Response to the letter from Starlinger et al.: "RE: Aliuskevicius M, Ostgaard SE, Hauge EM, et al. 2019".

Abstract

Journal of Orthopaedic ResearchVolume 38, Issue 6 p. 1206-1207 REPLYFree Access Response to the letter from Starlinger et al.: “RE: Aliuskevicius M, Ostgaard SE, Hauge EM, et al. 2019” First published: 10 February 2020 https://doi.org/10.1002/jor.24611AboutSectionsPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Dear Editor, We thank Starlinger et al for their interest in our recent publication in the Journal of Orthopedic Research entitled “Influence of ibuprofen on bone healing after Colles' fracture: a randomized controlled clinical trial.” We agree with the authors that patients' sex, age, presence or absence of osteoporosis, and body mass index (BMI) may influence bone metabolism and response mechanisms to injury. In our opinion, further influencing factors, such as smoking, endocrine diseases, and treatment of osteoporosis, also may influence the variation of bone biomarkers. Thus, Ibuprofen, theoretically, might have a different effect on the healing process of the bone, and future stratified studies might be advocated. Our study, however, was not designed or powered to control such cofounders as ethnicity, sex, and BMI.1 The fracture occurs predominantly in women who have osteoporosis, aged more than 50 years,2 and stratification, in this case, is somewhat tricky. By designing our study, we applied the central limit theorem, according to which all weight categories would be more or less equally represented in treatment groups if their size is approximating 30.3 We treated a local Danish homogeny population, all Caucasian individuals, and did not observe any severe obesity (Figure 1). We made further attempts to improve the internal validity by involving only one blinded person in performing the treatment and measuring the effects.4 One surgeon performed all the operations, and an independent statistician, who was unaware of the group assignments, performed all the analyses. Figure 1Open in figure viewerPowerPoint Distribution of weight categories in treatment groups. BMI, body mass index [Color figure can be viewed at wileyonlinelibrary.com] The results of our study demonstrate a high variation of CrossLaps and osteocalcin measurements during the follow-up. We have reanalyzed the biochemical outcomes assuming that both markers would reach their baseline after 1 year from the time of injury, and after completing a remodeling process.5 We looked at percentage changes from the baseline for each individual during the follow up (Figure 2). The interindividual variability from baseline, influenced by confounding factors, could be neutralized by using this model. The initial increase of bone biomarkers in intervention groups was not as high as in the Placebo group. Nevertheless, there were no significant differences, indicating that there is no harmful effect of Ibuprofen on the healing of distal radius fracture. Figure 2Open in figure viewerPowerPoint Values of bone biomarkers during 1-year follow-up. CI, confidence interval [Color figure can be viewed at wileyonlinelibrary.com] Our study reflects the everyday clinical situation and provides sufficient external validity6 allowing us to generalize and state that one weeks' treatment with Ibuprofen will not impair the bone healing in the distal radius. REFERENCES 1Aliuskevicius M, Østgaard SE, Hauge EM, Vestergaard P, Rasmussen S. Influence of ibuprofen on bone healing after collesʼ fracture: a randomized controlled clinical trial. J Orthop Res. 2020; 38: 545– 554. 2MacIntyre NJ, Dewan N. Epidemiology of distal radius fractures and factors predicting risk and prognosis. J Hand Ther. 2016; 29(2): 136- 145. https://doi.org/10.1016/j.jht.2016.03.003 3Kwak SG, Kim JH. Central limit theorem: the cornerstone of modern statistics. Korean J Anesthesiol. 2017; 70(2): 144- 156. https://doi.org/10.4097/kjae.2017.70.2.144 4Steckler A, McLeroy KR. The importance of external validity. Am J Public Health. 2008; 98(1): 9- 10. https://doi.org/10.2105/AJPH.2007.126847 5Sousa CP, Dias IR, Lopez-Peña M, et al. Bone turnover markers for early detection of fracture healing disturbances: a review of the scientific literature. An Acad Bras Cienc. 2015; 87(2): 1049- 1061. https://doi.org/10.1590/0001-3765201520150008 6Tunis SR, Stryer DB, Clancy CM. Practical clinical trials: increasing the value of clinical research for decision making in clinical and health policy. JAMA. 2003; 290(12): 1624- 1632. https://doi.org/10.1001/jama.290.12.1624 Volume38, Issue6June 2020Pages 1206-1207 FiguresReferencesRelatedInformation