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The aim of this work was to evaluate the usefulness of serum aminoterminal propeptide of type I collagen (PINP) in the early detection of bone metastases associated with prostatic carcinoma. The results were compared with those of bone isoenzyme of alkaline phosphatase (bAP). Levels of total alkaline phosphatase (TAP) and prostatic specific antigen (PSA), related to the existence of bone metastases, are also evaluated. Fifty-five male patients aged 70-80 years were studied. Nine presented a benign prostatic hyperplasia (BPH) and the rest clinically confirmed prostatic cancer. Cancer patients were classified in accordance with the staging grouping of the International Union Against Cancer/American Joint Committee on Cancer TNM 1992 Revision: stage 0 or BPH (n=9), I (n=6), II (n=12), III (n=18) and IV (n=10). According to this classification, patients of groups BPH, I, II and III have no evidence of metastases. Those of stage IV present any type of metastases. In the case of this work, all patients of group IV presented bone metastases. Some patients of group BPH, I and II were untreated. The rest of the patients were under treatment (radical prostatectomy, telecobaltotherapy or hormonal therapy) for a period of between 6 months and 15 years. Serum PSA (Quimioluminiscence, IMMULITE), PINP (RIA, Orion Diagnostica), bAP (IRMA, Tamdem R-Ostase, Hybritech), and TAP (autoanalyzer) were determined. We found the following sensitivities and specificities (relating the presence of bone metastases to values higher than the upper limit of normality and, in the case of PSA, to values higher than 100 microg/L): (1) PINP: 100% (10/10) and 87% (39/45), (2) bAP: 90% (9/10) and 82% (37/45), (3) TAP: 60% (6/10) and 93% (42/45), (4) PSA: 40% (4/10) and 100% (45/45). These results suggest that PINP and bAP are adequate biochemical markers of bone formation to be used in the detection of bone metastases in prostatic carcinoma, improving the sensitivity and specificity of TAP and PSA. With respect to PINP, bAP presents the disadvantage of its cross-reactivity with liver isoenzyme.

A comparative study was performed on the sensitivity of the determination of the available biochemical markers of bone formation--total and bone alkaline phosphatase (TAP and bAP, respectively), osteocalcin (BGP), procollagen I aminoterminal propeptide (PINP) and procollagen I carboxyterminal propeptide (PICP)--in the study of postmenopausal osteoporosis. The comparison between PINP and PICP, due to the recent development of the amino-terminal assay, is of special interest. The study included 26 untreated osteoporotic postmenopausal women, age 59 +/- 6 years (range 46-69 years) and 17 healty control postmenopausal women, age 56 +/- 7 years (range 48-70 years). We found a significant increase in the levels of bAP (p = 0.0021), BGP (p = 0.041), PINP (p = 0.0001) and PCIP (p = 0.0073), but not in the levels of TAP (p = 0.3389), in osteoporotic patients with respect to the control group. Serum PINP and bAP showed the highest diagnostic accuracy among the markers of bone formation studies, as can be deduced from the receiver operating characteristics (ROC) curves. In spite of their similar origin (amino-terminal and carboxy-terminal release from a procollagen molecule), the results obtained by measuring levels of PINP are significantly better than those found with PICP.

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Fragments derived from degradation of type I collagen C-telopeptide (CTX) can be nonisomerized (alpha) or beta-isomerized (beta) depending on the age of bone; i.e., mainly the alpha form is derived from new bone and the beta form from old bone. We have studied 41 female patients with anorexia nervosa (AN), aged 18.5 +/- 2.2 years (range 16-24 years), and with an evolution time between 1.5 and 11 years, and 31 healthy control females (C), with a mean age of 19 +/- 2.3 years (range 16-24 years). The AN patients showed a significant decrease in bone mass, with a mean Z-score of bone mineral density (BMD) of -3.2 +/- 0.8 (range -0.9 to -5.4). The aim of our study was to determine the levels of urinary alpha- and beta-CTX markers of bone resorption, the alpha/beta ratio (alpha/beta), and the level of bone alkaline phosphatase (bAP), a biochemical marker of bone formation, in order to relate them to the degree of osteopenia and the status of bone remodeling. Statistical analysis was by the Mann-Whitney test. The degree of osteopenia correlated with bAP levels (p = 0.0027) but not with the other parameters. Patients with AN were divided into three groups according to their levels of bAP: high (H), normal (N) or low (L). We found that BMD was significantly lower, and alpha- and beta-CTX were significantly higher, in groups H and N than in group L. Bone AP correlated significantly with alpha-CTX (p = 0.0042) and alpha/beta (0.0095) in the controls, but not with beta-CTX, while in AN patients bAP correlated with beta-CTX (p = 0.0000) and with alpha-CTX (p = 0.022) but not with the alpha/beta ratio. The ratio CTX/bAP (resorption/formation) was similar in AN patients and controls. It is concluded that: (1) patients with AN have a high degree of osteopenia which correlated with bAP levels; (2) urinary CTX fragments found in AN patients seem to come mainly from old bone (beta-CTX), while CTX found in healthy adolescent control females come from new bone (alpha-CTX). For this reason, alpha-CTX is more suitable than beta-CTX for measuring bone resorption in controls and beta-CTX is more suitable in patients with AN; (3) the resorption/formation ratio (CTX/bAP) was similar in AN patients and controls. From points (2) and (3) it is possible to suggest that, although bAP reflects bone formation in control females, this marker does not reflect effective bone mineralization in AN patients, a similar feature to that of patients with osteomalacia.

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