Johannes Keller

Osteoporosis represents the most common bone disease worldwide and results in a significantly increased fracture risk. Extrinsic and intrinsic factors implicated in the development of osteoporosis are also associated with delayed fracture healing and impaired bone regeneration. Based on a steadily increasing life expectancy in modern societies, the global implications of osteoporosis and impaired bone healing are substantial. Research in the last decades has revealed several molecular pathways that stimulate bone formation and could be targeted to treat both osteoporosis and impaired fracture healing. The identification and development of therapeutic approaches modulating bone formation, rather than bone resorption, fulfils an essential clinical need, as treatment options for reversing bone loss and promoting bone regeneration are limited. This review focuses on currently available and future approaches that may have the potential to achieve these aims.

The aim of this study was to evaluate the outcome of patients with a rupture of the Achilles tendon (ATR) treated percutaneously with the Dresden instrument in the hands of surgeons others than its inventors. 118 patients (FU rate: 77.1%) with an acute ATR treated with the Dresden instrument were retrospectively evaluated. The following data were evaluated: pain intensity, functional limitation, Hannover score, Achilles tendon total rupture score (ATRS), AOFAS ankle-hindfoot score, Tegner activity score, complications, maximum calf circumference (MCC) on both sides, and the Matles test for tendon lengthening. The effect of the time point of the surgery after trauma was examined. Hannover scores and ATRSs were good; AOFAS scores were excellent. Almost all patients returned to sporting activities postoperatively, and 66.1% were able to return to their previous level. The Tegner activity score revealed a slight posttraumatic decrease (p = 0.009) in the level of physical activity overall (pre-injury: 5.37 ± 0.15; postoperatively: 4.77 ± 0.15). The re-rupture rate was 2%. No sural nerve lesions and no infections were reported. Even after 3 years, there was still a difference in MCC that was correlated with inferior clinical score and AT lengthening. Patients treated within the first 2 days after ATR showed inferior clinical outcomes in terms of AOFAS score, ATRS, and functional limitations. Percutaneous ATR suture with the Dresden instrument is a safe and reliable method. Low complication and re-rupture rates, good clinical results, and a high rate of return to play support this fact. The time point of the operation may influence the outcome.

Key metabolic hormones, such as insulin, leptin, and adiponectin, have been studied extensively in obesity, however the pathophysiologic relevance of the calcitonin family of peptides remains unclear. This family includes calcitonin (CT), its precursor procalcitonin (PCT), and alpha calcitonin-gene related peptide (αCGRP), which are all encoded by the gene Calca. Here, we studied the role of Calca-derived peptides in diet-induced obesity (DIO) by challenging Calcr^−/− (encoding the calcitonin receptor, CTR), Calca^−/−, and αCGRP^−/− mice and their respective littermates with high-fat diet (HFD) feeding for 16 weeks. HFD-induced pathologies were assessed by glucose tolerance, plasma cytokine and lipid markers, expression studies and histology. We found that DIO in mice lacking the CTR resulted in impaired glucose tolerance, features of enhanced nonalcoholic steatohepatitis (NASH) and adipose tissue inflammation compared to wildtype littermates. Furthermore, CTR-deficient mice were characterized by dyslipidemia and elevated HDL levels. In contrast, mice lacking Calca were protected from DIO, NASH and adipose tissue inflammation, and displayed improved glucose tolerance. Mice exclusively lacking αCGRP displayed a significantly less improved DIO phenotype compared to Calca-deficient mice. In summary, we demonstrate that the CT/CTR axis is involved in regulating plasma cholesterol levels while Calca, presumably through PCT, seems to have a detrimental effect in the context of metabolic disease. Our study provides the first comparative analyses of the roles of Calca-derived peptides and the CTR in metabolic disease.