Category: Cerebral Palsy

date: 11/01/2002
author: Henderson RC, Lark RK, Kecskemethy HH, Miller F, Harcke HT, Bachrach SJ.
publication: J Pediatr. 2002 Nov;141(5):644-51.
pubmed_ID: 12410192

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.

date: 07/01/1999
author: Chad KE, Bailey DA, McKay HA, Zello GA, Snyder RE.
publication: J Pediatr 1999 Jul;135(1):115-7.
pubmed_ID: 10393617

After an 8-month physical activity intervention in children with cerebral palsy, increases in femoral neck bone mineral content (BMC) (9.6%), volumetric bone mineral density (v BMD) (5.6%), and total proximal femur BMC (11.5%) were observed in the intervention group (n = 9) compared with control subjects (n = 9; femoral neck BMC, -5. 8%; v BMD, -6.3%; total proximal femur BMC, 3.5%).

Publication Types:
? Clinical Trial
? Randomized Controlled Trial

date: 03/19/2004
author: Ward K, Alsop C, Caulton J, Rubin C, Adams J, Mughal Z.
publication: J Bone Miner Res. 2004 Mar;19(3):360-9. Epub 2004 Jan 27.
pubmed_ID: 15040823

The osteogenic potential of short durations of low-level mechanical stimuli was examined in children with disabling conditions. The mean change in tibia vTBMD was +6.3% in the intervention group compared with -11.9% in the control group. This pilot randomized controlled trial provides preliminary evidence that low-level mechanical stimuli represent a noninvasive, non-pharmacological treatment of low BMD in children with disabling conditions. INTRODUCTION: Recent animal studies have demonstrated the anabolic potential of low-magnitude, high-frequency mechanical stimuli to the trabecular bone of weight-bearing regions of the skeleton. The main aim of this prospective, double-blind, randomized placebo-controlled pilot trial (RCT) was to examine whether these signals could effectively increase tibial and spinal volumetric trabecular BMD (vTBMD; mg/ml) in children with disabling conditions. MATERIALS AND METHODS: Twenty pre-or postpubertal disabled, ambulant, children (14 males, 6 females; mean age, 9.1 +/- 4.3 years; range, 4-19 years) were randomized to standing on active (n = 10; 0.3g, 90 Hz) or placebo (n = 10) devices for 10 minutes/day, 5 days/week for 6 months. The primary outcomes of the trial were proximal tibial and spinal (L2) vTBMD (mg/ml), measured using 3-D QCT. Posthoc analyses were performed to determine whether the treatment had an effect on diaphyseal cortical bone and muscle parameters. RESULTS AND CONCLUSIONS: Compliance was 44% (4.4 minutes per day), as determined by mean time on treatment (567.9 minutes) compared with expected time on treatment over the 6 months (1300 minutes). After 6 months, the mean change in proximal tibial vTBMD in children who stood on active devices was 6.27 mg/ml (+6.3%); in children who stood on placebo devices, vTBMD decreased by -9.45 mg/ml (-11.9%). Thus, the net benefit of treatment was +15.72 mg/ml (17.7%; p = 0.0033). In the spine, the net benefit of treatment, compared with placebo, was +6.72 mg/ml, (p = 0.14). Diaphyseal bone and muscle parameters did not show a response to treatment. The results of this pilot RCT have shown for the first time that low-magnitude, high-frequency mechanical stimuli are anabolic to trabecular bone in children, possibly by providing a surrogate for suppressed muscular activity in the disabled. Over the course of a longer treatment period, harnessing bone’s sensitivity to these stimuli may provide a non-pharmacological treatment for bone fragility in children.

date: 10/01/1996
author: Brunner R, Doderlein L.
publication: J Pediatr Orthop B. 1996 Fall;5(4):232-8. Comment in: J Pediatr Orthop B. 1996 Fall;5(4):223-4.
pubmed_ID: 8897254

A retrospective study was made of 37 patients with 54 fractures that occurred without significant trauma. The morbidity and causes of these pathological fractures in patients with cerebral palsy were analyzed. The major causes for the fractures were long and fragile lever arms and stiffness in major joints, particularly the hips and knees. An additional factor was severe osteoporosis following a long period of postoperative immobilization. Seventy-four percent of the fractures occurred in the femoral shaft and supracondylar region. Stress fractures were rare (7%) and involved only the patella. Conservative treatment was sufficient in most cases but surgical fixation provided a good alternative for fractures of the femoral shaft. Intraarticular fractures with joint incongruity resulted in a decreased level of activity of the patient. Since osteoporosis is a major risk factor, patients with cerebral palsy should bear weight to prevent pathological fractures. Any stiffness of major joints and extended periods of immobilization should be avoided.

date: 07/01/2002
author: Henderson RC, Lark RK, Gurka MJ, Worley G, Fung EB, Conaway M, Stallings VA, Stevenson RD.
publication: Pediatrics. 2002 Jul;110(1 Pt 1):e5.
pubmed_ID: 12093986

OBJECTIVES: Diminished bone density and a propensity to fracture with minimal trauma are common in children and adolescents with moderate to severe cerebral palsy (CP). The purpose of this study was to provide a detailed evaluation of bone mineral density (BMD) and metabolism in this population and to assess the relationship of these measures to multiple other clinical, growth, and nutrition variables. METHODS: The study group consisted of 117 subjects ages 2 to 19 years (mean: 9.7 years) with moderate to severe CP as defined by the Gross Motor Functional Classification scale. Population-based sampling was used to recruit 62 of the participants, which allows for estimations of prevalence. The remaining 55 subjects were a convenience sampling from both hospital- and school-based sources. The evaluation included measures of BMD, a detailed anthropometric assessment of growth and nutritional status, medical and surgical history, the Child Health Status Questionnaire, and multiple serum analyses. BMD was measured in the distal femur, a site specifically developed for use in this contracted population, and the lumbar spine. BMD measures were converted to age and gender normalized z scores based on our own previously published control series (n > 250). RESULTS: Osteopenia (BMD z score <-2.0) was found in the femur of 77% of the population-based cohort and in 97% of all study participants who were unable to stand and were older than 9 years. BMD was not as low in the lumbar spine (population-based cohort mean +/- standard error z score: -1.8 +/- 0.1) as in the distal femur (mean z score: -3.1 +/- 0.2). Fractures had occurred in 26% of the children who were older than 10 years. Multiple clinical and nutritional variables correlated with BMD z scores, but interpretation of these findings is complicated by covariance among variables. In stepwise regression analyses, it was found that severity of neurologic impairment as graded by Gross Motor Functional Classification level, increasing difficulty feeding the child, use of anticonvulsants, and lower triceps skinfold z scores (in decreasing order of importance) all independently contribute to lower BMD z scores in the femur. CONCLUSIONS: Low BMD is prevalent in children with moderate to severe CP and is associated with significant fracture risk. The underlying pathophysiology is complex, with multiple factors contributing to the problem and significant variation between different regions of the skeleton.

date: 10/01/2006
author: Katz, Danielle,MD, Snyder, Bryan MD, PhD, Dodek, Anton MD, Holm, Ingrid MD Miller, Claire BS
publication: Abstract as published in the American Academy of Cerebral Palsy and Developmental Medicine (AACPDM) 2006 Conference Proceedings

Purpose: Pathologic fractures are a significant source of morbidity for non-ambulatory children with neuromuscular dysfunction. We hypothesize that increasing weight-bearing in non-ambulatory children will increase bone material density (BMD) and decrease fracture risk. The aim of this pilot study was to demonstrate that non-ambulatory children participating in a standing program for at least two hours a day will experience an increase in BMD in the weight bearing bones. We also evaluate the reliability of measuring BMD at the calcaneous (weight bearing bones) and distal forearm (non-weight bearing bone) using peripheral DXA in delayed, non-ambulatory children.

Methods: After receiving IRB approval, 12 non-ambulatory, quadriplegic children (ages 12-21) consented to participate in a 2 hour/day, 5 day/week standing program. A history, orthopaedic exam, determination of bone age, laboratory tests for metabolic bone disease and BMD at the calcaneal tuberosity and distal forearm metaphyses were obtained. Compliance with the prescribed standing program was monitored for 6 months. BMD was measured using peripheral DXA at baseline and every 3 months. Using Jan. 2003 BMD data as a baseline, the ratio of change in BMD at the calcaneous and distal forearm was evaluated as a function of percent compliance with standing program.

Results: Intrarater reliability for BMD measured by peripheral DXA was good: Pearson correlation for the calcaneous = 0.90 (p=0.01) and for the forearm = 0.96 (p=0.01). Paired t test between two sets of data measured at each site on the same day were not different for calcaneous (t=0.92, df=15, p=0.37) or forearm (t=0.05, df=15, p=0.96). Compliance with the standing program was inconsistent. No patients were 100% compliant. Patients tended to stand longer at the initiation of the study Jan.-April (Jan vs Apr, p = 0.018; Jan vs Jul, p = 0.89; Apr vs Jul, p = 0.063). Compliance (%) was positively correlated (r = -0.62) with increased calcaneous BMD measured in April. This is in contrast to forearm BMD measured at the same time; which was negatively correlated (r = -0.44) with standing compliance. This support the notion that standing preferentially increases bone mass in the weight-bearing bones. However the BMD at the calcaneous measured in July was decreased, perhaps reflecting the decreased compliance the with standing program over the succeeding interval April-July.

Conclusion: It is feasible to have non-ambulatory children participate in a rigorous standing program. The weight bearing ?dose? affects BMD at the calcaneous but the benefit appears to be transient if the intensive standing program is not sustained.

Significance: The intensive use of standers (10 hours/wk) may have a beneficial effect on BMD of weight bearing bones in non-ambulatory children.