Bone markers in the diagnosis of low turnover osteodystrophy in haemodialysis patients.
BACKGROUND
Renal osteodystrophy includes a number of low and high turnover bone histologic patterns which require a bone biopsy for their full identification. The role of intact PTH and several classical and more recent bone markers in the non-invasive diagnosis of renal bone disease in patients with CRF in HD requires further definition since available published data are limited.


METHODS
In addition to intact PTH, alkaline phosphatase (AP) and osteocalcin (BGP), bone alkaline phosphatase isoenzyme (BALP), tartrate resistant acid phosphatase (TRAP), C-terminal cross-linked peptide of collagen type 1 (ICTP) and deoxypyridinoline (DPD) were measured in the serum of 41 patients on haemodialysis, subjected at the same time to transiliac bone biopsy for histomorphometric, histodynamic and aluminium histochemical examination. Histodynamic evaluation following double tetracycline label, was carried out in 37 patients. The patients had no evidence of active cytolytic and cholestatic liver disease and a history of very limited aluminium exposure.


RESULTS
The patients had differing degrees of hyper-parathyroidism, with intact PTH ranging from normal to very elevated levels. Serum values of the markers BGP, ICTP and DPD, normally excreted through the kidneys, were on average very high. The correlation coefficients of the humoral parameters vs dynamic variables, such as BFR/BS, were high. The highest values were: intact PTH 0.798, AP 0.900, BALP 0.891, ICTP 0.807. The patients, grouped in low turnover osteodystrophy (LTO; 9), mixed osteodystrophy (MO; 9) and prevalent hyperparathyroidism (HP; 23), showed significant difference in the levels of most humoral and static and dynamic parameters (ANOVA). Bone aluminium histochemistry was negative in all cases. Discrimination of LTO patients from the other groups by humoral parameters, at the highest value of accuracy, showed 100% sensitivity and 93.7% specificity with a cut-off of 12.9 ng/ml for BALP; 88.9% sensitivity and 93.7% specificity with a cut-off of 21.5 ng/ml for DPD, and 88.9% sensitivity and 90.6% specificity with a cut-off of 79.7 pg/ml for intact PTH. The other markers had lower values. A standardized z-score approach for evaluation of all humoral parameters was also carried out. Using all variables, a correct classification of MO/HP and of LTO was possible in 93.8 and 88.9% of the cases, respectively. Predictive power was 96.8 and 80%, respectively for MO/HP and LTO. When the only variables used were intact PTH and BALP, a correct classification of MO/HP and LTO was possible in 90.6% and 88.9%, respectively. Predictive value of MO/HP was 96.7% and for LTO 72.7%. Predictive values using PTH and AP were 96.3% and 57.2%, respectively.


CONCLUSIONS
Intact PTH and several relatively new bone markers are of certain value in the non-invasive diagnosis of renal osteodystrophy. However some of the humoral markers carry the same quality of information and the use of intact PTH and BALP may be adequate in the discrimination of bone histologic patterns. In cases exempt from liver disease, PTH and AP may be used as a less costly alternative. Bone biopsy could be chiefly limited to cases with borderline humoral values and to all those with a suspected aluminium overload.
Pathophysiology and Hypertension Unit, La Sapienza University, Rome, Italy.
G
G
Coen
P
P
Ballanti
E
E
Bonucci
S
S
Calabria
M
M
Centorrino
V
V
Fassino
M
M
Manni
D
D
Mantella
S
S
Mazzaferro
I
I
Napoletano
D
D
Sardella
F
F
Taggi
D000328:Adult; D000469:Alkaline Phosphatase / Q000097:blood; D015415:Biomarkers; D001706:Biopsy; D001842:Bone and Bones / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D012080:Chronic Kidney Disease-Mineral and Bone Disorder / Q000175:diagnosis* / Q000378:metabolism*; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000097:blood; D008297:Male; D008875:Middle Aged; D010281:Parathyroid Hormone / Q000097:blood; D006435:Renal Dialysis
D015415:Biomarkers; D007527:Isoenzymes; D010281:Parathyroid Hormone; D000469:Alkaline Phosphatase