Heidi H. Kecskemethy

The relationship between fractures and DXA measures of BMD in the distal femur of children and adolescents with cerebral palsy or muscular dystrophy

Children with limited or no ability to ambulate frequently sustain fragility fractures. Joint contractures, scoliosis, hip dysplasia, and metallic implants often prevent reliable measures of bone mineral density (BMD) in the proximal femur and lumbar spine, where BMD is commonly measured. Further, the relevance of lumbar spine BMD to fracture risk in this population is questionable. In an effort to obtain bone density measures that are both technically feasible and clinically relevant, a technique was developed involving dual‐energy X‐ray absorptiometry (DXA) measures of the distal femur projected in the lateral plane. The purpose of this study is to test the hypothesis that these new measures of BMD correlate with fractures in children with limited or no ability to ambulate. The relationship between distal femur BMD Z‐scores and fracture history was assessed in a cross‐sectional study of 619 children aged 6 to 18 years with muscular dystrophy or moderate to severe cerebral palsy compiled from eight centers. There was a strong correlation between fracture history and BMD Z‐scores in the distal femur; 35% to 42% of those with BMD Z‐scores less than −5 had fractured compared with 13% to 15% of those with BMD Z‐scores greater than −1. Risk ratios were 1.06 to 1.15 (95% confidence interval 1.04–1.22), meaning a 6% to 15% increased risk of fracture with each 1.0 decrease in BMD Z‐score. In clinical practice, DXA measure of BMD in the distal femur is the technique of choice for the assessment of children with impaired mobility.

Revised Pediatric Reference Data for the Lateral Distal Femur Measured by Hologic Discovery/Delphi Dual-Energy X-Ray Absorptiometry

Background Lateral distal femur (LDF) scans by dual energy x-ray absorptiometry (DXA) are often feasible in children for whom other sites are not measurable. Pediatric reference data for LDF are not available for more recent DXA technology. Aims To assess older pediatric LDF reference data, construct new reference curves for LDF bone mineral density (BMD), and demonstrate the comparability of LDF BMD to other measures of BMD and strength assessed by DXA and by peripheral quantitative computed tomography (pQCT). Methods LDF, spine and whole body scans of 821 healthy children, 5 to 18 years of age, recruited at a single center were obtained using a Hologic Delphi/Discovery system. Tibia trabecular and total BMD (3% site), cortical geometry (38% site) (cortical thickness, section modulus, strain strength index) were assessed by pQCT. Sex and race-specific reference curves were generated using LMS-ChartMaker and Z-scores calculated and compared by correlation analysis. Results Z-scores for LDF BMD based on published findings demonstrated overestimation or underestimation of the prevalence of low BMD-for-age depending on the region of interest considered. Revised LDF reference curves were generated. The new LDF Z-scores were strongly and significantly associated with weight, BMI, spine and whole body BMD Z-scores, and all pQCT Z-scores. Conclusion These findings demonstrate the comparability of LDF measurements to other clinical and research bone density assessment modes, and enable assessment of BMD in children with disabilities, who are particularly prone to low trauma fractures of long bones, and for whom traditional DXA measurement sites are not feasible.

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.

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.

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.

Protocol for MRI of the hips after spica cast placement.

Background: In reduction of hip displacement in developmental dysplasia, concentric placement of the femoral head within the acetabulum is key. Magnetic resonance imaging (MRI) is an effective modality to assess the adequacy of the reduction, but sedation may be required due to the length of the examination. MRI is also more expensive than other imaging modalities. Our goal was to provide an MRI protocol that does not require sedation and can be performed in <15 minutes. Methods: We retrospectively reviewed 34 consecutive MRI studies performed without sedation after spica cast placement in 24 developmental hip dysplasia patients. The MRI examinations were performed with a variety of techniques. Sequences used were evaluated for contrast, resolution, and motion artifact. Results: Ninety-seven percent of studies were diagnostic, although 18% of examinations had significant motion artifact. Seven sequences were analyzed. T2-weighted fast spin echo sequences had the best overall scores and were performed in <3 minutes. T1 and fat-suppressed T2-weighted fast spin echo sequences did not score as well, and also required <3 minutes. Single-shot fast spin echo sequences scored poorly due to decreased contrast and resolution, despite shorter acquisition times of 20 to 40 seconds. Three-dimensional (3D) gradient recovery imaging scored poorly due to lower contrast and increased motion due to longer acquisition times of approximately 4 minutes. Both coronally and axially oriented sequences satisfactorily assessed femoral head position within the acetabulum. Conclusions: MRI is a useful tool in evaluating the hips without radiation exposure and without sedation in infants and toddlers after spica cast placement. Both axial and coronal T2 fast spin echo MRI sequences provided excellent anatomic definition and required ⩽3 minutes per sequence. Orthopaedic surgeons can request these 2 sequences for accurate assessment of concentric reduction with a potential study time of 15 minutes, obviating the need for sedation. Level of Evidence: Level II.

Assessment of Bone Mineral Density in Duchenne Muscular Dystrophy Using the Lateral Distal Femur

Objectives: To document lateral distal femur (LDF) bone mineral density (BMD) values in children with Duchenne muscular dystrophy (DMD) and to examine the potential for these measures to aid in their care. Methods: Forty-seven boys with DMD had a total of 82 studies of BMD at multiple sites (whole body, lumbar spine, distal femur). Measures were converted to age-adjusted z-scores and analyzed for ambulatory status, steroid use, and fracture history. Results: Bone mineral density z-scores were significantly lower in the whole body and LDF in children who were partially ambulatory and nonambulatory when compared with children who were always ambulatory. With a positive history of fracture, mean LDF z-scores were significantly lower when compared with mean z-scores of children with no fractures. Lateral distal femur BMD correlated with ambulation and fracture better than whole body and lumbar spine BMD. Conclusions: The LDF is recommended as a more sensitive alternative to lumbar spine for measure of BMD in children with DMD.

Bone mineral density in MPS IV A (Morquio syndrome type A).

Mucopolysaccharidosis IV A (MPS IV A), Morquio A, is caused by deficiency in lysosomal enzyme N-acetylgalactosamine-6-sulfate sulfatase (GALNS), which is responsible for the catabolism of the glycosaminoglycans (GAGs) keratan sulfate (KS) and chondroitin 6-sulfate (C6S). Accumulation of GAGs results in disrupted cartilage formation and skeletal dysplasia. In this prospective cross-sectional study, bone mineral density (BMD) of the whole body (WB), lumbar spine (LS), and lateral distal femur (LDF) was acquired by dual-energy X-ray absorptiometry (DXA) on patients with MPS IV A. Functional abilities, medical history, Tanner score, and laboratory results were reviewed. Age and sex-matched norms were used to calculate Z-scores. Participants included 18 patients (13 females; 16 were unrelated) with a mean age of 21.4years (3.3 to 40.8years). While every patient was able to bear weight, 9 were full-time ambulators. Whole-body DXA could be obtained on only 6 patients (5 full-time ambulators) because of respiratory compromise caused by the position, presence of hardware, or positioning difficulties. Mean WB Z-score was -2.0 (range-0.3 to -4.1). Technical issues invalidating LS DXA in 8 patients included kyphosis at the thoracolumbar junction resulting in overlap of vertebrae in the posterior-anterior view. Mean LS BMD Z-score in full-time ambulators was -3.4 (range-1.6 to -5.0) and in the non-/partial ambulator was -4.0 (-3.7 to -4.2). Lateral distal femur BMD was acquired on every patient, and average Z-scores were -2 or less at all sites; full-time ambulators exhibited higher BMD. In conclusion, the LDF proved to be the most feasible site to measure in patients with MPS IV A. The higher LDF values in ambulators suggest this should be a consideration in promoting bone health for this group.

Pamidronate Treatment to Prevent Reoccurring Fractures in Children With Cerebral Palsy.

Background: Some children with cerebral palsy (CP) have frequent fractures due to low bone mineral density and receive treatment with pamidronate, an intravenous bisphosphonate. Our review evaluates the outcome of pamidronate treatment in these children. Methods: A retrospective chart review was performed, and 32 patients (14 girls and 18 boys) with CP Gross Motor Function Classification System level III (2 patients), IV (3 patients), and V (27 patients) treated with 5 courses of pamidronate for low mineral density were identified. Patients with a minimum of 2 years of follow-up were included in the study. Data collection was a review of the demographics and pretreatment, peritreatment, and posttreatment fracture history. Results: The mean age at treatment was 11.6 years (range, 2.9 to 19.6 y). There were 102 fractures (mean duration 2.5 y) pretreatment and 28 fractures posttreatment. With an average follow-up of 6.4 years, posttreatment rate of fracture decreased to 0.10 fractures per year from the pretreatment rate of 2.4 fractures per year (P<0.001). The femur was the most common bone fractured both pretreatment (54%) and posttreatment (61%); the major site was the distal third of the femur. There were 11 fractures during the course of pamidronate treatment at a rate of 0.33 fractures per year. Only 11 patients (34%) sustained fracture posttreatment. No correlation with fracture pattern or occurrence was found with patient age, number of pretreatment fractures, or sex. Most fractures were caused by low-energy injuries, and most were managed nonoperatively. Conclusions: In patients with CP and disuse osteoporosis, the most common fracture sustained involved the distal femur via low-velocity injury, and most fractures were treated nonoperatively. Although the fracture pattern and the treatment remained unchanged, reoccurring fractures in these children can be effectively treated medically to interrupt the fracturing tendency. Level of Evidence: Level IV.

Longitudinal assessment of bone growth and development in a facility-based population of young adults with cerebral palsy

Osteoporosis is a significant clinical problem in persons with moderate to severe cerebral palsy (CP), causing fractures with minimal trauma. Over the past decade, most studies examining osteoporosis and CP have been cross‐sectional in nature, focused exclusively on children and adolescents and only involving one evaluation of bone mineral density (BMD). The purpose of this study was to assess BMD in a group including adults with CP, and changes in each individuals BMD over a 5‐ to 6‐year period.