The aetiology and pathophysiology of non-union is still unclear, but in this condition there is an abnormal bone metabolism. The paracrine matrix RAS has been implicated in the regulation of bone remodeling and injury responses, possibly via its effects on kinins. The influence of the local RAS or the genetic influence of the ACE/ BK2R genes to bone remodelling may thus be central to the disorder, or augmented in these conditions. We thus compared the distribution of the ACE I/D and BK2R “+9/-9” functional polymorphisms in patients with non-union and compared them to appropriate control. Gene analysis was performed on buccal cells collected from all subjects and the data was analysed for 59 patients (46 males, 13 females; mean age 40.1±15.7 years) with non-union and 81 control subjects (49 males, 32 females; mean age 51.4±22.81 years. The overall genotype distribution was consistent with Hardy-Wein-berg equilibrium for the overall and individual groups for ACE ( As the -9 allele is associated with greater gene transcription and higher mRNA expression of the receptor we combined the -9/-9 homozygous and -9/+9 heterozygous groups and compared them with the homozygous +9/+9 groups. This showed a significant difference between the non-union and control groups, with the +9/+9 homozygous being less prominent in the former ( The B2BKR -9 allele is associated with the incidence of non-union in fracture healing, in this first study to address this question. We found no association with either the In conclusion, with previous findings that the absence of the -9 allele of the B2BKR +9/-9 polymorphism is associated with greater gene transcription and higher mRNA expression of the receptor our findings are suggestive that increased BK activity via the B2BKR may predispose to the development of non-union.
Introduction:
Introduction: In the pathogenesis of steroid-associated femoral head necrosis only intra- and extravascular factors have been discussed. This study investigated the effect of long term glucocorticoid treatment on contraction of intraosseous femoral head arteries in a porcine model. Materials and Methods: From 24 immature female Danish Landrace pigs from 12 litters, 12 animals received 100 mg methylprednisolone daily for 3 months. Their 12 sister pigs served as controls and received no steroids. Resistance arteries (diameter approximately 250 μm) were isolated from the femoral head epiphyseal cancellous bone and mounted as ring preparations on a small vessel myograph for measurement of isometric force development. Results: Increasing doses of endothelin-1 evoked significantly stronger vasoconstriction after 3 months of methylprednisolone treatment. The vasocontractory response to increasing doses of noradrenaline was not altered by the previous methylprednisolone treatment. After submaximal precontraction by noradrenaline, vasorelaxation by