Multisystem Determinants of Low Bone Mineral Density in Scoliosis: Genetic, Endocrine, Nutritional, and Biomechanical Interactions
Main Article Content
Abstract
Scoliosis exists as a three-dimensional spinal deformity which develops through the combination of genetic elements, endocrine factors, biomechanical forces, and nutritional components. Research shows that bone mineral density (BMD) reduction exists as a widespread condition throughout adolescent idiopathic scoliosis (AIS), congenital scoliosis, and neuromuscular scoliosis patients. Dual-energy X-ray absorptiometry and high-resolution peripheral quantitative CT scans show that bone density is lower in both cortical and trabecular areas while microarchitectural changes occur which could lead to spinal curve development and growth. The development of skeletal abnormalities results from multiple biological pathways. Research studies using genome-wide and candidate-gene approaches have identified LRP5, VDR, COL1A1, and other essential genes which control osteoblast development and matrix structure. The process of bone formation receives additional influence from epigenetic changes which affect the methylation patterns of osteogenic transcription factors and estrogen-related genes. The specific microRNA patterns found in AIS patients disrupt BMP and SMAD signaling pathways which results in decreased osteogenic potential. The combination of endocrine disorders including estrogen metabolism changes, vitamin D deficiency, and elevated parathyroid hormone levels makes bone defects worse while scientists continue to study melatonin, leptin and growth hormone potential roles. The combination of nutritional deficiencies that affect calcium, magnesium, zinc, and vitamin K2 levels in patients leads to increased metabolic risk. The combination of reduced physical activity, restricted bracing use, and impaired mechanotransduction leads to decreased skeletal loading which prevents adolescents from reaching their peak bone mass. Research evidence supports a complex system model which demonstrates scoliosis and low BMD share common genetic, hormonal, nutritional, and mechanical factors that affect spinal structure and complete skeletal health. The combination of genetic tests with endocrine, nutritional, and biomechanical evaluations will help doctors identify at-risk patients better while developing specific treatments to enhance bone strength and control spinal curve growth.
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References
2. Cheng JC, Castelein RM, Chu WC, et al. Adolescent idiopathic scoliosis. Nat Rev Dis Primers. 2015;1: 15030.
3. Li XF, Li H, Liu ZD, Dai LY. Low bone mineral status in adolescent idiopathic scoliosis. Eur Spine J. 2008 Nov;17(11):1431-40.
4. Lam TP, Hung VW, Yeung HY, Tse YK, Chu WC, Ng BK, Lee KM, Qin L, Cheng JC. Abnormal bone quality in adolescent idiopathic scoliosis: a case-control study on 635 subjects and 269 normal controls with bone densitometry and quantitative ultrasound. Spine (Phila Pa 1976). 2011 Jul 1;36(15): 1211-7.
5. Du Q, Zhou X, Li JA, He XH, Liang JP, Zhao L, Yang XY, Chen N, Zhang SX, Chen PJ. Quantitative ultrasound measurements of bone quality in female adolescents with idiopathic scoliosis compared to normal controls. J Manipulative Physiol Ther. 2015 Jul-Aug;38(6):434-41.
6. Lee WT, Cheung CS, Tse YK, Guo X, Qin L, Lam TP, Ng BK, Cheng JC. Association of osteopenia with curve severity in adolescent idiopathic scoliosis: a study of 919 girls. Osteoporos Int. 2005 Dec;16 (12):1924-32.
7. Cheng JC, Qin L, Cheung CS, Sher AH, Lee KM, Ng SW, Guo X. Generalized low areal and volumetric bone mineral density in adolescent idiopathic scoliosis. J Bone Miner Res. 2000 Aug;15(8):1587-95.
8. Cheng JC, Hung VW, Lee WT, Yeung HY, Lam TP, Ng BK, Guo X, Qin L. Persistent osteopenia in adolescent idiopathic scoliosis--longitudinal monitoring of bone mineral density until skeletal maturity. Stud Health Technol Inform. 2006;123:47-51.
9. Danielewicz A, Wójciak M, Sowa I, Kusz M, Wessely-Szponder J, Dresler S, Latalski M. Metabolic Imbalances and Bone Remodeling Agents in Adolescent Idiopathic Scoliosis: A Study in Postmenarcheal Girls. Int J Mol Sci. 2023 Aug 27; 24(17):13286.
10. Ferrari SL, Deutsch S, Antonarakis SE, et al. LRP5 gene polymorphisms and osteoporosis. Bone. 2004;34(4):677-681.
11. Yin X, Wang H, Guo J, Zhang L, Zhang Y, Li L, Hou S. Association of vitamin D receptor BsmI rs1544410 and ApaI rs7975232 polymorphisms with susceptibility to adolescent idiopathic scoliosis: A systematic review and meta-analysis. Medicine (Baltimore). 2018 Jan;97(2):e9627.
12. Mann V, Hobson EE, Li B, Stewart TL, Grant SF, Robins SP, Aspden RM, Ralston SH. A COL1A1 Sp1 binding site polymorphism predisposes to osteoporotic fracture by affecting bone density and quality. J Clin Invest. 2001 Apr;107(7):899-907.
13. Gong Y, Slee RB, Fukai N, et al. LRP5 and osteoporosis-pseudoglioma syndrome. N Engl J Med. 2001;346(9):745-751.
14. Fabre S, Bourmaud M, Mabilleau G, Goulet R, Couturier A, Dentel A, Picaud S, Funck-Brentano T, Collet C, Cohen-Solal M. Lrp5 p.Val667Met Variant Compromises Bone Mineral Density and Matrix Properties in Osteoporosis. JBMR Plus. 2023 Mar 28;7(6):e10741.
15. Wu Y, Zhang H, Tang M, Guo C, Deng A, Li J, Wang Y, Xiao L, Yang G. High methylation of lysine acetyltransferase 6B is associated with the Cobb angle in patients with congenital scoliosis. J Transl Med. 2020 May 24;18(1):210.
16. Meng, Y.; Lin, T.; Liang, S.; Gao, R.; Jiang, H.; Shao, W.; Yang, F.; Zhou, X. Value of DNA Methylation in Predicting Curve Progression in Patients with Adolescent Idiopathic Scoliosis. EBioMedicine 2018, 36, 489–496.
17. Hui S, Yang Y, Li J, Li N, Xu P, Li H, Zhang Y, Wang S, Lin G, Li S, Qiu G, Zhao RC, Zhang J, Zhuang Q. Differential miRNAs profile and bioinformatics analyses in bone marrow mesenchymal stem cells from adolescent idiopathic scoliosis patients. Spine J. 2019 Sep;19(9):1584-1596.
18. Leboeuf D, Letellier K, Alos N, Edery P, Moldovan F. Do estrogens impact adolescent idiopathic scoliosis? Trends Endocrinol Metab. 2009 May;20 (4):147-52.
19. Kulis A, Goździalska A, Drąg J, Jaśkiewicz J, Knapik-Czajka M, Lipik E, Zarzycki D. Participation of sex hormones in multifactorial pathogenesis of adolescent idiopathic scoliosis. Int Orthop. 2015 Jun;39(6):1227-36.
20. Balioglu MB, Aydin C, Kargin D, Albayrak A, Atici Y, Tas SK, Kaygusuz MA. Vitamin-D measurement in patients with adolescent idiopathic scoliosis. J Pediatr Orthop B. 2017 Jan;26(1):48-52.
21. Zhu Q, Chen J, Chen C, Wang H, Yang S. Association between calcium-phosphorus balance and adolescent idiopathic scoliosis: A meta-analysis. Acta Orthop Traumatol Turc. 2019 Nov;53 (6):468-473.
22. Golub MS, Keen CL, Gershwin ME, Styne DM, Takeuchi PT, Ontell F, Walter RM, Hendrickx AG. Adolescent growth and maturation in zinc-deprived rhesus monkeys. Am J Clin Nutr. 1996 Sep;64(3): 274-82
23. Rondanelli M, Peroni G, Gasparri C, Infantino V, Naso M, Riva A, Petrangolini G, Perna S, Tartara A, Faliva MA. An overview on the correlation between blood zinc, zinc intake, zinc supplementation and bone mineral density in humans. Acta Ortop Mex. 2021 Mar-Apr;35(2):142-152.
24. Kuang X, Liu C, Guo X, Li K, Deng Q, Li D. The combination effect of vitamin K and vitamin D on human bone quality: a meta-analysis of randomized controlled trials. Food Funct. 2020 Apr 30;11(4): 3280-3297.
25. Gozdzialska A, Michalczyk A, Swiecki M, et al. Serum vitamin D and AIS severity. BMC Musculoskelet Disord. 2022;23(1):1133.
26. Gozdzialska A, Michalczyk A, Chudek J, et al. Vitamin D and back pain in scoliosis. BMC Musculoskelet Disord. 2022;23(1):935.