F Rauch

..Low cortical vBMD presumably reflects the underlying mineralization defect that is not entirely corrected by current treatment approaches...

..Rare recessive forms of OI, caused by mutations in genes involved in various aspects of bone formation, have been described as well...

..Recent research has shown that OI type V is caused by a recurrent c.-14C>T mutation in IFITM5. In the present study, we assessed all patients diagnosed with OI type V at our institutions for the presence of the IFITM5 mutation...

..Determining PEDF serum levels might facilitate the diagnosis of OI type VI...

..In conclusion, obese children and adolescents have increased muscle force and power. This partly compensates for the effect of high body weight on muscle performance...

..Several studies suggest that 24,25-dihydroxyvitamin D [24,25(OH)₂D] may have an effect on bone mass and metabolism...

..It remains largely unexplored how local and systemic signals are integrated to achieve site-specific changes in bone structure...

..The recommendations are presented here...

..Intravenous pamidronate treatment is beneficial to children and adolescents with osteogenesis imperfecta (OI), but the effects of prolonged therapy are not well characterized...

..Future research will have to address the question how periosteal bone cells manage to integrate mechanical, hormonal and other input to shape bones that are as strong as they need to be...

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..These data should facilitate the clinical use of peripheral quantitative computed tomography in young subjects...

..Cyclical iv pamidronate is a widely used symptomatic therapy of osteogenesis imperfecta (OI). What happens after treatment discontinuation is unknown...

..These results are compatible with the view that bone development is driven by muscle development, although the data do not exclude the hypothesis that the two processes are independently determined by genetic mechanisms...

..In analogy to the above model for OI, mechanical loads should be overestimated, resulting in increased densitometric parameters of bone strength. Indeed, lumbar spine areal bone mineral density is usually elevated in such patients...

..Remodeling during development is thus an age-dependent process that varies with location even within the same bone...

..These preliminary data suggest that intramuscular BTX-A injections can have a deleterious effect on the development of bones that are loaded by the injected muscles...

..These data should be useful to predict disease phenotype in newly diagnosed OI patients...

..Thus patients with haploinsufficiency mutations had a milder skeletal phenotype than patients with mutations affecting glycine residues, but there was no clear genotype-phenotype correlation among patients with helical glycine mutations...

..In a small pilot trial in children we noted improvements in standing function, lumbar spine bone mineral density, tibial bone mass, and calf muscle cross-sectional area...

..Quantitative histomorphometric analysis of transiliac bone biopsy samples is especially valuable in clinical studies, as this method provides safety and efficacy data that can not be obtained in any other way...

..Future studies should investigate whether oral risedronate is effective in reducing fracture rates in children and adolescents with mild OI type I...

..These data should facilitate the clinical use of peripheral quantitative computed tomography in young subjects...

..The ISCD Official Positions with respect to the above issues, as well as the rationale and evidence used to derive these positions, are presented here...

..In the past, research has focused on bone remodeling on trabecular surfaces. However, the key to an improved understanding of bone mass and strength development in children will lie with studies on bone modeling on periosteal surfaces...

..It is possible that this produces zones of localized bone fragility after pamidronate treatment is stopped in growing children...

..Patients with larger deficits in bone mass at baseline have a more marked bone mass gain during therapy...

..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...

..Thus, the process causing IJO appears to mainly affect bone surfaces that are in contact with the bone marrow cavity...

..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...

..In conclusion, multiple slice analysis may provide information on the dynamic turnover of metaphyseal trabeculae during growth...

..04). These data suggest that the bone marrow cavity of the distal radius may be slightly larger when puberty occurs later. Whether this marginal effect influences fracture risk in later life appears questionable...

..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...

..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...

..However, from a functional perspective, bones should not be as heavy as possible, but rather as stable as necessary. It is therefore important to create conditions that stimulate bones to become more stable...

..In conclusion, this preliminary study demonstrates that serum leptin decreases during GH treatment in children with GH deficiency...

..To examine bone development in children and adolescents who have uncomplicated idiopathic epilepsy and had received monotherapy with carbamazepine or valproic acid for at least 1 year...

..To identify parameters which predict individual growth response to recombinant human GH (rhGH) therapy and to combine these parameters in a prediction model...

..The purpose of the mechanically inefficient endocortical apposition in female puberty might be to create a reservoir of calcium for future pregnancy and lactation...

..Volumetric BMD is higher in women, partly because the size of the marrow cavity does not increase in girls as it does in boys...

..The highest variability was found for cellular parameters. The availability of reference material will greatly facilitate the use of histomorphometry in pediatrics...

..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...

..In conclusion, the WBV protocol used in this study appears to be safe in children with cerebral palsy and may improve mobility function but we did not detect a positive treatment effect on bone...

..However, the increase in specific grip force is similar in both genders and thus appears to be independent of sex hormones...

..It is possible that low mechanical stimulation due to inadequate muscle mass contributes to the bone deficit...

..Our results therefore suggest that intracortical remodeling is lower in postpubertal females than in males...

..Better mobility status, but not pamidronate treatment, seems to be predictive of delayed healing after fractures...

..Information on the use of oral bisphosphonate agents to treat pediatric osteogenesis imperfecta (OI) is limited...

..DXA allows the estimation of BMD(total) at skeletal sites, which have an approximately circular cross-section. The system presented here may help to interpret densitometric results in growing subjects on a physiological basis...

..Bone strength may not be adequate for the relatively high body weight of TS patients (+0.8 SD score), which could contribute to an increased propensity for fractures...

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..In moderate to severe forms of OI, pamidronate should be started as early as possible to treat or to prevent vertebral deformations...

..The long-term (>1 yr) effects of calcitriol replacement treatment have not been reported...

..We propose that future studies on bone development should address topics that can be derived from the mechanostat model...

..This study excludes type I collagen mutations in the pathogenesis of the disease and assigns this form of OI to a locus other than the ones containing the type I collagen genes...

..The disease has subsequently been localized to chromosome 3p22-24.1, which is outside the loci for type I collagen genes. The underlying genetic basis for the disease remains to be determined...

..04). CONCLUSIONS: Four years of cyclical intravenous pamidronate treatment led to a significant height gain in moderately to severely affected OI patients...

..However, the gains in mobility scores and reductions in fracture incidence during pamidronate treatment are less than in other OI types...

..It seems more likely that the observed abnormalities in osteoclast morphology are part of the mechanism of action of this drug...

..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...

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..The endocortical apposition rate is already very high at that site and apparently cannot be further increased to levels that would be necessary to keep bone strength adapted to the mechanical requirements...

..It is therefore prudent to reserve pamidronate treatment to infant OI patients who present with a moderate to severe phenotype...

..Results suggested that applying OP-1 early during distraction can accelerate bone formation by the activation of numerous pathways. This study provides further insights on strategies to improve bone regeneration rate in DO...

..To describe mechanographic tests that can be performed by patients with a range of functional abilities and to assess the reproducibility of test results in healthy adults and children...

..We are unaware of prior reports of this finding. We suggest that this deletion affects crucial amino acids that are important for the interaction and/or stabilization of CRTAP and P3H1...

..CONCLUSIONS: The mean oral bioavailability of 35- and 70-mg ALN tablets was less than 0.6%, comparable to adult studies. Adverse experiences from single-dose ALN were minor, and the drug was generally well-tolerated...

..These data indicate that BMPs participate in the translation of mechanical stimuli into a biological response during mandibular distraction osteogenesis...

..Thus, it appears that the lack of receptor protein in the target tissue impairs the effect of OP-1 given at the end of the distraction period. Possibly, OP-1 could be more useful when applied early in the distraction phase...

..There were no significant side effects noted during the time of follow-up. Thus, intravenous treatment with pamidronate seems to be safe and of some benefit in patients with OI type VII...

..Thus, it appears that SNWB occur more frequently in more severely affected OI patients and seem to develop mostly in utero...

..There is no evidence at present that these treatment induced morphological changes have any clinical implications...

..The aims of this retrospective work were to study the prevalence of radial head malalignment (dislocation or subluxation) in different types of osteogenesis imperfecta and to identify factors linked to it...

..4% (heel-rise test) of the averaged peak force measurements. Therefore measuring only the vertical component of ground reaction force in healthy participants is appropriate for the five tests used in the present study...

..Treatment of osteogenesis imperfecta by bisphosphonate therapy can improve bone mass in all types of the disorder, and while not being a cure for the disorder does improve the quality of life of the patient...

..The goal of the present study was to determine the repeatability of gait parameters measured by a force plate gait analysis system (Leonardo Mechanograph® GW)...

..The pathogenetic basis for this disorder remains to be elucidated...

..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...

..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...

..CONCLUSION: This study suggests that cyclical pamidronate treatment improves mobility, ambulation level, and muscle force in children with moderate to severe osteogenesis imperfecta...

..These results therefore suggest a role for the whole BMP signaling pathway including the Smad proteins in DO...

..Medical therapies other than bisphosphonates, such as growth hormone and parathyroid hormone, play a minor role at present. Gene-based therapy currently remains in the early stages of preclinical research...

..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...

..These observations suggest that mutations in this region of the collagen type I alpha 2 chain carry a high risk of abnormal limb development and intracranial bleeding...

..The underlying genetic defect remains to be elucidated...

..This functional approach to pediatric bone densitometric data should be adaptable to a variety of densitometric techniques...

..It is debatable whether the mild systemic mineralization defect warrants treatment with oral phosphorus supplementation if signs of rickets are absent...

..Both the mothers and babies remain well and free of fracture 14 and 16 months postpartum...

..The etiology is unclear but may involve cytokine release and/or hemodynamic compromise from fluid administration during the first infusion cycle. Close monitoring throughout the first treatment cycle is of paramount importance...

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..Although this treatment does not constitute a cure, it is an adjunct to physiotherapy, rehabilitation, and orthopaedic care. Gene-based therapy presently remains in the early stages of preclinical research...

..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...

..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...

..5-22.9 years of age. During the growing years, the two cortices of an iliac bone specimen differ with regard to bone cell activity on their surfaces, probably reflecting a modeling drift...

..Medical therapies other than bisphosphonates play a minor role at present. Gene-based therapy currently remains in the realm of preclinical research...

..In the present study, we did not find a case of ONJ among 278 pediatric patients who had received intravenous pamidronate during childhood or adolescence...

..Such patients should not be treated unless clear clinical benefit can be demonstrated in ongoing placebo-controlled trials...

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