ZOledronic acid as DIseAse-modifying drug in Knee osteoarthritis (ZODIAK)

Recruitment & Eligibility

Status: Completed

Sex: Not specified

Target Recruitment: 86

Inclusion Criteria

- Age between 40 and 70 years.
- Primary tibiofemoral (TF) knee OA according to clinical and radiographic ACR
criteria. When two knees are eligible, the most painful knee is chosen as index
knee. When knees are equally painful the index knee will be selected randomly.
The most affected compartment (MAC) of the index is defined as the TF
compartment with the most radiographic joint space loss.
- Pain in the index knee on at least 50% of the days of the previous month (NRS
between 4/10 and 8/10).
- At least one bone marrow lesion (BML) in the MAC of the index knee on MRI, as
judged by a trained researcher. A BML is defined on T2-weighted MRI sequences
as a zone of altered signal intensity in the bone and marrow, located
immediately beneath the articular cartilage and visible on at least two
consecutive slices.

Exclusion Criteria

- Severe structural OA of the MAC of the index knee on plain radiograph: grade
3 radiographic joint space narrowing of the index knee, according to the
Osteoarthritis Research Society International atlas.
- Planned or expected surgery of index knee in the next 2 years (physician
judgment).
- Intra-articular injection into the index knee: glucocorticoids, hyaluronic
acid, or platelet-rich plasma within the last 6 months.
- Knee pain from other causes than knee OA (e.g. fibromyalgia)
- Secondary OA, such as secondary to inflammatory joint disease, significant
trauma, metabolic disease, and/or extreme varus or valgus position of the knee
(i.e. more than 10º).
- Other self-reported diseases with potential effects on current bone
metabolism (e.g. thyroid or parathyroid disease, malignancy, bone fracture
within past 6 months).
- Self-reported disease that limits intestinal absorptive capacity (e.g. celiac
disease or short bowel syndrome).
- Previous allergic reaction to zoledronic acid, another bisphosphonate, or
other substances in the solute.
- Previous and/or current use of bisphosphonates, denosumab, teriparatide,
strontium ranelate, calcitonin and/or raloxifene.
- Current use of loop diuretics, glucocorticoids, aminoglycoside antibiotics.
- Uncontrolled or actively treated dental disease and/or otitis.
- Current or previous atrial fibrillation.
- Abnormal blood tests: serum ionized calcium higher than 1.32 mmol/l or lower
than 1.15 mmol/l, serum (25OH) vitamin D lower than 50 nmol/l, or estimated
creatinine clearance lower than 60 ml/min.
- Contraindications to MRI (e.g. claustrophobia, MRI-incompatible
devices/implants/foreign objects).
- Insufficient ability to communicate in Dutch.
- Pregnancy or lactation.
- Other factors that prevent subjects from adhering to the protocol.

Study & Design

Study Type: Interventional

Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
<p>Change in total mean cartilage thickness in the tibial and load-bearing femoral<br /><br>regions of the most affected compartment of the tibiofemoral joint of the index<br /><br>knee on MRI, 24 months vs. baseline.</p><br>

Secondary Outcome Measures

Name	Time	Method
<p>- Pain on a numeric rating scale at 6, 12, 18, and 24 months vs. baseline.<br /><br>- KOOS (Knee injury and Osteoarthritis Outcome Score) at 6, 12, 18, and 24<br /><br>months vs. baseline (pain, symptoms, daily activity, sport, quality of life).<br /><br>- Pain medication use at 6, 12, 18, and 24 months vs. baseline.<br /><br>- Bone marrow lesion size at 24 months vs. baseline.<br /><br>- Change in joint space width on standardized knee radiographs at 24 months vs.<br /><br>baseline.<br /><br>- Change in total mean cartilage thickness in the tibial and load-bearing<br /><br>femoral regions of the tibiofemoral compartment contralateral to the most<br /><br>affected compartmen of the index knee at 24 months vs. baseline.<br /><br>- Change in total mean cartilage thickness in the tibial and load-bearing<br /><br>femoral regions of the index knee at 24 months vs. baseline.<br /><br>- Safety.</p><br>