Zoledronic acid treatment results in retention of femoral head structure after traumatic osteonecrosis in young Wistar rats.
Osteonecrosis (ON) of the femoral head in childhood can lead to loss of femoral head architecture and subsequent deformity. When femoral head ON was surgically induced in 24 rats, zoledronic acid treatment and prophylaxis improved sphericity and maintenance of architecture at 6 weeks. This preliminary experiment supports the use of bisphosphonates in childhood ON.


BACKGROUND
We hypothesized that the bisphosphonate zoledronic acid could preserve femoral head structure while allowing bone repair.


METHODS
Osteonecrosis (ON) was surgically induced in the right femoral head of 24 female Wistar rats. The rats were randomized into three treatment groups and dosed subcutaneously with saline, zoledronic acid (0.1 mg/kg) at 1 and 4 weeks postoperation (ZA post), or zoledronic acid (0.1 mg/kg) given 2 weeks preoperation and at 1 and 4 weeks postoperation (ZA pre-post). After death at 6 weeks postoperation, undecalcified specimens were analyzed by DXA and standardized histomorphometric analysis.


RESULTS
Seventy-one percent of saline-operated femoral heads were aspherical (Mose score > 1), whereas only 13% and 0% of operated heads in the ZA-treated groups were aspherical (p < 0.05). DXA-measured bone mineral density in saline-treated femoral heads was reduced by 34% and 43% compared with the ZA-treated groups (p < 0.01). Histomorphometry showed decreases of 12% and 17% in bone volume (BV/TV) in saline groups compared with ZA post and ZA pre-post (p < 0.05), and a decrease in trabecular number (Tb.N) of 18% and 14% (p < 0.05), respectively. Bone formation rate (BFR) was increased by 56% in saline-treated operated heads over ZA post and was 4.8 times increased over the ZA pre-post group (p < 0.05). The differences in BV/TV and Tb.N in treated groups must therefore be caused by a reduction in bone turnover. Observational histology confirmed the retention of necrotic architecture in treated groups.


CONCLUSIONS
Zoledronic acid treatment and prophylaxis preserved femoral head architecture after traumatic ON in this rat model at 6 weeks. These data indicate that, by conserving femoral head architecture, bone repair may occur in conjunction with improved femoral head shape.
Little
David G
DG
Orthopaedic Research Unit, The Children's Hospital at Westmead, Westmead, New South Wales, Sydney, Australia. davidl3@chw.edu.au
Peat
Rachel A
RA
Mcevoy
Anthony
A
Williams
Paul R
PR
Smith
Elisabeth J
EJ
Baldock
Paul A
PA
D015502:Absorptiometry, Photon; D000367:Age Factors; D000818:Animals; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects; D004164:Diphosphonates / Q000494:pharmacology* / Q000627:therapeutic use*; D005260:Female; D005270:Femur Head / Q000000981:diagnostic imaging / Q000187:drug effects* / Q000473:pathology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use*; D010020:Osteonecrosis / Q000150:complications* / Q000188:drug therapy* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D014947:Wounds and Injuries / Q000150:complications* / Q000188:drug therapy / Q000473:pathology; D000077211:Zoledronic Acid
D004164:Diphosphonates; D007093:Imidazoles; D000077211:Zoledronic Acid