Systemic regulation of distraction osteogenesis: a cascade of biochemical factors.
This study investigates the systemic biochemical regulation of fracture healing in distraction osteogenesis compared with rigid osteotomy in a prospective in vivo study in humans. To further clarify the influence of mechanical strain on the regulation of bone formation, bone growth factors (insulin-like growth factor [IGF] I, IGF binding protein [IGFBP] 3, transforming growth factor [TGF] beta1, and basic FGF [bFGF]), bone matrix degrading enzymes (matrix-metalloproteinases [MMPs] 1, 2, and 3), human growth hormone (hGH), and bone formation markers (ALP, bone-specific ALP [BAP], and osteocalcin [OC]) have been analyzed in serum samples from 10 patients in each group pre- and postoperatively. In the distraction group, a significant postoperative increase in MMP-1, bFGF, ALP, and BAP could be observed during the lengthening and the consolidation period when compared with the baseline levels. Osteotomy fracture healing without the traction stimulus failed to induce a corresponding increase in these factors. In addition, comparison of both groups revealed a significantly higher increase in TGF-beta1, IGF-I, IGFBP-3, and hGH in the lengthening group during the distraction period, indicating key regulatory functions in mechanotransduction. The time courses of changes in MMP-1, bone growth factors (TGF-beta1 and bFGF), and hGH, respectively, correlated significantly during the lengthening phase, indicating common regulatory pathways for these factors in distraction osteogenesis. Significant correlation between the osteoblastic marker BAP, TGF-beta1, and bFGF suggests strain-activated osteoblastic cells as a major source of systemically increased bone growth factors during callus distraction. The systemic increase in bFGF and MMP-1 might reflect an increased local stimulation of angiogenesis during distraction osteogenesis.
Weiss
S
S
Stiftung Orthopädische Universitätsklinik, Ruprecht-Karls-Universität Heidelberg, Heidelberg-Schlierbach, Germany.
Baumgart
R
R
Jochum
M
M
Strasburger
C J
CJ
Bidlingmaier
M
M
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000097:blood*; D019382:Human Growth Hormone / Q000097:blood*; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood*; D020778:Matrix Metalloproteinase 2 / Q000097:blood*; D019278:Matrix Metalloproteinase 3 / Q000097:blood*; D008875:Middle Aged; D019857:Osteogenesis, Distraction; D010027:Osteotomy; D011446:Prospective Studies; D013997:Time Factors
D015415:Biomarkers; D016222:Fibroblast Growth Factor 2; D019382:Human Growth Hormone; D019278:Matrix Metalloproteinase 3; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1