title: Biochemical markers of bone turnover following high-dose chemotherapy and autografting in multiple myeloma.
abstract: The effect of high-dose chemotherapy and autografting on bone turnover in myeloma is not known. A study of 32 myeloma patients undergoing blood or marrow transplant (BMT), conditioned with high-dose melphalan, was done. Bone resorption was assessed by urinary free pyridinoline (fPyr) and deoxypyridinoline (fDPyr), expressed as a ratio of the urinary creatinine concentration. Bone formation was assessed by serum concentration of procollagen 1 extension peptide (P1CP) and bone-specific alkaline phosphatase (BSAP). Eighteen cases had normal fPyr and fDPyr at transplant, and in all but one of these cases the level remained normal throughout subsequent follow-up. In contrast, in 14 cases urinary fPyr and fDPyr levels were increased at transplant. In these cases, both fPyr and fDPyr fell to normal levels over the next few months (P = .0009 and.0019, respectively). fPyr and fDPyr levels at transplant and their trends post-BMT were unrelated to the use of pre-BMT or post-BMT bisphosphonate or post-BMT interferon. Nine cases had elevated P1CP or BSAP at transplant, which rapidly normalized. In most patients there was an increase in P1CP and/or BSAP several months post-transplant. In conclusion, increased osteoclast activity may be present even in apparent plateau phase of myeloma. High-dose chemotherapy with autografting may normalize abnormal bone resorption, although the effect may take several weeks to emerge and may be paralleled by increased osteoblast activity. The findings provide biochemical evidence that autografting may help normalize the abnormal bone turnover characteristic of myeloma. (Blood. 2000;96:2697-2702)
authors.affiliation: Jose Carreras BMT Unit, Department of Haematology, Royal Liverpool University Hospital, Liverpool, England.
authors.forename: R E
authors.initials: RE
authors.lastname: Clark
authors.forename: A J
authors.initials: AJ
authors.lastname: Flory
authors.forename: E M
authors.initials: EM
authors.lastname: Ion
authors.forename: B E
authors.initials: BE
authors.lastname: Woodcock
authors.forename: B H
authors.initials: BH
authors.lastname: Durham
authors.forename: W D
authors.initials: WD
authors.lastname: Fraser
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood*; D000596:Amino Acids / Q000652:urine*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology* / Q000627:therapeutic use; D015415:Biomarkers; D016723:Bone Remodeling; D001862:Bone Resorption / Q000097:blood / Q000188:drug therapy / Q000209:etiology* / Q000652:urine; D002330:Carmustine / Q000008:administration & dosage; D004002:Clodronic Acid / Q000627:therapeutic use; D003131:Combined Modality Therapy; D003561:Cytarabine / Q000008:administration & dosage; D018450:Disease Progression; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007527:Isoenzymes / Q000097:blood*; D008297:Male; D008558:Melphalan / Q000008:administration & dosage; D008875:Middle Aged; D009101:Multiple Myeloma / Q000097:blood / Q000150:complications* / Q000188:drug therapy / Q000628:therapy / Q000652:urine; D010010:Osteoclasts / Q000378:metabolism; D010446:Peptide Fragments / Q000097:blood*; D011034:Podophyllotoxin / Q000008:administration & dosage; D011347:Procollagen / Q000097:blood*; D019172:Transplantation Conditioning; D014182:Transplantation, Autologous; D016896:Treatment Outcome
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D007527:Isoenzymes; D010446:Peptide Fragments; D011347:Procollagen; C042813:procollagen type I carboxy terminal peptide; D003561:Cytarabine; D004002:Clodronic Acid; C015484:pyridinoline; C036020:deoxypyridinoline; D000469:Alkaline Phosphatase; D011034:Podophyllotoxin; D008558:Melphalan; D002330:Carmustine