Morphometric analyses of the kinetics of vascular and neural ingrowth into the interfragmental gap following osteotomy

Konrad Wolf, J. Hamar, E. Höcherl, T. Farkas, C. Pfister

Research output: Article


The transmitters and/or modulators Calcitonin gene-related peptide (CGRP), Substance P (SP), Neuropeptide Y (NPY) and Vasointestinal polypeptide (VIP) we posit are involved in bone growth, fracture healing and internal remodelling. We have immunohistochemical proof that neuropeptide positive fibers exist in normal bone and this finding convinced us that these substances affect the early phase of fracture healing. The exact timing of the appearance of neuropeptide positive fibers, localisation in bone, chemospecifity and mode of genesis is, thus far, unknown. Extensive research was carried out on a model of distance osteosynthesis in the rabbit tibia. The osteotomy was located at the synostosis between the fibula and tibia. The periost and the surrounding soft tissue were removed simultaneously. Primary and secondary antibodies were then used as an indirect immunohistochemical technique. Our findings are based on concrete stereological calculations of the length of nerve fibers rather than on conventional statistical evaluations. A 3 mm interfragmental gap was filled with vital granulation tissue, after distance osteosynthesis, with a plate. After histological preparation of tissue specimens from the interfragmental gap and the bone marrow beside the gap, the neuropeptides CGRP, Substance P and NPY, with the exception of VIP, were immunohistochemically expressed. Evidence of CGRP, SP and NPY positive nerve fibers first appeared in the interfragmental gap on the 15th day postoperatively. At that point in time the length of CGRP positive nerve fibers measured 54 mm/mm3 in the gap with an increased growth in the bone marrow of 124 mm/mm3. Substance P also showed interfragmental evidence indicating the length of nerve fibers to be 48 mm/mm3 without having reached the length of nerve fibers in the bone marrow of 82 mm/mm3. Our findings indicate that the sprouting of CGRP- and SP-positive nerve fibers originates in bone marrow. A vascularisation in the early stage of osteoneogenesis, after fracture, appears to be unattainable without nerval peptidergic influence and transmission.

Original languageEnglish
Pages (from-to)36-43
Number of pages8
JournalApplied Cardiopulmonary Pathophysiology
Issue number1
Publication statusPublished - dec. 1 2007


ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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