Biomedical subjects

Frank Rauch

Publications and source records attributed to Frank Rauch.

49 records · Page 3Linked to original sources

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

Rapid increase in grip force after start of pamidronate therapy in children and adolescents with severe osteogenesis imperfecta.

OBJECTIVE: To examine changes in grip force during pamidronate therapy in children and adolescents with severe osteogenesis imperfecta (OI). METHODS: Maximal isometric grip force of the nondominant hand was prospectively determined in 42 patients (age at the start of the study: 7.3-15.9 years; 18 girls) with severe forms of OI. Patients were treated with intravenous pamidronate infusions given in 4 monthly cycles, each cycle consisting of 3 infusions (1 mg pamidronate/kg body wt) on 3 successive days. RESULTS: At the start of pamidronate therapy, grip force was low compared with age-specific reference data (age z score mean +/- standard deviation: -2.7 +/- 2.1) but was normal for weight (weight z score: -0.1 +/- 1.8). Four months after the first pamidronate infusion cycle, grip force had increased significantly, whether related to age (age z score: -2.0 +/- 1.8) or to weight (weight z score: 0.6 +/- 1.5). At 2 years after the start of therapy, grip force z scores were not significantly different from the 4-month results. CONCLUSIONS: Maximal isometric grip force markedly increases after a single cycle of intravenous pamidronate in children with severe forms of OI, and this gain in grip force is maintained for at least 2 years.

Adolescent↗

PubMed2002

The muscle-bone relationship: methods and management - perspectives in glycogen storage disease.

UNLABELLED: Currently bone development is commonly presented as a process leading to the 'accumulation of peak bone mass'. Consequently, the usual approach to a suspected bone disorder in a child is to address the question are this child's bones as heavy as those of a healthy child of the same sex and age? However, from a functional perspective the aim of bone development should not be make bones as heavy as possible but to make them as stable as necessary. A functionally oriented approach should address two different questions: how strong are the bones? are they as strong as they need to be? It is clear that the bone has to be strong enough to withstand the mechanical forces to which it is exposed. CONCLUSION: since the main forces applied to bones are due to muscle action, the strength of a bone should be related to the force of the muscles attached to it.

Bone Density↗

PubMed2002

Low bone mass in glycogen storage disease type 1 is associated with reduced muscle force and poor metabolic control.

OBJECTIVE: To study the relation between muscle force, bone mass, and metabolic control in patients with glycogen storage disease type (GSD 1). STUDY DESIGN: Distal radius bone mass and density were evaluated in 19 patients with GSD 1 (15 GSD 1a, 4 GSD 1b) by means of peripheral quantitative computed tomography. Grip force was quantified with a dynamometer. RESULTS: Height, weight, bone mass, and grip force were significantly decreased in the patients with GSD 1a, mainly as the result of low values in the poorly controlled subgroup. Boys had lower bone mass than girls. Patients with GSD 1b had higher values for bone mineral density in the trabecular compartment. In most of the study participants bone mass appeared to be adequately adapted to the mechanical requirements imposed by muscle contraction. However, 3 patients with GSD 1a had evidence for a low bone mass. CONCLUSIONS: In GSD 1, both reduced muscle strength and a direct disease effect can contribute to low bone mass. The quality of treatment is crucial to prevent disturbances in musculoskeletal development.

Adolescent↗

PubMed2002

Fibrous dysplasia.

DEFINITION: Fibrous dysplasia (FD) of bone is a non-inheritable congenital disorder affecting both genders. It is characterized by expanding fibrous lesions, which contain bone-forming mesenchymal cells. PATHOPHYSIOLOGY: FD is caused by a somatic activating mutation of the alpha subunit of the Gs protein (Gsalpha). Bone mesenchymal cells produce a matrix of randomly distributed collagen fibres and islands of woven bone. Osteoclasts are responsible for the spread of the lesions. CLINICAL FINDINGS: The symptoms are bone pain, fracture, bone deformities and neurological deficits. Spontaneous regression of lesions does not occur. TREATMENT: Recently, an observational study of treatment with bisphosphonate has yielded promising results. There was a decreased intensity of bone pain, a decrease in biochemical markers of bone turnover and a radiographically apparent 'refilling of osteolytic sites' in about half of the patients. CONCLUSIONS: Very little is known about the effects of bisphosphonate treatment in children and adolescents with FD. Most patients report decreased bone pain after the first pamidronate infusion, which, in our view, justifies the use of this drug in severely affected patients. The many unanswered questions regarding this form of treatment can only be addressed when a large number of patients is treated in a standardized fashion, and data on the outcome are collected.

Adolescent↗

PubMed2002

The effects of intravenous pamidronate on the bone tissue of children and adolescents with osteogenesis imperfecta.

Cyclical pamidronate infusions increase bone mass in children suffering from osteogenesis imperfecta. The histological basis for these effects remains unknown. Therefore, we compared parameters of iliac bone histomorphometry from 45 patients before and after 2.4 +/- 0.6 years of pamidronate treatment (age at the time of the first biopsy, 1.4-17.5 years; 23 girls). Although biopsy size did not change significantly (P = 0.30), cortical width increased by 88%. Cancellous bone volume increased by 46%. This was due to a higher trabecular number, whereas trabecular thickness remained stable. Bone surface-based indicators of cancellous bone remodeling decreased by 26-75%. There was no evidence for a mineralization defect in any of the patients. These results suggest that, in the growing skeleton, pamidronate has a twofold effect. In remodeling, bone resorption and formation are coupled and consequently both processes are inhibited. However, osteoclasts and osteoblasts are active on different surfaces (and are thus uncoupled) during modeling of cortical bone. Therefore resorption is selectively targeted, and continuing bone formation can increase cortical width.

Adolescent↗

PubMed2002

Muscle analysis by measurement of maximal isometric grip force: new reference data and clinical applications in pediatrics.

Skeletal muscle development is one of the key features of childhood and adolescence. Determining maximal isometric grip force (MIGF) using a hand-held Jamar dynamometer is a simple method to quantify one aspect of muscle function. Presently available reference data present MIGF as a function of chronological age. However, muscle force is largely determined by body size, and many children undergoing muscle performance tests in the clinical setting suffer from growth retardation secondary to a chronic disorder. Reference data were established from simple regressions between age or log height and log MIGF in a population of 315 healthy children and adolescents aged 6 to 19 y (157 girls). These data were used to calculate age- or height-dependent SD scores (SDS) for MIGF in three pediatric patient groups. In renal graft recipients (n = 14), the age-dependent MIGF SDS was markedly decreased (-2.5 +/- 1.9; mean +/- SD). However, these patients had short stature (height SDS, -2.5 +/- 1.2), and the height-dependent MIGF SDS was close to normal (-0.4 +/- 1.5). Similarly, in cystic fibrosis patients (n = 13) age-dependent MIGF SDS was -1.6 +/- 1.6, but height-dependent MIGF SDS was -0.5 +/- 1.1. Children with epilepsy who were taking anticonvulsant therapy (n = 34) had normal stature, and consequently age- and height-dependent MIGF SDS were similar (0.4 +/- 1.0 and 0.4 +/- 0.8, respectively). In conclusion, MIGF determination provides information on an important aspect of physical development. Height should be taken into account to avoid misinterpretation.

Adolescent↗

PubMed2002

Osteogenesis imperfecta type VI: a form of brittle bone disease with a mineralization defect.

Osteogenesis imperfecta (OI) is a heritable disease of bone in which the hallmark is bone fragility. Usually, the disorder is divided into four groups on clinical grounds. We previously described a group of patients initially classified with OI type IV who had a discrete phenotype including hyperplastic callus formation without evidence of mutations in type I collagen. We called that disease entity OI type V. In this study, we describe another group of 8 patients initially diagnosed with OI type IV who share unique, common characteristics. We propose to name this disorder "OI type VI." Fractures were first documented between 4 and 18 months of age. Patients with OI type VI sustained more frequent fractures than patients with OI type IV. Sclerae were white or faintly blue and dentinogenesis imperfecta was uniformly absent. All patients had vertebral compression fractures. No patients showed radiological signs of rickets. Lumbar spine areal bone mineral density (aBMD) was low and similar to age-matched patients with OI type IV. Serum alkaline phosphatase levels were elevated compared with age-matched patients with type IV OI (409 +/- 145 U/liter vs. 295 +/- 95 U/liter; p < 0.03 by t-test). Other biochemical parameters of bone and mineral metabolism were within the reference range. Mutation screening of the coding regions and exon/intron boundaries of both collagen type I genes did not reveal any mutations, and type I collagen protein analyses were normal. Qualitative histology of iliac crest bone biopsy specimens showed an absence of the birefringent pattern of normal lamellar bone under polarized light, often with a "fish-scale" pattern. Quantitative histomorphometry revealed thin cortices, hyperosteoidosis, and a prolonged mineralization lag time in the presence of a decreased mineral apposition rate. We conclude that type VI OI is a moderate to severe form of brittle bone disease with accumulation of osteoid due to a mineralization defect, in the absence of a disturbance of mineral metabolism. The underlying genetic defect remains to be elucidated.

Adolescent↗

PubMed2002

Bone mineralization in polyostotic fibrous dysplasia: histomorphometric analysis.

Fibrous dysplasia (FD) of bone can be complicated by renal phosphate wasting. The effect of hypophosphatemia on normal and dysplastic bone of FD patients has not been well characterized. In this study, we compared serum phosphorus (sPi) levels to histomorphometric findings in 27 iliac bone samples from 23 children and adolescents (aged 4.2-16.4 years) with polyostotic FD. The samples were separated into two groups, based on the presence (n = 10) or absence (n = 17) of a dysplastic lesion within the specimen. Histomorphometric results were compared with those from 18 age-matched control subjects without metabolic bone disease. In dysplastic lesions, trabeculae were clearly thinner and increased in number. Osteoid indices, osteoblast surface per bone surface, and mineralization lag time were elevated in dysplastic areas, but there was no detectable effect of sPi concentrations on these indices. In nondysplastic bone tissue, low sPi levels were associated with mildly increased osteoid thickness and prolonged mineralization lag time. None of the 13 patients in whom hand X-rays were available at the time of biopsy had radiological signs of rickets. In conclusion, low sPi can cause a mild systemic mineralization defect in FD, but the more severe mineralization defect seen in dysplastic lesions is independent of sPi levels. It is debatable whether the mild systemic mineralization defect warrants treatment with oral phosphorus supplementation if signs of rickets are absent.

Adolescent↗

PubMed2002

Bone mineral content per muscle cross-sectional area as an index of the functional muscle-bone unit.

Bone densitometric data often are difficult to interpret in children and adolescents because of large inter- and intraindividual variations in bone size. Here, we propose a functional approach to bone densitometry that addresses two questions: Is bone strength normally adapted to the largest physiological loads, that is, muscle force? Is muscle force adequate for body size? To implement this approach, forearm muscle cross-sectional area (CSA) and bone mineral content (BMC) of the radial diaphysis were measured in 349 healthy subjects from 6 to 19 years of age (183 girls), using peripheral quantitative computed tomography (pQCT). Reference data were established for height-dependent muscle CSA and for the variation with age in the BMC/muscle CSA ratio. These reference data were used to evaluate results from three pediatric patient groups: children who had sustained multiple fractures without adequate trauma (n = 11), children with preterminal chronic renal failure (n = 11), and renal transplant recipients (n = 15). In all three groups mean height, muscle CSA, and BMC were low for age, but muscle CSA was normal for height. In the multiple fracture group and in renal transplant recipients the BMC/muscle CSA ratio was decreased (p <. 0.05), suggesting that bone strength was not adapted adequately to muscle force. In contrast, chronic renal failure patients had a normal BMC/muscle CSA ratio, suggesting that their musculoskeletal system was adapted normally to their (decreased) body size. This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques.

Adolescent↗

PubMed2002

Collagen markers deoxypyridinoline and hydroxylysine glycosides: pediatric reference data and use for growth prediction in growth hormone-deficient children.

BACKGROUND: In children and adolescents, markers of bone and collagen metabolism reflect the dynamics of skeletal growth and development. The aim of this study was to assess the relationship of the urinary collagen markers deoxypyridinoline (DPD) and hydroxylysine (Hyl) and its glycosides [galactosyl-Hyl (Gal-Hyl) and glucosyl-Gal-Hyl] with growth. METHODS: Urine samples from 240 apparently healthy children and adolescents (6-19 years; 124 girls) and from 51 prepubertal children with growth hormone (GH) deficiency (3-14 years; 14 girls) were analyzed. Urinary Hyl and its glycosides were quantified by HPLC, and DPD was assessed by chemiluminescence assay. Urinary concentrations of all markers were related to urinary creatinine. RESULTS: Multiple regression analysis revealed that only age and height velocity were independently associated with these markers in healthy children. In GH-deficient patients, the urinary excretion of both analytes after 4 weeks of GH therapy correlated significantly with the height increase during the first treatment year (r = 0.79 for Gal-Hyl; r = 0.70 for DPD; P <0.001 each). In a multivariate linear regression model using Gal-Hyl concentrations at 4 weeks, baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 80% of the variability in height gain during the first treatment year. A model using DPD concentrations at 4 weeks, in place of Gal-Hyl concentrations, as well as baseline concentrations of insulin-like growth factor 1 and height velocity after 3 months accounted for 83% of the variability. CONCLUSIONS: These urinary bone and collagen markers give some early indication of growth response, but the prediction of an individual marker is too imprecise to serve as a basis for clinical decisions. Markers of bone and collagen metabolism might be more useful as components of multivariate growth prediction models.

Adolescent↗

PubMedDate not supplied

High prevalence of coxa vara in patients with severe osteogenesis imperfecta.

The purpose of this study was to determine the incidence and clinical presentation of coxa vara in 283 patients with osteogenesis imperfecta (OI). The charts and X-rays of 150 girls and 133 boys with OI were reviewed. The patients were classified according to the Sillence classification modified by Glorieux: 94 type I, 90 type IV, 67 type III, 18 type V, 10 type VI, and 4 type VII. The mean age was 9.4 years (range 0.3-23.3). Twenty-nine patients (10.2%) had coxa vara (23 left and 20 right). Fifty-five percent of them were type III, 24% type IV, 13.8% type VI, and 3.4% each of types V and VII. The incidence of coxa vara was 6% in type V, 8% in type IV, 24% in type III, 25% in type VII, and 40% in type VI (P < 0.001 for difference between types I, III, and IV). The mean neck-shaft angle was 99 degrees (range 80-110 degrees), the average head-shaft angle was 104 degrees (range 90-120 degrees), and the mean Hilgenreiner-epiphyseal angle was 68 degrees (range 40-90 degrees). Twenty-five patients (36 hips) had previous femoral rodding before diagnosis and seven hips (all type III) had no history of rodding. Abduction and internal rotation of the hip joints were restricted in all patients with this deformity. All children with coxa vara had a Trendelenburg gait. In conclusion, coxa vara in OI is not rare, especially in severe forms of the disease. Regular clinical and radiologic follow-up is indicated in children with previous femoral rodding and in severely affected children, particularly those with OI type III.

Adolescent↗