Bone Healing
The natural repair process following bone fracture, involving inflammation, soft callus formation, hard callus formation, and remodelling over weeks to months. PTH analogues (teriparatide, abaloparatide) promote bone formation and are relevant to understanding peptide-based approaches to skeletal repair.
Technical Context
Fracture healing stages: haematoma formation (immediate — blood clot fills fracture gap, providing provisional scaffold and growth factor source), inflammatory phase (days 1-7 — macrophages and platelets release PDGF, TGF-β, BMP, VEGF, recruiting mesenchymal stem cells), soft callus formation (weeks 1-3 — cartilaginous callus bridges the fracture gap through endochondral ossification), hard callus formation (weeks 3-12 — cartilage is mineralised and replaced by woven bone through osteoblast activity), and remodelling (months to years — woven bone is remodelled to lamellar bone along stress lines by coordinated osteoblast/osteoclast activity). PTH analogues' relevance: intermittent PTH stimulates osteoblast differentiation and activity, potentially accelerating hard callus formation and increasing callus bone density. Some clinical trials have investigated teriparatide for fracture healing acceleration, with mixed results. BMPs (bone morphogenetic proteins) are the primary peptide/protein therapeutics approved for bone repair (BMP-2, BMP-7).