Osteoporosis In Children Research Articles

Early use of alendronate as a protective factor against the development of glucocorticoid-induced bone loss in childhood-onset rheumatic diseases: a cross-sectional study

BackgroundBisphosphonates are recommended for use as first-line therapy for the prevention and treatment of glucocorticoid-induced osteoporosis in adults. However, the appropriate usage of bisphosphonates for the prevention or treatment of glucocorticoid-induced osteoporosis in children remains unclear.MethodsWe performed a cross-sectional study to clarify the factors associated with the development of glucocorticoid-induced bone loss and osteoporosis in patients with childhood-onset rheumatic disease and to investigate the impact of the early use of alendronate. We recruited 39 patients with childhood-onset rheumatic disease who were evaluated to detect bone loss or osteoporosis at 3 months to 1.5 years after the initiation of treatment. The primary outcome of the study was the presence of bone loss or osteoporosis at the initial evaluation of the bone mineral density after at least 3 months of glucocorticoid therapy.ResultsBone loss and a history of fracture were found in 56 and 18% of the participants, respectively. Weekly oral alendronate therapy (median, 25.4 mg/m2) had been started by the time of the evaluation of osteoporosis in 46% of the participants and within 3 months after the start of glucocorticoid in 31% of the participants. There were no significant differences between the participants with bone loss (wBL group) and without bone loss (w/oBL group) in terms of gender, primary disease, or the age at the onset of primary disease. In terms of glucocorticoid use, there was no significant difference in the age at the start of glucocorticoid therapy, the length of glucocorticoid use, or the dose of glucocorticoids. The proportion of patients in the w/oBL group who received alendronate within 3 months after the start of glucocorticoid therapy was significantly greater than that in the wBL group. In the logistic regression analysis, only “alendronate therapy within 3 months after the start of glucocorticoid therapy” had a statistically significant effect on the development of bone loss (OR, 0.08; 95% CI, 0.02–0.43). The analysis did not reveal any factors associated with the development of osteoporosis.ConclusionsThe early use of alendronate may have a preventive effect against the development of bone loss in glucocorticoid-treated patients with childhood-onset rheumatic disease.

Anabolic Therapy for the Treatment of Osteoporosis in Childhood.

Numerous forms of osteoporosis in childhood are characterized by low bone turnover (for example, osteoporosis due to neuromuscular disorders and glucocorticoid exposure). Anti-resorptive therapy, traditionally used to treat osteoporosis in the young, is associated with further reductions in bone turnover, raising concerns about the long-term safety and efficacy of such therapy. These observations have led to increasing interest in the role of anabolic therapy to treat pediatric osteoporosis. While growth hormone and androgens appears to be relatively weak anabolic modulators of bone mass, emerging therapies targeting bone formation pathways (anti-transforming growth factor beta antibody and anti-sclerostin antibody) hold considerable promise. Teriparatide remains an attractive option that merits formal study for patients post-epiphyseal fusion, although it must be considered that adult studies have shown its effect is blunted when administered following bisphosphonate therapy. Mechanical stimulation of bone through whole body vibration therapy appears to be much less effective than bisphosphonate therapy for treating osteoporosis in children. New anabolic therapies which target important pathways in skeletal metabolism merit further study in children, including their effects on fracture risk reduction and after treatment discontinuation.

Secondary osteoporosis. Disease-Related Osteoporosis in Children.

Similarly to adult osteoporosis, childhood osteoporosis also is usually divided into primary and secondary causes. Primary osteoporosis includes genetic disorders represented by osteogenesis imperfecta. Secondary pediatric osteoporosis is associated with various diseases and glucocorticoid treatment, and malnutrition, impaired mobility, chronic inflammation and endocrine disorders can be risk factors. In growing children, mild osteoporosis can be spontaneously recovered by elimination of risk factors. However, initiation of treatment using drugs such as bisphosphonate should be considered in primary osteoporosis including osteogenesis imperfecta and severe secondary osteoporosis which cannot be spontaneously improved. Administration of bisphosphonate increased bone mineral density in pediatric patients, but long-term safety and efficacy need further investigation. Development of new drugs to treat osteogenesis imperfecta is underway, which include the antibodies against sclerostin and TGF-β.

Occlusal disharmony-induced stress causes osteopenia of the lumbar vertebrae and long bones in mice

Excessive exposure to glucocorticoids causes osteoporosis in children and adults. Occlusal disharmony is known to induce an increase in serum corticosteroid levels in murine models, but the influence of occlusal disharmony-induced stress on the bone mass during the growth period has not yet been clarified. The purpose of this study was to investigate whether occlusal disharmony-induced stress decreases bone mass. Five-week-old C57BL/6J male mice were used. A 0.5-mm increase in the vertical height of occlusion was used to induce occlusal disharmony for a period of 7 days. Serum corticosterone levels were significantly higher on post-induction day 7, with radiological evidence of osteopenia of the third lumbar vertebra and long bones of the hind limbs. Osteopenia was associated with a reduction of the mechanical properties of the tibia and femur, with significant suppression of bone formation parameters and an increase in bone resorption parameters, as evaluated by bone histomorphometric analysis of the tibial/femur metaphysis. Our findings at the level of bones were supported by our assessment of serum markers of systemic metabolism. Therefore, occlusal disharmony-induced stress may lead to osteopenia and reduce the mechanical strength of bone through an increase in serum glucocorticoid levels in mice.

Вторичный остеопороз у детей

Вторичный остеопороз у детей

Osteoporosis in childhood

The aim of this review is to highlight recent findings in prevention, diagnosis, and treatment of pediatric osteoporosis. Several genes are involved in bone mass acquisition, and various monogenic bone disorders characterized by reduced bone mineral density and increased bone fragility have been recently described. Moreover, many chronic diseases and/or their treatment have been associated with impaired bone mass acquisition. Pediatric osteoporosis should be adequately suspected and properly diagnosed in children at risk of fractures. Particularly, detection of vertebral fracture allows the diagnosis regardless of densitometric evaluation. Dual X-ray absorptiometry remains the most widely used densitometric technique in childhood, but interpretation of results should be made with caution because of different confounding factors. Bisphosphonates represent one of the main medical treatments of pediatric osteoporosis, and many different protocols have been proposed. Bisphosphonates administration should be characterized by a first phase, followed by a period of maintenance. Optimal route of administration, duration of therapy, and long-term safety of bisphosphonates treatment require further investigation. Careful monitoring of children at risk of fractures is essential to pose early diagnosis of osteoporosis. In children with persistent risk factors and reduced probability of spontaneous recovery, medical treatment with bisphosphonates should be considered.

Primary osteoporosis in children

Osteoporosis in childhood is uncommon, and it may be secondary to a spectrum of diverse conditions. Idiopathic juvenile osteoporosis is a primary osteoporosis of unknown aetiology present in previously well...

Technique, Safety, and Yield of Bone Biopsies for Histomorphometry in Children

PurposeTo evaluate image-guided bone biopsy for bone histomorphometry to assess osteoporosis in children with respect to safety and yield. Materials and MethodsA single-center retrospective review was performed of 79 bone biopsies in 73 patients performed between 2007 and 2015. Biopsies of the iliac bone were performed under general anesthesia, after tetracycline labeling, using a Rochester needle (Medical Innovations International, Inc, Rochester, Minnesota). Ultrasound and fluoroscopic guidance were used in all procedures. Biopsy technique, technical success, safety, and histomorphometry results (complete, incomplete, none) were analyzed. ResultsThere were 41 male patients (51.8%). Technical success was achieved in 76/79 (96%) procedures. Of 79 biopsies, 75 (95%) were uneventful. Unplanned overnight observation was required in 3 (minor SIR grade B), and prolonged hospital stay owing to hematoma causing nerve compression pain was required in 1 (major SIR grade D). Complete histomorphometric reports were obtained in 69 (87%) procedures, incomplete reports were obtained in 7 (9%), and no reports were obtained in 3(4%). Incomplete reports were insufficient to provide a definitive diagnosis or guide treatment. Histomorphometry impacted subsequent therapy in 69 (87%) biopsies. ConclusionsImage-guided bone biopsy for osteoporosis using the Rochester needle is a valuable and safe technique for establishing the diagnosis of osteoporosis and directing treatment based on histomorphometry results.

The Role of Mifamurtide in Chemotherapy-induced Osteoporosis of Children with Osteosarcoma.

Osteosarcoma is the most frequent malignant bone tumor in childhood and young adulthood. Long-term survivors of osteosarcoma patients show high prevalence of osteoporosis and fractures. The immunomodulatory mifamurtide, which modulates macrophages activity, improves disease outcome. To evaluate the role of mifamurtide on macrophage component of bone, the osteoclasts, during chemotherapy in children with osteosarcoma. Osteoclasts, obtained from peripheral blood cells of healthy donors were harvested in the presence or not of mifamurtide. Moreover, osteoclast cultures were obtained from osteosarcoma patients, at onset and during chemotherapy, alone or with mifamurtide. Pro-osteoporotic tartrateresistant acid phosphatase (TRAP), phosphokinase-β-2 (PKCβ2), vanilloid receptor type 1 (TRPV1), and anti-osteoporotic cannabinoid receptor type 2 (CB2) biomarkers were analyzed by bio-molecular (qPCR), biochemical (Western Blotting), and morphological (TRAP assay) approaches. Osteoclasts from osteosarcoma patients show significant increase of TRAP and decrease of CB2 with respect to osteoclasts from healthy donors. This osteoclast hyperactivity is more evident in osteoclasts from osteosarcoma patients during chemotherapy. Mifamurtide reduces pro-osteoporotic TRAP, PKCβ2, TRPV1 levels and increases CB2 in osteoclasts from healthy donors. Moreover, chemotherapy-induced effects on bone resorption markers are fully reverted in osteoclasts derived from osteosarcoma patients in chemotherapy plus mifamurtide. Our data suggest a new therapeutic role for mifamurtide as possible anti-resorption agent in chemotherapy-induced osteoporosis in children with osteosarcoma.

Recent Discoveries in Monogenic Disorders of Childhood Bone Fragility.

This review summarizes our current knowledge on primary osteoporosis in children with focus on recent genetic findings. Advances in genetic research, particularly next-generation sequencing, have found several genetic loci that associate with monogenic forms of inherited osteoporosis, widening the scope of primary osteoporosis beyond classical osteogenesis imperfecta. New forms of primary osteoporosis, such as those related to WNT1, PLS3, and XYLT2, have identified defects outside the extracellular matrix components and collagen-related pathways, in intracellular cascades directly affecting bone cell function. Primary osteoporosis can lead to severe skeletal morbidity, including abnormal longitudinal growth, compromised bone mass gain, and noticeable fracture tendency beginning at childhood. Early diagnosis and timely care are warranted to ensure the best achievable bone health. Future research will most likely broaden the spectrum of primary osteoporosis, hopefully provide more insight into the genetics governing bone health, and offer new targets for treatment.

Osteoporosis in Children with Chronic Illnesses: Diagnosis, Monitoring, and Treatment.

Osteoporosis is an under-recognized complication of chronic illness in childhood. This review will summarize recent literature addressing the risk factors, evaluation, and treatment for early bone fragility. Criteria for the diagnosis of pediatric osteoporosis include the presence of low trauma vertebral fractures alone or the combination of low bone mineral density and several long bone fractures. Monitoring for bone health may include screening for vertebral fractures that are common but often asymptomatic. Pharmacologic agents should be offered to those with fragility fractures especially when spontaneous recovery is unlikely. Controversies persist about the optimal bisphosphonate agent, dose, and duration. Newer osteoporosis drugs have not yet been adequately tested in pediatrics, though clinical trials are underway. The prevalence of osteoporosis is increased in children with chronic illness. To reduce the frequency of fragility fractures requires increased attention to risk factors, early intervention, and additional research to optimize therapy and potentially prevent their occurrence.

Prevention and treatment of glucocorticoid-induced osteoporosis in children

Prevention and treatment of glucocorticoid-induced osteoporosis in children

Pediatric Osteoporosis: Diagnosis and Treatment Considerations

Osteoporosis is now increasingly recognized in children due to the increased prevalence of disorders associated with bone loss. Fragility fractures represent the cardinal clinical features of pediatric osteoporosis and children presenting with fragility fractures deserve an accurate assessment to rule out a secondary cause. Indeed, in the pediatric population, a low bone mass is often a consequence of a chronic disease or its treatment; genetic bone disorders represent the cause of only a small fraction of cases. The position statement of the International Society for Clinical Densitometry guides physicians in interpreting densitometric data and making diagnoses of osteoporosis in children. Once a diagnosis of osteoporosis has been made, the aim is to identify children in whom bone status may deteriorate if left untreated. To date, bisphosphonates have represented the mainstay of treatment for pediatric osteoporosis. However, due to the peculiar pathophysiology of osteoporosis in this age group, a pharmacological agent with an anabolic effect on bone may provide clinicians with other therapeutic options in children. Multicenter studies are needed to optimize treatments and define optimal clinical response in treated children.

Interventions to prevent and treat corticosteroid-induced osteoporosis and prevent osteoporotic fractures in Duchenne muscular dystrophy.

Corticosteroid treatment is considered the 'gold standard' for Duchenne muscular dystrophy (DMD); however, it is also known to induce osteoporosis and thus increase the risk of vertebral fragility fractures. Good practice in the care of those with DMD requires prevention of these adverse effects. Treatments to increase bone mineral density include bisphosphonates and vitamin D and calcium supplements, and in adolescents with pubertal delay, testosterone. Bone health management is an important part of lifelong care for patients with DMD. To assess the effects of interventions to prevent or treat osteoporosis in children and adults with DMD taking long-term corticosteroids; to assess the effects of these interventions on the frequency of vertebral fragility fractures and long-bone fractures, and on quality of life; and to assess adverse events. On 12 September 2016, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, and CINAHL Plus to identify potentially eligible trials. We also searched the Web of Science ISI Proceedings (2001 to September 2016) and three clinical trials registries to identify unpublished studies and ongoing trials. We contacted correspondence authors of the included studies in the review to obtain information on unpublished studies or work in progress. We considered for inclusion in the review randomised controlled trials (RCTs) and quasi-RCTs involving any bone health intervention for corticosteroid-induced osteoporosis and fragility fractures in children, adolescents, and adults with a confirmed diagnosis of DMD. The interventions might have included oral and intravenous bisphosphonates, vitamin D supplements, calcium supplements, dietary calcium, testosterone, and weight-bearing activity. Two review authors independently assessed reports and selected potential studies for inclusion, following standard Cochrane methodology. We contacted study authors to obtain further information for clarification on published work, unpublished studies, and work in progress. We identified 18 potential studies, of which two, currently reported only as abstracts, met the inclusion criteria for this review. Too little information was available for us to present full results or adequately assess risk of bias. The participants were children aged five to 15 years with DMD, ambulant and non-ambulant. The interventions were risedronate versus no treatment in one trial (13 participants) and whole-body vibration versus a placebo device in the second (21 participants). Both studies reported improved bone mineral density with the active treatments, with no improvement in the control groups, but the abstracts did not compare treatment and control conditions. All children tolerated whole-body vibration treatment. No study provided information on adverse events. Two studies are ongoing: one investigating whole-body vibration, the other investigating zoledronic acid. We know of no high-quality evidence from RCTs to guide use of treatments to prevent or treat corticosteroid-induced osteoporosis and reduce the risk of fragility fractures in children and adults with DMD; only limited results from two trials reported in abstracts were available. We await formal trial reports. Findings from two ongoing relevant studies and two trials, for which only abstracts are available, will be important in future updates of this review.

OSTEOPOROSIS IN CHILDREN AND ITS RELEVANCE FOR PEDIATRIC SPORTS MEDICINE

The article is dedicated to one of the urgent problems of modern medicine – osteoporosis. Modern trends in the national epidemiology, risk factors, and diagnostic approaches are discussed. Particular attention is paid to the ambiguity and inconsistency of information on osteoporosis in childhood and adolescence, as well as the lack of convincing studies of this issue in children’s sports medicine. The authors conduct an analysis of the generally accepted approaches to the identification of risk groups for the development of osteoporosis in children, the predisposing factors and complex issues of diagnosing this condition are discussed in detail. The publication presents the results of our own observations of the most complex clinical cases in a group of children and adolescents involved in sports, including elite sports. A separate section is devoted to the analysis of pharmacological agents for the prevention and treatment of osteoporosis in children and young athletes. All presented data are in accordance with the legislation and rules of the World Anti-Doping Agency (WADA, 2017).

The Impact of Vitamin D Receptor Single Nucleotide Polymorphism on 1.25 (OH) Vitamin D3 and Bone Mineral Density in Egyptian Children with Beta-thalassemia

Background: Vitamin D Receptor (VDR) gene variation may associate with dysfunctions of vitamin D. The aim of this study is to evaluate VDR variation and its relation with Bone Mineral Density (BMD) values in Beta-thalassemia. Methods: The children included in this study divided into two groups, 76 TM children, and 51 ages and sex matched healthy controls. All children subjected to full history taking, clinical examination. Liver and kidney functions, serum calcium, phosphorous, alkaline phosphatase and vitamin D levels measurement. BMD was determined. VDR rs2228570 SNP was assayed by real time PCR. Results: There was a significant increase in phosphorus, alkaline phosphatase, frequency of the TT genotype and T allele of rs2228570 SNP of VDR and decrease in calcium, vitamin D levels and BMD in patients group. There was a significant increase of vitamin D levels and decrease in patients with TT genotype than both TC and CC. Also, There were significant increase in number and % of osteopenia and osteoporosis in patients group with TT genotype than both TC and CC (p<0.001). Conclusion: TT genotype and T allele affect vitamin D level, function and associated with decrease BMD and high frequency of osteopenia and osteoporosis in children with Beta thalassemia.

Causes of Osteoporosis in Pediatric Age Group Patients, Following at King Abdul Aziz University Hospital, Jeddah, Saudi Arabia: 12 Years Experience

Background: Osteoporosis in children has various underlying causes related to hereditary or secondary to different diseases like: hematological diseases, gastrointestinal diseases, renal diseases, endocrine diseases, druginduced and immobilization. Objective: To investigate the causes of osteoporosis in pediatrics age group presented to pediatric clinic in King Abdulaziz University Hospital. Methods:One hundred thirty one children and adolescents with osteoporosis, visiting pediatric clinic at King Abdulaziz University Hospital (KAUH), Jeddah, Saudi Arabia from 2003 to 2015. Seventy five patients had primary osteoporosis which represents 57.3% of the studied sample of the population. Secondary osteoporosis was found in Fifty six patients which represents 42.7% of the sample of the population. Various underlying causes of primary and secondary of osteoporosis were evaluated by reviewing medical records file. Results:The mean age group is 11.43 years. Primary osteoporosis specifically osteogenesis imperfecta accounts for 57.3% of the cases. Among the secondary cases, hematological diseases, gastrointestinal diseases, endocrine diseases, Renal disease, immobilization, chronic use of steroid, were the most common accounting for 9.2%, 9.2%, 6.9%, 6.1%, 6.1%, 5.4% of the cases respectively. Conclusion: Osteogenesis imperfecta is the most common cause of children osteoporosis at KAUH, Jeddah, Saudi Arabia. While secondary osteoporosis is still to be considered and screened for.

STUDY OF RELATIONSHIP BETWEEN SP1 POLYMORPHISM IN THE COLLAGEN TYPE I ALPHA -1 (COLIA1) GENE AND OSTEOPROSIS IN PATIENTS WITH BETA-THALASSEMIA.

Background:-Osteoporosis is an important cause of morbidity in patients with β-thalassemia. The pathogenesis of reduced bone mineral density (BMD) is multifactorial. A range of genetics factors have been implicated in patients with osteoporosis. Polymorphism at the Sp1 binding site of the collagen type I A 1(COLIA1) gene is thought to be an important factor in development of osteoporosis. Objective:-is to study the relationship between SP1 polymorphism in the collagen type 1 alpha 1 gene and the development of osteoporosis in patients with Beta thalassemia. Methods:-A total of 40 patients with β-thalassemia(21 females &19 males)aged 6-18 yearsand 40 healthy subjects cross matched with age and sex. Serum osteocalcin, serum alkaline phosphatase, calcium and DEXA were examined in all patients. The COLIA1 Sp1genotypes (SS, Ss, ss) were measured by digestion using restriction enzyme (Bal1) of DNA amplified by the polymerase chain reaction (PCR). Results:-SS (G/G) genotype in β-thalassemia major was30.7% and in β-thalassemia intermedia was 49.4% and the Ss (G/T) genotype in βT Major was 55.63% and in βT intermedia was 50.6%, the ss genotype (T/T) type in βTM was 13.67% only. The difference was statistically significant (p= 0.040). There was highly significant difference between thalassemia major and thalassemia intermedia compared to control group as regard Ca, OC, ALP and DEXA (P= 0.000). Conclusions:-Detection base substitutions at the Sp1 binding site on the COLIA1 gene in early years considering an important role in preventing osteoporosis in children with beta -thalassemia.and early mangment of these patients. Key words: Beta-thalassemia, COLIA1,osteoprosis.

Frequency of osteoporosis in children with Turner Syndrome and determining the optimal age of the onset of estrogen replacement theraphy

Frequency of osteoporosis in children with Turner Syndrome and determining the optimal age of the onset of estrogen replacement theraphy

The effect of low-dose intravenous bisphosphonate treatment on osteoporosis in children with quadriplegic cerebral palsy.

PurposeQuadriplegic children with cerebral palsy are more susceptible to osteoporosis because of various risk factors that interfere with bone metabolism. Pamidronate is effective for pediatric osteoporosis, but there are no guidelines for optimal dosage or duration of treatment in quadriplegic children with osteoporosis. We aimed to evaluate the efficacy of low-dose pamidronate treatment in these patients.MethodsTen quadriplegic patients on antiepileptic drugs (6 male, 4 female patients; mean age, 10.9±5.76 years), with osteoporosis and gross motor function classification system level V, were treated with pamidronate (0.5–1.0 mg/kg/day, 2 consecutive days) every 3–4 months in a single institution. The patients received oral supplements of calcium and vitamin D before and during treatment. The lumbar spine bone mineral density (BMD) z score and biochemical markers of bone metabolism were measured regularly during treatment.ResultsThe main underlying disorder was perinatal hypoxic brain damage (40%, 4 of 10). The mean cumulative dose of pamidronate was 4.49±2.22 mg/kg/yr, and the mean treatment period was 10.8±3.32 months. The BMD z score of the lumbar spine showed a significant increase from −4.22±1.24 before treatment to −2.61±1.69 during treatment (P=0.008). Alkaline phosphatase decreased during treatmentn (P=0.037). Significant adverse drug reactions and new fractures were not reported.ConclusionLow-dose pamidronate treatment for quadriplegic children with cerebral palsy increased lumbar BMD and reduced the incidence of fracture.