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.
We have investigated the effect of currents induced by electromagnetic fields on the healing of the tibia of sheep after osteotomy, using objective and quantifiable criteria wherever possible. A battery-powered, induction apparatus was developed and was enclosed within the cast applied to the limb, so that the treated fractures received pulsed magnetic fields for 24 hours a day while the animals were freely mobile. In all, 13 sheep were treated and 13 were used as controls. The response was assessed by radiography of the limb and of the excised bone, by histology, including measurement of the areas of callus, fibrocallus and cortical bone, and by measurement of the uptake and extraction of bone-seeking mineral. All the bones healed and no statistically significant differences between the treated animals and the controls were discovered except (at only P less than 0.05) in the uptake of bone-seeking mineral; this increased more rapidly in treated animals over the two to three weeks after osteotomy, although at six weeks the uptake in both groups was the same.