Enhancing bone mineral density in osteogenesis imperfecta: The role of Zoledronate acid, vitamin D, calcium and phosphate
Keywords:
Osteogenesis imperfecta , bone mineral density, zoledronic acid, Vitamin D, calcium, phosphateAbstract
Background and aim: Osteogenesis imperfecta (OI) is an uncommon genetic condition arising from type I collagen mutations, leading to bone fragility and recurrent fractures. Zoledronic acid is used to improve bone mineral density (BMD). The role of vitamin D, calcium, and phosphate in modulating BMD outcomes remains unclear. This study aimed to assess the effectiveness of zoledronic acid in increasing BMD in children with OI and its association with metabolic factors.
Methods: A retrospective study was conducted on 24 children with OI in East Java. All patients received zoledronic acid (0.05 mg/BW) every 4–6 months for ≥1 year. Clinical data, fracture history, vitamin D, calcium, phosphate, and dual-energy X-ray absorptiometry (DXA) results at baseline and 2 years were analyzed using paired t-test, logistic regression, and correlation tests.
Results: Most subjects were male, diagnosed at 20.0 ± 25.8 months, predominantly OI type III (95.8%). Mean treatment duration was 4.42 ± 2.69 years with a median of eight infusions. Absolute BMD (g/cm²) significantly increased at L1–4 (p=0.014), Total Body (p<0.001), and TBLH (p=0.013), though Z-score changes were not significant. Treatment cycles (OR=1.823;p=0.022) and duration (OR=2.572;p=0.022) predicted BMD improvement. Vitamin D (r=0.455;p=0.025) and calcium (r=0.484;p=0.017) correlated with Z-score BMD TBLH. Vitamin D deficiency was found0in 45.8% of patients.
Conclusions: Zoledronic acid improves absolute BMD in children with OI, particularly with long-term treatment, Vitamin D status supports bone response, emphasizing combined pharmacologic and nutritional management.
References
1. Brizola E, Shapiro JR. Bisphosphonate Treatment of Children and Adults with Osteogenesis Imperfecta: Unanswered Questions. Calcif Tissue Int. 2015 Aug 13;97(2):101–3. doi:10.1007/s00223-015-0021-6
2. Rochmah N, Marzuki NS, Agustiarini E, Pulungan AB. Osteogenesis imperfecta in children: Indonesian experiences. Int J Pediatr Endocrinol. 2013 Oct 3;2013(S1):P166. doi:10.1186/1687-9856-2013-S1-P166
3. Basel D, Steiner RD. Osteogenesis imperfecta: Recent findings shed new light on this once well-understood condition. Genet Med. 2009 Jun;11(6):375–85. doi:10.1097/GIM.0b013e3181a1ff7b
4. Bowden SA, Mahan JD. Zoledronic acid in pediatric metabolic bone disorders. Transl Pediatr. 2017 Oct;6(4):256–68. doi:10.21037/tp.2017.09.10
5. Pulungan A, Batubara J, Tridjaja B, et al. Clinical Profile and IV Bisphosphonate Therapy in Children with Osteogenesis Imperfecta in Cipto Mangunkusumo Hospital. Asia Pac J Paediatr Child Health. 2019;3:13–23.
6. DeLuca HF. Overview of general physiologic features and functions of vitamin D. Am J Clin Nutr. 2004 Dec;80(6):1689S-1696S. doi:10.1093/ajcn/80.6.1689S
7. Institute of Medicine. Dietary Reference Intakes for Calcium and Vitamin D. Washington, D.C.: National Academies Press; 2011. doi:10.17226/13050
8. Forlino A, Marini JC. Osteogenesis imperfecta. The Lancet. 2016 Apr;387(10028):1657–71. doi:10.1016/S0140-6736(15)00728-X
9. Van Dijk FS, Sillence DO. Osteogenesis imperfecta: Clinical diagnosis, nomenclature and severity assessment. Am J Med Genet A. 2014 Jun 8;164(6):1470–81. doi:10.1002/ajmg.a.36545
10. Glorieux FH, Bishop NJ, Plotkin H, et al. Cyclic Administration of Pamidronate in Children with Severe Osteogenesis Imperfecta. N Engl J Med. 1998 Oct;339(14):947–52. doi:10.1056/NEJM199810013391402
11. Rauch F, Glorieux FH. Osteogenesis imperfecta. The Lancet. 2004 Apr;363(9418):1377–85. doi:10.1016/S0140-6736(04)16051-0
12. Martanto TW, Japamadisaw A, Nurhayati D, Nelissen RGHH. Zoledronate Therapy in Osteogenesis Imperfecta: Perspectives in Indonesia Tertiary Hospital. J Bone Metab. 2024 Nov 30;31(4):290–5. doi:10.11005/jbm.24.767
13. Coccia F, Pietrobelli A, Zoller T, Guzzo A, Cavarzere P, Fassio A, et al. Vitamin D and Osteogenesis Imperfecta in Pediatrics. Pharmaceuticals. 2023 May 3;16(5):690. doi:10.3390/ph16050690
14. Vuorimies I, Toiviainen-Salo S, Hero M, Mäkitie O. Zoledronic Acid Treatment in Children with Osteogenesis Imperfecta. Horm Res Paediatr. 2011;75(5):346–53. doi:10.1159/000323368
15. Riaz M, Hafeez S, Ibrahim MN, et al. Safety and Efficacy of Zoledronic Acid in children with Osteogenesis Imperfecta. JCPSP. 2022 Sep 1;32(09):1165–9. doi:10.29271/jcpsp.2022.09.1165
16. van de Peppel J, van Leeuwen JPTM. Vitamin D and gene networks in human osteoblasts. Front Physiol. 2014 Apr 9;5. doi:10.3389/fphys.2014.00137
17. Li Y, Zhao P, Jiang B, Liu K, Zhang L, Wang H, et al. Modulation of the vitamin D/vitamin D receptor system in osteoporosis pathogenesis: insights and therapeutic approaches. J Orthop Surg Res. 2023 Nov 13;18(1):860. doi:10.1186/s13018-023-04320-4
18. Xu D, Gao HJ, Lu CY, Tian HM, Yu XJ. Vitamin D inhibits bone loss in mice with thyrotoxicosis by activating the OPG/RANKL and Wnt/β-catenin signaling pathways. Front Endocrinol (Lausanne). 2022 Nov 30;13. doi:10.3389/fendo.2022.1066089
19. Edouard T, Glorieux FH, Rauch F. Predictors and Correlates of Vitamin D Status in Children and Adolescents with Osteogenesis Imperfecta. J Clin Endocrinol Metab. 2011 Oct;96(10):3193–8. doi:10.1210/jc.2011-1480
20. Plante L, Veilleux LN, Glorieux FH, Weiler H, Rauch F. Effect of high-dose vitamin D supplementation on bone density in youth with osteogenesis imperfecta: A randomized controlled trial. Bone. 2016 May;86:36–42. doi:10.1016/j.bone.2016.02.013
21. Valeeva D, Akhiiarova K, Minniakhmetov I, Mokrysheva N, Khusainova R, Tyurin A. Complex Analysis of Micronutrient Levels and Bone Mineral Density in Patients with Different Types of Osteogenesis Imperfecta. Diagnostics. 2025 Jan 22;15(3):250. doi:10.3390/diagnostics15030250
22. Royal Children’s Hospital Melbourne. Clinical practice guideline: Vitamin D deficiency (pediatric) [Internet]. Melbourne; 2025 [cited 2025 Oct 12]. Report. Available from: https://www.rch.org.au/clinicalguide/guideline_index/Vitamin_D_deficiency/
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