JOURNAL OF BONE AND MINERAL RESEARCH Volume 7, Number 11, 1992 Mary Ann Liebert, Inc., Publishers zyxwvutsrq Utility of Type I Procollagen Propeptide Assays for Assessing Abnormalities in Metabolic Bone Diseases PETER R. EBELING, JAMES M. PETERSON, and B. LAWRENCE RIGGS ABSTRACT We measured type I procollagen carboxyl-terminal propeptide (PICP) by a commerclal radioimmunoassay and amino-terminal propeptide (PINP) by an enzyme-linked immunosorbent assay (ELISA) developed in our laboratory in serum from zyxwvut 75 normal women, 10 growing girls, 84 normal men, and 197 patients with various metabolic bone diseases. The molar concentrations of serum PINP were 100-fold higher than those of PICP, suggesting differences in the metabolism of PICP and PINP. In normal women, serum PICP val- ues correlated positively with age and serum PINP values correlated negatively with age zyx (r zyx = 0.28 and -0.32, respectively; zyxwvut P = 0.02). In normal men, however, PICP correlated negatively with age (r = -0.32, P = 0.003) whereas PINP did not change. As assessed by Z scores (SD from age- and sex-specific predicted normal mean), changes in serum PICP and PINP values were concordant in hypoparathyroidism (mean zy 2 scores for PICP and PINP, -0.63 and -1.48, respectively) and Cushing's syndrome (0.50 and 0.40) but were discordant in acromegaly (0.78 and -0.68), hyperthyroidism (1.33 and zyx -OM), untreated postmeno- pausal osteoporosis (-0.11 and 0.40), fluoride-treated postmenopausal osteoporosis (-0.61 and 1.08), Paget's disease (4.05 and -0.20), and chronic renal failure (1.45 and -0.50). With either assay, deviations from normal were less pronounced than the deviations of concurrently measured serum osteocalcin and bone alkaline phosphatase values. The deviations in these latter two values agreed better with those of PICP than with those of PINP, except in untreated or fluoride-treated osteoporotic patients. We conclude that for as- sessing abnormalities in bone formation in metabolic bone diseases, assays for serum PICP or PINP gener- ally are inferior to those for serum osteocalcin and bone alkaline phosphatase. INTRODUCTION ECAUSE CIRCULATING MARKERS of bone turnover can be B measured repeatedly and noninvasively, these mea- surements are useful in evaluating metabolic bone diseases. The most widely used markers of osteoblastic activity have been serum osteocalcin concentration and serum activity of the bone isoenzyme of alkaline phosphatase. Osteocal- cin (also called bone gla protein, or BGP), a noncollage- nous protein found only in bone and dentin, is a relatively minor constituent of the bone matrix and represents only 15% of the noncollagenous proteins") or less than 1% of the nonmineral bone compartment. However, type I colla- gen is the major collagen product synthesized by bone cells and represents more than 90% by weight of the nonmin- era1 component of bone. zyxw (I) The concentration of osteocal- cin in serum is a sensitive measure of bone turnover in metabolic bone disease~[~-~) and reflects mainly, if not ex- clusively, bone formation. ('+) The synthesis of osteocalcin by the osteoblast is independently regulated by 1,25-dihy- droxyvitamin DO. (lo) Bone alkaline phosphatase, a major osteoblast product, is also a sensitive index of bone forma- tion. In some conditions characterized by alterations in bone formation, however, circulating osteocalcin and bone alkaline phosphatase concentrations have been found to be dissociated. 16) Thus, measurement of serum type I procol- lagen has theoretical advantages over measurements of osteocalcin and bone alkaline phosphatase in serum. Division of Endocrinology and Metabolism, Department of Internal Medicine, Mayo Clinic and Mayo Foundation, Rochester, Minnesota. 1243