Study Into the Effect of Ibandronate for the Treatment of Bone Marrow Edema in Relation to Spontaneous or Non-traumatic Osteonecrosis of the Knee: A Randomized Double-blind, Placebo-controlled Trial
Condition: Osteonecrosis of the Knee; Bone Marrow Edema of the Knee
MeSH terms: Osteonecrosis; Edema
Study type: Interventional
Phase: Phase 3

Summary: 
      BACKGROUND: Bone marrow edema (BME) in the knee occurs as a localized inflammatory disease in
      relation to spontaneous or non-traumatic osteonecrosis (ON). Prognosis of BME/ON in the
      course after knee arthroscopy appears to be poor and in most cases results in knee
      arthroplasty. Treatment options of ON depend in general on the size of the lesion. Smaller
      lesions are managed by mechanical unloading and use of non-steroidal anti-inflammatory drugs,
      larger lesion in general requires osteotomy or arthroplasty. In animal studies it has been
      shown that bisphosphonates prevent resorption of necrotic bone during ischemic necrosis and
      revascularization. In humans, bisphosphonate treatment has been used successfully in bone
      marrow oedema and avascular necrosis of the femoral head.

      In an observational study using bisphosphonates (ibandronate, pamidronate) in patients with
      either spontaneous or (believed to be) arthroscopy-induced BME of the knee a significant
      rapid and sustained pain relief was observed with a mean decrease on the pain scale on the
      visual analogue scale of over 60% after 3 months and of 80% after 6 months. Our experience
      suggests an apparent beneficial effect of amino-bisphosphonates in the treatment of BME of
      the knee.

      AIM: This randomized, double-blind, placebo-controlled study aims to provide data on
      clinical, biochemical and radiological outcome of patients with bone marrow edema in relation
      to spontaneous or arthroscopy-induced ON of the knee treated with ibandronate or placebo.

      ENDPOINTS: The primary objective is to demonstrate the superiority of treatment with
      ibandronate compared to placebo regarding clinical outcome (pain [VAS score]) in spontaneous
      or arthroscopy-induced BME/ON of the knee after 12 weeks. Secondary objectives include a)
      clinical outcome (pain [VAS score]) after 24 weeks, b) the evaluation of the radiological
      outcome (MRI scan) at 12 and 48 weeks, c) the changes in biochemical markers of bone
      turnover, and d) the number of salvage therapies needed in case persistence is observed
      during placebo therapy.

      METHODS: The study is designed as a single-center, randomized double-blind,
      placebo-controlled trial. A total number of 30 patients with BME/ON will be recruited. Each
      patient will be randomized in a 1:1 ratio to receive ibandronate IV or placebo IV.
      Additionally, all patients will receive 500 mg calcium and 400 IU vitamin D per day
      throughout the study, and diclofenac/esomeprazole for initial 3 months (blinded treatment
      duration 24 weeks). Baseline and follow-up data collection will contain all variables needed
      for evaluation of clinical, biochemical and radiological evaluation of treatment efficacy.

      EXPECTED RESULTS: We hypothesize that treating patients with BME/ON of the knee, therapy with
      ibandronate will be superior in reducing pain, and radiological findings as compared to
      placebo.
    


Intervention name(s): Ibandronate IV; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): Ibandronate IV (Bonviva® IV), 10.5 mg divided in 4 single infusions within 2 weeks(1x1.5 mg, 3x3 mg), followed by a fifth infusion after 3 months (V4); Placebo IV, divided in 4 single infusions within 2 weeks, followed by a fifth infusion after 3 months (V4)
Intervention MeSH terms: Ibandronic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: osteonecrosis; bone marrow edema; ibandronate; bisphosphonate; knee