REDUCED SERUM LEVELS OF CARBOXY-TERMINAL PROPEPTIDE OF HUMAN TYPE-I PROCOLLAGEN IN A FAMILY WITH TYPE I-A OSTEOGENESIS IMPERFECTA

We measured serum levels of total alkaline phosphatase activity, osteo calcin, carboxy-terminal propeptide of human type I procollagen (PICP) , tartrate-resistant acid phosphatase activity (TRAP), and the fasting urinary hydroxyproline/creatinine ratio (OHPr/Cr) in seven affected m embers (four men, three women; age, 43.3 +/- 16.6 years [mean a SD]) o f a family with clinically diagnosed type I-A osteogenesis imperfecta (OI) and in eight (five men, three women) normal age-matched (38.2 +/- 10.3) relatives. Three boys with OI and three normal girls of the sam e family were also studied, although they were excluded from statistic al analysis. Bone mineral density was also determined at four differen t skeletal sites. Serum levels of PICP were measured with a radioimmun oassay (Farmos Diagnostica, Turku, Finland). There were no significant differences in mean values of the biomarkers studied between OI patie nts and normal relatives, with the only exception being serum levels o f PICP (35 +/- 7.5 v 219 +/- 107.5 mu g/L, P < .001). A significant re duction of BMD was found in OI patients compared with normal relatives at the lumbar (L) spine (680 +/- 61 v 1,128 +/- 92 mg/cm(2), P < .001 ), at the ultradistal radius ([UDR] 323 +/- 85 v 458 +/- 76, P < .006) , at the femoral neck ([F] 494 +/- 140 v 791 +/- 104, P < .001), and a t the junction of the distal and middle third of the radius ([MR] 639 +/- 71 v 717 +/- 52, P < .029). When the patients and control subjects were combined, there were significant positive correlations between s erum PICP and BMD values at various skeletal sites (L,P < .006; F,P < .05; UDR, P < .005; MR, P < .007). Our results suggest that decreased levels of serum PICP are typical of 01 type I patients, or at least of this family. This should be ascribed to a decreased amount of collage n produced, although the possibility of an abnormal sequence not recog nized by the antiserum used should also be considered. Densitometric r esults indicate that quantitative or qualitative defects of collagen s tructure may contribute to the fragility of 01 bone by interfering wit h complete mineralization and/or normal tissue structure. Copyright (C ) 1994 by W.B. Saunders Company