title: Biochemical measurements in the prediction of histologic subtype of renal transplant bone disease in women.
abstract: Renal transplant osteodystrophy encompasses several histologic subtypes. Bone histomorphometric examination reliably distinguishes these groups but is invasive, is time-consuming, and delays diagnosis. Establishing a noninvasive method of correctly predicting histologic subtype in an individual to direct management is an attractive proposition. We identified 19 female renal transplant recipients with histologic evidence of hyperparathyroid bone disease (HPTH) and 14 with adynamic bone (ADB). We evaluated serum osteocalcin and bone-specific alkaline phosphatase as bone formation markers and urinary hydroxyproline (Hypro) and deoxypyridinoline cross-links as bone resorption markers. Mean concentrations for all markers were higher in the HPTH group, reaching significance for Hypro (HPTH, 24.8 +/- 4.2 micromol/mmol creatinine; ADB, 13.2 +/- 5.0 micromol/mmol creatinine; P = 0.01). A cutoff of 16.4 micromol/mmol creatinine for Hypro (Youden's index, 0.65) gave a sensitivity of 93% and specificity and positive predictive value (PPV) of 72% in predicting HPTH. In combination, Hypro greater than 16.4 micromol/mmol creatinine and parathyroid hormone greater than 80 pg/mL gave a specificity of 100%, sensitivity of 32%, and PPV of 100%. Conversely, for predicting ADB, Hypro less than 15.1 micromol/mmol creatinine (Youden's index, 0.45) gave a specificity of 93%, sensitivity of 53%, and PPV of 91%. Hypro less than 15.1 micromol/mmol creatinine plus osteocalcin less than 6.8 microg/L gave a specificity of 84.2%, sensitivity of 64.3%, and PPV of 75%. Significant associations between markers and histomorphometry were evident only for Hypro and osteocalcin (with osteoblast surface) and all markers (except deoxypyridinoline cross-links) with cortical volume. Markers have limited utility in identifying histologic subtype (Hypro was most effective) and, with the exception of Hypro and osteocalcin, showed little association with cell surface markers of bone cell activity.
authors.affiliation: Division of Mineral Metabolism and Department of Clinical Chemistry, City Hospital, Nottingham, United Kingdom. cparker@doctors.org.uk
authors.forename: Cornelle R
authors.initials: CR
authors.lastname: Parker
authors.forename: Penelope J
authors.initials: PJ
authors.lastname: Blackwell
authors.forename: Anthony J
authors.initials: AJ
authors.lastname: Freemont
authors.forename: David J
authors.initials: DJ
authors.lastname: Hosking
mesh_terms: D000328:Adult; D000368:Aged; D000469:Alkaline Phosphatase / Q000097:blood; D000596:Amino Acids / Q000652:urine; D015415:Biomarkers / Q000097:blood / Q000652:urine; D015519:Bone Density / Q000502:physiology; D001862:Bone Resorption / Q000097:blood / Q000175:diagnosis / Q000652:urine; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000097:blood / Q000145:classification* / Q000473:pathology* / Q000652:urine; D003404:Creatinine / Q000097:blood / Q000378:metabolism; D005260:Female; D006801:Humans; D006909:Hydroxyproline / Q000652:urine; D016030:Kidney Transplantation / Q000009:adverse effects* / Q000473:pathology*; D008593:Menopause / Q000097:blood / Q000502:physiology / Q000652:urine; D008875:Middle Aged; D015675:Osteocalcin / Q000097:blood; D010281:Parathyroid Hormone / Q000097:blood; D011237:Predictive Value of Tests; D006113:United Kingdom; D016387:Women's Health
chemical_list: D000596:Amino Acids; D015415:Biomarkers; D010281:Parathyroid Hormone; D015675:Osteocalcin; C036020:deoxypyridinoline; D003404:Creatinine; D000469:Alkaline Phosphatase; D006909:Hydroxyproline