Increase in calcidiol level is associated with improved sternal bone healing after cardiac surgery with sternotomy-REINFORCE-D trial results
Language English Country England, Great Britain Media electronic
Document type Journal Article, Randomized Controlled Trial
PubMed
40551234
PubMed Central
PMC12186391
DOI
10.1186/s13063-025-08786-x
PII: 10.1186/s13063-025-08786-x
Knihovny.cz E-resources
- Keywords
- Bone healing, Calcidiol serum concentration, Cardiac surgery, Cholecalciferol, Sternotomy, Vitamin D,
- MeSH
- Time Factors MeSH
- Cholecalciferol * administration & dosage MeSH
- Double-Blind Method MeSH
- Wound Healing * drug effects MeSH
- Calcifediol * blood MeSH
- Cardiac Surgical Procedures * adverse effects MeSH
- Middle Aged MeSH
- Humans MeSH
- Postoperative Complications etiology MeSH
- Prospective Studies MeSH
- Aged MeSH
- Sternotomy * adverse effects MeSH
- Sternum * diagnostic imaging surgery MeSH
- Treatment Outcome MeSH
- Check Tag
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Randomized Controlled Trial MeSH
- Names of Substances
- Cholecalciferol * MeSH
- Calcifediol * MeSH
INTRODUCTION: Heart surgery is associated with a sternotomy in most patients. Low serum calcidiol level below 80 nmol/l carries the risk of bone loss as a risk factor in sternotomy healing. OBJECTIVES: The primary objective was to compare postoperative complications of sternotomy healing in two groups of patients treated with cholecalciferol or placebo. Secondary objectives were focused on the degree of sternal healing, length of hospitalization, number of days spent in ICU and mechanical ventilation, and number of repeated hospitalizations for sternotomy complications. METHODOLOGY: Monocentric, randomized, double-blind, placebo-controlled, prospective study was conducted from September 2016 to December 2020 at Na Homolce Hospital. Of the 216 originally recruited and randomized subjects, 141 completed the study. Seventy-two subjects were enrolled in the cholecalciferol arm, and sixty-nine subjects in the placebo arm. The detailed methodology has been published previously. The results are presented as a comparison between two groups: calcidiol above 80 nmol/l (saturated subjects) and the calcidiol lower or equal to 80 nmol/l (unsaturated subjects). RESULTS: Statistics include 141 subjects. After a 6-month follow-up, CT imaging and calcidiol levels were performed. PRIMARY OBJECTIVE: postoperative complications in sternotomy were not among the population under or above 80 nmol/l statistical difference (p = 0.907). SECONDARY OBJECTIVES: monitored parameters did not differ between individual arms. But the key was the state of saturation with calcidiol (> 80 nmol/l), which was associated with a significantly lower risk of complete non-healed sternotomy (p = 0.008). CONCLUSION: Optimal calcidiol level (> 80 nmol/l) indicates a positive trend towards greater sternal healing. Cholecalciferol oral administration can be considered as a safe method how to achieve the required calcidiol concentration. TRIAL REGISTRATION: EU Clinical Trials Register, EUDRA CT No: 2016-002606-39.
Department of Cardiac Surgery Na Homolce Hospital Prague Czech Republic
Department of Clinical Pharmacy Na Homolce Hospital Prague Czech Republic
Department of Clinical Pharmacy Regional Hospital Liberec Liberec Czech Republic
Department of Infectious Diseases Masaryk Hospital Usti and Labem Labem Czech Republic
Department of Occupational Medicine General University Hospital Prague Prague Czech Republic
Department of Pharmacology 2nd Faculty of Medicine Charles University Prague Prague Czech Republic
Department of Radiology Na Homolce Hospital Prague Czech Republic
See more in PubMed
Li AE. Evaluation of complications after sternotomy using single- and multidetector CT with three-dimensional volume rendering. Am J Roentgenol. 2003;181:1065–70. 10.2214/ajr.181.4.1811065. PubMed
Ridderstolpe L, Gill H, Granfeldt H, Ahlfeldt H, Rutberg H. Superficial and deep sternal wound complications: incidence, risk factors and mortality. Eur J Cardiothorac Surg. 2001;20:1168–75. 10.1016/S1010-7940(01)00991-5. PubMed
Schimmer C, Reents W, Berneder S, Eigel P, Sezer O, Scheld H, et al. Prevention of sternal dehiscence and infection in high-risk patients: a prospective randomized multicenter trial. Ann Thorac Surg. 2008;86:1897–904. 10.1016/j.athoracsur.2008.08.071. PubMed
Baillot R, Cloutier D, Montalin L, Cote L, Lellouche F, Houde C, et al. Impact of deep sternal wound infection management with vacuum-assisted closure therapyfollowed by sternal osteosynthesis: a 15-year review of 23,499 sternotomies. Eur J Cardiothorac Surg. 2010;37:880–7. 10.1016/j.ejcts.2009.09.023. PubMed
Heilmann C, Stahl R, Schneider C, et al. Wound complications after median sternotomy: a single-centre study. Interact Cardiovasc Thorac Surg. 2013;16(5):643–8. 10.1093/icvts/ivs554. PubMed PMC
Holick MF. Optimal vitamin D status for the prevention and treatment of osteoporosis. Drugs Aging. 2007;24(12):1017–29. 10.2165/00002512-200724120-00005. PubMed
Heaney RP, Dowell MS, Hale CA, Bendich A. Calcium absorption varies within the reference range for serum 25-hydroxyvitamin D. J Am Coll Nutr. 2003;22(2):142–6. 10.1080/07315724.2003.10719287. PubMed
Koester MC, Spindler KP. Pharmacologic agents in fracture healing. Clin Sports Med. 2006;25(1):63–73. 10.1016/j.csm.2005.08.004. PubMed
Eschle D, Aeschlimann AG. Is supplementation of vitamin d beneficial for fracture healing? A short review of the literature. Geriatr Orthop Surg Rehabil. 2011;2(3):90–3. 10.1177/2151458511408568. PubMed PMC
Burkiewicz CJ, et al. Vitamin D and skin repair: a prospective, double-blind and placebo controlled study in the healing of leg ulcers. Rev Col Bras Cir. 2012;39(5):401–7. 10.1590/S0100-69912012000500011. PubMed
Zittermann A, et al. Vitamin D status and the risk of major adverse cardiac and cerebrovascular events in cardiac surgery. Eur Heart J. 2013;34:1358–64. 10.1093/eurheartj/ehs468. PubMed
Stacy GS, et al. Evaluation of sternal bone healing with computed tomography and a quantitative scoring algorithm. Open Med Imaging J. 2014;8(1):29–35. 10.2174/1874347101408010029.
Čečrle M, Černý D, Sedláčková E, et al. Vitamin D for prevention of sternotomy healing complications: REINFORCE-D trial. Trials. 2020;21(1):1018. 10.1186/s13063-020-04920-z. Published 2020 Dec 11. PubMed PMC
Ettehad H. Changes in the serum level of vitamin D during healing of tibial and femoral shaft fractures. Trauma Mon. 2014;19(1):e10946. 10.5812/traumamon.10946. PubMed PMC
Gorter EA, Hamdy NA, Appelman-Dijkstra NM, Schipper IB. The role of vitamin D in human fracture healing: a systematic review of the literature. Bone. 2014;64:288–97. 10.1016/j.bone.2014.04.026. Epub 2014 May 2 PMID: 24792958. PubMed
Ucak HA, Uncu H, Disli S, Urgun OD, Abacioglu OO, Ciloglu O, Ucak D. Vitamin D status and post sternotomy bone healing; a prospective radiologic observational study. Med Sci. 2021;10(2):374–9. 10.5455/medscience.2021.01.010.
Shin YC, Kim SH, Kim DJ, Kim DJ, Kim JS, Lim C, Park KH. Sternal healing after coronary artery bypass grafting using bilateral internal thoracic arteries: assessment by computed tomography scan. Korean. Korean J Thorac Cardiovasc Surg. 2015;48(1):33–9. 10.5090/kjtcs.2015.48.1.33. Epub 2015 Feb 5. PMID: 25705595; PMCID: PMC4333848. PubMed PMC
Wang B, He D, Wang M, et al. Analysis of sternal healing after median sternotomy in low risk patients at midterm follow-up: retrospective cohort study from two centres. J Cardiothorac Surg. 2019;14:193. 10.1186/s13019-019-1000-1. PubMed PMC
Hoffmann K, Kopciuch D, Michalak M, et al. Adherence of obese patients from Poland and Germany and its impact on the effectiveness of morbid obesity treatment. Nutrients. 2022;14(18):3880. 10.3390/nu14183880. Published 2022 Sep 19. PubMed PMC
Ish-Shalom S, Segal E, Salganik T, Raz B, Bromberg IL, Vieth R. Comparison of daily, weekly, and monthly vitamin D3 in ethanol dosing protocols for two months in elderly hip fracture patients. J Clin Endocrinol Metab. 2008;93(9):3430–5. 10.1210/jc.2008-0241. PubMed
