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Use of bone turnover marker, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), in the assessment and monitoring of bone metastasis in prostate cancer.

BACKGROUND: We investigated whether a new marker of bone turnover, pyridinoline cross-linked carboxyterminal telopeptide of type I collagen (ICTP), could be useful in the assessment of bone metastasis and in monitoring of the response to treatment in patients with prostate cancer with bone metastasis. METHODS: In all, 58 patients with prostate cancer (25 with bone metastasis and 33 without bone metastasis) and 52 patients with benign prostate hypertrophy who were treated between June 1994-August 1997 were included in this study. All patients were newly diagnosed. RESULTS: Serum ICTP levels in patients with prostate cancer with bone metastasis were significantly higher than those in patients with prostate cancer without bone metastasis (P<0.0001) or with benign prostate hypertrophy (P<0.0001). No significant differences were observed in serum ICTP levels between patients with prostate cancer without bone metastasis and those with benign prostate hypertrophy. Serum ICTP levels correlated significantly with Soloway's grading system for bone scans. Serum ICTP levels in patients with bone metastasis showed a significant downward trend in response to hormonal treatment. CONCLUSIONS: The determination of serum ICTP levels is useful in the assessment of bone metastasis and in monitoring the response of bone metastasis to treatment to prostate cancer.

Aged↗

Diagnostic value of bone-turnover metabolites in the diagnosis of bone metastases in patients with lung carcinoma.

BACKGROUND: Several biochemical markers of bone formation and bone resorption have been developed recently. The authors evaluated the usefulness of new biomarkers, such as urinary deoxypyridinoline (D-PYD), serum pyridinoline cross-linked C-telopeptides of Type I collagen (1CTP), and urinary pyridinoline cross-linked N-telopeptides of Type I collagen (NTx), in the assessment of bone metastases in patients with lung carcinoma. METHODS: The serum concentrations of 1CTP and the urinary concentrations of D-PYD and NTx were measured in 100 lung carcinoma patients, of whom 20 patients had bone metastases and 80 patients did not. Receiver operating characteristic (ROC) curves were drawn for these markers to compare their usefulness in detecting bone metastases originating in lung carcinoma. RESULTS: Urinary concentrations of NTx in patients with bone metastases were significantly greater than in patients without bone metastases (147.1 +/- 129.3 pmol bone collagen equivalents [BCE]/micromol Cr vs. 47.2 +/- 29.9 pmol BCE/micromol Cr; P < 0.0001). Urinary concentrations of D-PYD in patients with bone metastases also were significantly greater than in patients without bone metastases (10.0 +/- 3.6 BCE/micromol Cr vs. 6.6 +/- 2.2 pmol BCE/micromol Cr; P = 0.0001). No significant difference was observed in serum concentrations of 1CTP between patients with and without bone metastases. A moderate but significant correlation was seen between NTx and D-PYD (correlation coefficient [R] = 0.435; P < 0.0001) and between D-PYD and 1CTP (R = 0.525; P < 0.0001). NTx had a better ROC curve than D-PYD and 1CTP (the areas under the ROC curve were 0.84, 0.79, and 0.62, respectively). Using the threshold of 62.5 pmol BCE/micromol Cr for NTx, sensitivity, specificity, and accuracy were 0.800, 0.737, and 0.750, respectively. CONCLUSIONS: In the current study, the measurement of NTx appeared to be most useful as a marker of bone metastases in patients with lung carcinoma.

Adult↗

In vivo bone formation by human bone marrow stromal cells: effect of carrier particle size and shape.

Successful closure of bone defects in patients remains an active area of basic and clinical research. A novel and promising approach is the transplantation of human bone marrow stromal cells (BMSCs), which have been shown to possess a significant osteogenic potential. The extent and quality of bone formation by transplanted human BMSCs strongly depends on the carrier matrix with which cells are transplanted; to date, hydroxyapatite/tricalcium phosphate (HA/TCP) supports far more osteogenesis than any other matrix tested. In order to further improve the technique of BMSC transplantation, we studied whether commercially available HA/TCP particles, clinically approved as an osteoconductive material and commercially available as particles measuring 0.5-1.0 mm diameter, is an optimum matrix for promoting bone development by BMSCs. HA/TCP and HA particles of varying size were sieved into a variety of size ranges, from <0.044 mm to 1.0-2.0 mm. Transplants were formed by mixing 40 mg aliquots of particles with cultured passaged human BMSCs. They were placed in subcutaneous pockets in immunocompromised Bg-Nu-XID mice and harvested 4 or 10 weeks later. The transplants were examined histologically; the presence of bone within each transplant was evaluated using histomorphometry or blindly scored on a semiquantitative scale. Transplant morphology and the amount of new bone varied in a consistent fashion based on particle size and shape. Transplants incorporating HA/TCP particles of 0.1-0.25 mm size demonstrated the greatest bone formation at both 4 and 10 weeks; larger or smaller particles were associated with less extensive bone formation, while a size of 0.044 mm represented a threshold below which no bone formation could be observed. Flat-sided HA particles measuring 0.1-0.25 mm formed no bone. The differences in bone formation were not attributable to the differences in cell attachment among the groups. Instead, the size and spatial and structural organization of the particles within BMSC transplants appear to determine the extent of bone formation. These findings provide necessary information for the successful clinical application of BMSC transplantation techniques.

Animals↗

Human parathyroid hormone-(1-34) prevents bone loss and augments bone formation in sexually mature ovariectomized rats.

A group of 3-month-old Sprague-Dawley rats were sham operated or ovariectomized and given daily injections of human PTH-(1-34) (8 or 16 micrograms per 100 g body weight) for 5 weeks. At the termination of the study histomorphometric techniques were used to examine changes in cortical and cancellous bone in the diaphysis and proximal metaphysis of the tibia. Ovariectomy resulted in a 50% decrease in cancellous bone that was accompanied by a 41 and 120% increase in osteoclasts and osteoblasts, respectively. In contrast, in the ovariectomized animals treated with PTH, the metaphyseal cancellous bone increased by over 300% to a level in excess of that present in the sham-operated control animals. The increase in cancellous bone induced by PTH was associated with an over 70% increase in osteoblasts and tetracycline-labeled area and an unexpected decrease in trabecular osteoclasts. In the tibial diaphysis PTH also decreased endosteal osteoclasts and at the same time increased osteoblast size and number as well as endosteal and periosteal bone formation; ovariectomy increased only periosteal bone formation. Our findings demonstrate that intermittent administration of PTH prevents ovariectomy-induced bone loss and augments cancellous and cortical bone formation in sexually mature ovariectomized rats. Although the basis of the bone anabolic action of PTH remains elusive, our data indicate that it may involve the uncoupling of bone formation and resorption such that the latter is inhibited as bone formation is enhanced. Our findings are also compatible with the view that intermittent administration of PTH increases bone mass, in part by stimulating the proliferation and differentiation of osteoblast progenitors while inhibiting osteoclast proliferation.

Animals↗

Reduced femoral neck bone density in the daughters of women with hip fractures: the role of low peak bone density in the pathogenesis of osteoporosis.

Low bone density in women with hip fractures ("senile" osteoporosis) may be due to excessive bone loss or low peak bone density. If excessive bone loss is responsible, then no reduction in bone density is expected in their daughters. If low peak bone density is responsible, then bone density should also be reduced in their daughters because genetic and family environmental factors influence the variability in bone density. Bone density was measured using dual-photon absorptiometry and expressed as a standardized deviation or Z score relative to 697 controls, adjusting for age, height, weight, and menopausal status. In 74 women with hip fractures, the Z score (mean +/- SEM) was -0.52 +/- 0.14 (P < 0.001) at the femoral neck, -1.04 +/- 0.17 (P < 0.001) at the femoral shaft, and -0.43 +/- 0.10 (P < 0.001) at the lumbar spine. In their 41 daughters, the Z score was -0.40 +/- 0.17 (P < 0.05) at the femoral neck, -0.41 +/- 0.19 (P < 0.001) at the femoral shaft, and 0.23 +/- 0.13 (NS) at the lumbar spine. We conclude that daughters of women with hip fractures are likely to be at increased risk for hip fractures themselves because they have reduced femoral neck bone density. Femoral neck fractures may not be entirely attributable to trauma; reduced bone density is likely to contribute and may be caused by the attainment of a lower peak femoral neck bone density.

Absorptiometry, Photon↗