The progression of structural joint damage is the leading cause of disability and socioeconomic costs associated with rheumatoid arthritis (RA). Remission and low clinical activity not always imply absence of progression of structural damage. The main objective of this study is to evaluate the progression of radiological damage in early RA patients currently treated with disease modifying anti-rheumatic drugs (DMARDs) and low disease activity to which treatment with zoledronic acid is added.

The investigators propose a randomized clinical trial in 94 patients with RA of less than 2 years of evolution that, being treated with DMARDs, present criteria of low disease activity (DAS28 < 3.2).

Patients will be randomized into two branches: zoledronic acid and no treatment. The primary study endpoint is the progression of radiological damage assessed in a blinded way by the difference in the Sharp-van der Heijde index (SHI) in radiographs of hands and feet after two years; the secondary variables: radiographic progression after one year, serum bone biomarkers (OPG, RANKL, DKK-1 and sclerostin) and adverse effects. In a subgroup of patients, the investigators shall evaluate the change in the size of hand erosions by multislice computed tomography and the evolution of periarticular osteoporosis and systemic bone mass by dual X-ray absorptiometry (DXA).

Inclusion Criteria:

1. Age equal or greater than 18 years
2. Patients with RA of less than 2 years of evolution
3. DMARD therapy (methotrexate alone or methotrexate, leflunomide or methotrexate within COBRA strategy) on stable dose for at least 6 weeks prior to study entry
4. Patients not treated with glucocorticoids or under stable dose of prednisone up to 5 mg / day or equivalent dose of another glucocorticoid
5. Low disease activity (DAS28 <3.2)
6. In case of premenopausal women, commitment to make contraceptive treatment up to 3 years after the last dose of zoledronic acid
7. Signed informed consent

Exclusion Criteria:

1. Previous or current treatment with biological drugs used for the treatment of RA (infliximab, adalimumab, etanercept, certolizumab, golimumab, rituximab, abatacept, tocilizumab)

2. Pretreatment with:

   1. Bisphosphonates in the 5 years prior to the onset of RA
   2. Calcitonin, raloxifene, bazedoxifene, strontium ranelate, teriparatide and denosumab in the year before the onset of RA

3. Contraindication to treatment with zoledronic acid:

   1. Hypersensitivity to bisphosphonates
   2. Hypocalcemia
   3. Glomerular filtration rate <35 mL / min
   4. Pregnant (negative pregnancy test) and lactating women
   5. Poor oral hygiene
   6. Pending invasive dental procedure

4. Serum levels of calcidiol lower than 25 nmol/L (10 ng/mL).

5. Simultaneous participation in another clinical trial