Patient description: The patient is a 53-year-old man complaining of frequent headaches, generalized bone pain and difficulty chewing that started 6 years ago and is getting worse. Examination shows bilateral swellings around the molars. The swellings have increased since his last examination. Several extraoral lesions of the head and face are detected. The swellings are non-tender and attached to the underlying bone. Further evaluation shows increased uptake of radioactive substance as well as an increase in urinary pyridinoline. The serum alkaline phosphatase is 300 IU/L (the normal range is 44- 147 IU/L). The patient's sister had the same problems. She was diagnosed with Paget's disease of bone when she was 52 years old. The diagnosis of Paget's Disease of Bone is confirmed and Bisphosphonate will be started as first-line therapy.

Clinical trial eligibility criteria: eligible ages (years): 18.0-65.0,  Multiple Myeloma Man or woman aged 18 to 65 years old; 2. Subjects are newly diagnosed MM patients which are scheduled by the investigators to be treated with vincristine, adriamycin and dexamethasone standard therapy. Stage II/III (according to Durie and Salmon criteria) with skeletal involvement, such as bone pain, bone lytic lesions, diffuse osteoporosis or pathologic fractures; 3. Life expectancy > 3 months; 4. Patient has measurable disease in which to capture response, defined as one or more of the following Serum M-protein level >10.0 g/L measured by serum protein electrophoresis or immunoglobulin electrophoresis; or Urinary M-protein excretion > 1 g/24 hours; or Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or Serum free light chains (by the Freelite test) > 2 X the upper limit of normal (ULN), in the absence of renal failure. 5. Performance status (PS) of ECOG ≤2.0, unless PS of 3-4 based solely on bone pain; 6. Patients must have a Platelets count≥50×109 cells /L; Absolute neutrophil count (ANC)≥0.75×109 cells /L; 7. Patients must have adequate hepatic function defined as Alanine transaminase(ALT) ≤ 2.5 × upper limit of normal(ULN); Aspartate transaminase (AST) ≤2.5×ULN; Total bilirubin ≤2×ULN; 8. Patients must have adequate renal function defined as creatinine clearance >30 ml /min; 9. Subjects (or their legally acceptable representatives) must have signed a informed consent document indicating that they understand the purpose of and procedures required for the study and are willing to participate in the study  Non-secretory MM, unless the patient has measurable lesions on computed tomography (CT), magnetic resonance imaging (MRI) and/or positron emission tomography (PET); 2. Peripheral neuropathy or neuropathy pain grade 2 or high as defined by National Cancer Institute Common Terminology for Adverse Events(NCI CTCAE) Version 3; 3. Uncontrolled or severe cardiovascular disease, including myocardial infarction (MI ) within 6 months of enrollment, New York Heart Association (NYHA) Class III or IV heart failure, uncontrolled angina, clinically significant pericardial disease, or cardiac amyloidosis; 4. History of allergy reaction attributable to compounds containing boron or mannitol; 5. Any serious, active disease or psychiatric illness that could potentially interfere with the completion of treatment according to this protocol or the investigator's decision; 6. Concurrent treatment with another investigational agent; 7. Female subject who is pregnant or breast-feeding