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): 18.0-999.0,  Multiple Myeloma History of histologically documented MM with relapsed or progressive disease after at least one line of prior therapy. 2. Patient has measurable disease in which to capture response, defined as one or more of the following: 1. Serum M-protein level > 1.0 gm/dl (10.0 g/L) measured by serum protein electrophoresis or immunoglobulin electrophoresis; or 2. Urinary M-protein excretion > 200 mg/24 hrs; or 3. Bone marrow plasmacytosis of > 30% by bone marrow aspirate and/or biopsy; or 4. Serum Free Light Chains (By the Freelite test) > 2X ULN, in the absence of renal failure 5. Radiographic evidence of disease 3. Performance status of < 2 as per ECOG scale, unless PS of 3-4 based solely on bone pain. 4. Patients must have a platelet count > 100,000/L and an ANC of at least 1,000/μl. 5. Patients must have adequate renal function defined as serum creatinine ≤2.5 mg/dL. 6. Patients must have adequate hepatic function defined as serum transaminases and direct bilirubin < 3 x the upper limit of normal. 7. Male or female adults of at least 18 years of age. 8. Voluntary written informed consent before performance of any study-related procedure not part of normal medical care, with the understanding that consent may be withdrawn by the subject at any time without prejudice to future medical care. 9. Female subject is either post-menopausal or surgically sterilized or willing to use an acceptable method of birth control (i.e., a hormonal contraceptive, intra-uterine device, diaphragm with spermicide, condom with spermicide, or abstinence) for the duration of the study. 10. Growth factors are allowed during the study 11. Male subject agrees to use an acceptable method for contraception for the duration of the study  Platelet count of <100x 10(9)/L within 14 days before enrollment. 2. Absolute neutrophil count (ANC) <1.0 x 10(9)/L 3. Serum creatinine ≥ 2.5 mg/dL within 14 days before enrollment. 4. Patient has >Grade 2 peripheral neuropathy within 14 days before enrollment. 5. Myocardial infarction within 6 months prior to enrollment or has New York Heart Association (NYHA) Class III or IV heart failure (see section 1.4), uncontrolled angina, severe uncontrolled ventricular arrhythmias, or electrocardiographic evidence of acute ischemia or active conduction system abnormalities. Prior to study entry, any ECG abnormality at Screening has to be documented by the investigator as not medically relevant. 6. Patients with a history of treatment for clinically significant ventricular cardiac arrhythmias. 7. Patient has hypersensitivity to bortezomib, boron or mannitol. 8. Chemotherapy or radiotherapy received within the previous 4 weeks of study enrollment. 9. Female subject is pregnant or breast-feeding. Confirmation that the subject is not pregnant must be established by a negative serum beta-human chorionic gonadotropin (beta-hCG) pregnancy test result obtained during screening. Pregnancy testing is not required for post-menopausal or surgically sterilized women. 10. Patient has received other investigational drugs with 14 days before enrollment 11. Serious medical or psychiatric illness likely to interfere with participation in this clinical study. 12. Diagnosed or treated for another malignancy within 3 years of enrollment, with the exception of complete resection of basal cell carcinoma or squamous cell carcinoma of the skin, an in situ malignancy, or low-risk prostate cancer after curative therapy. 13. POEMS Syndrome 14. Clinically significant hepatic dysfunction as noted by bilirubin or AST > 3 times the upper normal limit or clinically significant concurrent hepatitis. 15. Uncontrolled, active infection 16. Patients that have taken bisphosphonates within 30 days of screening will not be eligible for this trial. 17. Must not have received 90 days prior to enrolling in this trial