Review Question - QID 211431

Bone morphogenic protein-2 (BMP-2) plays a key role in the inflammatory phase of bone healing by recruiting mesenchymal stem cells to the site of bony injury.

Bone healing, as classically described, occurs in three primary stages. Immediately after a traumatic injury, the inflammatory phase occurs which corresponds with hematoma formation. There is an increased concentration of proteins and inflammatory cells to the fracture site which are capable of secreting cytokines and promoting mesenchymal stem cell differentiation. Pro-inflammatory cytokines include PDGF, TNF-alpha, TGF-beta, IL-1, IL-6, IL-10, and IL-12. Osteoblasts begin to proliferate during this phase, which leads to the reparative phase of healing (i.e., the second phase), where soft callus begins to form within a few weeks. As the callus continues to mature, it is eventually remodeled into woven bone and then further into lamellar bone, becoming stronger with each transformation. This process denotes the remodeling phase. Many variables impact this cascade, however, BMPs are important in recruiting the growth factors that allow healing to occur.

Hreha et al. described the use of BMP-2 in hindfoot arthrodesis. The thought behind the use was to harness BMP's osteoinductive abilities to promote fusion. They note in this review study that complications were low and BMP-2 augmentation did seem to lead to improved rates of fusion, therefore, its use is reasonable.

Lissenberg-Thunnissen et al. reviewed the use of BMPs in fracture healing, specifically to investigate its role in delayed unions. They noted that BMP-2 and BMP-7 had both shown positive previous results with regards to their roles in bone healing. While they acknowledged the clinic application of BMP is still somewhat controversial, they opined that as BMP products become cheaper and more optimized, they will be useful in promoting fracture healing in the clinical setting.

Illustration A is a chart detailing the three main phases of bone healing and their primary components.

Incorrect Answers:
Answer 1: Callus formation takes place during the repair phase of bone healing.
Answer 2: NSAID use affects the inflammatory phase of bone healing by down-regulating the COX enzyme and repressing inflammatory cells which stimulate osteoblastic differentiation.
Answer 3: TNF-alpha is an inflammatory cytokine that helps promote bone healing during the inflammatory phase and its absence would be a detriment.
Answer 5: Woven bone is remodeled into lamellar bone by a combination of osteoclasts and osteoblasts.