The biology of bone lengthening

Abstract

Distraction osteogenesis biologically resembles fracture healing with distinctive characteristics notably in the distraction phase of osteogenesis. In the latency phase of bone lengthening, like in the inflammatory phase of fracture repair, interleukines are released and act with growth factors released from platelets in the local haematoma, leading to attraction, proliferation and differentiation of mesenchymal stem cells into osteoblasts and other differentiated mesenchymal cells. These in turn produce matrix, collagen fibers and growth factors. A callus containing cells, collagen fibers, osteoid and cartilage matrix is formed. Provided stable fixation, distraction will trigger intramembranous bone formation. As distraction proceeds, the distraction gap develops five distinctive zones with unmineralized bone in the middle, remodelling bone peripherally, and mineralizing bone in between. During consolidation, the high concentration of anabolic growth factors in the regenerate diminishes with time as remodelling takes over to form mature cortical and cancellous bone. Systemic disease, congenital bone deficiencies, medications and substance abuse can influence the quality and quantity of regenerate bone, usually in a negative way. The regenerate bone can be manipulated when needed by using injection of mesenchymal stem cells and platelets, growth factors (BMP-2 and -7), and systemic medications (bisphosphonates and parathyroid hormone). Growth factors and systemic anabolic and antiresorptive drugs are prescribed on special indications, while distraction osteogenesis is not an authorized indication. To some extent, however, these compounds can be used off-label. Use in children presents special problems since growth factors and specific anabolic medications may involve a risk of inducing cancer.

Limb lengthening history, evolution, complications and current concepts

“…The process starts with a corticotomy, which is similar to a closed low-energy fissure fracture, and secure fixation of the two ends. Distraction can be of the callus or physis according to the site of application of the tension-stress effect [11].…”

Transcriptional activation of ENPP1 by osterix in osteoblasts and osteocytes

“…In vivo results showed co-distribution of ENPP1 and Osx in cortical bone and periosteum of 6 d postnatal mice. During development and regeneration, periosteum-derived stem cells and progenitor cells transfer or migrate to cortical bone to differentiate into osteoblasts and finally osteocytes (Ferretti and Mattioli-Belmonte et www.ecmjournal.org MM Gao et al Osterix regulates ENPP1 al., 2014;Hvid et al, 2016). Both in vitro and in vivo data showed similar expression pattern of ENPP1 and Osx in osteoblasts and osteocytes, suggesting the potential relationship between these two genes.…”

The periosteal requirement and temporal dynamics of BMP2‐induced middle phalanx regeneration in the adult mouse

“…These findings support the general conclusion that targeted growth factor treatment to modify/extend intrinsic repair mechanisms can be effective for enhancing regeneration following amputation. Stimulating skeletal regeneration by distraction osteogenesis also involves enhancing intrinsic repair mechanisms (Ilizarov, ); however, distraction osteogenesis induces the regeneration of new bone by direct ossification (Dhaliwal, Kunchur, & Farhadieh, ; Hvid, Horn, Huhnstock, & Steen, ) and so it is distinct from BMP2‐induced regeneration which stimulates formation of new bone de novo by endochondral ossification.…”