- Stage 1 – inflammatory/mineralizing rind (early weeks)
- Macrophages/foreign-body giant cells at the graft surface release matrix vesicles and TNAP, creating a thin, acellular, highly mineralized “rind” on the particle (dystrophic/mineralizing-macrophage calcification).
- Stage 2 – osteoblastic overbuild (2–3+ months)
- The mineral rind (plus macrophage cytokines like BMPs/TGF-β) can recruit/proximate osteoprogenitors, so osteoblasts lay a shell of bone over that rind. Because vascularity and osteoclast activity are poor, the new bone densifies rather than remodels, yielding sclerotic compact bone. Osteoblasts that become encased form osteocytes, but the lacuno-canalicular network is often sparse/disorganized.
- Failed remodeling → sclerosis (3–6 months)
- With scant TRAP+ osteoclasts and little marrow space, the complex stalls: persistent allograft core + mineral rind + osteoblast-laid bone = a dense, low-turnover, sclerotic complex.
