title: Biomarkers of bone remodeling in multiple myeloma patients to tailor bisphosphonate therapy.
abstract: BACKGROUND
  Patients with multiple myeloma may be susceptible to osteonecrosis of the jaw (ONJ) and stress fractures due to long-term aminobisphosphonate (aBP) therapy. However, it is unknown whether urinary N-telopeptide (NTX) or other bone biomarkers are predictive of skeletal-related events (SRE) or the impact of cessation of aBP therapy on bone remodeling.
  
  
  METHODS
  We studied markers of bone turnover over a 6-month period after a single dose of zoledronic acid in 29 patients with multiple myeloma in remission who previously received 8 to 12 doses of pamidronate or zoledronate (NCT00577642). Our primary objective was to determine the duration of time urinary NTX levels remain suppressed after a single dose of zoledronate. A secondary objective was to identify and correlate other markers of bone remodeling with NTX changes. Thirty cytokines, based on their possible role in bone remodeling, were tested using cytokine arrays. Candidates were confirmed by ELISA.
  
  
  RESULTS
  All patients had continued suppression of NTX levels, except 1 patient who had an increase in NTX levels associated with an SRE. GDF-15 and decorin were found to decrease, whereas bone-specific alkaline phosphatase (BSALP) increased. Although not significant in aggregate, osteopontin and osteoprotegerin levels increased in at least half of the patients.
  
  
  CONCLUSIONS
  Our data show that NTX levels continue to be suppressed after aBP therapy, and suggest that suppressed NTX levels may be predictive of freedom from SRE in this patient population. Furthermore, osteoblast suppression by aBP may be reversible in myeloma. These data provide the basis for less frequent dosing of aBPs.
authors: Massachusetts General Hospital Cancer Center;
authors: Chirayu G
authors: CG
authors: Patel
authors: Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, Massachusetts.
authors: Andrew J
authors: AJ
authors: Yee
authors: Massachusetts General Hospital Cancer Center;
authors: Tyler A
authors: TA
authors: Scullen
authors: Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, Massachusetts.
authors: Neeharika
authors: N
authors: Nemani
authors: Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, Massachusetts.
authors: Loredana
authors: L
authors: Santo
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts.
authors: Paul G
authors: PG
authors: Richardson
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts.
authors: Jacob P
authors: JP
authors: Laubach
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts.
authors: Irene M
authors: IM
authors: Ghobrial
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts.
authors: Robert L
authors: RL
authors: Schlossman
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts.
authors: Nikhil C
authors: NC
authors: Munshi
authors: LeBow Institute for Myeloma Therapeutics and Jerome Lipper Center for Multiple Myeloma Research, Dana-Farber Cancer Institute; and Harvard Medical School, Boston, Massachusetts.
authors: Kenneth C
authors: KC
authors: Anderson
authors: Massachusetts General Hospital Cancer Center; Harvard Medical School, Boston, Massachusetts nraje@partners.org.
authors: Noopur S
authors: NS
authors: Raje
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000652:urine*; D050071:Bone Density Conservation Agents / Q000008:administration & dosage*; D016723:Bone Remodeling / Q000187:drug effects* / Q000502:physiology; D001862:Bone Resorption / Q000139:chemically induced / Q000175:diagnosis / Q000652:urine; D024042:Collagen Type I / Q000652:urine; D016207:Cytokines / Q000652:urine; D004164:Diphosphonates / Q000008:administration & dosage*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007093:Imidazoles / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000188:drug therapy* / Q000378:metabolism; D009367:Neoplasm Staging; D010020:Osteonecrosis / Q000139:chemically induced / Q000175:diagnosis* / Q000652:urine; D000077268:Pamidronate; D010455:Peptides / Q000652:urine; D011379:Prognosis; D000077211:Zoledronic Acid
chemical_list: D014408:Biomarkers, Tumor; D050071:Bone Density Conservation Agents; D024042:Collagen Type I; D016207:Cytokines; D004164:Diphosphonates; D007093:Imidazoles; D010455:Peptides; C052929:collagen type I trimeric cross-linked peptide; D000077211:Zoledronic Acid; D000077268:Pamidronate