Bone Disorders In Children Research Articles

Bone Health and Antiepileptic Drugs in Children with Epilepsy: A Pilot Study

Epilepsy, a chronic neurological disorder necessitating prolonged antiepileptic medication, has been associated with deficiencies in vitamin D and related bone disorders in children. This study aims to investigate the prevalence of vitamin D deficiency, calcium deficiency, and bone diseases in children undergoing antiepileptic drug (AED) therapy. A retrospective study was conducted on 60 children (0-16 years old) with epilepsy at King Fahad Specialist Hospital-Dammam from 2016 to 2018. Participants were administered 800 IU/day of vitamin D for 6 months. Comprehensive assessments, including tests for calcium, phosphorus, 25-hydroxyvitamin D (25-OHD), 1,25-hydroxyvitamin D (1,25 OHD), parathyroid hormone (PTH), thyroid function [thyroid-stimulating hormone (TSH)], alkaline phosphatase (ALP), and bone density, were performed after 6 months of oral vitamin D supplementation. No significant associations were observed between age, sex, age of onset, duration of epilepsy, symptoms of vitamin D deficiency, dietary factors, and the levels of calcium, phosphorus, 25-OHD, 1,25-OHD, PTH, TSH, ALP, and bone scan. Carbamazepine (CBZ) was the only AED that affected bone metabolism in general (P = 0.024). Calcium was mostly found to be abnormal after using AED with vitamin D (800 IU/day) for 6 months (P = 0.05). 25-OHD deficiency was associated with use of CBZ in pediatric epilepsy. Considering its potential impact on bone metabolism, higher vitamin D doses may be advisable for children on long-term AED therapy to mitigate these abnormalities.

Bone Disorders in Pediatric Chronic Kidney Disease: A Literature Review.

Intense changes in mineral and bone metabolism are frequent in chronic kidney disease (CKD) and represent an important cause of morbidity and reduced quality of life. These disorders have conventionally been defined as renal osteodystrophy and classified based on bone biopsy, but due to a lack of bone biopsy data and validated radiological methods to evaluate bone morphology in children, it has been challenging to effectively assess renal osteodystrophy in pediatric CKD; the consequence has been the suboptimal management of bone disorders in children. CKD-mineral and bone disorder (CKD-MBD) is a new expression used to describe a systemic disorder of mineral and bone metabolism as a result of CKD. CKD-MBD is a triad of biochemical imbalances in calcium, phosphate, parathyroid hormone, and vitamin D; bone deformities and soft tissue calcification. This literature review aims to explore the pathogenesis, diagnostic approach, and treatment of CKD-MBD in children and the effects of renal osteodystrophy on growing skeleton, with a specific focus on the biological basis of this peculiar condition.

Glucocorticoid induced bone disorders in children: Research progress in treatment mechanisms.

Long-term or supra-physiological dose of glucocorticoid (GC) application in clinic can lead to impaired bone growth and osteoporosis. The side effects of GC on the skeletal system are particularly serious in growing children, potentially causing growth retardation or even osteoporotic fractures. Children's bone growth is dependent on endochondral ossification of growth plate chondrocytes, and excessive GC can hinder the development of growth plate and longitudinal bone growth. Despite the availability of drugs for treating osteoporosis, they have failed to effectively prevent or treat longitudinal bone growth and development disorders caused by GCs. As of now, there is no specific drug to mitigate these severe side effects. Traditional Chinese Medicine shows potential as an alternative to the current treatments by eliminating the side effects of GC. In summary, this article comprehensively reviews the research frontiers concerning growth and development disorders resulting from supra-physiological levels of GC and discusses the future research and treatment directions for optimizing steroid therapy. This article may also provide theoretical and experimental insight into the research and development of novel drugs to prevent GC-related side effects.

Metabolic Bone Disorders in Children with Inflammatory Bowel Diseases.

In recent years, there has been a noticeable increase in the incidence of inflammatory bowel diseases in the pediatric population. Entry observations demonstrate anemia, malabsorption, deficiencies in vitamin D and calcium. These aspects, together with the systemic action of pro-inflammatory cytokines and steroid therapy are widely recognized as factors influencing bone metabolism. Presently, however, there are very few studies that can be found in the scientific literature on metabolic disorders in patients with IBD, especially in the pediatric population as the coexistence has not been sufficiently examined and understood. This review aims to summarize the currently available literature, as well as assess which areas have information gaps and need further research.

Bisphosphonate treatment in the bone disorders in children: a systematic review

Summary Background: bisphosphonates use over three decades in a variety conditions in children. However, the evi-dence of its use is limited. Aims:systematic analysis of publications regarding the effectiveness and safety of bisphosphonates (BPs) in children. Methods. PubMed and eLIBRARY were searched for eligible articles of Rus-sian and foreign authors up to February 2021. According the PRISMA strategies, 35 studies (data of 2545 patients) were included into the analysis. Results. More than 80% patients suffered from nonbacterial osteomyelitis (NBO) and osteogenesis imperfecta (OI). BPs in children are effective for increasing the bone mineral density for decreased fracture incidence, to reduce bone pain, to re-lieve inflammation and to improve the quality of patients’ life. The most frequently adverse event was the first-dose effect, such as flu-like syndrome. In the age group under study, no severe adverse events characteristic of adults have been seen (mandibular necrosis). Conclusions. BPs are efficient and safe in children with OI, NBO and cere-bral palsy in order to restore the bone mineral density. Further research is required to strengthen the recom-mendations made, while the wider use of BPs require revision of current registration documents in accordance with global guidelines.

Zoledronic acid in pediatric metabolic bone disorders.

Zoledronic acid (ZA), a highly potent intravenous bisphosphonate (BP), has been increasingly used in children with primary and secondary osteoporosis due to its convenience of shorter infusion time and less frequent dosing compared to pamidronate. Many studies have also demonstrated beneficial effects of ZA in other conditions such as hypercalcemia of malignancy, fibrous dysplasia (FD), chemotherapy-related osteonecrosis (ON) and metastatic bone disease. This review summarizes pharmacologic properties, mechanism of action, dosing regimen, and therapeutic outcomes of ZA in a variety of metabolic bone disorders in children. Several potential novel uses of ZA are also discussed. Safety concerns and adverse effects are also highlighted.

Dental Manifestations of Pediatric Bone Disorders.

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 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.

Metabolic bone disorders in children with epilepsy

Metabolic bone disorders in children with epilepsy

Prevalence of Hyperparathyroidism, Mineral and Bone Disorders in Children with Advanced Chronic Kidney Disease.

To identify the prevalence and risk factors for secondary hyperparathyroidism in children with advanced stages of chronic kidney disease (CKD). A retrospective cross-sectional observational study of clinical and laboratory data of pediatric patients with CKD stage 3, 4 was conducted from 2005 through 2013 at a single center in the Kingdom of Saudi Arabia. One hundred nineteen children (60.5% boys) with mean age of 10.1±5.1 y were included in the study. The mean eGFR (estimated Glomerular Filtration Rate) was 18.3 ± 15.4 ml/min/1.73m(2) and the mean intact parathyroid hormone (iPTH) level was 62.2 ± 89.4 pmol/L. Patients with a high iPTH had lower eGFR than those who were euparathyroid (16 ± 13.4 vs. 29.7 ± 19ml/min/1.73m(2), respectively; p = 0.006), had lower calcium levels (2.2 ± 0.3 vs. 2.4 ± 0.3 mmol/L; p = 0.03) and a lower bicarbonate level (21.2 ± 4.2 vs. 23.3 ± 3.2 mmol/L; p = 0.04). Three children with hyperparthyrodism (4.9 %) had fractures, 16 (26.2 %) had bone deformities compared to 5 in the euoparathyroid group (p=0.012). Parathyroid hormone negatively correlated with the patient's eGFR (r=-0.55), serum calcium (r=-0.43), and positively correlated with serum phosphate (r=0.38). The single most important predictor of hyperparathyroidism in children in the present sample was eGFR.

Targeted sequencing of a pediatric metabolic bone gene panel using a desktop semiconductor next-generation sequencer.

Metabolic bone disorders in children frequently are heritable, but the expanding number of genes associated with these conditions makes it difficult to perform molecular diagnosis. In the present study, we therefore evaluated a semiconductor (SC)-based sequencing system for this purpose. A total of 65 DNA samples were analyzed comprising 24 samples from patients with 27 known pathogenic mutations, 6 samples from patients with prior negative Sanger sequencing, and 35 consecutive samples from patients with suspected heritable metabolic bone disorders who had not had prior molecular diagnosis. In the samples with known pathogenic mutations, 26 of 27 mutations were identified by SC sequencing. All single nucleotide variants were correctly identified, but a 7-nucleotide duplication in CYP27B1 was not detected. SC sequencing revealed two pathogenic mutations in the six samples where prior Sanger sequencing had failed to identify a mutation. Finally, pathogenic mutations were found in 27 samples of patients with unknown mutation status (15 in COL1A1, 9 in COL1A2, 1 in LEPRE1, 1 in LRP5, 1 in PHEX). Subsequent Sanger sequencing confirmed the mutations in all 27 samples. In conclusion, we found that SC sequencing is suitable for the diagnosis of heritable metabolic bone disorders in children.

Mineral and Bone Disorder in Children with Chronic Kidney Disease Stage I to V (Predialysis)

Purposes To evaluate the mineral and bone disorders in children with chronic kidney disease (CKD) stage I to V predialysis. Methods Pediatric subcohort of KNOW-CKD (KoreaN cohort study for Outcome in patients With CKD) enrolled children (younger than 20 years) with CKD stage I-V (pre-dialysis) from five major pediatric nephrology centers in Korea and collected medical data associated with CKD-mineral and bone disorder. Results Total number of 300 patients (male:female=199:101) was included in this study. Serum phosphorus (mean ± standard deviation 4.89±0.75, 4.6±0.83, 4.63±0.85, 5.13±1.37, 5.35±1.2 from CKD stage I to V, p =0.0002), fibroblast growth factor (FGF)-23 (32.29±42.04, 41.33±41.00, 70.68±121.06, 67.9±66.95, 121.74±139.36, p =0.0030) and the prevalence of hyperphosphatemia (8.51%, 10.64%, 25.53%, 25.53%, 29.79%, p =0.010) increased as CKD progressed. Intact parathyroid hormone (iPTH) increased (40.84±40.37, 44.13±20.2, 78.93±65.21, 181.39±183.86, 313.85±324.95, p p r =−0.608, p r =−0.4943, p r =0.3288, r =0.3342, p r =0.3214, p r =0.3609, p r =−0.2597, p =0.0006). The prevalence of patients with increased alkaline phosphatase level increased significantly as CKD progressed (5.66%, 15.09%, 39.62%, 16.98%, 22.64%, p =0.042), which was due to increased prevalence of hyperparathyroidism ( p p p p p =0.002). Conclusion As CKD progressed, hyperphosphatemia, hyperparathyroidism and 1,25D3 deficiency increased, serum FGF-23 level increased and urinary phosphorus excretion decreased in children with CKD stage I to V predialysis.

Bone disorders in children and adolescents with chronic HCV infection

Although several studies have demonstrated a higher incidence of bone disorders in HCV-infected adults, the bone turnover alterations occurring in children and adolescents with chronic hepatitis C has not been thoroughly focused yet. We performed a study on a cohort of 30 HCV infected caucasian children and adolescents to assess the prevalence of osteodystrophy and evaluate a possible prophylactic and therapeutic approach. Data regarding biochemical markers of bone metabolism were collected. Moreover, results of ultra-sonographic bone densitometry yearly performed were evaluated in comparison with data obtained from more than 500 healthy children and adolescents. Osteocalcin and telopeptide of the collagen molecule type-1, CTX, appeared higher than normal in 8/30 and in 7/30 cases respectively; the 25OH vitamin D values were normal in 25/28 cases. By densitometry osteoporosis was detected in 2 patients and osteopenia in other 5. After stratification of cases by age groups, the incidence of osteopenia/osteoporosis appeared higher among children than among adolescents. Osteocalcin levels tended to be higher in cases where hepatic fibrosis were not detected. The higher number of cases of osteopenia/osteoporosis in children than in adolescents is worthy of note, although not statistically significant. Ultrasound densitometry confirmed its important early diagnostic role in asymptomatic HCV infected children; moreover, also the increase in serum levels of osteocalcin may be considered as early marker of osteodystrophy of complementary value. Larger studies will be needed to confirm the efficacy and safety of antiviral and supportive care in these patients.

Mineral and bone disorders in children with chronic kidney disease

As children with chronic kidney disease (CKD) have a long lifespan, optimal control of bone and mineral homeostasis is essential not only for the prevention of debilitating skeletal complications and for achieving adequate growth but also for preserving long-term cardiovascular health. As the growing skeleton is highly dynamic and at particular risk of deterioration, close control of bone and mineral homeostasis is required in children with CKD. However, assessment of bone disease is hampered by the limited validity of biochemical parameters-major controversy exists on key issues such as parathyroid hormone target ranges and the lack of useful imaging techniques. The role of newly discovered factors in bone and mineral homeostasis, such as fibroblast growth factor 23, is not yet established. Even though scientific evidence is limited in children with CKD, ergocalciferol or cholecalciferol supplementation and the use of calcium-free phosphate binders is recommended. The new drug cinacalcet is highly promising; however, pediatric experience is still limited to observational data and the effect of cinacalcet on longitudinal growth and pubertal development is unknown. Randomized, controlled trials are underway, including studies of cinacalcet pharmacokinetics and pharmacodynamics in infants.

New therapies: calcimimetics, phosphate binders and vitamin D receptor activators

At present, new compounds are available to treat secondary hyperparathyroidism, namely calcimimetics, novel phosphorus binders and also novel vitamin D receptor activators. Calcimimetics increase the sensitivity of the parathyroid gland to calcium through spatial configurational changes of the calcium-sensing receptor. In addition, experimental studies have demonstrated that calcimimetics also upregulate both the calcium-sensing receptor and the vitamin D receptor. They are efficacious in children, though the experience in paediatric chronic kidney disease is still limited. Sevelamer, lanthanum carbonate and magnesium iron hydroxycarbonate are novel phosphorus binders available on the market. Several studies have demonstrated their efficacy and safety up to 6 years, though costs are the main limitation for a wider use. Since almost all the experience available on the new phosphorus binders comes from its use in adults, studies on children are needed in order to confirm the efficacy and safety of these products. Other new salts and polymers are also being developed. New vitamin D receptor activators, such as paricalcitol, are as effective at suppressing parathyroid hormone (PTH) as the traditional vitamin D receptor activators used for the past two decades, but they have a better and safer profile, showing fewer calcaemic and phosphoraemic effects while preserving the desirable effects of the vitamin D receptor activators on the cardiovascular system, hypertension, inflammation and fibrosis. Their use in children with chronic kidney disease has revealed similar responses to those of adults. The novel compounds discussed in this review should facilitate and improve the management of mineral and bone disorders in children with chronic kidney disease.

Calcium and bone disorders in children and adolescents

Acta PaediatricaVolume 99, Issue 1 p. 152-152 Calcium and bone disorders in children and adolescents Rolf Zetterström, Rolf Zetterström rolf.zetterstrom@actapaediatrica.seSearch for more papers by this author Rolf Zetterström, Rolf Zetterström rolf.zetterstrom@actapaediatrica.seSearch for more papers by this author First published: 08 December 2009 https://doi.org/10.1111/j.1651-2227.2009.01468.xRead the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume99, Issue1January 2010Pages 152-152 RelatedInformation

Calcium and bone disorders in children and Adolescents

Calcium and bone disorders in children and Adolescents

Osteodensitometrie bei Kindern und Jugendlichen mit chronisch entzündlichen Darmerkrankungen

To evaluate the quantity and severity of bone disorders in children and adolescents with inflammatory bowel diseases (IBD) and to examine the correlation to whole body growth. In this study 89 bone mineral density measurements were performed and retrospectively analyzed. Under consideration of growth retardation, over 65.2 % of the patients with Cohn's disease showed a reduced bone mineral density. Osteopenia/Osteoporosis is seldom seen in patients with ulcerative colitis, i. e., only 34.8 % showed a reduction in bone mineral density. Growth retardation and reduced bone mineral density are correlated. Patients with Cohn's disease and a body length below the 25th height percentile showed a reduced bone mineral density in 78.1 % of the cases. Patients with a body length below the 10th height percentile had a reduced bone mineral density in 83.3 % of the cases. These results demonstrate the value of osteodensitometric measurements in patients with chronic diseases, especially in children and adolescents with inflammatory bowel disease.

The bone mass concept: problems in short stature.

Bone densitometry is currently one of the mainstays in the evaluation of systemic bone diseases in adults and is also increasingly used to assess primary or secondary bone disorders in children and adolescents. The purpose of carrying out densitometric studies in such circumstances is to measure the densitometric indicators of bone stability. Following procedures which were established for diagnosing adult osteoporosis, a decrease in densitometric surrogates of bone stability is usually interpreted as indicating increased fracture risk. The most basic densitometric parameter is bone mineral content (BMC), which can be measured with most densitometric techniques. BMC is either defined as the mass of mineral contained in an entire bone or as the mass of mineral per unit bone length. While mineral mass can be expected to be a good surrogate for bone stability, BMC is obviously a size-dependent parameter, since small bones weigh less than big bones. This is a drawback in paediatric use, since many children and adolescents who are examined by densitometry suffer from chronic disorders and are small-for-age. Short children will have a lower BMC than their healthy age-matched peers, even if their (smaller) bones are otherwise completely normal.

A pediatric patient with acute low-back and pelvis pain

R ADIONUCLIDE BONE scan is well known to be highly sensitive for the diagnosis of bone disorders in children and has become one of the common examinations in pediatric nuclear medicine. Abnormal findings on bone scintigraphy alone are nonspecific and should be evaluated in light of clinical, laboratory, and radiologic data to solve the diagnostic dilemma. This case shows multifocal spondylitis and unilateral sacroiliitis--the common musculoskeletal complications of brucellosis. The recognition of such a condition in the endemic areas should be considered and can help to establish early diagnosis and treatment.

Sex steroid hormone receptors in normal and dysplastic bone disorders in children

Children with monostotic and polyostotic bone dysplasias often exhibit localized bone overgrowth. We investigated the presence of nuclear estrogen and nuclear progesterone receptors by solid-phase radioimmunoassay, immunocytochemistry, and radioligand binding in osteoblast cell cultures derived from the areas of overgrowth of membranous bone, noninvolved membranous bone, and normal membranous bone from children undergoing elective craniotomy. Membranous bone of normal children had demonstrable levels of nuclear estrogen and progesterone receptors identified by radioimmunoassay and immunocytochemical assay. Two- to threefold increased levels of these receptors (p less than 0.001 versus normals) were found in cultures derived from the involved bone of two children with monostotic fibrous dysplasia and in one patient with polyostotic dysplasia (McCune-Albright syndrome). The noninvolved bone in our patients with fibrous dysplasia exhibited nuclear sex steroid hormone receptor levels similar to those in the normal children. Radioligand binding studies demonstrated increased sex steroid hormone receptors in cultures derived from involved osteoblasts. The presence of an increased level of sex steroid hormone receptor was accompanied by increased alkaline phosphatase activity and increased production of osteocalcin in vitro compared to normal or noninvolved bone. The mechanisms by which sex steroid hormone receptor levels are increased in the ostotic dysplasias remain to be established.