Calcitonin Producing Tumour: Effects on Fracture Repair and Normal Bone in Rats

Abstract

The mechanical properties and the collagen metabolism of healing fractures and intact bones have been studied in rats with a transplanted, calcitonin (CT) secreting, medullary thyroid carcinoma (MCT). Sham operated animals served as controls. The MCT was transplanted beneath the kidney capsule. Seven months later, when the rats with MCT had increased circulating levels of CT, a standardized femoral fracture was produced in all the animals. The serum levels of CT were 3-40 times higher in tumour bearing rats than in controls in the period following the fracture. The fracture strength of rats with MCT was reduced by about 60 per cent compared to controls at 16 weeks after the fracture. The strength of intact femora (ultimate torsional moment) seemed to be progressively impaired by increasing levels of circulating CT. Also the strength of bone as a material (ultimate torsional stress) was reduced in the rats with MCT. The collagen synthesis was reduced in MCT rats, but the amounts of collagen in fractured or intact bones were not changed compared to controls. We conclude that chronic hypercalcitoninaemia due to MCT seems to have a negative influence both on fracture healing and on bone metabolism.

Calcium Metabolism and Oxidative Stress in Bone Fractures: Role of Antioxidants

“…In some of these studies, it was not possible to detect any beneficial effect of calcitonin on fracture healing between the animals [72,73]. In other studies calcitonin was found to have an adverse effect by way of decreased collagen formation and mineralization as well as decreased callus strength [73,74]. However, in the other studies [75,76] a positive effect on fracture healing was found, which is shown from the histological appearance of callus, biochemical and immunohistochemical findings and radiological appearance.…”

“…Of the above studies, they examined the effect of calcitonin upon secondary (osteocartilaginous) callus formation. In some of these studies, it was not possible to detect any beneficial effect of calcitonin on fracture healing between the animals [72,73]. In other studies calcitonin was found to have an adverse effect by way of decreased collagen formation and mineralization as well as decreased callus strength [73,74].…”

Calcitonin and granulation tissue formation in the rat

“…The studies of Ekeland et al [8,9] are methodologically satisfactory with accurate determination of histology, dynamics of connective tissue, and mineralization and tensile strength of the healing tissues. The studies of Ekeland et al [8,9] are methodologically satisfactory with accurate determination of histology, dynamics of connective tissue, and mineralization and tensile strength of the healing tissues.…”

“…Lupulescu and Habowsky [11] reported that salmon calcitonin accelerated wound repair in a morphological and autoradiographic study on rabbits. Although calcitonin therapy has been advocated in the treatment of fractures [6], several experimental studies have shown no effect of calcitonin on fracture healing [2,10] or even an adverse influence on fracture healing and on bone metabolism [7][8][9]. Although calcitonin therapy has been advocated in the treatment of fractures [6], several experimental studies have shown no effect of calcitonin on fracture healing [2,10] or even an adverse influence on fracture healing and on bone metabolism [7][8][9].…”

“…These earlier reports favor the view that calcitonin may play a role in the maturation of collagen and connective tissue cells. The rate of synthesis and turnover of collagen in bone and skin and the mineralization of bone were determined by measuring the amount of 14C-hydroxyproline and 85Sr in bone, skin, and healing wounds [8,9]. The rate of synthesis and turnover of collagen in bone and skin and the mineralization of bone were determined by measuring the amount of 14C-hydroxyproline and 85Sr in bone, skin, and healing wounds [8,9].…”