reagin (RPR) card test, fluorescent treponemal antibody absorption test (FTA-ABS), morbidity, and treatment regimen of all the syphilis-affected mothers and their newborns. Results: At the time of delivery, mean maternal age was 29.0±6.1 years old, and newborn gestational age was 38.0 weeks. In cases when syphilis was confirmed during the second and third trimesters of pregnancy, the newborn with CS had morbidity (p=0.004). The mean RPR titer was related to morbidity (p= 0.036). Positive results of FTA-ABS IgM (p<0.001) and pleocytosis in the cerebrospinal fluid (CSF) (p= 0.020) also increase morbidity. The most common symptoms were desquamation and skin rash, followed by hepatomegaly, neurodevelopmental disability, and bone abnormalities. The highest number of CS cases per 1,000 live births in this hospital was in 2014. Conclusion: CS is a preventable and treatable disease if physicians detect symptoms and provide appropriate treatment through RPR examinations during every trimester. General practitioners should be widely trained on various aspects including early detection, formal treatment, and regular follow-up. Additionally, medical services should be provided for the entire childbearing population regardless of the socioeconomic status.