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The effects of bisphosphonates on inflammatory markers and atherosclerosis

Year 2025, Volume: 7 Issue: 4, 447 - 450, 28.07.2025
https://doi.org/10.38053/acmj.1692472

Abstract

Aims: Atherosclerosis and osteoporosis are prevalent conditions associated with significant morbidity and mortality worldwide. Evidence of literature suggests that bisphosphonates (BP) may play a role in inhibiting atherogenesis. The pathophysiological mechanisms underlying both atherosclerosis and osteoporosis share similarities, and numerous studies have shown an association between osteoporosis and cardiovascular events. This study aims to evaluate the effects of oral BP therapy on vascular
inflammatory markers and carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in osteoporotic patients.
Methods: The study included 28 osteoporotic patients (study group) and 28 osteopenic patients (control group). BP therapy (alendronate 70 mg/week, risedronate 35 mg/week) was administered to the study group in a randomized controlled way. The patients of the both groups received daily supplements of calcium (1000 mg) and vitamin D (880 IU). Baseline and 12-month follow-up measurements included height, weight, body-mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), homocysteine levels, CIMT, and bone mineral density (BMD).
Results: At the 12-month follow-up, hs-CRP levels decreased significantly in the study group, while they increased slightly in the control group (p=0.032). Similarly, homocysteine levels showed a significant reduction in the study group compared to the control group (p=0.002). No significant change in CIMT was observed between the two groups over the study period.
Conclusion: Our findings suggest that while oral BPs may influence certain vascular inflammatory markers, such as hs-CRP and homocysteine but they do not have a significant effect on CIMT. BPs may exert anti-atherosclerotic effects through the mevalonate pathway, but the results of this study warrant further investigation with larger sample sizes to confirm the broader implications of BPs in atherosclerosis management.

References

  • Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836-843. doi:10.1056/NEJM200003233421202
  • Durga J, Verhoef P, Bots ML, Schouten E. Homocysteine and carotid intima-media thickness: a critical appraisal of the evidence. Atherosclerosis. 2004;176(1):1-19. doi:10.1016/j.atherosclerosis.2003.11.022
  • Hurst RT, Ng DWC, Kendall C, Khandheria B. Clinical use of carotid intima-media thickness: review of the literature. J Am Soc Echocardiogr. 2007;20(7):907-914. doi:10.1016/j.echo.2007.02.028
  • van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DAM, Witteman JCM. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam study. Circulation. 2004;109(9):1089-1094. doi:10.1161/01.CIR.0000120708. 59903.1B
  • Kavanagh KL, Guo K, Dunford JE, et al. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci U S A. 2006;103(20):7829-7834. doi:10.1073/pnas. 0601643103
  • Luckman SP, Hughes DE, Coxon FP, Graham R, Russel G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13(4):581-589. doi:10.1359/jbmr. 1998.13.4.581
  • Bonjour JP, Ammann P, Rizzoli R. Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines. Osteoporos Int. 1999;9(5):379-393. doi:10. 1007/s001980050161
  • Ylitalo R, Oksala O, Ylä-Herttuala S, Ylitalo P. Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med. 1994;123(5):769-776.
  • Daoud AS, Frank AS, Jarmolych J, Fritz KE. The effect of ethane-l-hydroxy-1, 1-diphosphonate (EHDP) on necrosis of atherosclerotic lesions. Atherosclerosis. 1987;67(1):41-48. doi:10.1016/0021-9150(87) 90263-2
  • Shioi A, Nishizawa Y, Jono S, Koyama H, Hosoi M, Morii H. β-Glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1995;15(11):2003-2009. doi:10.1161/01.atv.15.11.2003
  • McFarlane SI, Muniyappa R, Shin JJ, Bahtiyar G, Sowers JR. Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Endocrine. 2004;23(1):1-10. doi:10.1385/ENDO:23:1:01
  • von der Recke P, Hansen MA, Hassager C. The association between low bone mass at the menopause and cardiovascular mortality. Am J Med. 1999;106(3):273-278. doi:10.1016/s0002-9343(99)00028-5
  • Watts NB. Bisphosphonate treatment of osteoporosis. In: Orwoll ES, Bliziotes M, eds. Osteoporosis: Pathophysiology and Clinical Management, Contemporary Endocrinology.1st ed. Humana Press, Totowa, NJ. 2003.
  • Papapoulos S. Ibandronate: a potent new bisphosphonate in the management of postmenopausal osteoporosis. Int J Clin Pract. 2003; 57(5):417-422. doi:10.1111/j.1742-1241.2003.tb10518.x
  • van der Klift M, Pols HAP, Hak AE, Witteman JCM, Hofman A, Laet CEDH. Bone mineral density and the risk of peripheral arterial disease: the Rotterdam study. Calcif Tissue Int. 2002;70(6):443-449. doi:10.1007/s00223-001-2076-9
  • Vogt MT, Cauley JA, Kuller LH, Nevitt MC. Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res. 1997;12(2):283-289. doi:10.1359/jbmr.1997.12.2.283
  • Koshiyama H, Nakamura Y, Tanaka S, Minamikawa J. Decrease in carotid intima-media thickness after 1-year therapy with etidronate for osteopenia associated with type 2 diabetes. J Clin Endocrinol Metab.2000;85(8):2793-2796. doi:10.1210/jcem.85.8.6748
  • Celiloglu M, Aydin Y, Balci P, Kolamaz T. The effect of alendronate sodium on carotid artery intima-media thickness and lipid profile in women with postmenopausal osteoporosis. Menopause. 2009;16(4):689-693. doi:10.1097/gme.0b013e318194cafd
  • Delibasi T, Emral R, Erdogan MF, Kamel N. Effects of alendronate sodium therapy on carotid intima media thickness in postmenopausal women with osteoporosis. Adv Ther. 2007;24(2):319-325. doi:10.1007/BF02849900
  • Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S. Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen, and alendronate. Bone. 1996;18(6):621-627. doi:10.1016/8756-3282(96) 00085-3
  • Sato M, Grasser W, Endo N, et al. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest. 1991;88(6):2095-2105. doi:10.1172/JCI115539
  • Fleisch H. Bisphosphonates in bone disease: from the laboratory to the patient. 4th Edition. Academic Press; 2000.
  • Adami S, Braga V, Guidi G, Gatti D, Gerardi D, Fracassi E. Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. J Bone Miner Res. 2000;15(3):599-604. doi:10.1359/jbmr. 2000.15.3.599

The effects of bisphosphonates on inflammatory markers and atherosclerosis

Year 2025, Volume: 7 Issue: 4, 447 - 450, 28.07.2025
https://doi.org/10.38053/acmj.1692472

Abstract

Aims: Atherosclerosis and osteoporosis are prevalent conditions associated with significant morbidity and mortality worldwide. Evidence of literature suggests that bisphosphonates (BP) may play a role in inhibiting atherogenesis. The pathophysiological mechanisms underlying both atherosclerosis and osteoporosis share similarities, and numerous studies have shown an association between osteoporosis and cardiovascular events. This study aims to evaluate the effects of oral BP therapy on vascular
inflammatory markers and carotid intima-media thickness (CIMT), a surrogate marker of atherosclerosis, in osteoporotic patients.
Methods: The study included 28 osteoporotic patients (study group) and 28 osteopenic patients (control group). BP therapy (alendronate 70 mg/week, risedronate 35 mg/week) was administered to the study group in a randomized controlled way. The patients of the both groups received daily supplements of calcium (1000 mg) and vitamin D (880 IU). Baseline and 12-month follow-up measurements included height, weight, body-mass index (BMI), high-sensitivity C-reactive protein (hs-CRP), homocysteine levels, CIMT, and bone mineral density (BMD).
Results: At the 12-month follow-up, hs-CRP levels decreased significantly in the study group, while they increased slightly in the control group (p=0.032). Similarly, homocysteine levels showed a significant reduction in the study group compared to the control group (p=0.002). No significant change in CIMT was observed between the two groups over the study period.
Conclusion: Our findings suggest that while oral BPs may influence certain vascular inflammatory markers, such as hs-CRP and homocysteine but they do not have a significant effect on CIMT. BPs may exert anti-atherosclerotic effects through the mevalonate pathway, but the results of this study warrant further investigation with larger sample sizes to confirm the broader implications of BPs in atherosclerosis management.

Ethical Statement

Ethical Declarations Ethics Committee Approval: The study was initiated with the approval of the Ankara University Medical Faculty Clinical Researches Ethics Committee (Date: 2009, Decision No: 144-4338). Informed Consent: Written consent was obtained from the patient participating in this study. Conflict of Interest Statement: The authors have no conflicts of interest to declare. Financial Disclosure: The authors declared that this study has received no financial support. Author Contributions: All of the authors declare that they have all participated in the design, execution, and analysis of the paper, and that they have approved the final version.

References

  • Ridker PM, Hennekens CH, Buring JE, Rifai N. C-reactive protein and other markers of inflammation in the prediction of cardiovascular disease in women. N Engl J Med. 2000;342(12):836-843. doi:10.1056/NEJM200003233421202
  • Durga J, Verhoef P, Bots ML, Schouten E. Homocysteine and carotid intima-media thickness: a critical appraisal of the evidence. Atherosclerosis. 2004;176(1):1-19. doi:10.1016/j.atherosclerosis.2003.11.022
  • Hurst RT, Ng DWC, Kendall C, Khandheria B. Clinical use of carotid intima-media thickness: review of the literature. J Am Soc Echocardiogr. 2007;20(7):907-914. doi:10.1016/j.echo.2007.02.028
  • van der Meer IM, Bots ML, Hofman A, del Sol AI, van der Kuip DAM, Witteman JCM. Predictive value of noninvasive measures of atherosclerosis for incident myocardial infarction: the Rotterdam study. Circulation. 2004;109(9):1089-1094. doi:10.1161/01.CIR.0000120708. 59903.1B
  • Kavanagh KL, Guo K, Dunford JE, et al. The molecular mechanism of nitrogen-containing bisphosphonates as antiosteoporosis drugs. Proc Natl Acad Sci U S A. 2006;103(20):7829-7834. doi:10.1073/pnas. 0601643103
  • Luckman SP, Hughes DE, Coxon FP, Graham R, Russel G, Rogers MJ. Nitrogen-containing bisphosphonates inhibit the mevalonate pathway and prevent post-translational prenylation of GTP-binding proteins, including Ras. J Bone Miner Res. 1998;13(4):581-589. doi:10.1359/jbmr. 1998.13.4.581
  • Bonjour JP, Ammann P, Rizzoli R. Importance of preclinical studies in the development of drugs for treatment of osteoporosis: a review related to the 1998 WHO guidelines. Osteoporos Int. 1999;9(5):379-393. doi:10. 1007/s001980050161
  • Ylitalo R, Oksala O, Ylä-Herttuala S, Ylitalo P. Effects of clodronate (dichloromethylene bisphosphonate) on the development of experimental atherosclerosis in rabbits. J Lab Clin Med. 1994;123(5):769-776.
  • Daoud AS, Frank AS, Jarmolych J, Fritz KE. The effect of ethane-l-hydroxy-1, 1-diphosphonate (EHDP) on necrosis of atherosclerotic lesions. Atherosclerosis. 1987;67(1):41-48. doi:10.1016/0021-9150(87) 90263-2
  • Shioi A, Nishizawa Y, Jono S, Koyama H, Hosoi M, Morii H. β-Glycerophosphate accelerates calcification in cultured bovine vascular smooth muscle cells. Arterioscler Thromb Vasc Biol. 1995;15(11):2003-2009. doi:10.1161/01.atv.15.11.2003
  • McFarlane SI, Muniyappa R, Shin JJ, Bahtiyar G, Sowers JR. Osteoporosis and cardiovascular disease: brittle bones and boned arteries, is there a link? Endocrine. 2004;23(1):1-10. doi:10.1385/ENDO:23:1:01
  • von der Recke P, Hansen MA, Hassager C. The association between low bone mass at the menopause and cardiovascular mortality. Am J Med. 1999;106(3):273-278. doi:10.1016/s0002-9343(99)00028-5
  • Watts NB. Bisphosphonate treatment of osteoporosis. In: Orwoll ES, Bliziotes M, eds. Osteoporosis: Pathophysiology and Clinical Management, Contemporary Endocrinology.1st ed. Humana Press, Totowa, NJ. 2003.
  • Papapoulos S. Ibandronate: a potent new bisphosphonate in the management of postmenopausal osteoporosis. Int J Clin Pract. 2003; 57(5):417-422. doi:10.1111/j.1742-1241.2003.tb10518.x
  • van der Klift M, Pols HAP, Hak AE, Witteman JCM, Hofman A, Laet CEDH. Bone mineral density and the risk of peripheral arterial disease: the Rotterdam study. Calcif Tissue Int. 2002;70(6):443-449. doi:10.1007/s00223-001-2076-9
  • Vogt MT, Cauley JA, Kuller LH, Nevitt MC. Bone mineral density and blood flow to the lower extremities: the study of osteoporotic fractures. J Bone Miner Res. 1997;12(2):283-289. doi:10.1359/jbmr.1997.12.2.283
  • Koshiyama H, Nakamura Y, Tanaka S, Minamikawa J. Decrease in carotid intima-media thickness after 1-year therapy with etidronate for osteopenia associated with type 2 diabetes. J Clin Endocrinol Metab.2000;85(8):2793-2796. doi:10.1210/jcem.85.8.6748
  • Celiloglu M, Aydin Y, Balci P, Kolamaz T. The effect of alendronate sodium on carotid artery intima-media thickness and lipid profile in women with postmenopausal osteoporosis. Menopause. 2009;16(4):689-693. doi:10.1097/gme.0b013e318194cafd
  • Delibasi T, Emral R, Erdogan MF, Kamel N. Effects of alendronate sodium therapy on carotid intima media thickness in postmenopausal women with osteoporosis. Adv Ther. 2007;24(2):319-325. doi:10.1007/BF02849900
  • Frolik CA, Bryant HU, Black EC, Magee DE, Chandrasekhar S. Time-dependent changes in biochemical bone markers and serum cholesterol in ovariectomized rats: effects of raloxifene HCl, tamoxifen, estrogen, and alendronate. Bone. 1996;18(6):621-627. doi:10.1016/8756-3282(96) 00085-3
  • Sato M, Grasser W, Endo N, et al. Bisphosphonate action. Alendronate localization in rat bone and effects on osteoclast ultrastructure. J Clin Invest. 1991;88(6):2095-2105. doi:10.1172/JCI115539
  • Fleisch H. Bisphosphonates in bone disease: from the laboratory to the patient. 4th Edition. Academic Press; 2000.
  • Adami S, Braga V, Guidi G, Gatti D, Gerardi D, Fracassi E. Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol. J Bone Miner Res. 2000;15(3):599-604. doi:10.1359/jbmr. 2000.15.3.599
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Details

Primary Language English
Subjects ​Internal Diseases
Journal Section Research Articles
Authors

Canan Akkuş 0000-0003-4990-4927

Rifat Emral This is me 0000-0002-5732-2284

Publication Date July 28, 2025
Submission Date May 6, 2025
Acceptance Date July 7, 2025
Published in Issue Year 2025 Volume: 7 Issue: 4

Cite

AMA Akkuş C, Emral R. The effects of bisphosphonates on inflammatory markers and atherosclerosis. Anatolian Curr Med J / ACMJ / acmj. July 2025;7(4):447-450. doi:10.38053/acmj.1692472

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