AN EXPERIMENTAL STUDY EVALUATING THE INFLUENCE OF BISPHOSPHONATES ON DEPRESSION PATTERNS IN SWISS ALBINO MICE AND WISTER RATS
Objective: Bisphosphonates are used for treating osteoporosis. Few studies have reported their effect on alterations in comorbid behaviour such as depression. Therefore, present study was performed to investigate the effects of bisphosphonate drugs on depression in adult male Wister rats and Swiss albino mice.
Methods: The study was conducted on adult male Wister rats and Swiss albino mice, 36 of each type, equally divided into six groups. One group was classified as control group and the rest were treated as test groups. Initial photoperiod of 12 h was provided for acclimatization, prior to the start of the experiment. Drug administration was not performed in control group. Forced swimming test and tail suspension test were performed to investigate the antidepressant activity. Locomotor activity was performed to evaluate the action of drugs on the nervous system. Effects of the test drugs were compared with a standard drugâ€”amitriptyline. Results were statistically evaluated by one-way analysis of variance followed by Bonferroniâ€™s multiple comparison test. Pâ‰¤0.05 was considered significant.
Results: In forced swimming test, duration of immobility was significantly reduced in the standard and test drugs when compared to control group; however, it was not significant in all the four test groups as compared to that of amitriptyline-administered group (p>0.05). In tail suspension test, significant decrease (p<0.01) in the duration of immobility was observed with administration of drugs when compared to control group. Results of test groups were not found to be significant as compared to amitriptyline-treated group (p>0.05). Mean values of amitriptyline-, alendronate-, risedronate-, ibandronate-and etidronate-treated groups failed to show significant difference (p>0.05) when compared to control group suggesting homogeneity among the groups.
Conclusion: Bisphosphonates appeared to have an antidepressant activity. More extensive research is required to substantiate and elucidate the role of bisphosphonates in behavioural disorders such as depression.
2. Takkouche B, Montes-Martinez A, Gill SS, Etminan M. Psychotropic medications and the risk of fracture. Drug Saf 2007;30:171-84.
3. Rizzoli R, Cooper C, Reginster JY, Abrahamsen B, Adachi JD, Brandi ML, et al. Antidepressant medications and osteoporosis. Bone 2012;51:606-13.
4. Rauma PH, Pasco JA, Berk M, Stuart AL, Koivumaa-Honkanen H, Honkanen RJ, et al. The association between major depressive disorder, use of antidepressants and bone mineral density (BMD) in men. J Musculoskeletal Neuronal Interact 2015;15: 177-85.
5. Cizza G, Primma S, Csako G. Depression as a risk factor for osteoporosis. Trends Endocrinol Metab 2009;20:367-73.
6. Frey BN, Lord C, Soares CN. Depression during menopausal transition: a review of treatment strategies and pathophysiological correlates. Menopause Int 2008;14:123-8.
7. Aithal S, Hooli TV, Patil R, Varun HV, Swetha ES. Evaluation of antidepressant activity of topiramate in mice. Asian J Pharm Clin Res 2014;7:174-6.
8. Kastelan D, Vlak P, Lozo P, Gradiser M. Health-related quality of life among patients with postmenopausal osteoporosis treated with weekly and monthly bisphosphonates. Endocr Res 2010;35:165-73.
9. Citraro R, Gallelli L, Leo A, De Fazio P, Gallelli P, Russo E, et al. Effects of chronic sodium alendronate on depression and anxiety in a menopausal experimental model. Pharmacol Biochem Behav 2015;129:65-71.
10. Citraro R, Gallelli L, Leo A, De Fazio P, Gallelli P, Russo E, et al. Effects of chronic sodium alendronate on depression and anxiety in a menopausal experimental model. Pharmacol Biochem Behav 2015;129:65-71.
11. Sweetman SCM. The complete drug reference. 36th ed. London: Pharmaceutical Press; 2009. p. 1088-91.
12. Ghosh MN. Toxicity studies. Fundamentals of experimental pharmacology.4thed: Kolkata: Hilton and company; 2005. p. 176-83.
13. CastagnÃ© V, Moser P, Roux S, Porsolt RD. Rodent models of depression: forced swim and tail suspension behavioral despair tests in rats and mice. Chapter 8. Curr Protoc Neurosci 2011.
14. CastagnÃ© V, Moser P, Porsolt RD. Behavioral assessment of antidepressant activity in rodents. In: Buccafusco JJ. editor. Methods of Behavior Analysis in Neuroscience. 2nd edition. Boca Raton (FL): Chapter 6. CRC Press; 2009.
15. Yadav G, Garg VK, Thakur R, Khare P. Locomotor activity of methanolic extract of Saracaindica Bark. Adv Biol Res 2013;7:1-3.
16. Vogel HG. Drug discovery and evaluation: Pharmacological assays. 3rd Ed. New York: Springer; 2008.
17. DeMuth JE. Basic statistics and pharmaceutical statistical applications. 2nd ed. Boca Raton (FL): Chapman and Hall/CRC Press: Chapter 11. Multiple comparison tests; 2006. p. 229-66.
18. Konstantynowicz J, Kadziela-Olech H, Kaczmarski M, Zebaze RM, Iuliano-Burns S, Piotrowska-Jastrzebska J, et al. Depression in anorexia nervosa: a risk factor for osteoporosis. J Clin Endocrinol Metab 2005;90:5382-5.
19. Mussolino ME, Jonas BS, Looker AC. Depression and bone mineral density in young adults: results from NHANES III. â€ŽPsychosom Med 2004;66:533-7.
20. Umarani V, Sudhakar M, Ramesh A, Lakshmi BVS, Sandhyarani D. Protective effect of hydroalcoholic extract of Pueraria tuberosa against arsenic induced neurotoxicity in rats. Int J Res Pharmacol Chem 2016;6:350-62.
21. Tamai R, Sugiyama A, Kiyoura Y. Alendronate regulates cytokine production induced by lipid A through nuclear factorâ€ÎºB and Smad3 activation in human gingival fibroblasts. J Periodontal Res 2011;46:13-20.
22. Vogelzangs N, De Jonge P, Smit JH, Bahn S, Penninx BW. Cytokine production capacity in depression and anxiety. Transl Psychiatry 2016;6:e825.
23. D'Amelio P, Grimaldi A, Di Bella S, Tamone C, Brianza SZ, Ravazzoli MG, et al. Risedronate reduces osteoclast precursors and cytokine production in postmenopausal osteoporotic women. J Bone Miner Res 2008;23:373-9.
24. Pennanen N, Lapinjoki S, Urtti A, MÃ¶nkkÃ¶nen J. Effect of liposomal and free bisphosphonates on the IL-1Î², IL-6 and TNFÎ± secretion from RAW 264 cells in vitro. Pharm Res 1995;12:916-22.
25. Bianchi M, Franchi S, Ferrario P, Sotgiu ML, Sacerdote P. Effects of the bisphosphonate ibandronate on hyperalgesia, substance P, and cytokine levels in a rat model of persistent inflammatory pain. Eur J Pain 2008;12:284-92.
26. Raison CL, Rutherford RE, Woolwine BJ, Shuo C, Schettler P, Drake DF, et al. A randomized controlled trial of the tumor necrosis factor antagonist infliximab for treatment-resistant depression: the role of baseline inflammatory biomarkers. JAMA Psychiatry 2013;70:31-41.
27. Nagashima M, Takahashi H, Shimane K, Nagase Y, Wauke K. Osteogenesis and osteoclast inhibition in rheumatoid arthritis patients treated with bisphosphonates alone or in combination with pitavastatin over an 18-month follow-up after more than 4 y of treatment with bisphosphonates. Arthritis Res Ther 2012;14:1-8.
28. David AA, Schoeber J, Houston RE, Mohl VE, Wildman KM. Hyperparathyroidism. Am Fam Physician 1998;57:1795-802.
29. Pamulaparthi A, Prathap VR, Banala M, Nanna RS. Experimental evaluation of antidepressant and antianxiety activities of aqueous leaf extracts of Senna alata (l.) Roxb. using in vitro animal models. Int Curr Pharm Res 2016;8:60-3.
30. Rodan DA. Bisphosphonates and primary hyperparathyroidism. J Bone Miner Res 2002;17 Suppl 2:N150-3.
31. Knight MJ, Hyatt PJ. The effect of bisphosphonates on calcium and parathyroid hormone levels in patients with primary hyperparathyroidism over 2 y. Endocrine Abstracts; 2006. p. 12 P2.
32. Gill R, Balaji O, Kumari MK, Amberkar MB, Udupa KS. Zoledronic acid: a mischievous suspect for liver injury. Asian J Pharm Clin Res 2016;9:3-6.
33. Kennel KA, Drake MT. Adverse Effects of bisphosphonates: Implications for osteoporosis management. Mayo Clin Proc 2009;84:632â€“8.
34. Tanvetyanon T, Stiff PJ. Management of the adverse effects associated with intravenous bisphosphonates. Ann Oncol 2006;17:897-907.
35. Papapetrou PD. Bisphosphonate-associated adverse events. Hormones 2009,8:96-110.
36. Diab DL, Watts NB. Bisphosphonate drug holiday: who, when and how long. Ther Adv Musculoskelet Dis 2013; 5:107â€“11.
37. Black DM, Kelly MP, Genant HK, Palermo L, Eastell R, Bucci-Rechtweg C, et al. Bisphosphonates and fractures of the subtrochanteric or diaphyseal femur. N Engl J Med 2010;362:1761-71.