Creep substitution (3-12 weeks): angiogenesis, osteoblasts and osteoclasts introduced and work at the same time
Remodelling phase (>12 weeks)
Incorporation can be complete; no osteopenia during incorporation
Q4How is a cortical bone graft incorporated?▸
Initial incorporation at the host-graft junction by endochondral bone formation
Sequential action of osteoclast then osteoblast: graft bone removed by cutting cones then new bone laid down
50% loss of strength in 3-6 months, then fully returns over 1-2 years
Incorporation is not complete; initial osteopenia on X-ray during bone absorption
Called reverse creep substitution
Q5Compare autograft with allograft.▸
Autograft pros: osteogenesis, no immunogenicity, less chance of infection
Autograft cons: limited supply, donor site morbidity
Allograft requires donor consent, screening, processing and storage
Aim of bone bank processing: decrease immune sensitisation and disease transmission
Other sources include synthetic bone substitute and xenograft
Q6What are the methods of allograft preservation?▸
Fresh frozen at -70deg: preserves BMP, better mechanical strength; immunogenic, disease transmission risk; shelf life 2 years at -20deg, 5 years at -70deg
Freeze dry (lyophilise): less immunogenic, less disease transmission, longer shelf life; weak structure, no BMP - purely osteoconductive
Fresh
Q7How are bone grafts classified?▸
By source: autograft / allograft / synthetic / xenograft
By structure: cortical or cancellous
Q8By what mechanisms are bone grafts incorporated into host bone?▸
Inflammation
Osteoblast differentiation
Osteoinduction and osteoconduction
Remodelling
Q9What factors affect bone graft uptake?▸
Biological: local vs systemic
Mechanical
Think of the factors affecting fracture healing
Q10What are the non-vascularised sources of autograft?▸
Femoral head
ASIS
PSIS
Q11Describe the ASIS autograft harvest and the structure at risk.▸
2cm posterior to ASIS, 3cm wound along the crest
Subperiosteal elevation of iliacus
Lateral cutaneous nerve of thigh is at risk
Q12Describe the PSIS autograft harvest and the structures at risk.▸
1cm lateral to PSIS, longitudinal incision
Subperiosteal elevation of gluteal muscle
Superior cluneal nerve L1-3 (6cm lateral to PSIS) at risk
Superior gluteal NV (6cm inferior to PSIS) at risk
Q13What are the vascularised sources of autograft?▸
Wrist: 1,2 intercompartmental supraretinacular (ICSR) bone graft for scaphoid; 4,5 ICSR bone graft for lunate AVN
Fibular
Iliac crest (deep iliac circumflex artery)
Q14How is a bone bank set up and allograft processed?▸
Donor consent and screening (IVDU, blood for HIV, Hep B/C, syphilis, Rhesus status)
Exclusion criteria: HIV, Hep B/C, malignancy, RA/autoimmune disease, steroid
Made by acidic extraction of bone matrix from allograft, then sterilised (may decrease BMP availability)
Osteoconductive without structural support; minimally osteoinductive
Interproduct and interlot variability common
Q19How do bone morphogenic proteins work?▸
Osteoinductive; belong to the TGF-beta superfamily
Stimulate undifferentiated perivascular mesenchymal cells to differentiate into osteoblasts via serine-threonine kinase receptors
Activate intracellular signalling molecules called SMAD
rhBMP-2 and rhBMP-7 are FDA-approved for application in long bones and spine
BMP-2 marketed by Medtronic; BMP-7 by Stryker
Q20What are the contraindications to BMP?▸
Pregnancy
Allergy to bovine type I collagen
Infection
Tumor
Skeletal immaturity
Q21What are the complications of BMP?▸
Under- or overproduction of bone (heterotopic ossification)
Inflammatory responses / seroma formation
Not for cervical spine - increased cervical swelling
Early bone resorption
Q22How is DBM manufactured and what does the acidic extraction leave behind?▸
Acidic extraction of bone matrix from allograft removes the minerals
Leaves collagen, non-collagenous proteins and bone growth factors
BMP quantity is extremely low and variable
Sterilisation may decrease the availability of BMP
Fact check
rhBMP-2 and rhBMP-7 are FDA-approved for application in long bones and spine — outdated / imprecise — rhBMP-2 (INFUSE) is approved for anterior lumbar interbody fusion and acute open tibial shaft fractures; rhBMP-7 (OP-1) was approved via HDE only for recalcitrant long-bone nonunion and is no longer marketed in the US — source
Macropore 100-500mcg and micropore 10mcg increase remodelling surface area — unit error — pore sizes are measured in micrometres (um), not micrograms: macropores ~100-500um and micropores ~10um or less — source