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Assessment of Efficacy of Zoledronic Acid in the Treatment of Bone Marrow Edema Syndrome

Phase 3
Completed
Conditions
Bone Marrow Edema
Interventions
Drug: Placebo
Registration Number
NCT01348269
Lead Sponsor
Wuerzburg University Hospital
Brief Summary

The primary aim is to test the reduction of bone marrow edema syndrome after a singular intravenous treatment with Zoledronic Acid within 6 weeks compared to placebo. The volume of the edema is defined as biometric data measured by the use of MRT before and six weeks after treatment. The hypothesis has to be checked whether Zoledronic Acid is efficient in the treatment of painful bone marrow edema. A statistically significant reduction of the edema in the MRT is considered as evidence for efficacy.

Detailed Description

Not available

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
48
Inclusion Criteria
  • Men: age over ≥ 18 years or women: age over ≥ 18 years with finished reproductivity according to the following definition:
  • ≥ 12 month persistent natural (spontaneous) amenorrhoea (women aged <50: additionally: FSH >40MIE/ml and estrogen deficiency of <30pg/ml or a negative estrogen test)
  • status post hysterectomy and / or bilateral oophorectomy
  • finished reproduction planning
  • secure diagnosis of bone marrow edema using MRT
  • current osteologic basic laboratory values (≤ 4 weeks before V2) according to DVO criteria
  • presence of an personally signed informed consent for the participation in the study
Exclusion Criteria
    • subchondral bone loss or already occurred cartilage damage due to the bone marrow edema
  • reactive bone marrow edema with advanced arthrotic changes in the adjacent joint (grade III and IV according to Kellgren and Lawrence)

  • patients with edematous changes in bone marrow due to the diagnosis of M. Sudeck / algodystrophy / Complex Regional Pain Syndrome (CRPS)

  • patients with known hypo- and hyperparathyroidism, osteogenesis imperfecta, osteomalacia, M. Paget or another systemic skeletal diseases, except osteoporosis

  • patients with bone necrosis in the painful skeletal region

  • patients with infectious process at the affected bone or the adjacent joint and adjacent soft parts, respectively

  • patients with diagnosed or assumed rheumatoid arthritis, Lupus erythematodes, collagenosis or vasculitides

  • patients with advanced renal insufficiency (GFR according to Cockcroft

    / Gault ≤ 40 ml/min/KO)

  • patients with malignant diseases with osseous manifestation in anamnesis/history

  • status post malignant basic/primary disease with large dosed chemotherapy

  • current or massive dose therapy completed before less than 6 weeks (>7.5mg prednisolon equivalent) with glucocorticoids

  • patients with a malignant tumor disease within the past 5 years, independent from the affected organ system and independent from the implemented treatment, the presence of a relapse or metastatic invasion, except basal cell carcinoma and squamous-cell carcinoma of the skin Current treatment due to uveitis

  • vague/ambiguous hyper- or hypocalcemia, hyper- or hypophosphatemia

  • etiological vague/ambiguous AP-increase

  • symptomatic renal calculus or nephrocalcinosis within 2 years before V2

  • recent fracture within the last 3 months independent of the localisation

  • non consolidated fractures

  • previous treatment with i.v. bisphosphonates within the last 12 months

  • previous treatment with oral bisphosphonates within the last 12 months and longer than 3 months

  • pre-treatment with prostacyclin analogs (Ilomedin® / Iloprost®) within the past 6 months

  • Current treatment due to inflammatory diseases of the jaw area as well as planned tooth extractions or tooth extractions less than 6 months ago or oral surgery implant treatment

  • pregnancy or nursing period

  • patients immediately involved in the conduction of the trial and relatives

  • patients with current proceedings related to the bone marrow edema

  • patients for which the participation in the study carries an increased risk under consideration of the health condition due to the assessment of the investigator

  • participation in another clinical trial within 30 days before study start or during the trial

  • participation of patient who might be dependent on the investigator, also the spouse, parents or children

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
AclastaAclasta-
NaCl SolutionPlacebo-
Primary Outcome Measures
NameTimeMethod
Reduction of the Edema AreaWeek 6 after administration of a single intravenous dose of zoledronic acid (5 mg)

The volume of the edema in cm³ is defined as biometric data measured by the use of MRI before and six weeks after treatment. Edema volume at screening was set to 100%. Edema volume six weeks after study drug administration was provdied as percentage reduction compared to the value at screening

Secondary Outcome Measures
NameTimeMethod
Number of Days of IllnessAssessment at week 6

Number of days of illness assessed until week 6

Number of Participants With Adverse Events as a Measure of Safety and TolerabilityWeek 3, 6

including changes in the following parameters according to DVO guidelines: Calcium, Phosphate, Creatinin-Clearance (Cockcroft-Gault), Alkaline Phosphatase, γGT, CRP

Reduction of PainAssessment at week 6

Reduction of pain as measured by a visual analog scale (VAS). Range 0-100. Higher values indicating worse pain.

Quality of Life (Qualeffo-41 Questionnaire)Assessment at week 6

Quality of life as measured by the Qualeffo-41 questionnaire - a quality of life questionnaire in patients with vertebral fractures of the European Foundation for Osteoporosis

Number of Aseptic Bone Necrosis and Fatigue FracturesBaseline until end of study (week 12)

Assessment of number of patients withaseptic bone necrosis and/or fatigue fractures.

Reduction of Pain (VAS)Assessment at week 3

Reduction of pain as measured by a Visual Analog Scale (VAS). Range 0-100 with higher values indicating worse pain.

Subjective Estimation of Medical Condition (PDI)Assessment at week 6

Subjective estimation of medical condition as assessed by PDI (Pain Disability Index)

Number of Additional Medicinal VisitsAssessment at week 6

Aggregated number of unscheduled medicinal visits

Trial Locations

Locations (2)

Orthopedic Center for Musculoskeletal Research, Orthopedic Department, University of Wuerzburg

🇩🇪

Wuerzburg, Bavaria, Germany

Department of trauma, hand, reconstructive and plastic, University of Wuerzburg

🇩🇪

Wuerzburg, Bavaria, Germany

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