Bone Grafts and Substitutes

Complex fractures, nonunions, or tumor resections can leave bone defects. Autologous bone grafts are effective fillers, carrying both osteoinductive and osteoconductive properties. However, autografts require harvesting, which lead to increased operative time as well as donor site morbidities. The amount of autograft available may not be sufficient. Therefore, there is a demand for bone graft substitutes that can be readily applied.

Allografts

Bone allografts are widely used in hand surgery. Bones harvested from cadavers are typically freeze-dried and sometimes undergo further processing such as ethylene oxide treatment or γ-radiation for further sterilization. Allografts can also be prepared fresh or frozen, but such preparations are rarely used in hand surgery. While the osteoblasts and precursors are lost during the freeze-drying, allografts still provide favorable osteoconductive properties.

Allografts can come in several different forms such as cortical, cancellous, and corticocancellous. Cortical allografts are incorporated by creeping substitution with intramembranous ossification, while cancellous allografts are incorporated by enchondral ossification.

Demineralized bone matrix (DBM) is allograft that has been decalcified, leaving organic matrix behind. The trabecular network of collagen serves as a scaffold for bone formation. The growth factors and bone morphogenic proteins (BMPs) are maintained and can help induce cells to form bone. DBM does not provide mechanical strength. However, its soft consistency allows it to be placed into small defects or even be injected percutaneously.

Mineral Substitutes

Most bones are 60%–70% mineral by dry weight, with hydroxyapatite being the principal component of the mineral phase. Because hydroxyapatite has an unstable crystalline structure, rapid exchange between hydroxyapatite crystals and tricalcium phosphate (TCP) takes place in vivo. Both hydroxyapatites and TCP have been used as bone graft substitutes.

A prospective study from Germany demonstrated ingrowth and osseous integration of hydroxyapatite ceramic in augmentation of distal radius fracture fixation. Ceramics are produced by “sintering” where mineral salts are heated between 700°C and 1300°C. Sintering increases the mechanical strength but slows resorption.

Coralline hydroxyapatite, which is derived from marine coral, has porosity similar to cancellous bone. In a case series of 21 patients, coralline hydroxyapatite was used as a substitute for autograft to help maintain articular surface along with external fixation and K-wires. The authors reported maintenance of articular reduction in all patients and an average DASH score of 90.3.

TCP comes in different forms such as blocks, granules, and powders. It was initially used in the dental field in the 1980s, but its application has been expanded since. It can be used as bone void fillers by itself or as a composite graft mixed with other grafts or bone marrow aspirates ^, . In hand surgery, there are reported case series of TCP alone as a substitute for iliac crest bone grafting. Four out of four patients had union in wrist arthrodesis for rheumatoid patients. In a series of 17 patients undergoing corrective osteotomies of the distal radius, there was only one nonunion.

Calcium sulfate (Ca[SO4]) is also known as plaster of Paris and has been around for centuries. It provides structural support with better compressive strength than cancellous bone. It also has osteoconductive properties. The resorption of calcium sulfate is fast, with complete resorption around 13–14 weeks. The fast resorption can be an advantage for certain applications such as using antibiotics beads; a second surgery for beads removal can be avoided. However, as a bone graft substitute, calcium sulfate will only provide temporary structural strength. Jepegnanam et al. report hardware failures in two elderly patients where calcium sulfate was used as a bone graft substitute in distal radius corrective osteotomy. The authors hypothesized that the failures were due to new bone formation not occurring rapidly enough to replace the resorption of calcium sulfate.

Cements

Cements were developed to improve moldability of calcium phosphate and to allow better filling of defects. They are available as injectable liquid or putty that sets through isothermic reaction. In a study from Austria, unstable intraarticular distal radius fracture in menopausal, osteoporotic women were treated with percutaneous pinning alone or with pin and screw construct supplemented with cement. The former group was immobilized for 6 weeks, while the latter group was immobilized for 3 weeks. At 2 years, the cement group had better functional outcome, restoration of movement, and grip strength. Loss of reduction was also less frequent in the cement group. Cassidy et al. conducted a prospective randomized multicenter study with 323 distal radius fracture patients. The patients were treated with closed reduction and immobilization, with or without calcium phosphate cement injection. The method of immobilization was either a cast or external fixation with or without supplemental K-wires, depending on the surgeon’s preference. The group with cement augmentation had better grip strength, motion, use of hand, and social and emotional function at 6–8 weeks, but no difference was seen at 1 year.

Bone cements have been also used to fill voids after tumor removal. Enchondromas are common benign bone tumors frequently arising in hand. Several studies have reported the successful use of calcium phosphate cement or hydroxyapatite cement to fill defects after curettage of enchondromas. A biomechanical study on cadaveric enchondroma model has shown that calcium phosphate cement significantly increases strength of metacarpals. Rajeh et al. also reported a series of eight patients who had calcium phosphate cement injection after curettage of enchondromas in the hand. At a mean final follow-up at 16 months, 69.3% of the cement remained in the bone, with the mean pain score improving from 4.1 to 1.6. It should be noted that 2 patients with extraosseous cement leakage, with 1 patient requiring a revision surgery ( Figs. 13.1 and 13.2 ).

Injection of calcium phosphate cement after curettage of metacarpal enchondroma

Courtesy Craig Rodner MD

Fluoroscopic image of the metacarpal after cement injection

Courtesy Craig Rodner MD

Growth Factors

Growth factors are signaling molecules that play important roles in communication between cells. While growth factors naturally exist in the body, application of exogenous growth factors to promote bone healing has received much attention.

Recombinant forms of various growth factors are currently available, including BMP-2, BMP-7, TGF-β, and platelet-derived growth factor. BMP-2 and BMP-7 belong to the bone morphogenic protein family and have been shown to stimulate bone healing. In a prospective randomized control trial, 450 patients with open tibia fractures were treated with intramedullary rod. The groups that received BMP-2 in an absorbable collagen sponge had significantly decreased risk of failure and faster fracture healing than the control group, which did not receive any BMP-2. Recombinant human BMP-7, also known as osteogenic protein 1, has been used to treat tibial nonunions. In a multicenter, prospective randomized control of 122 patients undergoing intramedullary rod treatment, no difference in clinical outcomes were observed between groups treated with BMP-7 and autologous bone graft. At 9 months, 81% of the BMP-7 group and 85% of the autologous bone graft group had successful outcomes.

There have been reports of BMP use in hand surgery for treatment of nonunions. Ablove et al. reported a series of four patients who underwent screw exchange supplemented with BMP-2 for treatment of scaphoid nonunion. All four patients had union. Successful healing of chronic scaphoid nonunion with BMP with a single K-wire and cast immobilization has also been reported.

While these studies are encouraging, it should be noted that others report less successful results. Rice et al. reported a series of 27 patients with various sites of nonunion including phalanx, carpus, distal radius, and distal ulna. Treatment with BMP-2 yielded 89% union rate. By comparing their results to published rates for nonunion repair, they concluded that BMP-2 did not improve union rates. Another retrospective review case series revealed high complication rates. Brannan et al. reported six cases of revision ORIF with bone graft and BMP-2. The surgery was performed for nonunion despite previous scaphoid ORIF. Only one out of six patients healed without complications. Two patients had persistent nonunion after revision surgery. Four patients had significant heterotopic ossification, with one patient requiring revision surgery.