Background: Traumatic femoral head osteonecrosis in adolescents has a poor prognosis due to collapse and subsequent degenerative change. There are currently no satisfactory treatments available for this condition. Bisphosphonate therapy has improved outcome in animal models of osteonecrosis. We have evaluated bisphosphonate therapy as a novel strategy for adolescent traumatic osteonecrosis.

Methods: We established a protocol of identification of adolescents with osteonecrosis utilizing bone scans immediately after surgical treatment for hips at risk of osteonecrosis after trauma. Of a consecutive group of twenty-eight patients with either unstable slipped capital femoral epiphyses (SCFE) (22), femoral neck fracture (4) or hip dislocation (2), seventeen patients with osteonecrosis were identified. These patients (13 boys and 4 girls, mean age 12.6 years) and their families consented for treatment with intravenous bisphosphonates based on animal experimental evidence. Of the patients with osteonecrosis, twelve had presented with unstable SCFE, four with femoral neck fractures and one following traumatic hip dislocation. The average length of bisphosphonate treatment was 20.3 months (range 7 to 39). All patients were followed for at least 2 years.

Results: At mean follow-up of 38.7 months, fourteen patients (82%) were pain free. Clinically, all patients had a good to excellent outcome. The mean Harris Hip Score was 91.1, the Iowa Hip Rating was 92.1 and the Global PODCI score was 91.5. On radiographs, nine patients (53%) were rated as Stulberg I–II, six (35%) as Stulberg III, and two (12%) as Stulberg V.

Conclusion: Bisphosphonates therapy may play an adjunctive role in the treatment of adolescents with traumatic osteonecrosis.

Traumatic osteonecrosis of the femoral head in adolescents has a poor prognosis due to collapse and degenerative change. We hypothesised that early bisphosphonate treatment to reduce osteoclast activity could allow revascularisation and repair with maintenance of joint congruity.

Nine patients with documented osteonecrosis were treated with intermittent intravenous pamidronate (Aredia, Novartis) commencing within a mean 1 month of diagnosis (range, 5 to 91days). The dosing protocol has evolved over two years with the current dose being 9 mg/kg/year for 18 months. Mean follow up is 19.8 months (range, 13 to 30 months) with all patients followed for more than one year. There were 6 patients, who presented after unstable SCFE. Of these the index procedure had failed in three, requiring multiple early operations. The other three patients had sustained an inter-trochanteric fracture with a pelvic fracture, a traumatic hip dislocation and a femoral neck fracture respectively.

Eight of the patients are painfree. Six have been instructed to fully weight bear, while two can partial weight bear and one is non-weight bearing. Seven of 9 patients do not show significant resorption of the femoral heads at the most recent follow up. Of the two patients with significant resorption, one patient began to resorb after his medication was ceased, so it was recommenced. He has subsequently undergone a realignment procedure. The other patient had resorption of a section of the femoral head, which had not re-vascularised by 18 months, and this was elevated and bone grafted. These two hips are considered functional in the short term as they are currently pain free, but their deformity is expected to bring about early osteoarthritis in adult life.

This early experience lays the foundation for prospective clinical trials of bisphosphonate therapy in adolescents with osteonecrosis. It appears that bisphosphonate treatment protocols for adolescents will need to be prolonged. Our current practice is for a duration of around 18 months with normalisation of uptake on bone scan as the end point for therapy.

Introduction Traumatic osteonecrosis of the femoral head in adolescents has a poor prognosis due to femoral head collapse and degenerative change. We hypothesised that early bisphosphonate treatment to reduce osteoclast activity could allow revascularisation and repair with maintenance of joint congruity.

Methods Nine patients with documented osteonecrosis are presented. There were six patients, who presented after unstable SCFE. Of these the index procedure had failed in three, requiring multiple early operations. The other three patients had sustained an inter-trochanteric fracture with a pelvic fracture, a traumatic hip dislocation and a femoral neck fracture respectively. They were treated with intermittent intravenous pamidronate (Aredia, Novartis) commencing within a mean one month of diagnosis (range 5 to 91 days). The dosing protocol has evolved over two years with the current dose being 9 mg/kg/year for 18 months. Mean follow-up is 19.8 months (range 13 to 30 months) with all patients followed for more than one year.

Results Eight of the patients are painfree. Six have been instructed to fully weight bear, while two can partial weight bear and one is non-weight bearing. Seven of nine patients do not show significant resorption of the femoral heads at the most recent follow-up. Of the two patients with significant resorption, one patient began to resorb after his medication was ceased, so it was recommenced. He has subsequently undergone a realignment procedure. The other patient had resorption of a section of the femoral head, which had not re-vascularised by 18 months, and this was elevated and bone grafted. These two hips were considered functional in the short term as they were pain free, but their deformity was expected to bring about early osteoarthritis in adult life.

Conclusions This early experience lays the foundation for prospective clinical trials of bisphosphonate therapy in adolescents with osteonecrosis. It appears that bisphosphonate treatment protocols for adolescents will need to be prolonged. Our current practice is for a duration of around 18 months with normalisation of uptake on bone scan as the end point for therapy.

In relation to the conduct of this study, one or more of the authors is in receipt of a research grant from a non-commercial source.

Objective: To evaluate the effects of a new potent bisphosphonate on the formation, mineralisation, density, and mechanical properties of bone in distraction osteogenesis.

Methods: Thirty immature New Zealand White rabbits had a 10.5 millimetre lengthening of their tibia performed over 2 weeks using an Orthofix M-100 fixator. Ten control rabbits received saline only; 10 received the new bisphosphonate at the time of surgery, and 10 received a second dose at the end of distraction. Bone mineral content (BMC) and density (BMD) measurements were made at two, four and six weeks. Quantitative CT analysis of regenerate, proximal and distal bone, and corresponding segments in the non-operated limb was performed after culling. Mechanical testing was by 4-point bending.

Results: Bone mineral accrual was significantly faster in both treatment groups (ANOVA p< 0.01). BMD increased in all treated animals (ANOVA p< 0.01). Cross sectional area of regenerate at six weeks was increased by 49% in the single dosed group versus controls and by 59% in the re-dosed group. (ANOVA p< 0.01). BMC of the regenerate was increased by 92% in the single dose group and by 111% in the re-dosed group (ANOVA p< 0.01). Moment of inertia of the regenerate was significantly increased in both treated groups (ANOVA p< 0.05). The difference between single dose and controls was significant (p< 0.05), the difference between re-dosed and single dosed was not (p=0.5).

Conclusion: Bisphosphonate therapy significantly increased new bone formation, bone mineralisation and mechanical properties. Osteoporotic effects were reversed. This effect could have wide ranging implications for many orthopaedic practices

The bisphosphonate, pamidronate, has been used successfully in our hospital for the management of osteogenesis imperfecta with an excellent safety profile in growing children. We have performed several research studies on distraction osteogenesis in New Zealand white rabbits showing significant increases in new bone formation and the abolition of stress shielding osteopaenia using both pamidronate and zoledronic acid. Recent studies have shown that bisphosphonates positively effect osteoblasts as well as inhibiting osteoclastic bone resorption.

We present a series of early cases where this research has been used in humans. Two cases of pamidronate assisted distraction osteogenesis are presented, one of which also had congenital pseudarthrosis of the tibia, which united after pamidronate administration.

Two cases of post-traumatic avascular necrosis have been successfully treated such that osteolysis and collapse of the necrotic femoral head did not occur. Bisphosphonates may act to slow bone resorption while simultaneously increasing new bone formation, such that the mechanical integrity of the necrotic segment can be maintained during revascularisation.

A randomised controlled trial of bisphosphonates in distraction osteogenesis at our hospital has now received ethical approval. Newer bisphosphonates have proven their clinical value in osteogenesis imperfecta and adult osteoporosis, but other potential roles are emerging for these compounds, which have extremely potent effects on bone.

Aim: To examine the effect of the bisphosphonate zoledronic acid in doses of 0.1mg/kg on new bone formation and stress shielding in a distraction-osteogenesis model in New Zealand white rabbits.

Method: Thirty male rabbits underwent a right tibial osteotomy at eight weeks of age. Distraction of the osteotomy by 0.75mm/day was performed for two weeks followed by four weeks for consolidation. Group I was given saline infusions, Group II zoledronic acid at surgery, and Group III received zoledronic acid at surgery and again at two weeks. DXA scans evaluated BMC and BMD. Quantitative computerised tomography measured the cross-sectional areas. Four-point bend testing of both distracted and non-operated tibiae was performed in a standardised fashion.

Results: Bone mineral accretion between two and four weeks was significantly higher in treated versus saline groups, and was better maintained at six weeks (P< 0.01 ANOVA). Stress shielding osteopaenia that was seen in surrounding bone segments in Group I (controls) was abolished in the treated groups. By six weeks there was a 49% and 59% increase in cross sectional area of new bone in Groups II and III respectively (P< 0.01 ANOVA). Group II tibiae were 29% stronger in four-point bending, while Group III were 89% stronger than Group I (P< 0.01 ANOVA). There was little detectable effect on the non-operated tibiae.

Conclusions: Zoledronic acid administration significantly increased the rate and amount of new bone formation and its mineralisation. The increases in bone formation and retention translated to a significant, dose-dependent increase in strength. Further research into the role of zoledronic acid in orthopaedic surgery is indicated.