Biomedical subjects

Leonid Zeitlin

Publications and source records attributed to Leonid Zeitlin.

9 recordsLinked to original sources

PubMed2005

The effect of cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta type V.

Intravenous treatment with pamidronate is beneficial in children and adolescents with moderate to severe forms of osteogenesis imperfecta (OI) types I, III and IV, but there is little information on the effects of this treatment on the newly described OI type V. Here, we describe the results of 2 years of pamidronate treatment in 11 children and adolescents with OI type V (age at start of therapy 1.8 to 15.0 years; 6 girls). Pamidronate was given in intravenous cycles at a cumulative yearly dose of 9 mg/kg. The first infusion cycle was associated with fever and mild hypocalcemia in most patients, but no other short-term side effects were noted. Two years of pamidronate treatment led to a decrease in the urinary excretion of N-terminal telopeptide of type I collagen to 50% of baseline levels. Both the size and volumetric bone mineral density of lumbar vertebrae increased compared to age- and sex-matched reference data (P < 0.05 in both cases). Histomorphometry of transiliac bone samples showed an average increase of 86% in cortical thickness (N = 7; P = 0.005). No significant changes with treatment were observed in the age-related z scores of isometric maximal grip force and height. Fracture incidence decreased from 1.5 fractures per year before treatment to 0.5 fractures per year during the fist 2 years of treatment. Ambulation status improved in four patients and remained unchanged in the others. In conclusion, the intravenous pamidronate therapy has a similar effect in OI type V as it has in the other OI types.

Adolescent↗

PubMed2004

Delayed osteotomy but not fracture healing in pediatric osteogenesis imperfecta patients receiving pamidronate.

UNLABELLED: This study evaluated factors influencing fracture (n = 197) and osteotomy (n = 200) healing in children with moderate to severe OI. Pamidronate treatment was associated with delayed healing after osteotomy, but not after fracture. The data suggest that both pamidronate and mechanical factors influence bone healing in this cohort. INTRODUCTION: Intravenous pamidronate is widely used to treat children with moderate to severe osteogenesis imperfecta (OI). However, the effect of this treatment on bone healing is not well characterized. We therefore retrospectively analyzed the healing of lower limb fractures and osteotomies in children with moderate to severe OI, both before and after the start of pamidronate treatment. MATERIALS AND METHODS: Bone healing was evaluated on standard radiographs after 197 lower limb fractures (132 femur and 65 tibia) in 82 patients (age at fracture, 0.0-19.9 years) and 200 intramedullary rodding procedures in 79 patients (age at surgery, 1.2-19.8 years). Delayed healing was diagnosed when a fracture or osteotomy line was at least partially visible 12 months after the event. RESULTS: Delayed fracture healing was observed more frequently during than before pamidronate treatment. However, the effect of pamidronate was no longer significant when age differences were taken into account (odds ratio [OR], 1.76; 95% CI, 0.61-5.10). Better mobility status was a strong independent predictor of delayed healing after fractures that occurred during pamidronate treatment. After osteotomies, delayed healing was more frequent when pamidronate had been started before surgery (OR, 7.29; 95% CI, 2.62-20.3), and this effect persisted after adjustment for multiple confounders. During pamidronate treatment, older age (OR per year of age, 1.25; 95% CI, 1.06-1.47) and osteotomy of the tibia (OR, 3.51; 95% CI, 1.57-7.82) were independent predictors of delayed healing. CONCLUSIONS: This study suggests that pamidronate therapy is associated with delayed healing of osteotomy sites after intramedullary rodding procedures. Better mobility status, but not pamidronate treatment, seems to be predictive of delayed healing after fractures.

Absorptiometry, Photon↗

PubMed2003

Modern approach to children with osteogenesis imperfecta.

Osteogenesis Imperfecta (OI) is characterized by bone fragility. At least seven discrete types have been described ranging from mild disease to a lethal form. In a large number of cases, mutations in one of the two genes encoding type I collagen have been found. In forms recently described (types V, VI, VII), such mutations have been excluded. In two other forms, (Bruck, and osteoporosis - pseudoglioma syndromes) defects in other proteins have been characterized. In OI, bone fragility stems from: decreased bone mass, disturbed organization of bone tissue, and altered bone geometry (size and shape). Histologic studies have shown that increased bone turnover is the rule in OI bone. This justifies using bisphosphonates in order to reduce osteoclast mediated bone resorption. Initial results are encouraging. Cyclical intravenous pamidronate administration reduces bone pain and fracture incidence, and increases bone density and level of ambulation, with minimal side effects. Effects on bone include increase in size of vertebral bodies and thickening of cortical bone. These results allow for more efficacious corrective surgery using intramedullary rodding of the long bones and paravertegral instrumentation. Specific occupational and physiotherapy programs are integral parts of the treatment protocol. This multidisciplinary approach will prevail until strategies aiming at the correction of the basic defect(s) will have come to fruition.

Biopsy, Needle↗

PubMed2003

Osteogenesis imperfecta types I, III, and IV: effect of pamidronate therapy on bone and mineral metabolism.

Cyclical iv therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study we evaluated the effect of this therapy on bone and mineral metabolism in 165 patients with OI types I, III, and IV (age, 2 wk to 17.9 yr; 86 girls and 79 boys). All patients received iv pamidronate infusions on 3 successive days, administered at age-dependent intervals of 2-4 months. During the 3 d of the first infusion cycle, serum concentrations of ionized calcium dropped by 0.14 +/- 0.008 mmol (mean +/- SE; P < 0.001), and serum PTH levels transiently almost doubled (P < 0.001). At the same time, urinary excretion of the bone resorption marker type I collagen N-telopeptide related to creatinine (uNTX/uCr) decreased by 61-73% (P < 0.001). Two to 4 months later, ionized calcium had returned to pretreatment levels, and uNTX/uCr remained 30-35% lower than at baseline (P < 0.001). During 4 yr of pamidronate therapy (n = 40 patients), ionized calcium levels remained stable, but PTH levels increased by about 30% (P < 0.01). uNTX/uCr, expressed as a percentage of the age- and sex-specific mean value in healthy children, decreased from 132 +/- 13% (mean +/- SE) at baseline to 49 +/- 3% after 4 yr of therapy (P < 0.001). In conclusion, serum calcium levels can decrease considerably during and after pamidronate infusions, requiring close monitoring especially at the first infusion cycle. In long-term therapy, bone turnover is suppressed to levels lower than those in healthy children. The consequences of chronically low bone turnover in children with OI are unknown at present.

Adolescent↗

PubMed2003

Effect of pamidronate treatment in children with polyostotic fibrous dysplasia of bone.

Intravenous infusions with the bisphosphonate compound pamidronate decrease bone pain and reportedly can lead to refilling of dysplastic lesions in adults with fibrous dysplasia (FD) of bone. Here we describe the effects of this treatment approach in 18 children and adolescents (age at start of therapy, 6.2-17.5 yr; eight girls) with polyostotic FD, who received pamidronate for 1.2-9.1 yr (median, 3.8 yr). Treatment cycles with pamidronate (1-1.5 mg/kg.d on 3 consecutive days) were given every 4 months. Levels of serum alkaline phosphatase and urinary collagen type I N-telopeptide were elevated at baseline and decreased continuously during the first 3 yr of therapy. There was no radiographic evidence of filling of lytic lesions or thickening of the bone cortex surrounding the lesions in any patient. Histomorphometric results in dysplastic bone tissue of patients receiving pamidronate (n = 7; time of therapy, 1.4-4.8 yr) were similar to those of patients without medical therapy (n = 9). No serious side effects were noted. In conclusion, pamidronate therapy appears to be safe in children and adolescents with polyostotic FD. However, we found no clear evidence that pamidronate has an effect on dysplastic lesions in such patients.

Adolescent↗

PubMed2003

Bone mass, size, and density in children and adolescents with osteogenesis imperfecta: effect of intravenous pamidronate therapy.

Cyclical intravenous therapy with pamidronate improves the clinical course in children and adolescents with osteogenesis imperfecta (OI). In this study, we evaluated the effect of this therapy on lumbar spine bone mass (bone mineral content [BMC]), size (bone volume [BV]), and density (volumetric bone mineral density [vBMD]). Results from 56 patients (age, 0.2-15.9 years; 25 girls) on long-term pamidronate treatment were compared with those of 167 patients who had not received pamidronate before densitometry. In all patients who received pamidronate, BMC, BV, and vBMD increased above levels expected for untreated patients (p < 0.001 in each case). After 4 years of treatment, BMC, BV, and vBMD were 154%, 44%, and 65% higher, respectively, in treated than in untreated patients who were matched for age and OI type. A multiple regression model showed that baseline BMC was negatively associated with the increase in BMC. In conclusion, the bone mass increase in pediatric OI patients receiving pamidronate is caused by increases in both bone size and density. Patients with larger deficits in bone mass at baseline have a more marked bone mass gain during therapy.

Adolescent↗

PubMed2003

Height and weight development during four years of therapy with cyclical intravenous pamidronate in children and adolescents with osteogenesis imperfecta types I, III, and IV.

OBJECTIVES: Treatment with pamidronate improves the clinical course in children with osteogenesis imperfecta (OI), but theoretically might affect longitudinal growth. In this study we analyzed growth during cyclical intravenous pamidronate treatment in children and adolescents (age.04-15.6 years at baseline) with moderate to severe forms of OI types I, III, and IV. METHODS: The effect of 1 year of pamidronate treatment on height and weight was analyzed in 116 patients (OI-I, N = 29; OI-III, N = 42; OI-IV, N = 45). The results of 4 years of therapy were evaluated in 41 children (OI-I, N = 12; OI-III, N = 14; OI-IV, N = 15). RESULTS: Baseline height was low for age in all OI types. After 1 year of pamidronate therapy, height z scores had increased significantly in OI-III (by 0.3 +/- 0.8, mean +/- standard deviation; P =.04) and did not change in OI-I and OI-IV. Weight z scores increased significantly in OI-I (by 0.2 +/- 0.4, P =.01). After 4 years of pamidronate therapy, mean height z scores increased significantly in OI-IV (by 0.41 +/- 0.71, P =.04), whereas nonsignificant trends to increase were found for OI-I and OI-III. When height was expressed as a percentage of the result expected for untreated patients with the same OI type, long-term pamidronate therapy was associated with a significant height gain in all 3 OI types (P <.001). Eight patients who reached final height after 3.0 +/- 1.0 years of treatment were taller on average than expected for untreated patients (P =.04). CONCLUSIONS: Four years of cyclical intravenous pamidronate treatment led to a significant height gain in moderately to severely affected OI patients.

Adolescent↗

PubMed2003

[Updates in osteogenesis imperfecta].

Osteogenesis Imperfecta, a heterogenous group of inherited disorders, is characterized by both bone fragility and low bone mass. Since the Sillence classification of the disease, significant progress has been made in understanding the molecular, histological and genetical pathogenesis of the disease, and it led to expanded nosology. The multidisciplinary approach including rehabilitation, medications and surgery, may significantly improve the quality of life and prolong life expectancy.

Humans↗

PubMedDate not supplied

Divergent patterns of extracellular matrix protein expression in neonatal versus adult liver fibrosis.

The extracellular matrix (ECM) expression is subject to distinct changes during ontogeny, and the natural course of liver fibrosis in neonates is thought to differ from that in adults. We compared the expression and distribution of main ECM components between neonatal and adult liver fibrosis. Liver biopsies from infants with neonatal cholestasis and fibrosis were compared to adult biopsies exhibiting an equivalent stage of fibrosis. All biopsies were examined by immunohistochemistry (indirect ABC method) for the ECM proteins, collagens I, III, IV, and VI, laminin, and fibronectin. Infants (aged 1-8 months) with neonatal hepatitis (n = 3), extrahepatic biliary atresia (EHBA) (n = 5), and normal histology (n = 2) were compared with 9 adults (aged 17-70 years) with chronic hepatitis (n = 3), primary biliary cirrhosis (PBC) (n = 4), and normal histology (n = 2). Collagens I, III, and IV and fibronectin were significantly increased in neonatal hepatitis with mild fibrosis (score < or = 4) compared to adults with an equivalent fibrosis stage. This increase was particularly notable in perisinusoidal spaces. Laminin expression was increased in portal and perisinusoidal spaces both in neonatal hepatitis and extrahepatic biliary atresia with mild fibrosis. In infants with moderate to severe fibrosis (score > or = 6), only collagen I was increased in comparison to adults, whereas collagen VI expression was identical in all groups, irrespective of the degree of fibrosis. Expression of matrix proteins was not different in infants and adults without fibrosis. The increased perisinusoidal deposition of certain ECM components in infants with active hepatitis and mild fibrosis may point to an underlying difference in the mechanism or stimulus of fibrogenesis in neonates as compared to adults.

Adolescent↗