The effect of osteoclastic activity on tendon-to-bone healing: an experimental study in rabbits.
BACKGROUND
Healing of a tendon graft in a bone tunnel depends on bone ingrowth into the interface between tendon and bone. Excessive osteoclastic activity may contribute to bone resorption, tunnel widening, and impaired healing. We hypothesized that inhibition of osteoclastic activity by osteoprotegerin (OPG) would increase bone formation around a tendon graft in anterior cruciate ligament reconstruction in a rabbit model, while increased osteoclastic activity due to the application of receptor activator of nuclear factor-kappa B ligand (RANKL) would impair bone ingrowth.


METHODS
Sixty skeletally mature, male New Zealand White rabbits underwent bilateral anterior cruciate ligament reconstruction. OPG (100 microg per tunnel) or RANKL (10 microg per tunnel) was delivered to the tendon-bone interface with use of a synthetic calcium phosphate carrier vehicle. Twenty animals were killed at two, four, and eight weeks after surgery. Two rabbits from each group were prepared for histological evaluation, and the other rabbits were used for biomechanical testing.


RESULTS
A significantly greater amount of bone surrounded the tendon at the healing tendon-bone interface in the OPG-treated limbs compared with the controls and the RANKL-treated limbs at all time-points (p < 0.05). There were significantly fewer osteoclasts in the OPG-treated limbs compared with the controls and the RANKL-treated limbs (p < 0.05). The average tunnel area in the OPG group was significantly smaller than that in the RANKL group (p = 0.003 at two weeks and p = 0.004 at four weeks). The femur-anterior cruciate ligament-tibia complex of the OPG-treated limbs had significantly increased stiffness compared with RANKL-treated limbs at eight weeks (p = 0.04).


CONCLUSIONS
Osteoprotegerin significantly improves bone formation around the grafted tendon and improves the stiffness at the healing tendon-bone junction in a rabbit model.
Rodeo
Scott A
SA
Laboratory for Soft Tissue Research, The Hospital for Special Surgery, 535 East 70th Street, New York, NY 10021, USA. rodeos@hss.edu
Kawamura
Sumito
S
Ma
C Benjamin
CB
Deng
Xiang-hua
XH
Sussman
Patrick S
PS
Hays
Peyton
P
Ying
Liang
L
D000818:Animals; D016118:Anterior Cruciate Ligament / Q000378:metabolism / Q000601:surgery; D000070598:Anterior Cruciate Ligament Injuries; D008297:Male; D016348:Osseointegration / Q000187:drug effects* / Q000502:physiology; D010010:Osteoclasts / Q000187:drug effects / Q000502:physiology; D053244:Osteoprotegerin / Q000494:pharmacology*; D053245:RANK Ligand / Q000494:pharmacology*; D011817:Rabbits; D013710:Tendons / Q000637:transplantation*; D014945:Wound Healing / Q000187:drug effects* / Q000502:physiology
D053244:Osteoprotegerin; D053245:RANK Ligand; C505688:TNFSF11 protein, human