Bone 71 (2015) 89–93
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Original Full Length Article
Adults with spastic cerebral palsy have lower bone mass than those with dyskinetic cerebral palsy Wonjin Kim a, Su Jin Lee a, Young-Kwon Yoon b, Yoon-Kyum Shin c,d, Sung-Rae Cho c,d,e,⁎, Yumie Rhee a,e,⁎⁎ a
Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea Graduate School of Medicine, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea Department of Rehabilitation Medicine, Severance Hospital, Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea d Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea e Avison Biomedical Research Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea b c
a r t i c l e
i n f o
Article history: Received 9 April 2014 Revised 5 September 2014 Accepted 5 October 2014 Available online 12 October 2014 Edited by: Nuria Guanabens Keywords: Cerebral palsy Bone mineral density Spasticity
a b s t r a c t Adults with cerebral palsy (CP) are known to have low bone mass with an increased risk of fragility fracture. CP is classified into two major types: spastic (pyramidal) and dyskinetic (extrapyramidal). Spastic CP is the most common and is characterized by muscle hypertonicity and impaired neuromuscular control. By contrast, dyskinetic CP is characterized by mixed muscle tone with involuntary movements. The aim of this study was to elucidate the relationship between bone metabolism and subtype of CP. Fifty-eight adults with CP (aged 18 to 49 years, mean age 33.2 years; 32 men, 26 women) were included in this cross-sectional analysis. Lumbar spine and femoral bone mineral density (BMD) Z-scores were measured. Bone markers, including C-telopeptide of type I collagen (CTx) and osteocalcin (OCN), were also analyzed. Among these participants, 30 had spastic CP and 28 had dyskinetic CP. The Z-scores of lumbar spine BMD did not differ between the two types. However, the Z-scores of femur trochanteric BMD were significantly lower in participants with spastic CP than in those with dyskinetic CP (−1.6 ± 1.2 vs. −0.9 ± 1.1, p b 0.05). Seventy-four percent of participants with either type of CP had abnormally elevated CTx, while about 90% of participants showed normal OCN levels. When participants were subclassified into nonambulatory and ambulatory groups, the nonambulatory group had significantly lower BMD in the femur, including the trochanteric and total regions, whether they were spastic or dyskinetic (p b 0.05). Because the type of CP affects bone mass, nonambulatory spastic CP participants showed the lowest total hip region BMD among the four groups. These results reveal that reduced weight bearing and immobility related to CP cause a negative bone balance because of increased bone resorption, which leads to a lower bone mass. In addition, hypertonicity of the affected limbs in participants with spastic CP resulted in lower bone mass than in those with dyskinetic CP. Type of CP and degree of ambulatory function in adults with CP should be regarded as important factors affecting bone metabolism. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Cerebral palsy (CP) has been described as a group of permanent disorders in the development of movement and posture that result in the limitation of activity and are attributed to nonprogressive disturbances that occurred in the growing fetal or infant brain. The motor disorders of CP are frequently associated with disturbances of sensation,
⁎ Correspondence to: S.-R. Cho, Department of Rehabilitation Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea. Fax: +82 2 363 2795 ⁎⁎ Correspondence to: Y. Rhee, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea. Fax: +82 2 393 6884 E-mail addresses: [email protected] (S.-R. Cho), [email protected] (Y. Rhee).
http://dx.doi.org/10.1016/j.bone.2014.10.003 8756-3282/© 2014 Elsevier Inc. All rights reserved.
perception, cognition, communication, and behavior caused by epilepsy or by secondary musculoskeletal problems [1]. CP is usually classified into two major types: spastic (pyramidal) and dyskinetic (extrapyramidal). Spastic CP is the most common type and is characterized by increased muscle tone and pathological reflexes: either increased reflexes, known as hyperreflexia, or pyramidal signs [2]. Increased muscle tone in spasticity features an increased velocitydependent resistance. By contrast, dyskinetic CP is characterized by mixed muscle tone with involuntary, uncontrolled, repetitive, and occasionally stereotyped movements. Primitive reflex patterns predominate and muscle tone varies [2]. Because of their developmental problems, people with CP face a number of medical complications during their growing years: gastrointestinal reflux, aspiration syndromes, respiratory infections, seizures, and contractures. In addition, they are prone to suffer common age-
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related conditions such as atherosclerosis, muscle wasting, osteoarthritis, bone loss, and low-trauma fractures [3]. There have been several studies on low bone mass in children and young adults with CP [4–7]. In these reports, children with moderate to severe functional disabilities of CP showed low bone mass in the lumbar spine and hip [5,7]. Several factors influence their lower bone mineral density (BMD), such as poor nutrition, anticonvulsant medications, and decreased weight bearing or bone loading because of functional disabilities [8]. Previous studies have shown that people with CP or muscular dystrophy [4] or with stroke [9] have low BMD because of immobilization and disuse of the affected sites. These studies proposed that the decreased mechanical force of muscles in the affected sites might decrease anabolic influences on bone metabolism. Moreover, as there are two types of CP, which result in different muscle tonicity and movements, it bears consideration that while immobilization usually results in bone loss, moderate loading by motion might exert positive effects on bone. In other words, the dynamic and hyperkinetic muscle movements featured in dyskinetic CP might be beneficial for bone density compared with the limited movements derived from muscle spasm and hypertonicity of spastic CP. Although many studies have previously reported low BMD in children with CP, data about low bone mass in adults with CP are limited, and there are no reports on differences in bone metabolism between CP subtypes combined with concurrent classification of ambulatory function. We hypothesized that adults with CP, who show different muscle tones and movements, would have lower BMD than normal populations, and sought to confirm this hypothesis. We divided people with CP by their CP subtype and their ambulatory abilities (nonambulatory vs. ambulatory). Participants with the spastic type of CP had lower BMD compared with those with the dyskinetic type. In addition, the nonambulatory subgroups had lower bone mass, specifically in the hip region. 2. Materials and methods 2.1. Participants This study was a retrospective cross-sectional investigation of adults with CP. Fifty-eight participants, aged 18 to 49 years, who were diagnosed with CP, were recruited into this study. There were 32 men and 26 women. Their types of CP were defined by characteristic movement patterns and muscle tone. Baseline characteristics including age, height, weight, and body mass index (BMI) were measured. Based on the gross motor function classification system (GMFCS) [10], functional independence measure (FIM) [11], and modified Barthel index (MBI) [12], the participants were subdivided into nonambulatory and ambulatory groups based on their ambulatory abilities. Two participants in the spastic CP group were excluded from the subgroup analysis because they underwent orthopedic surgery within 12 months of beginning the study, which made it difficult to measure their functional capacities. The study protocol was approved by Institutional Review Board of Yonsei University Health System (IRB, No. 4-2012-0751).
interassay CV b 3.5%); and 25-hydroxyvitamin D (25(OH)D) (by D3RIA-CT; Biosource; intraassay CV b 11.0%, interassay CV b 12.5%). BMD in the lumbar spine (L1–L4), femur neck, femur trochanter, and total hip was measured in all participants by dual-energy X-ray absorptiometry (Delphi A, version 12.6; Hologic, Waltham, MA, USA). 2.3. Assessment of ambulatory function Functional outcomes and ambulatory function were measured using various methods. Manual muscle test (MMT) grading at the hip region was performed to measure muscular strength. As mentioned above, GMFCS, FIM, and MBI were applied to determine the functional capacities of participants with CP, and were used to define their ambulatory function. The GMFCS is a standardized system to classify gross motor function, specifically developed for adults with CP [10]. The GMFCS is divided into five levels: level I, walking without limitation; level II, walking with limitations; level III, walking using a handheld mobility device; level IV, self-mobile with limitations; and level V, being transported in a manual wheelchair. The FIM is composed of 18 items on a seven-level scale with scores from 18 (total assistance) to 126 (complete independence), that assess basic activities of daily living in areas of self-care, sphincter control, transfer, locomotion, communication, and social cognition [11,13]. The MBI is composed of 10 items such as feeding, bathing, grooming, dressing, bladder and bowel control, toileting, transfer, mobility, and stair climbing with scores from 0 (totally dependent) to 100 (independent) [12,13]. The participants were subdivided into two groups by their ambulatory abilities. The nonambulatory group consisted of participants who depend on assistance during movement or who use a wheelchair (GMFCS IV–V). By contrast, the ambulatory group consisted of participants who are ambulatory without need of help. The person may use gait aids, or supervision may be needed for safety (GMFCS I–III). 2.4. Statistical analysis All analyses were performed using SPSS statistical software (version 18.0; SPSS, Chicago, IL, USA). We performed the Shapiro–Wilk test to identify whether or not data were normally distributed. Continuous variables with a normal distribution are expressed as means ± SD unless otherwise indicated. A p value b 0.05 was considered significant. Differences between the two types of CP were compared using Student's t test. Because we subdivided participants with each type of CP into subgroups according to their ambulatory ability as determined by the GMFCS, continuous variables were compared using Student's t test in each group. Multiple regression analysis was used to identify the interaction effect between subtypes of CP and the participants' ambulatory abilities. We used total hip BMD as the outcome measure, and age, sex, and BMI were included as covariates. In this model, dummy variables (reference category dyskinetic ambulatory group) were used to create an interaction term. 3. Results
2.2. Biochemical analysis and BMD
3.1. Baseline characteristics of CP participants
Routine chemistry measurements, including calcium and phosphate, were performed using standard automated techniques. Blood samples were collected in the morning after an overnight fast. Bone turnover markers were measured using the following methods: osteocalcin (OCN) (by enzyme-linked immunosorbent assay (ELISA); CIS Bio International, Gif-sur-Yvette, France; intraassay coefficient of variation (CV) b 2.0%, interassay CV b 5.0%); C-telopeptide of type I collagen (CTx) (by ELISA with Osteomark; Ostex International, Seattle, WA, USA; intraassay CV b 5.8%, interassay CV b 5.9%); intact parathyroid hormone (by IRMA; Biosource, Nivelles, Belgium; intraassay CV b 2.7%,
Fifty-eight adults with CP (32 men and 26 women; mean age, 33.2 ± 9.3 years) were included in this study. Participants were divided into two groups according to whether they had spastic or dyskinetic CP, which are the major types of CP; there were 30 adults with spastic CP and 28 with dyskinetic CP. The baseline clinical, laboratory, and rehabilitative parameters in these two groups are shown in Table 1. The mean age of the spastic group was younger than that of the dyskinetic group (29.6 ± 9.2 vs 37.0 ± 7.8 years, p b 0.05). Metabolic parameters, serum calcium, phosphorus, and bone turnover markers, and rehabilitative parameters, showed no significant differences between the groups.
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3.2. Different distributions of bone turnover markers revealing negative bone balance
Table 1 Baseline characteristics of participants with spastic and dyskinetic CP.
Age (years) Men (%) BMI (kg/m2) OCN (ng/mL) CTx (ng/mL) Calcium (mg/dL) Phosphorus (mg/dL) PTH (pg/mL) 25(OH)D (ng/mL) MMT hip total MBI total FIM total Lumbar spine BMD g/cm2 Z-Score Femur neck BMD g/cm2 Z-Score Femur trochanter BMD g/cm2 Z-Score Total hip BMD g/cm2 Z-Score
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Spastic (n = 30)
Dyskinetic (n = 28)
pa
29.6 ± 9.2 18 (60.0) 22.4 ± 3.9 32.8 ± 22.2 0.97 ± 0.6 8.9 ± 0.6 3.9 ± 0.7 21.6 ± 7.6 13.1 ± 5.3 6.5 ± 5.7 55.1 ± 31.5 90.5 ± 25.3
37.0 ± 7.8 14 (50.0) 20.5 ± 3.6 22.8 ± 9.1 0.80 ± 0.5 8.8 ± 0.4 4.0 ± 0.5 20.0 ± 10.1 9.3 ± 4.3 3.7 ± 4.5 55.3 ± 34.0 82.4 ± 27.0
0.002 0.453 0.076 0.092 0.367 0.530 0.398 0.600 0.027 0.048 0.985 0.272
0.874 ± 0.14 −1.1 ± 1.2
0.937 ± 0.14 −0.5 ± 1.2
0.098 0.066
0.717 ± 0.13 −0.9 ± 1.2
0.722 ± 0.13 −0.5 ± 1.1
0.877 0.214
0.531 ± 0.11 −1.6 ± 1.2
0.570 ± 0.11 −0.9 ± 1.1
0.197 0.036
0.739 ± 0.14 −1.5 ± 1.2
0.777 ± 0.13 −0.9 ± 1.1
0.300 0.055
Data for continuous variables are expressed as mean ± SD. BMI, body mass index; OCN, osteocalcin; CTx, C-telopeptide of type I collagen; PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D; MMT, manual muscle test; MBI, modified Barthel index; FIM, functional independence measure; BMD, bone mineral density. a p-Values calculated by Student's t test.
However, vitamin D level was significantly higher in the spastic group (13.1 ± 5.3 vs. 9.3 ± 4.3 ng/mL in the spastic vs. the dyskinetic group, p b 0.05). No differences were observed between the spastic and dyskinetic groups with respect to lumbar spine or femoral neck BMD Z-scores (lumbar spine, −1.1 ± 1.2 vs. − 0.5 ± 1.2; femoral neck, −0.9 ± 1.2 vs. − 0.5 ± 1.1, respectively, p = NS). However, femur trochanteric BMD Z-scores were significantly lower in the spastic group than in the dyskinetic group (− 1.6 ± 1.2 vs. − 0.9 ± 1.1, p b 0.05) despite the younger age and higher vitamin D level of participants with spastic CP.
Fig. 1 demonstrates the distribution of CTx and OCN. CTx levels were scattered widely over the normal reference range, with 74% of all participants exceeding the upper normal range of CTx. However, OCN levels were within the normal reference range in 90% of participants. This pattern did not differ between men and women (Fig. 1). The different distributions of these markers suggested that negative bone balance occurred in adults with CP. 3.3. Differences in bone mass according to functional abilities of CP subjects We subdivided participants with spastic and dyskinetic CP into two groups based on their ambulatory ability: i.e., into nonambulatory and ambulatory groups. Table 2 presents the clinical, laboratory, and rehabilitative characteristics and BMD of these groups. Of the participants with spastic CP, 15 were nonambulatory and 13 were ambulatory, while among those with dyskinetic CP, 12 were nonambulatory and 16 were ambulatory. BMI, bone turnover markers, and serum calcium and phosphorus did not differ significantly based on ambulatory category. The mean scores of MBI and FIM were significantly higher in the ambulatory groups with both types of CP (Table 2). The ambulatory groups with both types of CP had significantly higher Z-scores for femur trochanter and total hip BMD than did the nonambulatory groups (spastic type: − 1.2 ± 0.9 vs. − 2.2 ± 0.9 in the femur trochanter; −1.2 ± 1.0 vs. −2.0 ± 1.0 in the total hip; dyskinetic type: −0.3 ± 1.0 vs. −1.7 ± 0.9 in the femur trochanter; −0.4 ± 1.0 vs. − 1.6 ± 1.0 in the total hip, ambulatory vs. nonambulatory groups, respectively; p b 0.05), whereas the lumbar spine and femur neck BMD Z-scores showed no significant differences among the four groups. Because we found that both the type of CP and the degree of ambulatory function affected the bone metabolism of participants, we compared the BMD considering these two factors simultaneously (Fig. 2). As participants with spastic CP had lower BMD than did those with dyskinetic CP, and nonambulatory participants had lower BMD than did ambulatory participants, ambulatory participants with dyskinetic CP were defined as the reference group. Nonambulatory participants with spastic CP had significantly lower BMD than did the reference group (p b 0.001). These results demonstrate that different types of CP and
Fig. 1. Distribution of bone turnover markers in adults with CP. Normal ranges of CTx and OCN for people under the age of 50 are expressed as a deviant crease line (CTx, 0–0.5 ng/mL; OCN, 14–45 ng/mL; filled squares = men; empty squares = women). In both types of CP, CTx was distributed widely from 0 to 3.0 ng/mL, whereas most serum OCN values were within the normal range. CTx, C-telopeptide of type I collagen; OCN, osteocalcin.
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Table 2 Baseline characteristics of nonambulatory and ambulatory groups of participants with spastic and dyskinetic CP. pa
Spastic
Number Age (years) BMI (kg/m2) OCN (ng/mL) CTx (ng/mL) Calcium (mg/dL) Phosphorus (mg/dL) PTH (pg/mL) 25(OH)D (ng/mL) MMT hip total MBI total FIM total Lumbar spine BMD g/cm2 Z-score Femur neck BMD g/cm2 Z-score Femur trochanter BMD g/cm2 Z-Score Total hip BMD g/cm2 Z-Score
pa
Dyskinetic
Nonambulatory
Ambulatory
Nonambulatory
Ambulatory
15 29.4 ± 9.6 21.4 ± 2.7 35.1 ± 27.3 1.07 ± 0.8 8.7 ± 0.7 3.7 ± 0.8 21.3 ± 7.6 11.9 ± 6.0 7.3 ± 5.9 35.9 ± 22.6 73.0 ± 21.3
13 31.2 ± 9.2 23.4 ± 3.6 26.8 ± 10.1 0.72 ± 0.4 9.2 ± 0.4 4.2 ± 0.5 22.0 ± 8.3 14.6 ± 3.6 5.6 ± 5.6 81.0 ± 26.8 111.7 ± 11.6
0.627 0.111 0.448 0.266 0.073 0.163 0.855 0.286 0.455 0.001 b 0.001
12 36.1 ± 9.0 19.4 ± 3.9 24.7 ± 9.8 0.95 ± 0.6 8.9 ± 0.4 3.9 ± 0.5 16.1 ± 8.3 9.4 ± 4.7 4.3 ± 4.0 26.0 ± 27.4 62.0 ± 19.5
16 37.8 ± 7.0 21.4 ± 3.2 21.2 ± 8.8 0.66 ± 0.3 8.7 ± 0.5 4.1 ± 0.5 24.3 ± 10.7 9.2 ± 4.1 3.3 ± 5.0 75.5 ± 20.9 99.7 ± 19.3
0.868 ± 0.13 −1.2 ± 1.2
0.888 ± 0.15 −0.9 ± 1.3
0.722 0.487
0.873 ± 0.11 −1.0 ± 1.0
0.986 ± 0.14 −0.1 ± 1.1
0.032 0.029
0.691 ± 0.13 −1.2 ± 1.3
0.725 ± 0.11 −0.7 ± 0.9
0.469 0.260
0.689 ± 0.13 −0.9 ± 1.2
0.748 ± 0.12 −0.2 ± 1.0
0.235 0.129
0.475 ± 0.09 −2.2 ± 0.9
0.565 ± 0.08 −1.2 ± 0.9
0.001 0.008
0.500 ± 0.07 −1.7 ± 0.9
0.623 ± 0.10 −0.3 ± 1.0
0.002 0.001
0.687 ± 0.12 −2.0 ± 1.0
0.764 ± 0.12 −1.2 ± 1.0
0.101 0.044
0.703 ± 0.10 −1.6 ± 0.9
0.833 ± 0.13 −0.4 ± 1.0
0.008 0.004
0.587 0.161 0.440 0.250 0.195 0.541 0.118 0.939 0.555 b 0.001 b 0.001
Data are expressed as mean ± SD. BMI, body mass index; OCN, osteocalcin; CTx, C-telopeptide of type I collagen; PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D; MMT, manual muscle test; MBI, modified Barthel index; FIM, functional independence measure; BMD, bone mineral density. a p values calculated by Student's t test.
degrees of ambulatory function affect the bone metabolism of adults with CP. 4. Discussion CP includes a heterogeneous group of early-onset, nonprogressive, neuromuscular disorders that originate from damaged fetal or infant brain [14]. CP is one of the most common causes of childhood physical disability. The overall median incidence is estimated to be 2.4 per 1000 live births [15,16]. Although CP is defined as a collection of static and nonprogressive disorders, it is superimposed on the dynamic processes of development and aging [14]. Over 90% of people with CP live
Fig. 2. BMD of the total hip in nonambulatory participants with spastic CP was significantly lower than that in other groups. X: types of CP (spastic vs. dyskinetic), Y: ambulatory abilities (nonambulatory vs. ambulatory), Z: BMD (g/cm2). Multiple regression analysis was performed and the data were adjusted for age, sex, and BMI. Ambulatory participants with dyskinetic CP were considered as the reference group. The numbers shown under the graph show the unstandardized coefficient (β) compared with the reference group (dark gray bar). The numbers in parentheses refer to the p value.
beyond 18 years of age with several medical problems [17]. Among these problems, osteoporosis is associated with the morbidity of other health problems in the aging adult with CP [18]. Many studies have reported low bone mass in children with CP [4,5, 7,8,19]. Henderson et al. reported that in children with moderate to severe CP, BMD is decreased in the distal femur and lumbar spine [6]. Indeed, in these children, the Z-scores of the distal femur are much lower than those of the lumbar spine [6]. In children with quadriplegia associated with CP, low bone mass, reduced mobility, and poor nutrition were the most significant risk factors for having low BMD [8]. A recently published study of 536 children born with CP showed that a higher grade of GMFCS was associated with an increased risk of fractures [20]. Because of the difficulty of establishing an adult CP registry, there are limited data about osteoporosis in adults with CP. King et al. reported that in 48 young people with CP (age 5 to 48 years, mean age 15 years, 18 participants (37.5%) over 18 years), BMD in the lumbar spine was distinctly reduced compared with that in age- and sex-matched controls [5]. This study revealed that nonambulatory children and young adults with functional disabilities showed markedly reduced bone mass [5]. Our study classified adults with CP into two major types based on their characteristic movement patterns and muscle tone: spastic (pyramidal) or dyskinetic (extrapyramidal). Spastic CP is the most common type, and accounts for 70% to 80% of CP cases [21]. Spastic CP is characterized by increased muscle tone and poverty of movement. Muscles continually contract, making limbs rigid and stiff [22]. The problem is essentially one of impairment of neuromuscular control stemming from an upper motor neuron lesion in the brain, the corticospinal tract, or the motor cortex. Because of the limited movements and the reduced range of motion of the affected joints caused by muscle hypertonia, weight bearing or bone loading is significantly diminished, which can negatively influence bone metabolism. Accordingly, our data revealed that adults with spastic CP had lower BMD than those with the dyskinetic type. Dyskinetic CP, however, is characterized by fluctuating muscle tone. It is referred to as extrapyramidal because the dyskinesia stems from an injury in the brain outside of the pyramidal tract. Dyskinetic CP comprises up to 20% of all cases of CP. Fluctuating muscle tone
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with slow or fast, often repetitive, involuntary movement is the main feature of dyskinetic CP [23]. In our study, we found that these characteristic hyperkinetic and dynamic movement patterns coupled with sufficient joint range of motion may have had an anabolic effect on bone by repetitive loading, resulting in higher BMD than is observed in people with spastic CP. Weight, age, functional level, nutritional state, previous fracture history, and use of anticonvulsants have been found to affect BMD in children and adolescents with CP [7]. An association between physical activity and BMD has previously been reported in children with CP. Femoral neck bone mineral content and volumetric BMD in children with CP increases significantly after physical intervention [24]. More recently, Yoon et al. [25] suggested that BMI and functional level, as defined by FIM and ambulatory function, could be important factors affecting bone metabolism in adults with CP. In accordance with bone strength–muscular force dynamics, mechanical pressure increases bone strength, so weight bearing has also been found to be an important factor affecting BMD [26]. In the current study, independently living adults with CP showed higher BMD than wheelchair- or other instrument-dependent individuals. Our study revealed that ambulatory ability is an important factor that influences bone health in adults with CP of any type. This relationship was only significant in the region of the femur trochanter and the total hip. This indicates that weight loading on the femur has the most significant effect on BMD. There were no meaningful differences in lumbar spine BMD between the groups. Our study also revealed a relationship between muscle spasticity, ambulatory ability, and BMD in accordance with previous studies demonstrating that bone density was not related to severity of spasticity, but rather to muscle mass and functional ability in spinal-cord injured patients [27,28]. These results may reverse the general impression of the previous reports that people with muscle spasticity show a greater protective effect with respect to their bone densities [29–31]. We also analyzed bone turnover markers in our participants. The results were quite interesting in that 75% of the participants had elevated serum CTx levels, whereas OCN levels were mostly within the normal reference range. This finding indicates that reduced weight bearing and immobilization of people with CP cause a negative bone balance because of a higher rate of bone resorption than bone formation. In this study, most participants had vitamin D insufficiency or deficiency. Vitamin D insufficiency is very prevalent in the general population throughout Korea. In a previous study associated with the Korea National Health and Nutrition Examination Survey, only 13.2% of men and 6.7% of women had a sufficient vitamin D level, and the mean vitamin D level was 21.2 ± 7.5 ng/mL in men and 18.2 ± 7.1 ng/mL in women [32]. In our study, the average vitamin D concentration was much lower, with no participant showing a sufficient vitamin D level, which suggests that vitamin D deficiency could have contributed to low bone density and elevated bone resorption. However, the vitamin D level was higher in the spastic group that showed lower BMD than in the dyskinetic group with higher BMD, which means that in these adults with CP, muscle tone was more important than vitamin D level for BMD. Our study has some limitations. First, this is a retrospective, crosssectional study. Therefore, longitudinal data on BMD and actual events of fragility fracture are currently being collected in our institute. Second, the number of participants was limited. Studies including larger numbers of adults CP will help to validate the effect of differences in the type of CP and ambulatory ability on bone loss. In summary, the spastic CP group had lower BMD than the dyskinetic group. These results reveal that hypertonicity with clonus and muscle spasms in the affected limbs in people with spastic CP results in greater deterioration of bone mass than in those with dyskinetic CP. Moreover, the independently ambulatory subgroup of both types of CP had higher BMD than did the nonambulatory subgroup. In conclusion, differences in type of CP and ambulatory ability should be considered as important factors affecting bone metabolism in adults with CP.
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Original Full Length Article
Adults with spastic cerebral palsy have lower bone mass than those with dyskinetic cerebral palsy Wonjin Kim a, Su Jin Lee a, Young-Kwon Yoon b, Yoon-Kyum Shin c,d, Sung-Rae Cho c,d,e,⁎, Yumie Rhee a,e,⁎⁎ a
Department of Internal Medicine, Severance Hospital, Endocrine Research Institute, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea Graduate School of Medicine, Yonsei University, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea Department of Rehabilitation Medicine, Severance Hospital, Research Institute of Rehabilitation Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea d Brain Korea 21 PLUS project for Medical Science, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea e Avison Biomedical Research Center, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea b c
a r t i c l e
i n f o
Article history: Received 9 April 2014 Revised 5 September 2014 Accepted 5 October 2014 Available online 12 October 2014 Edited by: Nuria Guanabens Keywords: Cerebral palsy Bone mineral density Spasticity
a b s t r a c t Adults with cerebral palsy (CP) are known to have low bone mass with an increased risk of fragility fracture. CP is classified into two major types: spastic (pyramidal) and dyskinetic (extrapyramidal). Spastic CP is the most common and is characterized by muscle hypertonicity and impaired neuromuscular control. By contrast, dyskinetic CP is characterized by mixed muscle tone with involuntary movements. The aim of this study was to elucidate the relationship between bone metabolism and subtype of CP. Fifty-eight adults with CP (aged 18 to 49 years, mean age 33.2 years; 32 men, 26 women) were included in this cross-sectional analysis. Lumbar spine and femoral bone mineral density (BMD) Z-scores were measured. Bone markers, including C-telopeptide of type I collagen (CTx) and osteocalcin (OCN), were also analyzed. Among these participants, 30 had spastic CP and 28 had dyskinetic CP. The Z-scores of lumbar spine BMD did not differ between the two types. However, the Z-scores of femur trochanteric BMD were significantly lower in participants with spastic CP than in those with dyskinetic CP (−1.6 ± 1.2 vs. −0.9 ± 1.1, p b 0.05). Seventy-four percent of participants with either type of CP had abnormally elevated CTx, while about 90% of participants showed normal OCN levels. When participants were subclassified into nonambulatory and ambulatory groups, the nonambulatory group had significantly lower BMD in the femur, including the trochanteric and total regions, whether they were spastic or dyskinetic (p b 0.05). Because the type of CP affects bone mass, nonambulatory spastic CP participants showed the lowest total hip region BMD among the four groups. These results reveal that reduced weight bearing and immobility related to CP cause a negative bone balance because of increased bone resorption, which leads to a lower bone mass. In addition, hypertonicity of the affected limbs in participants with spastic CP resulted in lower bone mass than in those with dyskinetic CP. Type of CP and degree of ambulatory function in adults with CP should be regarded as important factors affecting bone metabolism. © 2014 Elsevier Inc. All rights reserved.
1. Introduction Cerebral palsy (CP) has been described as a group of permanent disorders in the development of movement and posture that result in the limitation of activity and are attributed to nonprogressive disturbances that occurred in the growing fetal or infant brain. The motor disorders of CP are frequently associated with disturbances of sensation,
⁎ Correspondence to: S.-R. Cho, Department of Rehabilitation Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea. Fax: +82 2 363 2795 ⁎⁎ Correspondence to: Y. Rhee, Department of Internal Medicine, Yonsei University College of Medicine, 50-1 Yonsei-ro, Seodaemun-gu, Seoul, Republic of Korea. Fax: +82 2 393 6884 E-mail addresses: [email protected] (S.-R. Cho), [email protected] (Y. Rhee).
http://dx.doi.org/10.1016/j.bone.2014.10.003 8756-3282/© 2014 Elsevier Inc. All rights reserved.
perception, cognition, communication, and behavior caused by epilepsy or by secondary musculoskeletal problems [1]. CP is usually classified into two major types: spastic (pyramidal) and dyskinetic (extrapyramidal). Spastic CP is the most common type and is characterized by increased muscle tone and pathological reflexes: either increased reflexes, known as hyperreflexia, or pyramidal signs [2]. Increased muscle tone in spasticity features an increased velocitydependent resistance. By contrast, dyskinetic CP is characterized by mixed muscle tone with involuntary, uncontrolled, repetitive, and occasionally stereotyped movements. Primitive reflex patterns predominate and muscle tone varies [2]. Because of their developmental problems, people with CP face a number of medical complications during their growing years: gastrointestinal reflux, aspiration syndromes, respiratory infections, seizures, and contractures. In addition, they are prone to suffer common age-
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related conditions such as atherosclerosis, muscle wasting, osteoarthritis, bone loss, and low-trauma fractures [3]. There have been several studies on low bone mass in children and young adults with CP [4–7]. In these reports, children with moderate to severe functional disabilities of CP showed low bone mass in the lumbar spine and hip [5,7]. Several factors influence their lower bone mineral density (BMD), such as poor nutrition, anticonvulsant medications, and decreased weight bearing or bone loading because of functional disabilities [8]. Previous studies have shown that people with CP or muscular dystrophy [4] or with stroke [9] have low BMD because of immobilization and disuse of the affected sites. These studies proposed that the decreased mechanical force of muscles in the affected sites might decrease anabolic influences on bone metabolism. Moreover, as there are two types of CP, which result in different muscle tonicity and movements, it bears consideration that while immobilization usually results in bone loss, moderate loading by motion might exert positive effects on bone. In other words, the dynamic and hyperkinetic muscle movements featured in dyskinetic CP might be beneficial for bone density compared with the limited movements derived from muscle spasm and hypertonicity of spastic CP. Although many studies have previously reported low BMD in children with CP, data about low bone mass in adults with CP are limited, and there are no reports on differences in bone metabolism between CP subtypes combined with concurrent classification of ambulatory function. We hypothesized that adults with CP, who show different muscle tones and movements, would have lower BMD than normal populations, and sought to confirm this hypothesis. We divided people with CP by their CP subtype and their ambulatory abilities (nonambulatory vs. ambulatory). Participants with the spastic type of CP had lower BMD compared with those with the dyskinetic type. In addition, the nonambulatory subgroups had lower bone mass, specifically in the hip region. 2. Materials and methods 2.1. Participants This study was a retrospective cross-sectional investigation of adults with CP. Fifty-eight participants, aged 18 to 49 years, who were diagnosed with CP, were recruited into this study. There were 32 men and 26 women. Their types of CP were defined by characteristic movement patterns and muscle tone. Baseline characteristics including age, height, weight, and body mass index (BMI) were measured. Based on the gross motor function classification system (GMFCS) [10], functional independence measure (FIM) [11], and modified Barthel index (MBI) [12], the participants were subdivided into nonambulatory and ambulatory groups based on their ambulatory abilities. Two participants in the spastic CP group were excluded from the subgroup analysis because they underwent orthopedic surgery within 12 months of beginning the study, which made it difficult to measure their functional capacities. The study protocol was approved by Institutional Review Board of Yonsei University Health System (IRB, No. 4-2012-0751).
interassay CV b 3.5%); and 25-hydroxyvitamin D (25(OH)D) (by D3RIA-CT; Biosource; intraassay CV b 11.0%, interassay CV b 12.5%). BMD in the lumbar spine (L1–L4), femur neck, femur trochanter, and total hip was measured in all participants by dual-energy X-ray absorptiometry (Delphi A, version 12.6; Hologic, Waltham, MA, USA). 2.3. Assessment of ambulatory function Functional outcomes and ambulatory function were measured using various methods. Manual muscle test (MMT) grading at the hip region was performed to measure muscular strength. As mentioned above, GMFCS, FIM, and MBI were applied to determine the functional capacities of participants with CP, and were used to define their ambulatory function. The GMFCS is a standardized system to classify gross motor function, specifically developed for adults with CP [10]. The GMFCS is divided into five levels: level I, walking without limitation; level II, walking with limitations; level III, walking using a handheld mobility device; level IV, self-mobile with limitations; and level V, being transported in a manual wheelchair. The FIM is composed of 18 items on a seven-level scale with scores from 18 (total assistance) to 126 (complete independence), that assess basic activities of daily living in areas of self-care, sphincter control, transfer, locomotion, communication, and social cognition [11,13]. The MBI is composed of 10 items such as feeding, bathing, grooming, dressing, bladder and bowel control, toileting, transfer, mobility, and stair climbing with scores from 0 (totally dependent) to 100 (independent) [12,13]. The participants were subdivided into two groups by their ambulatory abilities. The nonambulatory group consisted of participants who depend on assistance during movement or who use a wheelchair (GMFCS IV–V). By contrast, the ambulatory group consisted of participants who are ambulatory without need of help. The person may use gait aids, or supervision may be needed for safety (GMFCS I–III). 2.4. Statistical analysis All analyses were performed using SPSS statistical software (version 18.0; SPSS, Chicago, IL, USA). We performed the Shapiro–Wilk test to identify whether or not data were normally distributed. Continuous variables with a normal distribution are expressed as means ± SD unless otherwise indicated. A p value b 0.05 was considered significant. Differences between the two types of CP were compared using Student's t test. Because we subdivided participants with each type of CP into subgroups according to their ambulatory ability as determined by the GMFCS, continuous variables were compared using Student's t test in each group. Multiple regression analysis was used to identify the interaction effect between subtypes of CP and the participants' ambulatory abilities. We used total hip BMD as the outcome measure, and age, sex, and BMI were included as covariates. In this model, dummy variables (reference category dyskinetic ambulatory group) were used to create an interaction term. 3. Results
2.2. Biochemical analysis and BMD
3.1. Baseline characteristics of CP participants
Routine chemistry measurements, including calcium and phosphate, were performed using standard automated techniques. Blood samples were collected in the morning after an overnight fast. Bone turnover markers were measured using the following methods: osteocalcin (OCN) (by enzyme-linked immunosorbent assay (ELISA); CIS Bio International, Gif-sur-Yvette, France; intraassay coefficient of variation (CV) b 2.0%, interassay CV b 5.0%); C-telopeptide of type I collagen (CTx) (by ELISA with Osteomark; Ostex International, Seattle, WA, USA; intraassay CV b 5.8%, interassay CV b 5.9%); intact parathyroid hormone (by IRMA; Biosource, Nivelles, Belgium; intraassay CV b 2.7%,
Fifty-eight adults with CP (32 men and 26 women; mean age, 33.2 ± 9.3 years) were included in this study. Participants were divided into two groups according to whether they had spastic or dyskinetic CP, which are the major types of CP; there were 30 adults with spastic CP and 28 with dyskinetic CP. The baseline clinical, laboratory, and rehabilitative parameters in these two groups are shown in Table 1. The mean age of the spastic group was younger than that of the dyskinetic group (29.6 ± 9.2 vs 37.0 ± 7.8 years, p b 0.05). Metabolic parameters, serum calcium, phosphorus, and bone turnover markers, and rehabilitative parameters, showed no significant differences between the groups.
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3.2. Different distributions of bone turnover markers revealing negative bone balance
Table 1 Baseline characteristics of participants with spastic and dyskinetic CP.
Age (years) Men (%) BMI (kg/m2) OCN (ng/mL) CTx (ng/mL) Calcium (mg/dL) Phosphorus (mg/dL) PTH (pg/mL) 25(OH)D (ng/mL) MMT hip total MBI total FIM total Lumbar spine BMD g/cm2 Z-Score Femur neck BMD g/cm2 Z-Score Femur trochanter BMD g/cm2 Z-Score Total hip BMD g/cm2 Z-Score
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Spastic (n = 30)
Dyskinetic (n = 28)
pa
29.6 ± 9.2 18 (60.0) 22.4 ± 3.9 32.8 ± 22.2 0.97 ± 0.6 8.9 ± 0.6 3.9 ± 0.7 21.6 ± 7.6 13.1 ± 5.3 6.5 ± 5.7 55.1 ± 31.5 90.5 ± 25.3
37.0 ± 7.8 14 (50.0) 20.5 ± 3.6 22.8 ± 9.1 0.80 ± 0.5 8.8 ± 0.4 4.0 ± 0.5 20.0 ± 10.1 9.3 ± 4.3 3.7 ± 4.5 55.3 ± 34.0 82.4 ± 27.0
0.002 0.453 0.076 0.092 0.367 0.530 0.398 0.600 0.027 0.048 0.985 0.272
0.874 ± 0.14 −1.1 ± 1.2
0.937 ± 0.14 −0.5 ± 1.2
0.098 0.066
0.717 ± 0.13 −0.9 ± 1.2
0.722 ± 0.13 −0.5 ± 1.1
0.877 0.214
0.531 ± 0.11 −1.6 ± 1.2
0.570 ± 0.11 −0.9 ± 1.1
0.197 0.036
0.739 ± 0.14 −1.5 ± 1.2
0.777 ± 0.13 −0.9 ± 1.1
0.300 0.055
Data for continuous variables are expressed as mean ± SD. BMI, body mass index; OCN, osteocalcin; CTx, C-telopeptide of type I collagen; PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D; MMT, manual muscle test; MBI, modified Barthel index; FIM, functional independence measure; BMD, bone mineral density. a p-Values calculated by Student's t test.
However, vitamin D level was significantly higher in the spastic group (13.1 ± 5.3 vs. 9.3 ± 4.3 ng/mL in the spastic vs. the dyskinetic group, p b 0.05). No differences were observed between the spastic and dyskinetic groups with respect to lumbar spine or femoral neck BMD Z-scores (lumbar spine, −1.1 ± 1.2 vs. − 0.5 ± 1.2; femoral neck, −0.9 ± 1.2 vs. − 0.5 ± 1.1, respectively, p = NS). However, femur trochanteric BMD Z-scores were significantly lower in the spastic group than in the dyskinetic group (− 1.6 ± 1.2 vs. − 0.9 ± 1.1, p b 0.05) despite the younger age and higher vitamin D level of participants with spastic CP.
Fig. 1 demonstrates the distribution of CTx and OCN. CTx levels were scattered widely over the normal reference range, with 74% of all participants exceeding the upper normal range of CTx. However, OCN levels were within the normal reference range in 90% of participants. This pattern did not differ between men and women (Fig. 1). The different distributions of these markers suggested that negative bone balance occurred in adults with CP. 3.3. Differences in bone mass according to functional abilities of CP subjects We subdivided participants with spastic and dyskinetic CP into two groups based on their ambulatory ability: i.e., into nonambulatory and ambulatory groups. Table 2 presents the clinical, laboratory, and rehabilitative characteristics and BMD of these groups. Of the participants with spastic CP, 15 were nonambulatory and 13 were ambulatory, while among those with dyskinetic CP, 12 were nonambulatory and 16 were ambulatory. BMI, bone turnover markers, and serum calcium and phosphorus did not differ significantly based on ambulatory category. The mean scores of MBI and FIM were significantly higher in the ambulatory groups with both types of CP (Table 2). The ambulatory groups with both types of CP had significantly higher Z-scores for femur trochanter and total hip BMD than did the nonambulatory groups (spastic type: − 1.2 ± 0.9 vs. − 2.2 ± 0.9 in the femur trochanter; −1.2 ± 1.0 vs. −2.0 ± 1.0 in the total hip; dyskinetic type: −0.3 ± 1.0 vs. −1.7 ± 0.9 in the femur trochanter; −0.4 ± 1.0 vs. − 1.6 ± 1.0 in the total hip, ambulatory vs. nonambulatory groups, respectively; p b 0.05), whereas the lumbar spine and femur neck BMD Z-scores showed no significant differences among the four groups. Because we found that both the type of CP and the degree of ambulatory function affected the bone metabolism of participants, we compared the BMD considering these two factors simultaneously (Fig. 2). As participants with spastic CP had lower BMD than did those with dyskinetic CP, and nonambulatory participants had lower BMD than did ambulatory participants, ambulatory participants with dyskinetic CP were defined as the reference group. Nonambulatory participants with spastic CP had significantly lower BMD than did the reference group (p b 0.001). These results demonstrate that different types of CP and
Fig. 1. Distribution of bone turnover markers in adults with CP. Normal ranges of CTx and OCN for people under the age of 50 are expressed as a deviant crease line (CTx, 0–0.5 ng/mL; OCN, 14–45 ng/mL; filled squares = men; empty squares = women). In both types of CP, CTx was distributed widely from 0 to 3.0 ng/mL, whereas most serum OCN values were within the normal range. CTx, C-telopeptide of type I collagen; OCN, osteocalcin.
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Table 2 Baseline characteristics of nonambulatory and ambulatory groups of participants with spastic and dyskinetic CP. pa
Spastic
Number Age (years) BMI (kg/m2) OCN (ng/mL) CTx (ng/mL) Calcium (mg/dL) Phosphorus (mg/dL) PTH (pg/mL) 25(OH)D (ng/mL) MMT hip total MBI total FIM total Lumbar spine BMD g/cm2 Z-score Femur neck BMD g/cm2 Z-score Femur trochanter BMD g/cm2 Z-Score Total hip BMD g/cm2 Z-Score
pa
Dyskinetic
Nonambulatory
Ambulatory
Nonambulatory
Ambulatory
15 29.4 ± 9.6 21.4 ± 2.7 35.1 ± 27.3 1.07 ± 0.8 8.7 ± 0.7 3.7 ± 0.8 21.3 ± 7.6 11.9 ± 6.0 7.3 ± 5.9 35.9 ± 22.6 73.0 ± 21.3
13 31.2 ± 9.2 23.4 ± 3.6 26.8 ± 10.1 0.72 ± 0.4 9.2 ± 0.4 4.2 ± 0.5 22.0 ± 8.3 14.6 ± 3.6 5.6 ± 5.6 81.0 ± 26.8 111.7 ± 11.6
0.627 0.111 0.448 0.266 0.073 0.163 0.855 0.286 0.455 0.001 b 0.001
12 36.1 ± 9.0 19.4 ± 3.9 24.7 ± 9.8 0.95 ± 0.6 8.9 ± 0.4 3.9 ± 0.5 16.1 ± 8.3 9.4 ± 4.7 4.3 ± 4.0 26.0 ± 27.4 62.0 ± 19.5
16 37.8 ± 7.0 21.4 ± 3.2 21.2 ± 8.8 0.66 ± 0.3 8.7 ± 0.5 4.1 ± 0.5 24.3 ± 10.7 9.2 ± 4.1 3.3 ± 5.0 75.5 ± 20.9 99.7 ± 19.3
0.868 ± 0.13 −1.2 ± 1.2
0.888 ± 0.15 −0.9 ± 1.3
0.722 0.487
0.873 ± 0.11 −1.0 ± 1.0
0.986 ± 0.14 −0.1 ± 1.1
0.032 0.029
0.691 ± 0.13 −1.2 ± 1.3
0.725 ± 0.11 −0.7 ± 0.9
0.469 0.260
0.689 ± 0.13 −0.9 ± 1.2
0.748 ± 0.12 −0.2 ± 1.0
0.235 0.129
0.475 ± 0.09 −2.2 ± 0.9
0.565 ± 0.08 −1.2 ± 0.9
0.001 0.008
0.500 ± 0.07 −1.7 ± 0.9
0.623 ± 0.10 −0.3 ± 1.0
0.002 0.001
0.687 ± 0.12 −2.0 ± 1.0
0.764 ± 0.12 −1.2 ± 1.0
0.101 0.044
0.703 ± 0.10 −1.6 ± 0.9
0.833 ± 0.13 −0.4 ± 1.0
0.008 0.004
0.587 0.161 0.440 0.250 0.195 0.541 0.118 0.939 0.555 b 0.001 b 0.001
Data are expressed as mean ± SD. BMI, body mass index; OCN, osteocalcin; CTx, C-telopeptide of type I collagen; PTH, parathyroid hormone; 25(OH)D, 25-hydroxyvitamin D; MMT, manual muscle test; MBI, modified Barthel index; FIM, functional independence measure; BMD, bone mineral density. a p values calculated by Student's t test.
degrees of ambulatory function affect the bone metabolism of adults with CP. 4. Discussion CP includes a heterogeneous group of early-onset, nonprogressive, neuromuscular disorders that originate from damaged fetal or infant brain [14]. CP is one of the most common causes of childhood physical disability. The overall median incidence is estimated to be 2.4 per 1000 live births [15,16]. Although CP is defined as a collection of static and nonprogressive disorders, it is superimposed on the dynamic processes of development and aging [14]. Over 90% of people with CP live
Fig. 2. BMD of the total hip in nonambulatory participants with spastic CP was significantly lower than that in other groups. X: types of CP (spastic vs. dyskinetic), Y: ambulatory abilities (nonambulatory vs. ambulatory), Z: BMD (g/cm2). Multiple regression analysis was performed and the data were adjusted for age, sex, and BMI. Ambulatory participants with dyskinetic CP were considered as the reference group. The numbers shown under the graph show the unstandardized coefficient (β) compared with the reference group (dark gray bar). The numbers in parentheses refer to the p value.
beyond 18 years of age with several medical problems [17]. Among these problems, osteoporosis is associated with the morbidity of other health problems in the aging adult with CP [18]. Many studies have reported low bone mass in children with CP [4,5, 7,8,19]. Henderson et al. reported that in children with moderate to severe CP, BMD is decreased in the distal femur and lumbar spine [6]. Indeed, in these children, the Z-scores of the distal femur are much lower than those of the lumbar spine [6]. In children with quadriplegia associated with CP, low bone mass, reduced mobility, and poor nutrition were the most significant risk factors for having low BMD [8]. A recently published study of 536 children born with CP showed that a higher grade of GMFCS was associated with an increased risk of fractures [20]. Because of the difficulty of establishing an adult CP registry, there are limited data about osteoporosis in adults with CP. King et al. reported that in 48 young people with CP (age 5 to 48 years, mean age 15 years, 18 participants (37.5%) over 18 years), BMD in the lumbar spine was distinctly reduced compared with that in age- and sex-matched controls [5]. This study revealed that nonambulatory children and young adults with functional disabilities showed markedly reduced bone mass [5]. Our study classified adults with CP into two major types based on their characteristic movement patterns and muscle tone: spastic (pyramidal) or dyskinetic (extrapyramidal). Spastic CP is the most common type, and accounts for 70% to 80% of CP cases [21]. Spastic CP is characterized by increased muscle tone and poverty of movement. Muscles continually contract, making limbs rigid and stiff [22]. The problem is essentially one of impairment of neuromuscular control stemming from an upper motor neuron lesion in the brain, the corticospinal tract, or the motor cortex. Because of the limited movements and the reduced range of motion of the affected joints caused by muscle hypertonia, weight bearing or bone loading is significantly diminished, which can negatively influence bone metabolism. Accordingly, our data revealed that adults with spastic CP had lower BMD than those with the dyskinetic type. Dyskinetic CP, however, is characterized by fluctuating muscle tone. It is referred to as extrapyramidal because the dyskinesia stems from an injury in the brain outside of the pyramidal tract. Dyskinetic CP comprises up to 20% of all cases of CP. Fluctuating muscle tone
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with slow or fast, often repetitive, involuntary movement is the main feature of dyskinetic CP [23]. In our study, we found that these characteristic hyperkinetic and dynamic movement patterns coupled with sufficient joint range of motion may have had an anabolic effect on bone by repetitive loading, resulting in higher BMD than is observed in people with spastic CP. Weight, age, functional level, nutritional state, previous fracture history, and use of anticonvulsants have been found to affect BMD in children and adolescents with CP [7]. An association between physical activity and BMD has previously been reported in children with CP. Femoral neck bone mineral content and volumetric BMD in children with CP increases significantly after physical intervention [24]. More recently, Yoon et al. [25] suggested that BMI and functional level, as defined by FIM and ambulatory function, could be important factors affecting bone metabolism in adults with CP. In accordance with bone strength–muscular force dynamics, mechanical pressure increases bone strength, so weight bearing has also been found to be an important factor affecting BMD [26]. In the current study, independently living adults with CP showed higher BMD than wheelchair- or other instrument-dependent individuals. Our study revealed that ambulatory ability is an important factor that influences bone health in adults with CP of any type. This relationship was only significant in the region of the femur trochanter and the total hip. This indicates that weight loading on the femur has the most significant effect on BMD. There were no meaningful differences in lumbar spine BMD between the groups. Our study also revealed a relationship between muscle spasticity, ambulatory ability, and BMD in accordance with previous studies demonstrating that bone density was not related to severity of spasticity, but rather to muscle mass and functional ability in spinal-cord injured patients [27,28]. These results may reverse the general impression of the previous reports that people with muscle spasticity show a greater protective effect with respect to their bone densities [29–31]. We also analyzed bone turnover markers in our participants. The results were quite interesting in that 75% of the participants had elevated serum CTx levels, whereas OCN levels were mostly within the normal reference range. This finding indicates that reduced weight bearing and immobilization of people with CP cause a negative bone balance because of a higher rate of bone resorption than bone formation. In this study, most participants had vitamin D insufficiency or deficiency. Vitamin D insufficiency is very prevalent in the general population throughout Korea. In a previous study associated with the Korea National Health and Nutrition Examination Survey, only 13.2% of men and 6.7% of women had a sufficient vitamin D level, and the mean vitamin D level was 21.2 ± 7.5 ng/mL in men and 18.2 ± 7.1 ng/mL in women [32]. In our study, the average vitamin D concentration was much lower, with no participant showing a sufficient vitamin D level, which suggests that vitamin D deficiency could have contributed to low bone density and elevated bone resorption. However, the vitamin D level was higher in the spastic group that showed lower BMD than in the dyskinetic group with higher BMD, which means that in these adults with CP, muscle tone was more important than vitamin D level for BMD. Our study has some limitations. First, this is a retrospective, crosssectional study. Therefore, longitudinal data on BMD and actual events of fragility fracture are currently being collected in our institute. Second, the number of participants was limited. Studies including larger numbers of adults CP will help to validate the effect of differences in the type of CP and ambulatory ability on bone loss. In summary, the spastic CP group had lower BMD than the dyskinetic group. These results reveal that hypertonicity with clonus and muscle spasms in the affected limbs in people with spastic CP results in greater deterioration of bone mass than in those with dyskinetic CP. Moreover, the independently ambulatory subgroup of both types of CP had higher BMD than did the nonambulatory subgroup. In conclusion, differences in type of CP and ambulatory ability should be considered as important factors affecting bone metabolism in adults with CP.
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