Tuesday, 10:00 – 11:30, A7
Bone Health of Cerebral Palsy Patients
Philip Nowicki, MD
616-267-2600 [email protected]
Objective:
1. Identify effective methods for the practical application of concepts related to improving the
delivery of services for persons with developmental disabilities
2. Identify advances in clinical assessment and management of selected healthcare issues related
to persons with developmental disabilities
Notes:
4/3/2014
Bone Health In Cerebral Palsy Patients
Philip Nowicki, MD FAAP
Pediatric Orthopaedic Surgeon
Helen DeVos Children’s Hospital
Assistant Professor of Surgery
Michigan State University College of Human
Medicine
Introduction
Overview
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Definitions
Bone metabolism
Bone Density
Fracture Risk
Low BMD Treatment
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Definitions
• Cerebral Palsy
– STATIC encephalopathy to the immature
developing brain that may be due to anoxic or
hypoxic
yp
brain injury
j y
– Diagnosis made OVER TIME
• Bone Mineral Density (BMD)
– Measures amount of Ca/Phos in area of bone
– Helps determine fracture risk
Normal Bone Metabolism
emedicalppt.blogspot.com
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extras.springer.com
Bone Structure/Anatomy
http://antranik.org/wp‐content/uploads/2011/09/microscopic‐structure‐of‐compact‐bone.png?473d22
Abnormal Bone
http://www.eurospine.org/cm_data/osteoporosis_fig01.jpg
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Abnormal Bone Metabolism
• Osteopenia 2° deficiency of bone tissue development
• Determined by GMFCS level
Osteoporosis in Children
• Defined by International Society of Clinical Densitometry
• Not based on BMD alone
• Current Definition:
fi i i
– BMD Z‐score < ‐2.0 for age, gender, body size ✚
Significant h/o fracture:
• 2 upper extremity fractures
• 2 vertebral compression fractures
• Single lower extremity fracture
Bone Density
• DXA scan gold standard
• Comparison Values determined in CP pts
• Different than in adults
– Lumbar spine (same)
– Distal femur
• Due to associated hip & knee contractures
– Total body
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DXA Scan
• Gold Standard for determining BMD
• Values differ between adult and pediatric pts
• Adults‐ T‐scores
– SD from mean of HEALTHY ref population
• Peds‐ Z‐scores
– SD from mean of AGE and SEX matched controls
– Every SD drop equals 10‐
20%  in BMD
Houlihan CM, Stevenson RD. Bone density in cerebral palsy. Phys Med Rehab Clin N Am 2009;20:493‐508.
DXA values
• Performed differently in CP pts due to joint contractures
• Lateral Distal Femur used
– Due to spine/hip implants, accommodate for joint contractures
– Common area of fx and low BMD
– Scan pt in comfortable side‐
lying position
• 3 areas of distal femur evaluated: metaphysis, metadiaphyseal, cortical bone regions
http://www.ithacarad.com/Dexa2.jpg
DXA Scan CP Pts
Harcke HT, et al. Lateral femoral scan: an alternative method for assessing bone mineral density in children with cerebral palsy. Pediatr Radiol 1998;28:241‐6.
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DXA Scan CP Ptd
Harcke HT, et al. Lateral femoral scan: an alternative method for assessing bone mineral density in children with cerebral palsy. Pediatr
Radiol 1998;28:241‐6.
Bone Density in CP
• 86% pts > 9 yoa had osteopenia of distal femur
• Fx risk DOUBLES w/ every standard deviation  BMD
• Wren et al: – CP pts all levels low bone density in tibias
– Spine deficits greater in more involved children
– Even higher functioning pts (GMFCS I/II) have 
lower extremity bone accrual
Bone Density in CP
• Henderson et al (2005)‐
– Large bone health study of CP pts
– Longitudinal study CP quads‐ decreased BMD associated w/ poor nutritional status
– Osteopenia is manifestation of growth failure
Osteopenia is manifestation of growth failure
– Pts w/ lowest BMD: spastic quad,  mobility, poor nutrition
– Non‐ambulatory significantly lower BMD than ambulators
• Need long term studies to determine how peds
CP pts will fair as adults
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Low Bone Density Factors
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Poor Nutrition
Non‐ambulatory
Post‐op Immobilization
Anti‐Seizure medications (Dilantin)
Poor Nutrition
• Poor nutrition factors:
– PO motor feeding difficulties
– Food/Volume intolerances
– GERD
– Lack of sunlight exposure
– Pharmocological
Anti‐Seizure Meds
• Phenytoin, Phenobarbitol, Carbamazepine
– CYP 450 Enzyme induction – Increased clearance/catabolism of Vit D into non‐
active metabolites
–2
2° hyperparathyroidism and 
hyperparathyroidism and  bone turnover
bone turnover
• Valproic acid
– 10%  reduction BMD
– May cause renal dysfunction w/  Ca & Phos loss
– May also directly activate osteoblasts/osteoclasts to increase bone turnover
• Carbamezapine
– Induces bone turnover 2° osteoclast activation
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Fracture Risk Factors
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Osteopenia/Thin bone cortices
Stiff joints/contractures
Poor balance/falls
Seizures Previous Fx
Poor nutrition/gastrostomy tube
Fracture Risk
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Prevalence Fxs CP pts‐ 5 to 60%
Most common region‐ distal femur
66% in non‐ambulatory pts
Usually minimal trauma involved
2 to 6x  fx risk in pts w/ CP and SZS d/o
4% per year fx incidence in moderate to severe CP pts
Fracture Morbidity
• Most fractures occur in lower extremity (i.e., distal femur)
• CP pts have  fx risk than nl children, especially from 13‐15 yoa (Maruyama)
• Cause pain, decubiti, further bone loss, difficuly
w/c positioning/transport
• High cost for med care: $10,000 per pt, $150 million in U.S. per annum (Apkon)
– Loss of school time for pt, loss of work time for caregiver
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Screening
• Lab levels
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Serum albumin
Calcium
Phosphorus
Alk Phos
25‐OH Vit D
• DXA scan
– Baseline for all GMFCS IV and V pts upon fracturing (Apkon & Kecskemethy)
• All pts who sustain lower extremity fracture
Osteopenia Tx
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Physical Therapy
Standers
Low amplitude mechanical loading (vibration)
Optimize nutrition
Calcium + Vit D supplementation
Bisphosphanates
Physical Activity/Therapy
• Weight bearing and resistance exercise important for development of bone mass
• Bones adjust strengthen in proportion to amount of stress placed on them
• Chad et al‐
Chad et al
– 8 months of weight bearing physical activity significantly  total proximal femur and femoral neck BMC
– Control patients (no weight bearing)  6% study period
• Little current evidence evaluating effect of PT on CP pts and BMD
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Standing Frames
• Anti‐gravity
• Theoretically, similar to resistant exercising, especially with dynamic standers
http://www.rifton.com/~/media/images/rifton/blog/blog‐
images/2013/bonemineraldensitychildrencerebralpalsy.jpg
Standing Frames
• Caulton et al‐
– 26 non‐ambulatory CP pts, upright/semi‐prone standers
– Avg 48 min/day x 5days/week x9 months
– Increased BMD of spine, not tibia
• Katz et al‐
– 12 non‐ambulatory CP pts, upright stander
– 2 hrs/day, 5 days/week, 6 months
– BMD femur and calcaneous
 when compliant w/ standing program
http://presentessempreco.com/images/standing%20frame.jpg
Vibration Therapy
• Low‐amplitude, high frequency vibration
• Usually incorporated as vibrating platform in standing frame
• Ward et al‐
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– Children w/ limited mobility, RCT on vibrating platform vs sham platform and DXA assessment
– BMD  6.3% in tibia BMD and 5.5% spine BMD 10
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Nutrition
• Optimize nutritional parameters
• Regular assessment by dietician
• Consider G‐tube placement for supplemental nutrition
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– Arrowsmith et al‐
• G‐tube supplementation  total body protein and muscle mass, NOT  BMD but did not  over time either
Vit D Metabolism
Houlihan CM, Stevenson RD. Bone density in cerebral palsy. Phys Med Rehab Clin N Am 2009;20:493‐508.
Vit D/Ca
• Shaw et al‐ did not find vit D status to coincide w/ magnitude of osteopenia
• Jekovec‐Vrhovsec et al‐
– 23 CP quad pts, spine BMD, 9 mos supplementation Vit D and Ca
– Pts w/ supplementation had significant 
w/ supplementation had significant  BMD over those w/o
BMD over those w/o
• Bischof et al‐
– Vit D supplementation  fx rate in children w/ severe CP and rickets
• Henderson et al (2002)‐
– 9%  BMD in mod to severe affected CP pts when given Ca and Vit D supplementation
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Vit D/Ca
• AAP intake recommendations:
– 400 IU/d if exclusively and partially breast‐fed infant
– 400 IU/D if non
400 IU/D if non‐breast
breast fed and < 1000 mL/d of Vit
fed and < 1000 mL/d of Vit
D fortified milk for all children > 1 year old – 800 mg/day Calcium for children <9 years – 1200‐1500 mg/day Calcium for children 9‐18 years Bisphosphanates
http://www.medscape.org/viewarticle/520178_5
Bisphosphanates
• Henderson et al‐
– RCT w/ placebo arm w/ IV pamidronate
– 89% increase in distal femur BMD over 18 months in quadriplegic CP
– No pt in bisphosphanate group had fx (3 in control did)
• Grissom et al‐
Grissom et al
– OI and CP pts, IV pamidronate, DXA scans
– BMD both groups >4.0, all 3 femur regions improved in BMD
– 88% reduction fx rate
• Allington et al‐
– Cyclic IV pamidronate 18 non‐ambulatory CP pts
–  BMD,  pain w/ manipulation, no add’l fxs 12 months after infusions
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Bisphosphanates
• Iwasaki et al‐
– When treated with both Vit D and risedronate, BMD  more than with Vit D alone
• Paksu et al‐
– 36
36 pts, CP quad
pts CP quad
– Weekly PO alendronate x 12 months
– After 1 year,  serum Ca and Phos,  BMD and z‐
score
• Unal et al‐
– PO alendronate more cost effective than IV pamidronate to  BMD
Treatment
Houlihan CM, Stevenson RD. Bone density in cerebral palsy. Phys Med Rehab Clin N Am 2009;20:493‐508.
Conclusions
• Bone health important in overall care of CP pts
• More study required regarding outcomes of various bone health modalities in CP pts
Screening is important especially after
• Screening is important, especially after fracture
• Multiple tx options for  BMD available, combo of all should be utilized to maintain bone health in CP population
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References
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Gage JR, et al. The Identification and treatment of gait problems in cerebral palsy. Clinics in Developmental Medicine Mac Keith Press Lavenham, Suffolk 2009
Henderson RC, et al. Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy. Pediatrics 2002;110:e5‐15.
Wren TAL, et al. Bone density and size in ambulatory children with cerebral palsy. Dev Med Child Neurol
2011;53:137‐41.
Henderson RC, et al. Bisphosphanates to treat osteopenia in children with quadripelgic cerebral palsy: a randomized placebo‐controlled clinical trial. J Pediatrics 2002;141:644‐51.
Henderson RC, et al. Longitudinal changes in bone density in children and adolescents with moderate to severe cerebral palsy J Pediatrics 2005; 146:769 75
severe cerebral palsy. J Pediatrics 2005; 146:769‐75.
Chad KE, et al. The effect of a weight‐bearing physical activity program on bone mineral content and estimated volumetric density in children with spastic cerebral palsy. J Pediatrics 1999;135:115‐7.
Maruyama K, et al. Bone fracture in physically disabled children attending schools for handicapped children in Japan. Environ Health Prev Med 2010;15:135‐40.
Samaniego EA, Sheth RD. Bone consequences of epilepsy and antiepileptic medications. Sem Ped Neuro
2007;14:196‐200.
Shaw NJ, et al. Osteopenia in cerebral palsy. Arch Dis Child 1994;71:235‐8.
Grissom LE, et al. Bone densitometry in pediatric patients treated with pamidronate. Pediatr Radiol
2005;35:511‐7.
Apkon SD, Kecskemethy HH. Bone health in children with cerebral palsy. J Ped Rehab Med 2008;115‐21.
Harcke HT, et al. Lateral femoral scan: an alternative method for assessing bone mineral density in children with cerebral palsy. Pediatr Radiol 1998;28:241‐6.
References
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Jekovec‐Vrhovsek M, et al. Effect of vitamin D and calcium on bone mineral density in children with CP and epilepsy in full‐time care. Dev Med Child Neuro 2000;42:403‐5.
Ward K, et al. Low magnitude mechanical loading is osteogenic in children with disabling conditions. J Bone Min Res 2004;19:360‐9.
Caulton JM, et al. A randomized controlled trial of standing programme on bone mineral density in non‐ambulant children with cerebral palsy. Arch Dis Child 2004;89:131‐5.
Katz D, et al. Can using standers increase bone density in non‐ambulatory children? Abstract as published in the American Academy of Cerebral Palsy and Dev medicine Conference (AACPDM) 2006 Conference Proceedings.
Cohen M, et al. Evidence‐based review of bone strength in children and youth with cerebral palsy. J Child Neurol
2009;24:959‐67.
Bischof F, et al. Pathological long‐bone fractures in residents with cerebral palsy in a long‐term care facility in South Africa. Dev Med Child Neurol 2002;44:119‐22.
Iwasaki T, et al. Secondary osteoporosis in long‐term bedridden patients with cerebral palsy. Pediatr Int
2008;50:269‐75.
Houlihan CM, Stevenson RD. Bone density in cerebral palsy. Phys Med Rehab Clin N Am 2009;20:493‐508.
Coppola G, et al. Bone mineral density in a population of children and adolescents with cerebral palsy and mental retardation with or without epilepsy. Epilepsia 2012;53:2172‐7.
Allington N, et al. Cyclic administration of pamidronate to treat osteoporosis in children with cerebral palsy or a neuromuscular disorder: a clinical study. Acta Orthop Belg 2005;71:91‐7.
Ko CH, et al. Risk factors of long bone fracture in non‐ambulatory cerebral palsy children. Hong Kong Med J 2006;12:426‐31.
Arrowsmith F, et al. The effect of gastrostomy tube feeding on body protein and bone mineralization in children with quadriplegic cerebral palsy. Dev Med Child Neuro 2010;52:1043‐7.
Thank You
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