100 Adults with Spinal Muscular Atrophy at the Dawn of Treatment: A Bone Health Focus
DOI:
https://doi.org/10.17161/rrnmf.v6i4_2025.24296Keywords:
Spinal muscular atrophy, fracture, bone, neuromuscular diseaseAbstract
Introduction
As disease-modifying treatments for spinal muscular atrophy (SMA) are implemented, co-morbidities in adults including osteo-pathologies are increasingly recognised. Guidance for managing such issues is incomplete.
We present data on bone health from, to our knowledge, the UK’s largest single-centre adult SMA cohort.
Objectives
We aimed to quantify the following in our cohort:
- Fracture incidence and location
- Implementation of bone density scanning
- Vitamin D status and supplementation
Methods
Retrospective case note review was performed for 100 adult patients (51% male; 49% female, average age 32), at the National Hospital for Neurology and Neurosurgery from 2022-2025. SMA subtypes were SMA3 (N=55), SMA2 (N=44) and SMA1 (N=1). Where available ethnicities were: White (N=57), Asian (N=13), Black (N=4), Mixed (N=2) and Other (N=4).
Results
Fracture incidence was 25% (N=25), of which 85% (N=29) affected the lower limb(s). Most fractures (80%) (N=20) occurred in SMA3 patients. 50% (N=10) of SMA3 patients with a history of fractures, subsequently lost the ability to walk.
Bone density scans were recorded in 40% (N=10) of patients who had fractures (90% of scans occurred post fracture), and in 17% (N=13) of non-fracture patients.
Of the overall cohort, 39% (N=39) were vitamin D deficient or insufficient, and 60% (N=60) were prescribed cholecalciferol.
Conclusions
The high fracture rate is particularly pertinent, given that lower limb fractures can accelerate ambulation loss in SMA3 patients. Consistency in bone-density scanning is lacking and generally reactive to fracture occurrence. This highlights the importance of bone health considerations in adult SMA patients.
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References
1. Lefebvre S, Bürglen L, Reboullet S, Clermont O, Burlet P, Viollet L, et al. Identification and characterization of a spinal muscular atrophy-determining gene. Cell. 1995 Jan;80(1):155–65. DOI: 10.1016/0092-8674(95)90460-3. PMID: 7813012
2. Prior TW. Perspectives and diagnostic considerations in spinal muscular atrophy. Genetics in Medicine. 2010 Mar;12(3):145–52. DOI: 10.1097/GIM.0b013e3181c5e713. PMID: 20057317
3. Feldkötter M, Schwarzer V, Wirth R, Wienker TF, Wirth B. Quantitative Analyses of SMN1 and SMN2 Based on Real-Time LightCycler PCR: Fast and Highly Reliable Carrier Testing and Prediction of Severity of Spinal Muscular Atrophy. The American Journal of Human Genetics. 2002 Feb;70(2):358–68. DOI: 10.1086/338627. PMID: 11791208
4. Zerres K, Rudnik-Schöneborn S. Natural history in proximal spinal muscular atrophy. Clinical analysis of 445 patients and suggestions for a modification of existing classifications. Arch Neurol. 1995 May;52(5):518–23. DOI: 10.1001/archneur.1995.00540290108025. PMID: 7733848
5. Wang C, Finkel R, Bertini E, Schroth M, Simonds A, Wong B, et al. Consensus Statement for Standard of Care in Spinal Muscular Atrophy. J Child Neurol. 2007 Aug 1;22(8):1027–49. DOI: 10.1177/0883073807305788. PMID: 17761659
6. Groen EJN, Talbot K, Gillingwater T. Advances in therapy for spinal muscular atrophy: promises and challenges. Nat Rev Neurol. 2018 Apr 9;14(4):214–24. DOI: 10.1038/nrneurol.2018.4. PMID: 29422644
7. Singh R, Singh N. Mechanism of Splicing Regulation of Spinal Muscular Atrophy Genes. Adv Neurobiol. 2018; 20:31-61. doi: 10.1007/978-3-319-89689-2_2. PMID: 29916015
8. Chen B, Gong Y, Zhou T. The Impact of Nusinersen and Risdiplam on Motor Function for Spinal Muscular Atrophy Type 2 and 3: A Meta-Analysis. J Coll Physicians Surg Pak. 2024 Aug;34(8):948–55. DOI: 10.29271/jcpsp.2024.08.948. PMID: 39113515
9. Whitney G, Knierbein N, Daunter A. Prevalence of morbidities across the lifespan for adults with spinal muscular atrophy: a retrospective cohort study. Orphanet J Rare Dis. 2023 Aug 31;18(1):258. DOI: 10.1186/s13023-023-02872-6. PMID: 37653507
10. Osman A, Wasserman H, Horn PS, Broomall E. Bone mineral density changes in patients on drug therapy for spinal muscular atrophy. Neuromuscular Disorders. 2025 Mar; 48:105300. DOI: 10.1016/j.nmd.2025.105300
11. Shanmugarajan S, Tsuruga E, Swoboda KJ, Maria BL, Ries WL, Reddy S V. Bone loss in survival motor neuron ( Smn −/− SMN2 ) genetic mouse model of spinal muscular atrophy. J Pathol. 2009 Sep 11;219(1):52–60. DOI: 10.1002/path.2566. PMID: 19434631
12. D’Amico A, Mercuri E, Tiziano FD, Bertini E. Spinal muscular atrophy. Orphanet J Rare Dis. 2011 Dec 2;6(1):71. DOI: 10.1186/1750-1172-6-71. PMID: 22047105
13. Birnkrant D, Bushby K, Bann C, Apkon S, Blackwell A, Brumbaugh D, et al., Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol. 2018;17(3):251-267. doi:10.1016/S1474-4422(18)30024-3. PMID: 29395989
14. Quinlivan R, Messer B, Murphy P, Astin R, Mukherjee R, Khan J, et al. ANSN. Adult North Star Network (ANSN): Consensus Guideline For The Standard Of Care Of Adults With Duchenne Muscular Dystrophy. J Neuromuscul Dis. 2021;8(6):899-926. doi: 10.3233/JND-200609. PMID: 34511509
15. Opsomer M, Iterbeke L, Borghs H, De Cuyper T, Dejaeger M, Dupont P, et al. Fractures in Hereditary Neuromuscular Disorders: Frequency, Risk Factors, and Implications. Eur J Neurol. 2025 Mar 4;32(3). DOI: 10.1111/ene.70099. PMID: 40040345
16. Trancho C, Stickney B, Kinirons S, Uher D, Kanner CH, Rao AK, et al. Low Bone Mass in Ambulatory Spinal Muscular Atrophy: A Proactive Approach for an Often-Overlooked Impairment. J Clin Med. 2024 Feb 27;13(5):1336. DOI: 10.3390/jcm13051336
17. Mercuri E, Finkel RS, Muntoni F, Wirth B, Montes J, Main M, et al. Diagnosis and management of spinal muscular atrophy: Part 1: Recommendations for diagnosis, rehabilitation, orthopedic and nutritional care. Neuromuscular Disorders. 2018 Feb;28(2):103–15. DOI: 10.1016/j.nmd.2017.11.005. PMID: 29290580
18. Hewamadduma C, Chapman L, McNicholas S, Cousins O, Borg L, Navalgaria A, et al. ‘Un-picking the Bone-health Management’ in Adult Spinal Muscular Atrophy (SMA) Patients: Multi-centre UK Audit (P3-10.001). Neurology. 2024 Apr 9;102(7_supplement_1). DOI: 10.1212/WNL.0000000000205704
19. McCoy E, Lakhotia A, Rogers A. Improving Bone Health Screening in Patients with Spinal Muscular Atrophy: A Quality Improvement Initiative (P8-11.034). Neurology. 2025 Apr 8;104(7_Supplement_1). DOI: 10.1212/WNL.0000000000208989
20. Moon R, Harvey N, Curtis E, de Vries F, van Staa T, Cooper C. Ethnic and geographic variations in the epidemiology of childhood fractures in the United Kingdom. Bone. 2016 Apr; 85:9–14. DOI: 10.1016/j.bone.2016.01.015. PMID: 26802259
21. Curtis EM, van der Velde R, Moon RJ, van den Bergh JPW, Geusens P, de Vries F, et al. Epidemiology of fractures in the United Kingdom 1988–2012: Variation with age, sex, geography, ethnicity and socioeconomic status. Bone. 2016 Jun;87:19–26. DOI: 10.1016/j.bone.2016.03.006. PMID: 26968752
22. National Institute for Clinical Excellence. Fractures (non-complex): assessment and management. 2016. Available at https://www.nice.org.uk/guidance/ng38 (accessed in July 2025)
23. Henman PD, Turner C, Aird J, Atherton WG, Campbell D, Carpenter C, et al. Development of a guideline for orthopaedic management in the care of children and young people with Duchenne muscular dystrophy in the UK National Health Service. J Child Orthop. 2025 Jun 24:18632521251348972. DOI: 10.1177/18632521251348972. PMID: 40575436
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Copyright (c) 2025 Rebecca Johnson, Matthew Parton, Apoorva Kumar, Dr. Mahalekshmi Desikan, Alexandra Dungavel, Mary Benoy, Dr. Rosaline Quinlivan
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