Clinical Trial to Assess Efficacy, Tolerability of Rising Doses of Clodronate in Painful Knee Osteoarthritis Patients

Inclusion Criteria: * Female and male patients aged 50 up to 75 years at ICF signature. * Diagnosis of knee OA according to the American College of Rheumatology, confirmed by Rx during the screening (a Rx performed in the last 3 months before Baseline is accepted). * Kellgren-Lawrence radiographic score between 2 and 3 degrees in the tibiofemoral joint. * Symptomatic knee OA (pain) since at least 6 months with a knee pain (VAS) ranging between 40 and 80 mm at Screening visit (the figure should be confirmed at Baseline). * Female patients of childbearing potential must have a negative pregnancy test before each treat-ment and during the Visit 5 - Week 4 and they must use adequate methods of contraception throughout the course of the study. * A signed ICF by the patient after exhaustive study discussion with the investigators. Exclusion Criteria: * BMI \> 35 kg/m² (Class II obesity). * Joint instability due to other reasons than knee OA, such as f.i. algo dystrophic syndrome, either partial or complete rupture of internal / externals ligaments, kneecap instability, etc. * Otherwise located lower limb pain, such as hip pain. * Other musculoskeletal disorders related to the target knee. * Any treatment with IA drugs in the last 3 months before Day 0 - Baseline (including any formulation of corticosteroids or hyaluronic acid injections). * Corticosteroid use by any systemic route, and hyaluronic acid injection or intraarticular corticosteroids for any other joint in the previous month will not be permitted. * Any treatment with systemic non-steroidal anti-inflammatory drugs (NSAIDs) in the week before enrolment, or any steroid anti-inflammatory drugs and chondroprotective drugs in the thirty (30) days before month before Baseline. * Any treatment with systemic bisphosphonates in the last twelve (12) months before Baseline. * Any treatment with Glucosamine or Chondroitin sulfate, Diacerein and Matrix metalloproteinase (MMP) inhibitors in the 4 weeks before Baseline. * Any treatment with Denosumab in the twelve (12) months before Baseline. * Any treatment with Paracetamol in the twelve (12) hours before Baseline. * Any knee surgery in the past or knee arthroplasty. * Any diagnostic or surgical arthroscopy of the knee in the six (6) months before Baseline. * Any jaw osteonecrosis in the last twenty-four (24) months before Baseline or at a risk of jaw osteonecrosis. * Any known hypersensitivity to the drug in the study to its excipients or other bisphosphonates, and any hypersensitivity to Paracetamol (rescue drug). * Any participation in a clinical study in which the last administration of the investigational medicinal product was within two (2) weeks before consenting to study participation (i.e.signing ICF). * Inadequate organ function defined by the following laboratory parameters: 1. Absolute Neutrophil Count (ANC) \< 1500/μl. 2. Hemoglobin (Hb) \< 9 g/dl (\< Hb 5.6 mmol/L) 3. Platelet Count \< 100.000/μl 4. Serum Creatinine \> 1.5 x Upper limit normal (ULN) or estimated Glomerular Filtration Rate (eGFR) \< 60 mL/min (as per Cockroft-Gault formula). 5. Alanine aminotransferase (ALT) or Aspartate aminotransferase (AST)\> 1.5 x Upper limit normal(ULN). 6. Serum Total Bilirubin \> 1.5 x Upper limit normal (ULN). * Pregnant or breastfeeding women, or women planning to become pregnant during the study. * Any positive or suspected history of alcoholism or drug use. * Clinically significant (i.e.) gastrointestinal, renal, hepatic, pulmonary, cardiovascular or neurological disease that could interfere with the outcome of the study or the patient's ability to comply with study requirements. * Patients unwilling or unable to comply with the protocol.