Eficacia y seguridad a largo plazo del polimetilmetacrilato (PMMA) en pacientes osteoporóticos tratados mediante vertebroplastia percutánea / Long-term efficacy and safety of polymethylmethacrylate (PMMA) in osteoporotic patients treated by percutaneous vertebroplasty

OBJETIVO: Actualmente, existen pocos datos sobre la influencia a largo plazo del polimetilmetacrilato (PMMA) en la integridad de los cuerpos vertebrales tras la vertebroplastia percutánea (VP). Resulta de interés investigar la posible relación entre esta técnica y la aparición con el tiempo de fenómenos de osteólisis o la fragmentación del cemento en las vértebras intervenidas. El objetivo de este trabajo fue investigar si, a largo plazo, existe una pérdida de efectividad y/o seguridad de la VP con PMMA. MATERIAL Y MÉTODOS: Se analizaron radiografías de pacientes intervenidos correspondientes al post-operatorio inmediato y al estudio radiológico más reciente (VP hace más de 15 años). Con ambos estudios radiológicos, describimos: la altura del cuerpo vertebral, la angulación de platillos y la presencia de osteólisis alrededor del cemento en el tiempo. RESULTADOS: Un total de 7 pacientes intervenidos mediante VP con PMMA hace 15 o más años accedieron a realizarse una nueva radiografía en nuestro Centro. Tras el análisis de sus imágenes post-operatorias (inmediatas y a 15 ó más años de la cirugía), no se observó en ninguna de las vértebras intervenidas pérdida de altura del cuerpo vertebral cementado, diferencias de angulación en los platillos, presencia de osteólisis alrededor del cemento o fragmentación del PMMA inyectado. CONCLUSIÓN: El PMMA inyectado en el cuerpo vertebral mantiene una situación estable en el tiempo (más de 15 años). No se observan cambios en la interfaz hueso-PMMA, osteólisis y/o cambios en la altura de los cuerpos vertebrales en los casos analizados

OBJETIVE: Currently, there are limited data on the long-term influence of polymethylmethacrylate (PMMA) on the integrity of vertebral bodies after percutaneous vertebroplasty (PVP). Interesting investigation is being carried out into the possible relationship between this technique and the appearance over time of osteolytic phenomena or cement fragmentation in the intervened vertebrae. The objective of our study was to investigate whether there is a loss of effectiveness and/or safety of PVP with PMMA in the long term. MATERIAL AND METHOD: X-rays were analyzed of intervened patients corresponding to the immediate post-operative and the most recent radiological study (PVP more than 15 years previous). With both radiological studies, we describe: the height of the vertebral body, the angulation of lamellar plates and osteolytic presence around the cement over time. RESULTS: A total of 7 patients operated by PVP with PMMA 15 or more years earlier agreed to have a new radiograph in our center. After the analysis of their post-operative images (immediate and 15 or more years after surgery), no loss of height of the cemented vertebral body, differences in angulation in the lamellar plates, presence of osteolysis around the vertebrae was observed in any of the involved vertebrae cement or fragmentation of the injected PMMA. CONCLUSIONS: PMMA injected into the vertebral body remains stable over time (more than 15 years). There are no changes in the bone-PMMA interface, osteolysis and/or changes in the height of the vertebral bodies in the cases analyzed

Effects of Cyclosporine, Tacrolimus, and Rapamycin on Osteoblasts.

PURPOSE: One factor that can contribute to severe bone loss after transplantation is the direct action of immunosuppressants on bone cells. The aim of this work was to study the effects of cyclosporine (CsA), tacrolimus (FK-506), and rapamycin (RAPA) on the release of three local factors directly implicated in bone-remodeling regulation and apoptosis of human osteoblasts: interleukin (IL)-6, osteoprotegerin, and receptor activator of nuclear factor κß (RANKL). BASIC PROCEDURES: Human osteoblasts were obtained from five different patients who underwent orthopedic surgery. These cells were treated with what are considered to be a clinically high dose and an acceptable dose of each immunosuppressant-RAPA 50 ng/mL and 12 ng/mL, FK-506 20 ng/mL and 5 ng/mL, CsA 1000 ng/mL and 250 ng/mL-or vehicle. Apoptotic cell death was quantified using flow cytometry of DNA content in permeabilized, propidium iodide-stained cells. IL-6 was measured using enzyme-linked immunosorbent assay (ELISA; Quantikine Human IL6, R&D Systems, Minneapolis, Minn, United States). Messenger RNA (mRNA) expression of osteoprotegerin, RANKL, and IL-6 was measured using quantitative RT-PCR. MAIN FINDINGS: A significant increase in IL-6 (mRNA and released protein) was observed in the presence of FK-506 and RAPA. Addition of RAPA to the cultures of osteoblasts produced a significant increase in the OPG/RANKL ratio. A significant increase in osteoblast apoptosis was observed in the cells treated with FK-506 and RAPA 24 hours after the addition of immunosuppressants. CsA did not produce any significant changes in osteoblasts. PRINCIPAL CONCLUSIONS: These results suggest that an increase in osteoblast apoptosis by osteoblasts may be one of the mechanisms by which bone loss occurs after RAPA and FK-506 treatments.

Usefulness of bone turnover markers as predictors of mortality risk, disease progression and skeletal-related events appearance in patients with prostate cancer with bone metastases following treatment with zoledronic acid: TUGAMO study.

BACKGROUND: Owing to the limited validity of clinical data on the treatment of prostate cancer (PCa) and bone metastases, biochemical markers are a promising tool for predicting survival, disease progression and skeletal-related events (SREs) in these patients. The aim of this study was to evaluate the predictive capacity of biochemical markers of bone turnover for mortality risk, disease progression and SREs in patients with PCa and bone metastases undergoing treatment with zoledronic acid (ZA). METHODS: This was an observational, prospective and multicenter study in which ninety-eight patients were included. Patients were treated with ZA (4 mg every 4 weeks for 18 months). Data were collected at baseline and 3, 6, 9, 12, 15 and 18 months after the beginning of treatment. Serum levels of bone alkaline phosphtase (BALP), aminoterminal propeptide of procollagen type I (P1NP) and beta-isomer of carboxiterminal telopeptide of collagen I (ß-CTX) were analysed at all points in the study. Data on disease progression, SREs development and survival were recorded. RESULTS: Cox regression models with clinical data and bone markers showed that the levels of the three markers studied were predictive of survival time, with ß-CTX being especially powerful, in which a lack of normalisation in visit 1 (3 months after the beginning of treatment) showed a 6.3-times more risk for death than in normalised patients. Levels of these markers were also predictive for SREs, although in this case BALP and P1NP proved to be better predictors. We did not find any relationship between bone markers and disease progression. CONCLUSION: In patients with PCa and bone metastases treated with ZA, ß-CTX and P1NP can be considered suitable predictors for mortality risk, while BALP and P1NP are appropriate for SREs. The levels of these biomarkers 3 months after the beginning of treatment are especially important.

Biochemical markers of bone turnover and clinical outcome in patients with renal cell and bladder carcinoma with bone metastases following treatment with zoledronic acid: The TUGAMO study.

BACKGROUND: Levels of bone turnover markers (BTM) might be correlated with outcome in terms of skeletal-related events (SRE), disease progression, and death in patients with bladder cancer (BC) and renal cell carcinoma (RCC) with bone metastases (BM). We try to evaluate this possible correlation in patients who receive treatment with zoledronic acid (ZOL). METHODS: This observational, prospective, and multicenter study analysed BTM and clinical outcome in these patients. Serum levels of bone alkaline phosphatase (BALP), procollagen type I amino-terminal propeptide (PINP), and beta-isomer of carboxy-terminal telopeptide of type I collagen (ß-CTX) were analysed. RESULTS: Patients with RCC who died or progressed had higher baseline ß-CTX levels and those who experienced SRE during follow-up showed high baseline BALP levels. In BC, a poor rate of survival was related with high baseline ß-CTX and BALP levels, and new SRE with increased PINP levels. Cox univariate analysis showed that ß-CTX levels were associated with higher mortality and disease progression in RCC and higher mortality in BC. Bone alkaline phosphatase was associated with increased risk of premature SRE appearance in RCC and death in BC. CONCLUSION: Beta-isomer of carboxy-terminal telopeptide of type I collagen and BALP can be considered a complementary tool for prediction of clinical outcomes in patients with BC and RCC with BM treated with ZOL.

Risk in dosing regimens for 25-OH vitamin D supplementation in chronic haemodialysis patients.

INTRODUCTION: 25-OH vitamin D (25-OHvitD) insufficiency or deficiency should be treated in haemodialysis (HD) patients, although the 25-OHvitD target, drug or dosing regimens are unclear. AIMS: To describe factors associated with 25-OHvitD levels in HD patients and to assess the effect of three dosing regimens to supplement 25-OHvitD (calcifediol) on serum calcium (Ca), phosphate (P), parathyroid hormone (PTH), 25-OHvitD and 1,25-OHvitD. METHODS: Two hundred and seventeen patients from three HD units were studied. Demographic and biochemical data were collected at baseline. Two different 25-OHvitD assays were used. One hundred and sixty-seven patients were treated with various calcifediol dosing regimens. The same biochemical determinations were repeated after 3 months of treatment. RESULTS: At baseline, 12.9% of patients had 25-OHvitD <10 ng/ml. In multivariate linear regression, the season (lower in winter) and the assay method were determinants of 25-OHvitD concentration. Following calcifediol supplementation, 25-OHvitD, calcium and phosphate increased, while PTH diminished with statistical significance. After treatment, there were positive correlations between 25-OHvitD and Ca (r = 0.28, p < 0.0001) or 1,25-OHvitD (r = 0.75, p < 0.0001) that were not observed in the baseline dataset. High concentrations of post-treatment 25-OHvitD were associated with higher 1,25-OHvitD levels. Calcemia increased more in those treated with concomitant active vitamin D or those having suppressed baseline PTH, while PTH decreased more in those having above-target PTH levels. CONCLUSIONS: Standardisation of methods to determine 25-OHvitD blood levels is needed. In HD patients, calcifediol increased 25-OHvitD, calcemia and phosphatemia and lowered PTH. Caution should be exercised with the higher calcifediol dosing regimens, especially in patients with suppressed PTH or on vitamin D receptor activators.

The effectiveness of intermittent rat parathyroid hormone (1-34) treatment on low bone mass due to oestrogen or androgen depletion in skeletally mature rats.

Rat parathyroid hormone (PTH) 1-34 (4 microg/kg/day) was applied for 2.5 months to 9 month-old rats immediately after ovariectomy or orchidectomy or to 15 month-old rats with low bone mass which had been castrated 6 months before in order to know the effects on serum biochemistry parameters, lumbar and femoral bone mineral density, histology, cancellous and cortical bone histomorphometry, mineralisation content profile in cortical bone by backscattered-electron microscopy, and femoral torsion biomechanical testing. In ovariectomised rats, preventive PTH treatment avoided cancellous bone loss in tibial metaphysis and partially in lumbar vertebra, while in cortical bone, PTH increased endosteal resorption and periosteal formation. In intervention study, PTH did not restore cancellous bone but a strong endosteal and periosteal new bone formation was detected. In orchidectomised rats, PTH, in preventive study, avoided cancellous bone loss in metaphysis and lumbar vertebra, and a mild new bone formation in cortical bone was found. In intervention study, PTH maintained baseline cancellous bone mass, but in cortical bone a strong endosteal and periosteal new bone formation was detected. The PTH-induced new bone formation was confirmed by histology and by mineral content profiles. After castration, biomechanical properties were affected in females but not in male rats and PTH reverted this effect.

Bone disease induced by phenytoin therapy: clinical and experimental study.

Previous studies have made references to prolonged treatment with phenytoin as a possible risk factor in the development of osteoporosis and/or osteomalacia. We studied a group of 30 epileptic patients who were under long-term treatment with phenytoin (DPH) in an ambulatory regimen. We found the prevalence of osteoporosis to be 3.3% and of osteopenia to be 56.6%, affecting predominantly the femur, without any significant decrease in bone mineral density of the lumbar spine. These patients were showing signs of bone turnover uncoupling with increases in bone resorption markers. At this time, they also exhibited slight alterations in their phosphocalcium metabolism with trends to hypocalcemia and secondary hyperparathyroidism that was found not to be caused by a vitamin D deficiency as the serum levels of 25(OH)D and 1,25(OH)(2)D were normal. With the aims of corroborating these results and to investigate the physiopathological effects on the bone induced by anticonvulsant drugs we developed a further experimental study in which we administered DPH over a 6-week period with a dose of 5 g/kg/day to male Wistar rats that were in the growth phase. This treatment produced a decrease in overall BMD and bone mineral content in the femur. We did not find osteomalacia in the vertebral biopsy, but the administration of DPH to these animals decreased trabecular volume as well as lessened the thickness of osteoid edges together with an uncoupling in bone turnover. There was also a marked decrease in bone formation and a tendency towards increased bone resorption. We have also found a decrease in resistance to fracture by torsion in the biomechanical assay, which translates into an increase in bone fragility. In these male Wistar rats, the administration of DPH produced a tendency towards increasing the markers of resorption and, though changes in serum levels of calcium and phosphorus were not observed, to provoke an increase in the parathyroid hormone levels; with normal levels of 1,25(OH)(2)D which has produced the same inclination in rats as in humans.

Effect of risedronate on bone mass, remodelling and biomechanical strength in orchidectomized rats.

BACKGROUND: The ability of risedronate to prevent and/or treat orchidectomy-induced osteoporosis in male rats was studied. METHODS: Ninety-five 10-week-old male Wistar rats were sham-operated or orchidectomized. Prevention study: Sham: sham-operated rats; ORX: orchidectomized rats; ORX + RSD: orchidectomized rats, treated for 6 weeks with risedronate. Animals were sacrificed 6 weeks after surgery. Treatment study: Sham(1) and ORX(1): sham and orchidectomized rats sacrificed 3 months after orchidectomy; Sham(2), ORX(2) and ORX(2) + RSD: sham-operated, and orchidectomized rats treated with placebo or risedronate for 6 weeks starting 3 months after orchidectomy, and then sacrificed. Risedronate (0.5 mg/kg/day) and placebo (saline) were administered via oral gavage. After sacrifice, bone mineral density by DEXA, bone volume (BV/TV), osteocalcin (BGP), and serum carboxyterminal telopeptide of collagen type I (CTX) were measured. Femur low-rate torsion testing was performed. RESULTS: Orchidectomy produced an increase in bone remodelling with loss of BV/TV, without effects on torsional strength. Risedronate treatment partially prevented these effects. In the treatment study, risedronate reduced bone remodelling and restored BV/TV to levels higher than those of the sham group, improving biomechanical parameters. CONCLUSIONS: These results suggest that risedronate could be used as a prevention or treatment of male osteoporosis due to hypogonadism.

Maintained malnutrition produces a progressive decrease in (OPG)/RANKL ratio and leptin levels in patients with anorexia nervosa.

OBJECTIVE: Osteoprotegerin (OPG) and receptor activator of nuclear factor-kappaB ligand (RANKL) are key factors in bone remodeling in patients with anorexia nervosa (AN) and osteopenia. The purpose of this study was to investigate basal serum levels of OPG, RANKL and leptin, as well as bone mineral density (BMD) measured by DEXA at lumbar vertebrae L1-L4, and their evolution during one year in two groups of patients with AN. MATERIAL AND METHODS: Group I included 10 adolescent girls suffering from malnutrition and secondary amenorrhea with an evolution of more than one year at the beginning of the study who received oral estrogen treatment throughout the follow-up period. Group II comprised 10 girls with malnutrition and secondary amenorrhea with an evolution of less than one year who received nutritional treatment only. All parameters were compared with those of a control group of 19 healthy, age-matched girls with normal BMI and regular menstrual cycles. RESULTS: The OPG/RANKL ratio was significantly decreased (p<0.05) after 1 year in group I, a fact that was due to an increase (p<0.05) in serum RANKL values. A correlation between OPG/RANKL and BMD was found in group I at the beginning of the study (r = 0.95; p<0.001). Patients in this group showed lower BMD values (p<0.01), both at diagnosis and at the end of the study, than those of group II patients, who showed normal BMD values. CONCLUSION: The decrease in the OPG/RANKL ratio in girls with AN could partly explain the increase in bone loss that occurs in these patients.

Modulation of survival in osteoblasts from postmenopausal women.

Osteoblast survival is one of the determinants of postmenopausal osteoporosis development. Recent data from animal experiments suggest that cytokines, in particular Fas ligand (FasL), contribute to postmenopausal osteoporosis. We now address the effect of Fas activation in postmenopausal osteoblast survival and the potential modulatory effect of estrogen and raloxifene analog (LY117018). The expression of Fas mRNA, Fas protein, and the sensitivity to Fas-induced apoptosis were studied in primary cultures of human osteoblasts from postmenopausal women and in osteoblastic MG-63 cells. Human postmenopausal osteoblasts constitutively expressed Fas receptors in the cell surface. TNFalpha increased the expression of Fas mRNA and cell surface Fas expression. Neither estradiol nor raloxifene analog prevented this increase in Fas expression. In addition, activation of Fas receptor resulted in apoptosis of postmenopausal osteoblasts. While TNFalpha did not induce human osteoblast apoptosis, it did increase the lethal effect of Fas activation. Therapeutic concentrations of estradiol or raloxifene analog did not modulate lethal cytokine-induced apoptosis. Both postmenopausal osteoblasts and MG-63 cells express FasL. FasL expression was not modulated by TNFalpha. In conclusion, estrogen and raloxifene analog do not appear to affect the sensitivity of postmenopausal osteoblasts to Fas-mediated apoptosis.

Effects of 17beta-estradiol, tamoxifen and raloxifene on the protein and mRNA expression of interleukin-6, transforming growth factor-beta1 and insulin-like growth factor-1 in primary human osteoblast cultures.

We investigated the effects of 17betaestradiol and two selective estrogen receptor modulators, tamoxifen and raloxifene, on the expression and release of constitutive and interleukin-1-stimulated interleukin (IL)-6, transforming growth factor-beta1 (TGF-beta1) and insulin-like growth factor-1 by osteoblasts in primary culture from trabecular bone of healthy post-menopausal women. After 24 h incubation with 10(-8) M concentration of these compounds, there was no decrease in: a) the constitutive or IL-1beta-induced levels of IL-6 protein released to culture medium; b) the constitutive IL-6 mRNA expression after incubation of osteoblasts with 10(-8) M 17betaestradiol or 10(-8) M tamoxifen for 1, 3, 6, 24 or 30 h. Although a decrease after 30 h of treatment with 10(-8) M, raloxifene was found in mRNA IL-6 expression, and this fact was not reflected by a decrease in the release of IL-6 protein to the culture medium after 48 h of incubation with 10(-8) M or 10(-7) M raloxifene. Tumoral growth factorTGF-betal expression was not influenced by incubation with these compounds. Gene expression of IGF-I increased following 24 or 30 h incubation with 10(-8) M 17beta-estradiol and 30 h incubation with raloxifene. Tamoxifen did not affect IGF-I expression. In conclusion, the effects of estradiol or tamoxifen on bone metabolism do not appear to be mediated through the regulation of osteoblast IL-6 release or synthesis, but raloxifene produces a decrease in mRNA IL-6 expression. The actions of estradiol, tamoxifen and raloxifene do not appear to be mediated by tumoral growth factor TGF-beta1. On the other hand, an increase in IGF-I synthesis induced by raloxifene and estradiol could mediate, in part, the effects of these compounds on bone.

[Secreted tumor markers and breast cancer]. / Marcadores tumorales de secreción y cáncer de mama.

The tumor secretion markers used most in the daily practice are reviewed, emphasizing the physiological aspects having great practical usefulness. Likewise, the possible value of other recently described substances which could be introduced into the daily practice in the near future is explained.

Short- and long-term effects of calcium and exercise on bone mineral density in ovariectomized rats.

At the level of prevention of bone mineral loss produced by ovariectomy, the aim of the present study was to determine the effect produced by supplementation of Ca in the diet and a moderate exercise programme (treadmill), simultaneously or separately, in ovariectomized rats, an experimental model of postmenopausal bone loss. Female Wistar rats (n 110, 15 weeks old) were divided into five groups: (1) OVX, rats ovariectomized at 15 weeks of age, fed a standard diet; (2) SHAM, rats sham operated at 15 weeks of age, fed a standard diet; (3) OVX-EX, ovariectomized rats, fed a standard diet and performing the established exercise programme; (4) OVX-Ca, ovariectomized rats fed a diet supplemented with Ca; (5) OVX-EXCa, ovariectomized rats with the exercise programme and diet supplemented with Ca. The different treatments were initiated 1 week after ovariectomy and were continued for 13 weeks for subgroup 1 and 28 weeks for subgroup 2, to look at the interaction of age and time passed from ovariectomy on the treatments. Bone mineral density (BMD) was determined, at the end of the study, in the lumbar spine (L2, L3 and L4) and in the left femur using a densitometer. Bone turnover was also estimated at the end of the study, measuring the serum formation marker total alkaline phosphatase (AP) and the resorption marker serum tartrate-resistant acid phosphatase (TRAP). As expected, OVX rats showed a significant decrease (P<0.05) in BMD, more pronounced in subgroup 2, and a significant increase in AP and TRAP with regard to their respective SHAM group. The simultaneous treatment with Ca and exercise produced the best effects on lumbar and femoral BMD of ovariectomized rats, partially avoiding bone loss produced by ovariectomy, although it was not able to fully maintain BMD levels of intact animals. This combined treatment produced a significant increase in AP, both in subgroups 1 and 2, and a decrease in TRAP in subgroup 1, with regard to OVX group. The exercise treatment alone was able to produce an increase in BMD with regard to OVX group only in subgroup 1 of rats (younger animals and less time from ovariectomy), but not in subgroup 2. In agreement with this, there was an increase of AP in both subgroups, lower than that observed in animals submitted to exercise plus Ca supplement, and a decrease of TRAP in subgroup 1, without significant changes in this marker in the older rats. Ca treatment did not produce any significant effect on BMD in OVX rats in both subgroups of animals, showing a decrease of AP and TRAP levels in the younger animals with no significant variations in markers of bone remodelling in the older female rats compared with their respective OVX group.

Pravastatin therapy increases procollagen I N-terminal propeptide (PINP), a marker of bone formation in post-menopausal women.

BACKGROUND: The aim of our study was to evaluate whether pravastatin treatment affected biochemical markers of bone turnover. METHODS: Thirty-six hypercholesterolemic post-menopausal women, not on hormonal replacement therapy, were selected from a population study evaluating factors affecting cholesterol response to pravastatin. After a 6-week period on a 30% fat diet, participants received treatment with 20 mg/day of pravastatin during a 16-week follow-up period. Pre- and post-treatment samples were analyzed for procollagen I aminoterminal peptide (PINP) and bone alkaline phosphatase (bAP) as markers of bone formation, carboxyterminal telopeptide of collagen I (CTX) as a marker of bone resorption, and procollagen III aminoterminal propeptide (PIIINP) as a marker of fibrogenesis. RESULTS: Total cholesterol decreased from 7.26+/-0.83 to 6.1+/-0.77 mmol/l with pravastatin treatment. PINP levels significantly increased (from 33.6+/-13 to 37.4+/-16, p=0.03) without changes in bAP or CTX. Individual changes in PINP correlated with individual reduction in cholesterol levels (r=0.337, p=0.04). There was no significant change in PIIINP concentration. CONCLUSIONS: Pravastatin treatment increased PINP levels, a marker of bone formation, in hypercholesterolemic, post-menopausal women, without affecting bone resorption. PIIINP concentration, a marker of liver fibrogenesis, was not affected by the treatment.

Biochemical markers of bone remodeling and bone sialoprotein in ankylosing spondylitis.

The aim of this work was to determine bone mineral density (BMD) in a group of patients with ankylosing spondylitis (AS) and to study alterations in bone remodeling in these patients. Eighteen patients (16 males and two females) with AS, mean age 44.7, range 21-75, and 18 age- and sex-matched healthy controls were studied. BMD was evaluated by dual energy X-ray absorptiometry. The following biochemical markers of bone remodeling were studied: formation - serum amino and carboxyterminal propeptides of procollagen I (PINP and PICP); resorption - urinary total and free deoxypyridinoline and pyridinoline (TDpyr, FDpyr, TPyr and FPyr), crosslinked aminoterminal telopeptides of collagen I (NTX), carboxyterminal telopeptide of collagen I (CTX) and serum bone sialoprotein (BSP). Receiver operating characteristic (ROC) curves of markers were also performed. We found a decrease of bone mass and an increase in TPyr, FPyr, TDpyr, FDpyr, NTX and BSP in AS, but no significant differences were found in PICP, PINP and CTX. FDpyr, FPyr and TPyr showed the highest discrimination between patients and controls according to the results of the ROC curves. TPyr/TDpyr was higher in AS than in controls. We found osteopenia, with a normal formation and a significant increase in bone resorption in AS. FDpyr, FPyr and TPyr seem to present the best sensitivity for the study of alterations of bone resorption in this pathology, although NTX, TDpyr and BSP also show significant differences. The elevation in the ratio TPyr/TDpyr in AS compared to controls indicates that in AS there is a type I-collagen degradation in tissues different from bone.

A variation in Bone Alkaline Phosphatase levels that correlates positively with bone loss and normal levels of aminoterminal propeptide of collagen I in girls with anorexia nervosa.

Anorexia nervosa (AN) is a very extended pathology among adolescent girls nowadays. These patients show a high degree of osteopenia; hence, study of their bone remodelling is of great interest. Serum bone alkaline phosphatase (bAP) and aminoterminal propeptide of procollagen I (PINP) provide good sensitivity in the analysis of bone alterations in postmenopausal osteoporosis. The aim of this study was to compare the usefulness of bAP and PINP in the study of bone remodelling in AN, and their possible correlation with the degree of osteopenia in this pathology. In order to help in the interpretation of the results, levels of the beta-isomer of urinary carboxyterminal propeptide of collagen I (beta-CTX) have also been included. Serum bAP (IRMA) Tandem R-Ostase, Hybritech), PINP (RIA, Orion Diagnostica) and CTX (CrossLaps ELISA, Osteometer) were determined in 41 girls with AN, aged 18.5+/-2.2 years (mean+/-SD) and in 31 healthy control women, aged 19+/-2.3 years. Bone mineral density (BMD) in lumbar spine was measured by DEXA in the AN group. We found that 41 of the 43 patients had BMD z-scores under -2. No significant differences were found in the levels of serum bAP nor in PINP and beta-CTX levels between controls and patients, although values in the AN group were highly variable. All the BMD z-score values were negative, and their absolute value correlates positively with bAP (P = 0.0279) and almost with beta-CTX (P = 0.0921) but not with PINP (P = 0.4627). Bone AP correlates with PINP in control girls (P = 0.017), but not in the AN group (P = 0.3573). Patients with AN were divided into three groups according to their levels of bAP: low (I), normal (II) or high (III). Patients with the highest bAP levels also presented the highest increase in bone resorption, according to their beta-CTX levels, and the highest degree of osteopenia. However, values of PINP were similar in the three groups of patients. The bAP/beta-CTX ratios in subgroups I, II and III of AN patients were 0.035, 0.065 and 0.073, a finding that suggests that bAP is not indicating the real degree of bone mineralization in these patients, because it is a contradiction that the formation/resorption ratio should be higher in the patients who have the highest bone loss. These results could suggest that bone loss in AN is produced by an increase in bone resorption (beta-CTX), without variations in bone matrix formation (PINP); bAP levels are a good marker in the follow-up of osteopenia degree, but not a real indicator of bone mineralization, a similar situation to that of osteomalacia.

Aminoterminal propeptide of type I collagen and bone alkaline phosphatase in the study of bone metastases associated with prostatic carcinoma.

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.