Statin and Bone Health

Summary

This study aims to evaluate the impact of simvastatin on the bone density of postmenopausal women with type 2 diabetes over a duration of 18 months, using a randomized controlled trial design. Aiming to recruit 240 patients, half of them will be randomly assigned to receive simvastatin treatment, while the other half will receive ezetimibe, also a lipid-lowering agent with no known effect on bone. Bone density will be measured at the baseline and the end of the study for comparison of the changes between the simvastatin and the ezetimibe groups. This is an investigator-initiated study. The principal investigator and the study team will be responsible for ensuring that the study is conducted in compliance with this protocol and the study data collected are verified against the relevant source documents. All participants will undergo clinical and biochemical assessments at baseline of the trial. Participants will be seen by an endocrinologist at baseline and subsequent follow-up visits at 3, 6, 12 and 18 months respectively.

Timeline

Start

2022-04-13

Primary completion

2024-12-31

Completion

2025-06-30

Publications

• Background Chow S, Shao J, Wang H. Sample Size Calculations in Clinical Research. 2nd Ed. Chapman & Hall/CRC Biostatistics Series. 2008. 58 p.
• Background Safaei H, Janghorbani M, Aminorroaya A, Amini M. Lovastatin effects on bone mineral density in postmenopausal women with type 2 diabetes mellitus. Acta Diabetol. 2007 Jun;44(2):76-82. doi: 10.1007/s00592-007-0246-6. Epub 2007 May 27.
• Background Pisani P, Renna MD, Conversano F, Casciaro E, Di Paola M, Quarta E, Muratore M, Casciaro S. Major osteoporotic fragility fractures: Risk factor updates and societal impact. World J Orthop. 2016 Mar 18;7(3):171-81. doi: 10.5312/wjo.v7.i3.171. eCollection 2016 Mar 18.
• Background Tatangelo G, Watts J, Lim K, Connaughton C, Abimanyi-Ochom J, Borgstrom F, Nicholson GC, Shore-Lorenti C, Stuart AL, Iuliano-Burns S, Seeman E, Prince R, March L, Cross M, Winzenberg T, Laslett LL, Duque G, Ebeling PR, Sanders KM. The Cost of Osteoporosis, Osteopenia, and Associated Fractures in Australia in 2017. J Bone Miner Res. 2019 Apr;34(4):616-625. doi: 10.1002/jbmr.3640. Epub 2019 Jan 7.
• Background Lee PCH, Woo YC, Lam KSL. Fighting the Health Challenges of Diabetes in Hong Kong: A Window Into Mainland China. Am J Public Health. 2018 Dec;108(12):1623-1624. doi: 10.2105/AJPH.2018.304740. No abstract available.
• Background 55th EASD Annual Meeting of the European Association for the Study of Diabetes : Barcelona, Spain, 16 - 20 September 2019. Diabetologia. 2019 Sep;62(Suppl 1):1-600. doi: 10.1007/s00125-019-4946-6. No abstract available.
• Background Ma L, Oei L, Jiang L, Estrada K, Chen H, Wang Z, Yu Q, Zillikens MC, Gao X, Rivadeneira F. Association between bone mineral density and type 2 diabetes mellitus: a meta-analysis of observational studies. Eur J Epidemiol. 2012 May;27(5):319-32. doi: 10.1007/s10654-012-9674-x. Epub 2012 Mar 27.
• Background Janghorbani M, Van Dam RM, Willett WC, Hu FB. Systematic review of type 1 and type 2 diabetes mellitus and risk of fracture. Am J Epidemiol. 2007 Sep 1;166(5):495-505. doi: 10.1093/aje/kwm106. Epub 2007 Jun 16.
• Background Lui DTW, Lee CH, Chan YH, Chow WS, Fong CHY, Siu DCW, Tse HF, Woo YC, Lam KSL. HbA1c variability, in addition to mean HbA1c, predicts incident hip fractures in Chinese people with type 2 diabetes. Osteoporos Int. 2020 Oct;31(10):1955-1964. doi: 10.1007/s00198-020-05395-z. Epub 2020 May 8.
• Background Liao CC, Lin CS, Shih CC, Yeh CC, Chang YC, Lee YW, Chen TL. Increased risk of fracture and postfracture adverse events in patients with diabetes: two nationwide population-based retrospective cohort studies. Diabetes Care. 2014 Aug;37(8):2246-52. doi: 10.2337/dc13-2957. Epub 2014 May 7.
• Background Yun-Ning Cheung E, Pik-Shan Kong A, Siu-Him Lau E, Yee-Kwan Chow E, On-Yan Luk A, Ching-Wan Ma R, Ping Lam T, Yuk-Wai Lee W, Chun-Yiu Cheng J, Ebeling PR, Chung-Ngor Chan J. Association of hip fractures with cardiometabolic-renal risk factors in Southern Chinese patients with type 2 diabetes - the Hong Kong Diabetes Register. J Diabetes Investig. 2021 Sep;12(9):1739-1748. doi: 10.1111/jdi.13529. Epub 2021 Mar 15.
• Background Lecka-Czernik B. Diabetes, bone and glucose-lowering agents: basic biology. Diabetologia. 2017 Jul;60(7):1163-1169. doi: 10.1007/s00125-017-4269-4. Epub 2017 Apr 22.
• Background Leslie WD, Aubry-Rozier B, Lamy O, Hans D; Manitoba Bone Density Program. TBS (trabecular bone score) and diabetes-related fracture risk. J Clin Endocrinol Metab. 2013 Feb;98(2):602-9. doi: 10.1210/jc.2012-3118. Epub 2013 Jan 22.
• Background Karlson BW, Palmer MK, Nicholls SJ, Lundman P, Barter PJ. A VOYAGER Meta-Analysis of the Impact of Statin Therapy on Low-Density Lipoprotein Cholesterol and Triglyceride Levels in Patients With Hypertriglyceridemia. Am J Cardiol. 2016 May 1;117(9):1444-8. doi: 10.1016/j.amjcard.2016.02.011. Epub 2016 Feb 17.
• Background Ferrari SL, Abrahamsen B, Napoli N, Akesson K, Chandran M, Eastell R, El-Hajj Fuleihan G, Josse R, Kendler DL, Kraenzlin M, Suzuki A, Pierroz DD, Schwartz AV, Leslie WD; Bone and Diabetes Working Group of IOF. Diagnosis and management of bone fragility in diabetes: an emerging challenge. Osteoporos Int. 2018 Dec;29(12):2585-2596. doi: 10.1007/s00198-018-4650-2. Epub 2018 Jul 31.
• Background Cho NH, Shaw JE, Karuranga S, Huang Y, da Rocha Fernandes JD, Ohlrogge AW, Malanda B. IDF Diabetes Atlas: Global estimates of diabetes prevalence for 2017 and projections for 2045. Diabetes Res Clin Pract. 2018 Apr;138:271-281. doi: 10.1016/j.diabres.2018.02.023. Epub 2018 Feb 26.
• Background Man LP, Ho AW, Wong SH. Excess mortality for operated geriatric hip fracture in Hong Kong. Hong Kong Med J. 2016 Feb;22(1):6-10. doi: 10.12809/hkmj154568. Epub 2015 Oct 9.
• Background Authors/Task Force Members; ESC Committee for Practice Guidelines (CPG); ESC National Cardiac Societies. 2019 ESC/EAS guidelines for the management of dyslipidaemias: Lipid modification to reduce cardiovascular risk. Atherosclerosis. 2019 Nov;290:140-205. doi: 10.1016/j.atherosclerosis.2019.08.014. Epub 2019 Aug 31. No abstract available.
• Background Oryan A, Kamali A, Moshiri A. Potential mechanisms and applications of statins on osteogenesis: Current modalities, conflicts and future directions. J Control Release. 2015 Oct 10;215:12-24. doi: 10.1016/j.jconrel.2015.07.022. Epub 2015 Jul 28.
• Background Moon HJ, Kim SE, Yun YP, Hwang YS, Bang JB, Park JH, Kwon IK. Simvastatin inhibits osteoclast differentiation by scavenging reactive oxygen species. Exp Mol Med. 2011 Nov 30;43(11):605-12. doi: 10.3858/emm.2011.43.11.067.
• Background Chung YS, Lee MD, Lee SK, Kim HM, Fitzpatrick LA. HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients. J Clin Endocrinol Metab. 2000 Mar;85(3):1137-42. doi: 10.1210/jcem.85.3.6476.
• Background Nakashima A, Nakashima R, Ito T, Masaki T, Yorioka N. HMG-CoA reductase inhibitors prevent bone loss in patients with Type 2 diabetes mellitus. Diabet Med. 2004 Sep;21(9):1020-4. doi: 10.1111/j.1464-5491.2004.01292.x.
• Background Bouxsein ML, Eastell R, Lui LY, Wu LA, de Papp AE, Grauer A, Marin F, Cauley JA, Bauer DC, Black DM; FNIH Bone Quality Project. Change in Bone Density and Reduction in Fracture Risk: A Meta-Regression of Published Trials. J Bone Miner Res. 2019 Apr;34(4):632-642. doi: 10.1002/jbmr.3641. Epub 2019 Jan 23.
• Background Graham DJ, Staffa JA, Shatin D, Andrade SE, Schech SD, La Grenade L, Gurwitz JH, Chan KA, Goodman MJ, Platt R. Incidence of hospitalized rhabdomyolysis in patients treated with lipid-lowering drugs. JAMA. 2004 Dec 1;292(21):2585-90. doi: 10.1001/jama.292.21.2585. Epub 2004 Nov 22.
• Background Charles EC, Olson KL, Sandhoff BG, McClure DL, Merenich JA. Evaluation of cases of severe statin-related transaminitis within a large health maintenance organization. Am J Med. 2005 Jun;118(6):618-24. doi: 10.1016/j.amjmed.2005.02.008.
• Background Knopp RH, Gitter H, Truitt T, Bays H, Manion CV, Lipka LJ, LeBeaut AP, Suresh R, Yang B, Veltri EP; Ezetimibe Study Group. Effects of ezetimibe, a new cholesterol absorption inhibitor, on plasma lipids in patients with primary hypercholesterolemia. Eur Heart J. 2003 Apr;24(8):729-41. doi: 10.1016/s0195-668x(02)00807-2.
• Background Mei J, Yeung SS, Kung AW. High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. J Clin Endocrinol Metab. 2001 Nov;86(11):5217-21. doi: 10.1210/jcem.86.11.8040.
• Background Holick MF. Vitamin D deficiency. N Engl J Med. 2007 Jul 19;357(3):266-81. doi: 10.1056/NEJMra070553. No abstract available.

Drugs

Indications