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0INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED
MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
GLUCOCORTICOIDS INDUCED OSTEOPOROSIS: A MEDICINE INDUCED DISEASE
1Asim Rahman, 2Divyadarshan Lohani, 3Alieha binti Ashraf, 4Dr. Md. Faheem Haider
1Student, Faculty of Pharmacy, Integral University, Lucknow.
2Student, Faculty of Pharmacy, Integral University, Lucknow.
3Student, Faculty of Pharmacy, Integral University, Lucknow.
4Associate Professor, Department of Pharmaceutics, Faculty of Pharmacy, Integral University,
Uttar Pradesh, India https://doi.org/10.5281/zenodo.13842056 Abstract. Diseases such as cancer, inflammation, respiratory, and autoimmune diseases are treated or managed using glucocorticoids (GCs), but this GC therapy has a significant side effect, which is the induction of osteoporosis, also termed glucocorticoids-induced osteoporosis (GIOP). The GIOP leads to an increase in bone absorption through decreasing the level of osteoblasts (bone-forming cells) and increasing the level of osteoclasts (bone-deleting cells), which leads to suppression of bone formation.
Keywords: glucocorticoids (GC), Osteoblast, Osteoclast, Osteoporosis, Bone.
Introduction to Osteoporosis
Administering the GCs in low dose for over a period of 3 months will lead to induction of osteoporosis, and the risk of osteoporosis is directly proportional to the duration and dosage of the GC being administered. The factors that influence the GIOP are age, sex, previous fractures, and other diseases. GIOP can be managed and treated if detected early through pharmacological interventions and non-pharmacological interventions such as exercises and food [1]
The most common metabolic disorder, which is currently affecting approximately around 200 million people worldwide, is osteoporosis, which remains underdiagnosed and untreated only to be identified when bone fracture occurs or a reduction in the bone mineral density is shown up in the blood test. Postmenopausal women and the elderly age group are most prevalent to this disease. The fracture-prone area of the body affected by osteoporosis includes the hip, wrist, and vertebral column [2].
Causes of Osteoporosis:
Imbalance between the osteoblast cell and the osteoclast cell plays a key role in the process of this diseases with chronic glucocorticoid therapy are prone to fractures of the femoral neck of the hip and vertebrae. As the GC therapy is started, there is a rapid bone loss (3-5%) followed by a steady phase (0.5-1%) each year. Prednisolone (2.5-7.5 mg daily), which is a low dose, can also be a factor in fracture risk if the dose is surged [3] Drugs which cause osteoporosis Cancer medicines Thiazolidinediones Proton pump inhibitors Antiepileptics medicines Glucocorticoids Introduction to Glucocorticoids
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" _25-26 SEPTEMBER, 2024_
The steroid hormones glucocorticoids (GCs) are commonly used to treat cancer, autoimmune diseases, and inflammation. To demonstrate its therapeutic and wide physiological effects, GCs bind to the GC receptor (GR) [4]. The GR is a member of the nuclear receptor superfamily of ligand-inducible transcription factors, which regulate a variety of physiological activities like as development, metabolism, and reproduction through gene transcription. The unliganded GR is mostly found in the cytoplasm, but it effectively and swiftly translocates to the nucleus upon hormone binding [5].
Mechanism of GIOP:
Gc leads to decreased calcium absorption in the stomach, increasing osteoclastogenesis and promoting the death of osteoblasts and osteocytes. The decrease in these cells leads to the reduction in bone formation and an increase in bone resorption, contributing to osteoporosis [6].
The effect of excess glucocorticoids on the formation and function of osteoblast, decreased osteogenic cell fate of stromal progenitor cells, suppressed proliferation of osteoprogenitors.
Some glucocorticoids drugs are beclomethasone, betamethasone, budesonide, cortisone, dexamethasone and many more [7].
Treatment of GIOP:
Treating and managing GIOP involves both non-pharmacological and pharmacological interventions, Bisphosphonates are used to prevent bone resorption, while calcium and vitamin D supplements are essential for maintaining bone health. Other treatments include calcitonin, denosumab, and teriparatide. Lifestyle modifications, such as a diet rich in calcium and vitamin D, regular weight-bearing exercise, and smoking cessation, are also recommended to prevent and manage GIOP [8].
Emerging therapies and investigational agents targeting bone resorption are lasofoxifene and cathepsin K inhibitors, and emerging and investigational agents targeting bone formation are donepezil and anti-sclerostin antibodies [9].
Glucocorticoid-induced osteoporosis is a serious side effect of long-term GC therapy. Early intervention, including risk assessment and appropriate treatment, is crucial in preventing fractures and managing osteoporosis in patients undergoing GC therapy [10].
Factors leading to osteoporosis
Gc drug, and the disease they are used Beclomethasone [11] Allergic Rhinitis COPD
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS"
_25-26 SEPTEMBER, 2024_
Asthma Nasal polyps Betamethasone [12] Skin conditions
Rheumatic and Autoimmune disorders Respiratory conditions Fetal Lung Maturation Budesonide [13] COPD
Inflammatory bowel disease Eosinophilic Esophagitis Cortisone [14] Arthritis
Tendinitis and bursitis Allergic Reactions Dexamethasone [15] Autoimmune Disease Allergic reactions and anaphylaxis Inflammatory bowel disease
Conclusion: Glucocorticoid-induced osteoporosis is a serious side effect of long-term GC
therapy. Early intervention, including risk assessment and appropriate treatment, is crucial in
preventing fractures and managing osteoporosis in patients undergoing GC therapy.
REFERENCES
1. Rahman A, Haider F. A comprehensive review on glucocorticoids induced osteoporosis: A medication caused disease. Steroids. 2024 May 15:109440.
2. Mohamed AM. An overview of bone cells and their regulating factors of differentiation. Malays J Med Sci. 2008 Jan;15(1):4-12. PMID: 22589609; PMCID: PMC3341892.
3. Weaver CM, Gordon CM, Janz KF, et al. The National Osteoporosis Foundation's position statement on peak bone mass development and lifestyle factors: a systematic review and implementation recommendations. Osteoporos Int. 2016; 27(4):1s281-1386.
4. Timmermans S, Souffriau J and Libert C (2019) A General Introduction to Glucocorticoid Biology. Front. Immunol. 10:1545. doi: 10.3389/fimmu.2019.01545.
5. Kennedy, C. C., Papaioannou, A., & Adachi, J. D. (2006). Glucocorticoid-Induced Osteoporosis. Women's Health, 2(1), 65-74. doi:10.2217/17455057.2.1.65
6. M.D. Heitzer, I.M. Wolf, E.R. Sanchez, S.F. Witchel, D.B. DeFranco, Glucocorticoid receptor physiology, Rev. Endocr. Metabol. Disord. 8 (4) (2007) 321-330, https://doi.org/10.1007/s11154-007-9059-8.
7. C. Iacopo, F. Alberto, M. Daniela, E.V. Cristina, G. Luigi, Updates in epidemiology, pathophysiology and management strategies of glucocorticoidinduced osteoporosis, Exp. Rev. Endocrinol. Metabol. (2020), https://doi.org/ 10.1080/17446651.2020.1772051.
8. M. Ciriaco, P. Ventrice, G. Russo, M. Scicchitano, G. Mazzitello, F. Scicchitano, E. Russo, Corticosteroid-related central nervous system side effects, J. Pharmacol. Pharmacother. 4 (Suppl 1) (2013 Dec) S94-S98, https://doi.org/10.4103/0976- 500X.120975.
INTERNATIONAL SCIENTIFIC AND PRACTICAL CONFERENCE "STATUS AND DEVELOPMENT PROSPECTS OF FUNDAMENTAL AND APPLIED MICROBIOLOGY: THE VIEWPOINT OF YOUNG SCIENTISTS" 25-26 SEPTEMBER, 2024
9. Shiraki,M.; Yamazaki,Y.; Shiraki,Y.; Hosoi,T.; Tsugawa,N.; Okano,T. Highlevelofserumundercarboxylated osteocalcin in patients with incident fractures during bisphosphonate treatment. J. Bone Min. Metab. 2010, 28, 578-584. [CrossRef].
10. Martin, T.J.; Sims, N.A. Osteoclast-derived activity in the coupling of bone formation to resorption. Trends. Mol. Med. 2005, 11, 76-81. [CrossRef].
11. Bateman ED, Hurd SS, Barnes PJ, et al. Global strategy for asthma management and prevention: GINA executive summary. Eur Respir J. 2008 Jan;31(1):143-78. DOI: 10.1183/09031936.00138707.
12. Sidbury R, Davis DM, Cohen DE, et al. Guidelines of care for the management of atopic dermatitis: Section 3. Management and treatment with phototherapy and systemic agents. J Am Acad Dermatol. 2014 Jun;71(6):327-49. DOI: 10.1016/j.jaad.2014.03.030.
13. Feagan BG, Sandborn WJ, Gasink C, et al. Ustekinumab as induction and maintenance therapy for Crohn's disease. N Engl J Med. 2016 Nov 17;375(20):1946-1960. DOI: 10.1056/NEJMoa1602773.
14. Aletaha D, Smolen JS. Diagnosis and management of rheumatoid arthritis: a review. JAMA. 2018 Oct 2;320(13):1360-1372. DOI: 10.1001/jama.2018.13103.
15. Dorrington AM, Selinger CP, Parkes GC, Smith M, Pollok RC, Raine T. The historical role and contemporary use of corticosteroids in inflammatory bowel disease. Journal of Crohn's and Colitis. 2020 Sep 1;14(9):1316-29.
