The interaction between Sillence type and BMD in osteogenesis imperfecta.

Clinical studies with bisphosphonates in children with osteogenesis imperfecta (OI) show an increase in BMD and a decrease in fracture rate. Bone strength in children with OI is not only influenced by changes in BMD but also by changes in collagen I structure of the organic bone matrix. Therefore, we studied the interaction between these two factors in a cross-sectional, single center study including 54 children. We assumed that vertebral deformities in OI represent an unbalance between load and bone strength. Body weight was considered to be a well quantifiable load on vertebral bodies. BMD served as a marker, representing the amount of bone tissue available for vertebral load bearing, and the Sillence classification, either type I or III/IV, as a marker representing the quality of the organic bone matrix. Independent associations were observed between the prevalence of vertebral deformities and (1) Sillence type (OR: 5.7, 95%Cl:1.2-26.8), (2) BMD (OR: 0.003, 95%Cl: 0-0.25) and (3) body weight (OR: 1.15, 95%Cl: 1.05-1.25). Regarding the anthropometrical differences among the different types of OI, the BMD/body weight ratio was introduced to evaluate the BMD in relation to body size. Prevalent vertebral deformities were associated with low BMD/body weight ratios (OR: 0.04, 95%Cl: 0.008-0.2) in OI type I, but no association was found in type III/IV. It was concluded that BMD and Sillence type have independent relationships with vertebral deformities. The BMD/body weight ratio correlates with vertebral deformities in children with OI type I. Its meaning in types III/IV needs further research with larger samples because of the relatively high prevalence of vertebral deformities in this group.

Osteogenesis imperfecta in childhood: prognosis for walking.

OBJECTIVES: We studied the predicted value of disease-related characteristics for the ability of children with osteogenesis imperfecta (OI) to walk. STUDY DESIGN: The severity of OI was classified according to Sillence. The parents were asked to report the age at which the child achieved motor milestones, the fracture incidence, and the age and localization of the first surgical intervention. The present main means of mobility was classified according to Bleck. RESULTS: There were 76 replies to the 98 questionnaires, of which 70 were included (type I, 41; type III, 11; type IV, 18). The type of OI was strongly associated with current walking ability, as was the presence of dentinogenesis imperfecta. Patients with type III and IV had a lower chance of ultimately walking compared with those with type I. Children with more than 2 intramedullary rods in the lower extremities had a reduced chance of walking than patients without rods. Rolling over before 8 months, unsupported sitting before 9 months, the ability to get in sitting position without support before 12 months, and the ability to get in a standing position without support before 12 months showed positive odds ratios. In Bleck > or = 4, multivariate analysis revealed that only the presence of rodding (yes/no) in the lower extremities had additional predictive value to the type of OI. The presence of dentinogenesis imperfecta and rodding (yes/no) had additional value in Bleck > or = 5. CONCLUSION: The type of OI is the single most important clinical indicator of the ultimate ability to walk. Information about motor development adds little. The early achievement of motor milestones contributes to the ability of independent walking when the type of OI is uncertain. Intramedullary rodding of the lower extremities is primarily related to the severity of the disease and in this way provides consequences for the ability to walk.

Osteogenesis imperfecta: profiles of motor development as assessed by a postal questionnaire.

UNLABELLED: This study was performed to achieve more detailed information regarding the age and sequence in the development of motor milestones in the different types of osteogenesis imperfecta (OI). The parents of 98 patients with a diagnosis of OI were sent a questionnaire regarding the age at which patients achieved motor milestones. All patients were attending the outpatient clinic for children with OI at the Wilhelmina Children's Hospital. The motor milestones were classified into static motor milestones and dynamic motor milestones and all data were checked with health care records. The age of development of motor milestones was compared to reference values of the healthy population. The severity of the disease was classified according to Sillence based on clinical, genetic and radiological data. The age of intramedullary rodding of the first nail in the lower and upper extremity and the localisation was noted. A total of 76 parents responded to the 98 questionnaires (78%). In OI type I, a delay exists in achieving motor milestones, comparable to the 95th percentile of the normal population. In type III, the development of all motor milestones was significantly delayed compared to types I and IV with a discrepancy between static and dynamic milestones. In OI type IV, a retardation in motor development developed after the milestone 'sitting without support' was achieved. Motor development in types I and IV was not influenced by intramedullary rodding of the lower extremities, since rodding was rarely performed before the milestone 'unsupported standing' was achieved. In type III, the influence of intramedullary rodding on the age of achieving motor milestones remains questionable. CONCLUSION: The severity of osteogenesis imperfecta has a large influence on the age and sequence in the development of motor milestones. No influence of intramedullary rodding of the lower extremities on motor development was found in osteogenesis imperfecta types I and IV, whereas the influence in type III remains questionable.

Pyridinium cross-links in bone of patients with osteogenesis imperfecta: evidence of a normal intrafibrillar collagen packing.

The brittleness of bone in patients with osteogenesis imperfecta (OI) has been attributed to an aberrant collagen network. However, the role of collagen in the loss of tissue integrity has not been well established. To gain an insight into the biochemistry and structure of the collagen network, the cross-links hydroxylysylpyridinoline (HP) and lysylpyridinoline (LP) and the level of triple helical hydroxylysine (Hyl) were determined in bone of OI patients (types I, III, and IV) as well as controls. The amount of triple helical Hyl was increased in all patients. LP levels in OI were not significantly different; in contrast, the amount of HP (and as a consequence the HP/LP ratio and the total pyridinoline level) was significantly increased. There was no relationship between the sum of pyridinolines and the amount of triple helical Hyl, indicating that lysyl hydroxylation of the triple helix and the telopeptides are under separate control. Cross-linking is the result of a specific three-dimensional arrangement of collagens within the fibril; only molecules that are correctly aligned are able to form cross-links. Inasmuch as the total amount of pyridinoline cross-links in OI bone is similar to control bone, the packing geometry of intrafibrillar collagen molecules is not disturbed in OI. Consequently, the brittleness of bone is not caused by a disorganized intrafibrillar collagen packing and/or loss of cross-links. This is an unexpected finding, because mutant collagen molecules with a random distribution within the fibril are expected to result in disruptions of the alignment of neighboring collagen molecules. Pepsin digestion of OI bone revealed that collagen located at the surface of the fibril had lower cross-link levels compared with collagen located at the inside of the fibril, indicating that mutant molecules are not distributed randomly within the fibril but are located preferentially at the surface of the fibril.

Long-term follow-up of conservatively treated popliteal cysts in children.

This study was undertaken to determine the long-term outcome of conservatively treated popliteal cysts in children. It was based on a review of 20 cysts, none of which were initially treated surgically. The records of children with popliteal cysts between 1986 and 1992 were studied, and a group of patients without other diseases or other physical abnormality in the knee region was selected. Twenty-one patients were included and were subjected to a clinical and ultrasound investigation. Three were lost to follow-up, leaving 18 patients with 20 cysts available for analysis. In the follow-up period, which ranged from 5 to 10 years, 14 cysts were treated conservatively with a mean follow-up of 7 years, whereas 6 cysts were operated on after a mean period of 2 years. Of the conservatively treated cysts, eight had disappeared and six had shrunk. Although spontaneous remission is not to be expected in all cases, asymptomatic popliteal cysts in children can be treated conservatively with good results.

Complications of the Bailey-Dubow elongating nail in osteogenesis imperfecta: 34 children with 110 nails.

The Bailey-Dubow nail, inserted in the femur or tibia of 34 children with osteogenesis imperfecta (OI), was studied retrospectively. Comparing the various groups of OI, no significant difference was found. Location of the nail (tibia or femur) did not influence the complication rate significantly. The reoperation rate was 29%, a rate comparable to that reported in earlier studies. The part of the nail located around the knee had a significantly higher migration rate (P = 0.005 at obturator ends and P = 0.007 at sleeve ends). Migration of the nail was the reason to reoperate in 50% of the patients. Better anchoring of the T-piece will substantially decrease the complication rate. In consideration of the different functional capacities of the OI population, the complications are likely related more to the hardware than to the patient.

Defective collagen crosslinking in bone, but not in ligament or cartilage, in Bruck syndrome: indications for a bone-specific telopeptide lysyl hydroxylase on chromosome 17.

Bruck syndrome is characterized by the presence of osteoporosis, joint contractures, fragile bones, and short stature. We report that lysine residues within the telopeptides of collagen type I in bone are underhydroxylated, leading to aberrant crosslinking, but that the lysine residues in the triple helix are normally modified. In contrast to bone, cartilage and ligament show unaltered telopeptide hydroxylation as evidenced by normal patterns of crosslinking. The results provide compelling evidence that collagen crosslinking is regulated primarily by tissue-specific enzymes that hydroxylate only telopeptide lysine residues and not those destined for the helical portion of the molecule. This new family of enzymes appears to provide the primary regulation for controlling the different pathways of collagen crosslinking and explains why crosslink patterns are tissue specific and not related to a genetic collagen type. A genome screen identified only a single region on chromosome 17p12 where all affected sibs shared a cluster of haplotypes identical by descent; this might be the BS (Bruck syndrome) locus and consequently the region where bone telopeptidyl lysyl hydroxylase is located. Further knowledge of this enzyme has important implications for conditions where aberrant expression of telopeptide lysyl hydroxylase occurs, such as fibrosis and scar formation.

Osteogenesis imperfecta in childhood: treatment strategies.

Osteogenesis imperfecta (OI) is a skeletal disorder of remarkable clinical variability characterized by bone fragility, osteopenia, variable degrees of short stature, and progressive skeletal deformities. Additional clinical manifestations such as blue sclerae, dentinogenesis imperfecta, joint laxity, and maturity onset deafness are described in the literature. OI occurs in about 1 in 20,000 births and is caused by quantitative and qualitative defects in the synthesis of collagen I. Depending on the severity of the disease, a large impact on motor development, range of joint motion, muscle strength, and functional ability may occur. Treatment strategies should primarily focus on the improvement of functional ability and the adoption of compensatory strategies, rather than merely improving range of joint motion and muscle strength. Surgical treatment of the extremities may be indicated to stabilize the long bones to optimize functional ability and walking capacity. Surgical treatment of the spine may be indicated in patients with progressive spinal deformity and in those with symptomatic basilar impression.

Spinal complications in osteogenesis imperfecta: 47 patients 1-16 years of age.

We examined in a cross-sectional study, 47 children (mean age 7.7 (1-16) years) with osteogenesis imperfecta (OI) to find the prevalence of spinal deformities and to correlate these observations with anthropometry. The associations between dentinogenesis imperfecta, joint hypermobility and spinal deformities were also studied. Disproportion in stature in OI type I and type IV was mainly caused by spinal involvement, as evidenced by a greater decrease in body height than in leg length. In OI type I, the decrease in sitting height was mainly caused by platyspondyly, whereas in OI types III and IV, it was also caused by progressive scoliosis and kyphosis. Scoliosis was present in 22 children, and pathological kyphosis in 18, mainly in the severe OI types. Basilar impression was observed in 10 children, mainly in type III. Children with dentinogenesis imperfecta seemed to be prone to develop scoliosis, pathological kyphosis and basilar impression. Children with generalized joint hypermobility were less prone to develop scoliosis and basilar impression. Our observations may contribute to a better understanding of the risk factors for progressive spinal deformities in OI.

Multiple congenital contractures.

A cross-sectional study of 28 patients with multiple congenital contractures of miscellaneous origin is presented. We describe the clinical, genetic, and neurological diagnosis and the involvement of upper and lower extremities and spine. All treatments that patients received so far as well as functional outcome were studied. We compared these factors in children with anterior horn cell degeneration (AHCD) or amyoplasia with those of children with contractures of other origin. A correct genetical diagnosis of multiple congenital contracture is important because children with AHCD will need more extensive treatment than others, and their functional outcome seems to be worse.

Urological problems after surgical treatment of scoliosis in children with myelomeningocele.

PURPOSE: We assessed urological problems and complications after scoliosis surgery in children with myelomeningocele. MATERIALS AND METHODS: A total of 16 children with myelodysplasia underwent surgery for scoliosis using different surgical techniques and instrumentation systems. Mean patient age at operation as 11 years and mean postoperative followup was 3 years. All patients had urological assessment before and after surgery, including urodynamics. RESULTS: Urological problems after surgical correction of scoliosis developed in 6 patients (38%). Three girls had difficulty performing clean intermittent self-catheterization postoperatively because of altered body posture, a genital pressure sore and a plaster body cast, respectively. In 4 patients, including 1 girl with problems performing clean intermittent self-catheterization, lower urinary tract function was altered, leading to upper urinary tract deterioration in 1 and worsening of urinary incontinence in 3. CONCLUSIONS: Children with myelomeningocele have a high incidence of urological complications after surgical treatment of scoliosis. Anticipation of the problems and a thorough postoperative urological evaluation, including urodynamics, can reduce morbidity and facilitate appropriate treatment.

Intramedullary rodding in type III osteogenesis imperfecta. Effects on neuromotor development in 10 children.

We studied retrospectively gross motor development and the impact of intramedullary rodding in 10 children with type III osteogenesis imperfecta (OI). There was a pronounced delay in motor development and the order in achieving gross motor milestones differed from the normal developmental sequence. Static milestones developed at an earlier stage than dynamic milestones. Intramedullary rodding of the lower extremities prior to the age of 3.5 years enhanced neuromotor development, especially regarding the milestones supported standing, rolling from prone to supine and crawling with abdomen on the floor. The different sequence in achieving gross motor milestones should have implications for future rehabilitation programs and for orthopedic surgery.

Destructive synovitis in contralateral Perthes' disease. A report of 2 cases.

2 boys had unilateral Perthes' disease at the age of 5 years. After 6 and 7 years, respectively, both patients developed contralateral femoral head necrosis with rapid destruction leading to ankylosis of the hip. Histology of the synovium showed nonspecific synovitis. Both patients fulfilled criteria for oligo-articular juvenile chronic arthritis (JCA). The association with Perthes' disease suggests a common etiology.

Gemfibrozil treatment of the high triglyceride-low high-density lipoprotein cholesterol trait in men with established atherosclerosis.

OBJECTIVE: To study the short-term efficacy, tolerability and safety of the treatment with gemfibrozil 600 mg twice daily or placebo in male patients with established atherosclerosis, with a lipid profile matching the 'high triglyceride-low high-density lipoprotein (HDL) cholesterol trait'. DESIGN: Double-blind randomized placebo controlled prospective trial. SETTING: Amsterdam Lipid Research Clinic at the Academic Medical Centre of the University of Amsterdam and the Slotervaart Training Hospital affiliated to the University of Amsterdam, Amsterdam, the Netherlands. SUBJECTS: Thirty-five male patients, age 30-70, with established atherosclerosis and the high triglyceride-low HDL cholesterol trait. MAIN OUTCOME MEASURES: Plasma total cholesterol, triglycerides, lipoproteins, apolipoproteins A1 and B100, clinical and laboratory safety parameters. RESULTS: Seventeen patients in the gemfibrozil group and 16 patients in the placebo group completed the study period. Compliance was considered adequate. Mean (+/- standard deviation) plasma HDL cholesterol levels increased 20.3% (+/- 12.22) from 0.82 to 0.99 mmol L-1 in the gemfibrozil group against 9.9% (+/- 18.31) from 0.79 to 0.87 mmol L-1 in the placebo group (P = 0.001). Mean plasma triglyceride level fell 49.5% (+/- 14.27) from 3.65 to 1.82 mmol L-1 in the gemfibrozil group against an increase of 13.6% (+/- 40.31) from 3.62 to 4.01 mmol L-1 in the placebo group (P < 0.001). Although plasma HDL cholesterol and triglyceride levels improved in all patients, normalization of these lipoproteins was only observed in approximately half of them. Plasma total and low-density lipoprotein (LDL) cholesterol levels, as well as plasma levels of apolipoprotein (apo) A1, B100 and lipoprotein [Lp(a)], did not show significant alterations compared to the placebo. All safety parameters were comparable between the two groups and remained within the reference limits. Gemfibrozil was well tolerated during treatment. Minor inconveniences were equally distributed between the two treatment groups. CONCLUSIONS: Gemfibrozil is an effective and safe drug in patients with coronary heart disease (CHD) and the high triglyceride-low HDL cholesterol trait.