A Comparison of Lumbar Spine and Lateral Distal Femur Bone Density in Girls With Rett Syndrome.

INTRODUCTION/BACKGROUND: Patients with Rett syndrome (RS) are at risk for low bone mineral density (BMD) and femoral fractures. In patients with RS, assessment with lateral distal femur (LDF) dual-energy X-ray absorptiometry (DXA) is recommended and clinically relevant. This study is the first to assess LDF BMD in girls with RS, and to compare LDF BMD results with lumbar spine BMD results in RS. Method Eleven girls (mean age 8.4 yr) with molecularly diagnosed RS and clinical DXA scan(s) were identified; medical charts were retrospectively reviewed. Baseline and serial lumbar spine and LDF BMD Z-scores were evaluated based on patients' ambulation status, presence of epilepsy, and mutation type. Results At the time of first scan, 8 of 11 patients had normal lumbar spine BMD and low LDF BMD Z-scores. Two patients had fracture history. Fully ambulatory (3) patients had higher lumbar spine and LDF BMD than partially (5) and nonambulatory (3) patients. Patients with epilepsy had lower average BMD at all sites. No difference was seen in lumbar spine or LDF BMD in patients with high-risk BMD mutations. Seven patients had serial DXA scans with an average observation of 5.1 yr (range 3.1 yr to 6.2 yr). Lumbar spine BMD over time was variable, while LDF bone mass accrual occurred at a lower rate than typically developing girls. Conclusion Females with RS exhibited lower BMD Z-scores at the LDF than at the lumbar spine. LDF and lumbar spine results were discordant. Ambulatory status and the presence of epilepsy were related to BMD. LDF BMD accrual deviated from normal as patients aged.

Lower extremity bone mineral density in children with congenital spinal dysfunction.

AIM: To assess lower extremity bone mineral density (BMD) of children with congenital spinal dysfunction and examine factors that may influence BMD in this population. METHOD: Forty-four children (25 females, 19 males) aged 6 to 18 years (mean 11 y 11 mo, SD 3 y 6 mo) with congenital spinal dysfunction (35 with myelomeningocele, seven with lipomas, one with sacral agenesis, one with caudal regression) were enrolled in the study. A health survey including ambulatory status, history of bladder augmentation, and history of fracture was administered. Each participant had a physical examination including Tanner stage and neurological level. Dual-energy X-ray absorptiometry scans of the lateral distal femur (LDF) and, when possible, lumbar spine were obtained. We reported LDF BMD results as z-scores for three regions of interest (metaphyseal, metadiaphyseal, and diaphyseal). Univariable and multivariable analyses examined relationships between LDF BMD and the other variables. RESULTS: BMD was significantly related to ambulatory status (14 non-ambulatory, 15 partly ambulatory, 15 fully ambulatory) and neurological level (13 with low-level lesions, 15 medium-level, 16 high-level) in the univariable analysis (p<0.01 for both in all three regions). Neither history of fracture, nor Tanner stage, nor history of bladder augmentation showed a significant relationship to BMD. The significance of ambulatory status and neurological level in the univariable analysis failed to persist in the multivariable analysis of this study with a small sample size. INTERPRETATION: The LDF measurement proved to be a viable technique for assessing BMD in children with congenital spinal dysfunction. LDF BMD was sensitive to differences in three categories of ambulation. The overall influence of neurological level was not deemed as important as ambulation.

Fracture after bisphosphonate treatment in children with cerebral palsy: the role of stress risers.

BACKGROUND: In the nonambulatory cerebral palsy (CP) population with a prior history of fracture, the use of pamidronate is not always effective in preventing further fractures. OBJECTIVE: To test the hypothesis that when fractures occur after cyclic pamidronate, they will be at the proximal or distal end of a pamidronate band. MATERIALS AND METHODS: Retrospective review of our CP patient database revealed 53 children who had received one or more complete courses of pamidronate therapy (five cycles over 12 months). Medical records were screened to identify children who had sustained a fracture or fractures after completing treatment. RESULTS: Of 53 patients treated with pamidronate, only 14 sustained fractures after treatment. Radiographs were available for 11 patients, showing 19 fractures. Sixty-three percent of these fractures were located at a junction with pamidronate bands but not within the bands. CONCLUSIONS: We propose stress risers as the mechanism for fractures that have occurred where bone mineral density abruptly changes as a result of cyclic administration of pamidronate. We show a theoretical example of how alternative dosing might reduce the ratio and therefore decrease the chance of formation of a stress riser.

Decreased fracture incidence after 1 year of pamidronate treatment in children with spastic quadriplegic cerebral palsy.

AIM: The aim of this study was to assess the rate of fracture before and after a 1-year course of intravenous pamidronate in children with spastic quadriplegic cerebral palsy (CP) who had previously experienced fractures. METHOD: Twenty-five children (nine males, 16 females) with quadriplegic CP in Gross Motor Function Classification System (GMFCS) level IV or V who were treated with intravenous pamidronate for approximately 1 year were identified. All participants had previously experienced at least one non-traumatic fracture. Each received 15 doses of pamidronate over a mean of 13.6 months. Post-treatment observation ranged from 1 to 10 years 6 months (mean 4 y 1 mo). The fracture rate before and after commencement of treatment was calculated using the person-years method. RESULTS: The participants had experienced a total of 86 fractures before treatment began, occurring over 280.6 person-years, giving a fracture rate of 30.6% per year. During the post-treatment observation period, totalling 107.5 person-years, 8 of the 25 children experienced a total of 14 fractures. This fracture rate of 13.0% per year is a statistically significant decrease (p=0.02). INTERPRETATION: Pamidronate treatment lowered the rate of fracture, and a 1-year course appears to provide a protective effect after treatment ends. For the majority of participants, this effect lasted 4 years or longer. However, a subset of children suffered a fracture soon after the drug was discontinued. In these children, a longer course of treatment appears to have been necessary.

Are the cognitive functions of children with Down syndrome related to their participation?

AIM: There is a lack of investigation into the functional developmental profile of children with Down syndrome. On the basis of current international health paradigms, the purpose of this study was to assess the developmental profile of these children. METHOD: Sixty children (33 males, 27 females) with Down syndrome (age range 6-16y; mean age 9y 3mo, SD 28.8mo), who had received standard, holistic, early intervention, were assessed. Of these, 42 (70%) had congenital anomalies, 12 had severe congenital heart defects. Participants were assessed on measures of cognitive function (Beery-Buktenica Developmental Test of Visual-Motor Integration; Stanford-Binet Intelligence Scale) and participation (Vineland Adaptive Behaviour Scales). RESULTS: No difference was found on any measure on the basis of severity of congenital anomaly. Results showed improvements in age-related body function and correlations between specific body functions and participation. No decline in IQ was found with age, and significant correlations between IQ and all other measures were noted. Although sex differences were found in the body functions of short-term memory and motor function, no difference in measures of activity performance and participation was found. INTERPRETATION: Our findings emphasize the need for paediatric Down syndrome intervention to encourage improved body functions while emphasizing the acquisition of functional skills that enable enhanced participation in age-appropriate activities.

Quantifying weight bearing while in passive standers and a comparison of standers.

Mechanical loading plays an important role in skeletal health, and this is a major reason standing devices are widely used with non-ambulatory persons. However, little is known about the true axial loading that occurs while in a stander, or the factors which may impact loading. The purpose of this study was to quantify weight borne while in a stander, and to directly compare different standers. Load measuring footplate adaptors were designed and fabricated specifically for this study. Weight bearing loads in 20 non-ambulatory persons with quadriplegic cerebral palsy aged 6 to 21 years (median 14 y) were continuously monitored during routine 30-minute standing sessions. Fourteen participants were female, six were male; one was Gross Motor Function Classification System (GMFCS) Level IV, and 19 were GMFCS Level V. Each participant was monitored on four to six occasions over an 8-week period, two to three times in each of two different standers (total 108 standing sessions). Weight bearing loads ranged widely from 37 to 101% of body weight. The difference between standers was as much as 29% body weight. There is wide variance in the actual weight borne while in passive standers. The type of stander utilized is one factor which can significantly affect the amount of weight borne.

Growth and nutritional status in residential center versus home-living children and adolescents with quadriplegic cerebral palsy.

OBJECTIVE: To describe growth and nutrition in nonambulatory youth (<19 years of age) with cerebral palsy (CP) living in residential centers compared with similar youth living at home. STUDY DESIGN: A multicenter, cross-sectional, single observational assessment of 75 subjects living in a residential care facility compared with 205 subjects living at home. Primary outcome measures included anthropometric measures of height, weight, triceps, and subscapular skinfolds, and mid-upper-arm muscle area. Z scores were calculated from reference values for healthy children. Age, use of a feeding tube, and Gross Motor Functional Classification System (GMFCS) level were included as important confounders. RESULTS: Use of a feeding tube was associated with higher skinfold Z scores, and a significantly higher percentage of the residential subjects had a feeding tube. Height, weight, and arm-muscle area Z scores all diverged (negatively) from reference values with age, and the residential subjects were on average older than the home-living subjects. After controlling for age, GMFCS level and use of a feeding tube, residential living was associated with significantly greater weight, height, skinfold thicknesses, and mid-arm muscle area Z scores. CONCLUSION: Poor growth and nutrition in children with CP is a prevalent, important, and complex problem. Although factors intrinsic to the condition of CP likely play a significant role, it is also clear that environmental factors, including the living situation of the child, can have an impact.

Pamidronate treatment and posttreatment bone density in children with spastic quadriplegic cerebral palsy.

Little is known about the long-term effects of a course of pamidronate treatment on bone mineral density (BMD) of children with spastic quadriplegic cerebral palsy (SQCP). Nine patients with SQCP who had low bone density and/or history of previous fracture(s) were studied during treatment and more than 1 yr after cyclic pamidronate treatment ended. Over the 12 mo of treatment, spine BMD increases raised average Z-score from -4.0 to -2.8. In the distal femoral metaphysis, BMD increase raised average Z-score from -3.6 to -1.7. Observations posttreatment ranged from 12 to 49 mo. Changes in BMD were variable among individuals. Group spine Z-score an average of 34 mo posttreatment approached pretreatment value. Six of eight patients had final distal femur posttreatment Z-scores the same or better than pretreatment baseline an average of 27.1 mo later. While most but not all gains in BMD were lost over the first 2 yr after treatment, no patient sustained fracture during or after treatment for a cumulative follow-up of more than 27 patient-yr.

An unexpected finding in an eight-year-old child with cerebral palsy and weight loss.

Poor weight gain is frequently seen in children with cerebral palsy. This is most commonly due to poor oral-motor coordination, resulting in inadequate caloric intake. We present the case of an eight-year-old girl with Aicardi syndrome who had been an exclusively oral feeder and who was noted to have had a 10-lb weight loss over the previous months when she was admitted to the hospital with seizures. Due to ongoing diminished oral intake, a barium swallow was performed, which revealed a filling defect. The mass that was removed at surgery proved to be a lactobezoar, a very uncommon finding in a child of this age.

Bone densitometry in pediatric patients treated with pamidronate.

BACKGROUND: Increasing numbers of children are being treated with the bisphosphonate pamidronate for low bone mineral density, particularly children with increased risk of fractures caused by bone disorders or low/non-weight bearing. OBJECTIVE: To determine the effect of intravenous pamidronate on the bone mineral density of children with osteogenesis imperfecta and spastic quadriplegic cerebral palsy. MATERIALS AND METHODS: Charts of 38 children with osteogenesis imperfecta (n=20) and spastic quadriplegic cerebral palsy (n=18) treated with pamidronate were retrospectively reviewed. Patients were selected for treatment because of prior fracture and/or abnormally low bone mineral density. All received intravenous pamidronate at two-month to eight-month intervals and were periodically examined using dual energy X-ray absorptiometry. RESULTS: All patients had abnormally low bone mineral density prior to treatment. Lumbar spine bone mineral density and z-scores showed serial improvement in 31 of 32 patients. Spine bone mineral density increased 78+/-38.1% in OI and 47.4+/-39.0% in children with cerebral palsy. The area of greatest lateral distal femur bone mineral density improvement was in the metaphysis adjacent to the growth plate, with a 96+/-87.8% improvement in the osteogenesis imperfecta group and 65.7+/-55.2% improvement in the cerebral palsy group. Increases in bone mineral density exceeded that expected for age-specific growth. This was demonstrated by improvement in both spine and femur z-scores for both groups. No children with spastic quadriplegic cerebral palsy experienced fractures after the first week of treatment, whereas patients with osteogenesis imperfecta continued to have fractures but at a decreased rate. CONCLUSIONS: Intravenous pamidronate given at 3- to 4-month intervals proved to be effective in increasing bone mineral density in patients with osteogenesis imperfecta and spastic quadriplegic cerebral palsy. The greatest gains in bone mineral density were observed in the children with osteogenesis imperfecta, but they did continue to fracture, albeit at a decreased rate. Children with cerebral palsy gained bone mineral density and did not continue to fracture.

Bisphosphonates to treat osteopenia in children with quadriplegic cerebral palsy: a randomized, placebo-controlled clinical trial.

OBJECTIVE: To evaluate in a double-blind, placebo-controlled clinical trial the safety and efficacy of intravenous pamidronate to treat osteopenia in nonambulatory children with cerebral palsy. STUDY DESIGN: Six pairs of subjects generally matched within each pair for age, sex, and race completed the protocol. One member of each pair randomly received plain saline placebo, the other pamidronate. Drug/placebo was administered intravenously daily for 3 consecutive days, and this 3-day dosing session was repeated at 3-month intervals for one year. Evaluations were continued for 6 months after the year of treatment. Bone mineral density (BMD) was measured in the distal femur, a site specifically developed for use in this contracted population, and the lumbar spine. RESULTS: In the metaphyseal region of the distal femur, BMD increased 89% +/- 21% (mean +/- SEM) over the 18-month study period in the pamidronate group compared with 9% +/- 6% in the control group. Age-normalized z scores increased from -4.0 +/- 0.6 to -1.8 +/- 1.0 in the pamidronate group and did not significantly change in the control group (-4.2 +/- 0.3 to -4.0 +/- 0.3). The first dosing with pamidronate caused a transient drop in serum calcium that was asymptomatic and not treated. No other potentially adverse effects were noted. CONCLUSIONS: In this small controlled clinical trial, pamidronate was found to be a safe and very effective agent to increase BMD in nonambulatory children with cerebral palsy.