Inclusion Criteria:

• Patients with symptomatic MM as defined by IMWG requiring anti-myeloma therapy.
  • Monoclonal plasma cells in the bone marrow greater than or equal to 10% and/or presence of a biopsy-proven plasmacytoma
  • Monoclonal protein present in the serum and/or urine
• Creatinine clearance < 30 mL/min, not eligible for bisphosphonate. Estimated glomerular filtration rate will be calculated using Cockcroft-Gault equation.
• Serum calcium or albumin-adjusted serum calcium ≥ 2.1 mmol/L (8.4 mg/dL) and ≤ 2.9 mmol/L (11.5 mg/dL) (Reference range 8.5-10.8 mg/dL)
• Able to tolerate daily supplementation of calcium and vitamin D
• Vitamin D level ≥ 30 ng/mL after repletion
• Participants must have normal organ as defined below:
  • Total bilirubin ≤ 2.0 x ULN
  • AST(SGOT) ≤2.5 × institutional upper limit of normal
  • ALT(SGPT) ≤2.5 × institutional upper limit of normal
• Plan to receive anti-myeloma therapies.
• Age ≥ 18 years.
• ECOG performance status ≤ 2
• Life expectancy greater than 6 months
• 0-3 lines of prior anti-myeloma therapy.
• Subjects with reproductive potential must be willing to use, in combination with his/her partner, 2 highly effective methods of effective contraception or practice sexual abstinence throughout the study and continue for 5 months after the study duration. Subjects who are surgically sterile (e.g. history of bilateral tubal ligation, hysterectomy) or whose sexual partner is sterile (e.g. history of vasectomy) are not required to use additional contraceptive measures.
• Ability to understand and the willingness to sign a written informed consent document.

Exclusion Criteria:

• Prior administration of denosumab.
• Active IV bisphosphonate use in the last 3 months.
• POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes).
• Plasma cell leukemia.
• Prior history or current evidence of osteonecrosis/osteomyelitis of the jaw.
• Active dental or jaw condition which requires oral surgery, including tooth extraction.
• Non-healed dental/oral surgery, including tooth extraction.
• Planned invasive dental procedures during the course of study.
• Evidence of any of the following conditions per subject self-report or medical chart review
  • Any prior invasive malignancy within 5 years of enrollment that may affect outcome of study
  • Any non-invasive malignancy not treated with curative intent or with known active disease within 5 years before enrollment that may affect outcome of study
  • Major surgery or significant traumatic injury occurring within 4 weeks before enrollment
  • Active infection with Hepatitis B virus or Hepatitis C virus
  • known infection with human immunodeficiency virus (HIV)
  • Active infection requiring IV anti-infective therapy
• Subject is pregnant or breast feeding, or planning to become pregnant within 5 months after the end of treatment.
• Female subject of child-bearing potential is not willing to use, in combination with her partner, 2 methods of highly effective contraception during treatment and for 5 months after the end of treatment.
• Clinically significant hypersensitivity to denosumab 120 mg.
• Known sensitivity to any of the products to be administered during the study (e.g. calcium, or vitamin D).
• Subject is receiving or is less than 14 days since ending other experimental drug (no marketing authorization for any indication).
• Any major medical or psychiatric disorder that, in the opinion of the investigator, might prevent the subject from completing the study or interfere with the interpretation of the study results.