Protecting the joints of mice and men

Abstract

Meija-Carval et al. present a novel murine model for the study of haemophilic synovitis. The model appears suitable for assessing and quantifying joint disease in mice and the appropriate control animals are included. Thus, the results are likely reliable and of a high evidence grade. The study, however, can be questioned from an ethical point of view. The aims of the project were ‘…to test the hypothesis that a minimum number of haemarthroses negatively impacts on joint function and this would be reflected by decreased physical performance of experimental animals’. The results support the following conclusions: ‘(i) haemophilic mice can be trained to ambulate on a rotating rod; (ii) acute haemarthrosis temporarily impairs their ability to ambulate and (iii) following recovery from acute injury, mice developing synovitis demonstrated inferior physical ability compared with mice not developing synovitis’. The experimental animals were anaesthetized at time of the experimental injury but ‘on the third day were forced to exercise on the Rotarod’. The results show, as expected, higher morbidity among the experimental animals, i.e. they lose weight and perform less well in their physical function. Obviously, the animals are adversely affected. The discussion opens with the statement: ‘The data presented here demonstrate for the first time, the ability to monitor the impact on joint bleeding and the development of synovitis on physical performance’. I do not agree with the authors. The disease haemophilia was first described in the Babylonian Talmud, fourth century, Yevamoth 64 BC where it is stated: ‘For it was taught: if she circumcised her first child and he died (as a result of bleeding from the operation), and a second one also died, she must not circumcise her third child’ [1]. Thus, haemophilia is a very serious bleeding disorder with known consequences: acute joint bleeds with severe pain and physical impairment, other serious bleeding into the brain and viscera, and development of chronic joint disease resulting in serious handicap. In the beginning of the 1900s, the median life span among persons with haemophilia in Sweden was 11 years. As late as the period 1943–57, the median age at death was as low as 19 years [2]. Efficacious treatment during the last 50 years has been accompanied by increase in life expectancy [3]. With the introduction of prophylaxis in Europe during the late 1950s and early 1960s, joint outcome has markedly improved [4-7], benefiting quality of life and showing cost effectiveness [7, 8]. In Europe, the decades-long observation by clinicians of the obvious benefit of haemophilia treatment, notably the effectiveness of prophylaxis, has been supported by well-designed cohort studies. Thus, randomized clinical trials comparing prophylaxis with on demand therapy have never been performed, as they have been considered both unnecessary and unethical, and long-term outcome in haemophilia requires decades of follow-up in observational studies [9]. In some parts of North America, the European experience has not been accepted and therefore not only mice but also young children have suffered in the name of science [10]. The murine model described by Meja-Carvajal et al. may have a potential for further study of the pathophysiology of joint disease and the development of better treatment. However, the aims of their study and their results have been observed and confirmed in humans for decades, not to say thousands of years, in other parts of the world. Ethical awareness and readiness to learn from colleagues in other parts of the world must be the leading star for doctors treating patients. The author has stated that he has no interests which might be perceived as posing a conflict or bias.