Implications of high-dosage bisphosphonate treatment on bone tissue in the jaw and knee joint.

Bisphosphonates are bone antiresorptive agents traditionally used on a relatively large scale for treatment of bone metabolic diseases and on a smaller scale for bone metastasis treatment. A study on the effects of bisphosphonate treatment on healthy instead of diseased animals will give more insight into the basic mechanisms of bisphosphonates and their effects on different bone sites. We aimed to assess the effect of BP on the mouse knee and jaw joint. Three-month old female C57BL/6 mice were used (twenty-four and eighteen control and experimental group, respectively). At baseline and after treatment with zoledronic acid (ZA) for one, three or six months, we combined bone assessment via µCT and additional histology. Our results showed that, in the knee joint, ZA treatment increased TMD, bone volume, trabecular thickness but did not influence cortical thickness. In both control and ZA group, a higher trabecular TMD compared to cortical TMD was seen. Unseen in the knee joint, ZA treatment in the jaw joint resulted in bone-site specific changes in mineralization; a significant time-dependent higher TMD was evident in the subchondral bone compared to the most distal region of the condyle. MicroCT images revealed the presence of mineral in this region and histology showed that this region did not contain mature bone tissue but cartilage-like tissue. Our data indicate the possibility of site-specific negative side effects, i.e., disturbing normal mandibular development under the influence of bisphosphonate therapy.

Cardiac surgery risk-stratification models.

Risk models are widely used to predict outcomes after cardiac surgery. Not only is risk modelling applied in the assessment of the relative impact of specific risk factors on surgical outcomes, but also in patient counselling, the selection of treatment options, comparison of postoperative results, and quality-improvement programmes. At least 19 risk-stratification models exist for open-heart surgery. The focus of risk models was originally on pre-operative prediction of mortality. However, major morbidity is in general more common than mortality and the ability to predict only operative mortality is not an adequate method of determining surgical outcome. Multiple intra- and postoperative variables have been excluded in the majority of models and the possible effect of their future inclusion remains to be seen. The unique patient population of sub-Saharan Africa requires a unique risk model that reflects the patient population and levels of care.