Systemic zoledronate precoating of a bone graft reduces bone resorption during remodeling

Abstract

Background Cartilage degeneration often occurs after osteosynthesis of a devascularized intermediary fragment in a joint fracture, in mosaic-plasty or in wholejoint toe-to-finger transplantation. Hypothetically, the degeneration is secondary to a collapse of the transferred subchondral bone as it remodels during high mechanical load. Bisphosphonates are used to reduce resorption of necrotic bone. We tested a systemic pretreatment before harvesting the graft in order to protect the bone and cartilage against collapse and secondary arthrosis.Methods Rats were given one zoledronate injection and bone grafts were harvested. The grafts were frozen, thawed and placed into bone chambers, and implanted into another batch of rats. Graft resorption and new bone formation was measured by histomorphometric analysis and compared with untreated grafts.Results In the remodeled area of the controls, the graft was almost totally resorbed and replaced by bone marrow. In the zoledronate-treated specimens, the graft remained and the graft trabeculas were lined with new bone. By histomorphometry, the total amount of bone (graft plus new bone) within the remodeled area was 16% in the zoledronate-treated grafts and 5% in the controls (p = 0.003).Interpretation A bone graft can be pretreated with bisphosphonate and remain protected against resorption once implanted again.

A collagen–hydroxyapatite scaffold allows for binding and co-delivery of recombinant bone morphogenetic proteins and bisphosphonates

“…An emerging paradigm in orthopedics is the concept of synergistically harnessing anabolic and anticatabolic drug treatments for improved bone healing [44][45][46][47] . BPs alone inhibit bone resorption and do not promote bone formation.…”

Local treatment of cancellous bone grafts with BMP-7 and zoledronate increases both the bone formation rate and bone density

“…Bisphosphonates have a strong affinity for calcium phosphate and are chemically bonded to the bone mineral (Rogers et al 2000) regardless of whether they are administered systemically (Tägil et al 2006) or locally (Aspenberg and Åstrand 2002). In consequence, a graft can be treated locally by simply soaking it in a bisphosphonate solution before implantation, thereby protecting the new-forming bone from the increased resorption caused by the BMP.…”

Effect of risedronate in a minipig cartilage defect model with allograft

“…They reduce markers of cartilage degradation and bone resorption 8 in osteoarthritis patients and inhibit the bone resorption associated with bone graft. 9 They have also been shown to be efficacious in inhibiting the bone remodeling associated with experimentally-produced cartilage lesions. 10,11 The question then arises as to whether bisphosphonates might be used to inhibit the bone resorption associated with cartilage transplantation.…”