Avascular Necrosis of Femoral Head
Conditions
Keywords
avascular necrosis of femoral head, bisphosphonate, collapse
Brief summary
The purpose of this study is to test the effect of zoledronic acid over 2 years in preventing early collapse and progression of joint dome depression (≥ 2 mm by X-ray) of the femoral head in patients with large (\> 30%: criteria according to Kim et al) nontraumatic osteonecrosis.
Detailed description
Until now, the best treatment option in early (precollapse) large osteonecrosis femoral head is vascularizing fibular graft. However, it requires high microsurgical technique. Also it needs very long operation time (3-6hours), and morbidity associated with surgery is not low. In early stage osteonecrosis, osteoclasts are activated and resorb the necrotic portion of bone and osteoblasts are followed to lay down new bone. This process can weaken the bone function to support loading and can lead to collapse of bone. Bisphophonate can inhibit this osteoclastic bone resorption and enhance osteoblastic new bone formation. Recently, everyday oral intake of alendronate with vitamin D and calcium had a high success rate to prevent the collapse and decrease of hip joint pain in a short-term follow-up. However, the compliance or adherence to everyday oral intake is questionable. Moreover, the exact comparison based on MRI according to various classifications is not available currently. There is no report about the effect of zoledronic acid to prevent early collapse and progression of joint dome depression (≥2 mm by X-ray) of the early stage large nontraumatic osteonecrosis of the femoral head or its effect on MRI signal change after infusion of zoledronic acid in noncollapsed cases (estimated about 30% of cases) The investigators need a controlled randomized multicenter interventional study about the efficacy of bisphophonates in the treatment of ONFH.
Interventions
DRUGzoledronic acid (aclasta)
Once-yearly administration of 5mg zoledronic acid intravenously (dosage of treatment of osteoporosis) (+ calcium:1,200mg/day, VitD:800IU/day) during study period
Sponsors
Novartis Korea Ltd.
Seoul National University Bundang Hospital
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
19 Years to 65 Years
Healthy volunteers
No
Inclusion criteria
* Patient who agree to clinical trial * Patient who are more than 18 years of age * Osteonecrosis of the femoral head * Steinberg stage I, II non traumatic osteonecrosis of femoral head * Necrotic area of \> 30% (HJ Kim et al ) * JIC (Japanese Investigation Committee): C1 or C2 lateral lesion (by X-ray or MRI)
Exclusion criteria
* Patients who are pregnant (patients who are of child bearing potential who are not practicing a reliable contraceptive method (oral, subcutaneous, mechanical, or surgical contraception) * Patients who have contraindicated condition to zoledronic acid such as chronic renal failure (calculated creatinine clearance less than 35.0 ml/min), severe heart disease such as atrial fibrillation, sensitive to bisphosphonates and hypocalcemia (serum calcium less than 8 mg/dl or 2.0 mmol/L) * Patients who have collapsed lesion including subchonral fracture * Patients who have multiple lesion of osteonecrosis of femoral head * Patients who received other kinds of bisphophonates or anabolic agents before zoledronic acid use * Patients with any medical or psychiatric condition which, in the Investigator's opinion would preclude the participant from adhering to the Protocol or completing the trial per protocol * Patients who are considered potentially unreliable and patients who may not reliably attend study visits
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Number of Participants With Femoral Head Collapse Within 24 Months | Measurements were done at 6, 12, 24 months |
Secondary
| Measure | Time frame |
|---|---|
| Collpase Rate of Femoral Head | Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) |
| Change of HHS (Harris Hip Scores), WOMAC Score, SF-36 | Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) |
| Time to Collapse of Femoral Head | Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) |
| Time to Total Arthroplasty or Joint Preserving Surgery | Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m) |
Countries
South Korea
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Aclasta aclasta group
zoledronic acid (aclasta): Once-yearly administration of 5mg zoledronic acid intravenously (dosage of treatment of osteoporosis) (+ calcium:1,200mg/day, VitD:800IU/day) during study period | 55 |
| Control control group | 55 |
| Total | 110 |
Baseline characteristics
| Characteristic | Aclasta | Control | Total |
|---|---|---|---|
| Age, Continuous | 43.8 years STANDARD_DEVIATION 11.8 | 45.2 years STANDARD_DEVIATION 11.6 | 44.5 years STANDARD_DEVIATION 11.5 |
| Sex: Female, Male Female | 16 Participants | 14 Participants | 30 Participants |
| Sex: Female, Male Male | 39 Participants | 41 Participants | 80 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 55 | 0 / 55 |
| serious Total, serious adverse events | 0 / 55 | 0 / 55 |
Outcome results
Primary
Number of Participants With Femoral Head Collapse Within 24 Months
Time frame: Measurements were done at 6, 12, 24 months
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Aclasta | Number of Participants With Femoral Head Collapse Within 24 Months | 29 participants |
| Control | Number of Participants With Femoral Head Collapse Within 24 Months | 22 participants |
Secondary
Change of HHS (Harris Hip Scores), WOMAC Score, SF-36
Time frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)
Secondary
Collpase Rate of Femoral Head
Time frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)
Secondary
Time to Collapse of Femoral Head
Time frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)
Secondary
Time to Total Arthroplasty or Joint Preserving Surgery
Time frame: Measurement will be done at 0m, 3m, 6m, 9m, 12m, 18m, 24m)