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Biomedical subjects

S Minisola

Publications and source records attributed to S Minisola.

At least 55 records · Page 3Linked to original sources

The measurement of urinary amino-terminal telopeptides of type I collagen to monitor bone resorption in patients with primary hyperparathyroidism.

This study was carried out in order to evaluate clinical usefulness of cross-linked N-telopeptides (NTx) of type I collagen determination, in patients with primary hyperparathyroidism. Twenty-six consecutive patients (6 males and 20 females, aged 56.3 +/- 15.0, SD, yrs) with primary hyperparathyroidism were studied in basal conditions and, ten of them, after surgical cure of the disease. Cross-linked collagen peptides were measured by enzyme-linked immunosorbent assay and conventional markers of bone turnover according to standard procedures. Bone densitometry at the lumbar spine and proximal femur was performed using dual-energy X-ray absorptiometry. Bone mineral density, was also assessed at the junction of the distal and middle third of the radius and at the ultradistal radius of the non-dominant arm by a dual photon densitometer. Mean urinary NTx values (194.2 +/- 121.9 pmoles bone collagen equivalents/mumoles creatinine) were significantly higher (p < 0.001) in respect to those found in normal subjects. The mean increase of Z score values of both serum tartrate resistant acid phosphatase activity (1.4 +/- 1.8) and the fasting hydroxyproline/creatinine ratio (1.45 +/- 2.0) was significantly lower (p < 0.02) in respect to that of NTx Z score values (3.3 +/- 3.3); the latter values were not significantly different than mean Z score values of serum osteocalcin (4.0 +/- 3.9), serum alkaline phosphatase activity (2.6 +/- 2.6) and urinary calcium/creatinine ratio (3.2 +/- 3.3). We found a significant inverse correlation between NTx values and both lumbar spine (p < 0.01) and ultradistal radius bone mineral density (p < 0.05); a modest inverse correlation was also observed between serum tartrate resistant acid phosphatase activity and lumbar spine bone mineral density (p < 0.04). Following successful adenoma removal, the percentage decrease of both NTx and hydroxyproline was similar in patients with increased bone turnover rate; major discrepancies were observed in patients with normal values of NTx, the telopeptide reduction being greater than that of hydroxyproline. Finally, in a hypercalcemic patient with metastatic parathyroid cancer, telopeptide excretion was shown to be more sensitive in respect to urinary hydroxyproline when evaluating the effects of antiresorptive therapy. Our results seem to indicate that amongst the markers with good sensitivity, NTx is the only one that is inversely related with bone mineral density at two different skeletal sites. This assay should therefore have a place in both the initial screening and medical follow-up of patients with this glandular disorder; in fact, in both situations an increased urinary excretion of this marker should warn about the possibility of hidden bone loss.

Absorptiometry, Photon↗

Pulmonary lymphangioleiomyoma in a patient with multiple endocrine neoplasia type I.

The multiple endocrine neoplasia (M.E.N.) syndromes consist of a group of proliferative disorders that selectively target specific sets of endocrine and soft tissue cells. Here we report a case of lymphangioleiomyoma of the lung in a patient with multiple endocrine neoplasia Type I (M.E.N. I). This is the first time such an association has been reported. In our opinion it could possibly be ascribed to the genetic predisposition to proliferative disorders of patients with M.E.N. syndromes.

Female↗

Serum osteocalcin and bone mineral density at various skeletal sites: a study performed with three different assays.

The purposes of this study were threefold: (1) to compare values obtained by three conventional radioimmunoassays for serum bone-gla-protein (BGP) in a population of normal women, (2) to study the relationship between serum BGP and bone mineral density (BMD) measured at four different skeletal sites (lumbar spine, proximal femur, proximal and ultradistal radius), and (3) to compare the results obtained by the three assays with conventional markers of bone turnover. Ninety-seven normal women (age range 25 to 75 years, mean +/- 1 SD = 54.3 +/- 10.9 years) were studied. Three independent assays were used to measure serum osteocalcin levels: a heterologous radioimmunoassay (RIA) (A) (Incstar Co., Stillwater, Minn.), a homologous RIA (B) (Nichols Institute, San Juan Capistrano, Calif.), and a two-site immunoradiometric assay (C) (Cis Biointernational, Gif-sur-Yvette, France). Mean +/- SD values of serum osteocalcin in the group as a whole were 4.05 +/- 1.37 microg/L by assay A, 6.03 +/- 2.90 microg/L by assay B, and 22.67 +/- 7.52 microg/L by assay C. Serum osteocalcin levels increased linearly with age; however, no correlation between serum BGP (whatever the assay used) and age was observed when only postmenopausal women were taken into account. When the effect of age was held constant by means of partial correlation analysis, only serum BGP levels measured by assays B and C were still inversely related with lumbar spine and ultradistal radius BMD; the latter assay was also weakly correlated with Ward's triangle BMD. After all the biochemical and clinical variables taken into consideration were introduced in a multiple regression equation, serum BGP still represented an important predictor of ultradistal radius and lumbar spine BMD only. Regarding relationships with other markers of bone turnover, the assay C in general showed the highest r values. In conclusion, our results indicate that commercially available BGP assays differ analytically and clinically; furthermore for the first time they show the existence of an inverse correlation between serum osteocalcin levels (which reflects bone turnover at the time of examination) and bone mass (which at a given time represents the balance of all previous metabolic events), after the influence of aging is excluded.

Adult↗

Age-related changes in the global skeletal uptake of technetium-99m methylene diphosphonate in healthy women.

A short-term evaluation of global skeletal uptake (GSU) of technetium-99m methylene diphosphonate (MDP) was performed in 40 healthy female subjects with a wide age range in order to investigate the clinical performance of the technique and to detect the age-related changes in bone turnover. The results obtained were compared with measurements of the main biochemical markers of skeletal metabolism. We found that GSU increases progressively with age, independently of concomitant changes in renal function; significant correlations with biochemical markers of bone formation were also found. Therefore, the method appears to provide useful information concerning the bone turnover rate, and is also applicable to elderly people owing to its simplicity.

Adult↗

Case report: reversal of decreased bone mass by antibiotic treatment in a patient with Whipple's disease.

Whipple's disease is a rare systemic illness, with the main clinical feature being severe malabsorption syndrome. Bone involvement in the disease has rarely been described in previous articles. The authors report a case in which an extensive skeletal evaluation was carried out. Even though osteomalacia is generally considered the most typical metabolic bone disease of malabsorption syndromes, bone biopsy demonstrated that osteoporosis was the prominent histologic feature in this patient. On the basis of serial bone mineral density measurements, antibiotic treatment was able to reverse the initial reduced bone mass.

Anti-Infective Agents↗

Quantitative ultrasound assessment of bone in patients with primary hyperparathyroidism.

Quantitative ultrasound measurements were done in a group of 26 patients (4 males and 22 females, aged 55.4 +/- 14.2 years) with primary hyperparathyroidism, and the results were compared with bone mineral density (BMD) carried out at various skeletal sites. Speed of sound (SOS), broadband ultrasound attenuation (BUA), and stiffness were measured with the Achilles ultrasound bone densitometer (Lunar Corp., Madison, WI). Mean +/- SD values of SOS, BUA, and stiffness in patients with primary hyperparathyroidism were 1522 +/- 38 m/seconds, 111 +/- 16 dB/MHz, and 80.4 +/- 19.8%, respectively. There were significant differences of mean T-score BUA values (-0.63 +/- 1.11) compared with corresponding T-score BMD values found at ultradistal (-1.85 +/- 1.73, P < 0.01), proximal radius (-2.40 +/- 2.13, P < 0.001), and total femoral (-1.60 +/- 1.32, P < 0.001) sites. Correlation coefficients between both SOS and BUA values with BMD measurements at specific skeletal sites varied, but stiffness correlated moderately (0.6-0.9) with BMD. Our data strongly indicate that in patients with primary hyperparathyroidism, bone structure of some skeletal sites, as evaluated by BUA measurement, is compromised to a lesser extent than BMD. In this respect it is interesting to note the lack of significant differences (in terms of mean T-score values) in the comparison of two sites of mostly trabecular composition, that is, the lumbar level (-1.17 +/- 1.54) and the femoral Ward's triangle (-0.99 +/- 1.25). Our results seem to lend further support to the hypothesis that in primary hyperparathyroidism cancellous bone architecture might be preferentially maintained.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Temporal relationship between bone loss and increased bone turnover: a longitudinal study following natural menopause.

We report the results of a longitudinal study aimed at better defining concomitant changes of both bone mineral density (BMD) and of four independent markers of bone turnover (serum osteocalcin, serum alkaline phosphatase activity, fasting urinary hydroxyproline/creatinine and calcium/creatinine ratio) following natural menopause. The results obtained indicate that, within a relatively short period of time since cessation of gonadal function, conventional markers of bone turnover behave differently. In fact, while the mean values of hydroxyproline/creatinine ratio (felt to be a marker of bone resorption) rise immediately at the first control (19.7 +/- 11.7 months), the bone formation markers gradually increase and, as far as serum osteocalcin levels are concerned, this increment appears to be long-lasting. As a result of these changes, a negative skeletal balance follows, which is documented by the prolonged reduction of bone mineral density during the entire observation period. Mean +/- SD % measured yearly bone loss was -2.83 +/- 2.6. There was a highly significant correlation between initial and final BMD values (r = 0.908, p < 0.001; r2 = 82.5) and a weak inverse correlation (r = -0.298, p < 0.046) between initial serum alkaline phosphatase values and % yearly bone loss. In conclusion, measurement of the biological indices of bone remodelling following natural menopause indicate that the increase in osteogenesis is delayed compared to that of bone resorption; furthermore, in the immediate postmenopausal period, the actual bone mass should be considered the best predictor of future bone mass. The inverse correlation found between % yearly bone loss and serum alkaline phosphatase values seems to emphasize the importance of increased bone turnover as an independent predictor of bone loss.

Aged↗

Serum concentrations of osteocalcin in pregnant women with multinodular thyroid goiter undergoing treatment with levothyroxine.

In this study we measured serum osteocalcin (Bone Gla-Protein) to investigate bone metabolism in pregnant women with multinodular thyroid goiter undergoing treatment with levothyroxine (L-T4). Serum concentration of BGP was measured in 18 pregnant women and in 20 non-pregnant women (ages raging from 21-34 years) receiving L-T4 (75-125 micrograms/day). Venous blood samples for RIA determination of serum BGP, plasma thyroid hormone (T3, T4, free T3, free T4) and TSH were collected from the two groups. The samples of the pregnant women group were collected before pregnancy (at the moment the disease was diagnosed without L-T4 therapy) during pregnancy (at the 3rd, 6th and 9th month) and one month after delivery. The normal TSH levels (measured with Irma method) before pregnancy, were significantly reduced during treatment with L-T4 during pregnancy and after delivery (p < 0.005), respectively. Also in the control group TSH levels were reduced during treatment. Serial measurement of serum BGP before pregnancy, (3.4 +/- 1 ng/ml) during pregnancy (3rd: 4.2 +/- 1.5 ng/ml; 6th: 4.2 +/- 1.4 ng/ml; 9th: 2.8 +/- 1.6 ng ml, month respectively) and one month after delivery (3.5 +/- 1.3 ng/ml) did not demonstrate significant variations. Furthermore, in the control group the BGP levels were 3.2 +/- 1.7 ng/ml. There was no correlation between BGP, thyroid hormones and TSH in these groups. These data indicate that the administration of moderate doses of L-T4 in pregnant and in non-pregnant women did not modify the serum BGP levels.

Adult↗

Circulating levels of insulin-like growth factor binding protein 3 (IGFBP-3) and insulin-like growth factor I (IGF-I) in perimenopausal women.

The study investigated possible menopause-related changes in circulating insulin-like growth factor binding protein 3 (IGFBP-3) levels and their relationship with insulin-like growth factor I (IGF-I) plasma levels. Forty-three healthy women, aged 45-55 years, were studied (22 premenopausal and 21 postmenopausal, matched for age and body mass index); in all subjects plasma IGF-I and IGFBP-3 levels were measured by radioimmunoassay. No difference was found between mean IGFBP-3 plasma levels in the two groups studied (premenopausal 3.42 +/- 0.49 v postmenopausal 3.46 +/- 0.58 mg/l), while mean IGF-I levels were significantly lower in postmenopausal as compared with premenopausal women (136.7 +/- 37.86 v 175.7 +/- 51.91 ng/ml, p < 0.02). Multiple regression analysis showed no significant effect of age, body mass index and years since menopause on IGFBP-3 levels; however, considering the IGF-I/IGFBP-3 ratio as a possible parameter of circulating free somatomedin C, an inverse correlation was found with years since menopause (n = 43, r = -0.499, p < 0.001). We conclude that lack of oestrogen induces different effects on circulating IGF-I and IGFBP-3, possibly reflecting a real decrease in IGF-I activity.

Endopeptidases↗

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, osteocalcin, 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 members (four men, three women; age, 43.3 +/- 16.6 years [mean +/- SD]) of 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 same family were also studied, although they were excluded from statistical analysis. Bone mineral density was also determined at four different skeletal sites. Serum levels of PICP were measured with a radioimmunoassay (Farmos Diagnostica, Turku, Finland). There were no significant differences in mean values of the biomarkers studied between OI patients and normal relatives, with the only exception being serum levels of PICP (35 +/- 7.5 v 219 +/- 107.5 micrograms/L, P < .001). A significant reduction of BMD was found in OI patients compared with normal relatives at the lumbar (L) spine (680 +/- 61 v 1,128 +/- 92 mg/cm2, 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 at the junction of the distal and middle third of the radius ([MR] 639 +/- 71 v 717 +/- 52, P < .029).(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase↗

Serum carboxy-terminal propeptide of human type I procollagen in patients with primary hyperparathyroidism: studies in basal conditions and after parathyroid surgery.

This study was carried out in order to evaluate serum carboxy-terminal propeptide of human type I procollagen (PICP) in patients with primary hyperparathyroidism and to examine its changes following parathyroidectomy. Seventeen patients (four males and 13 famels, aged 53.8 +/- 3.1 SEM years) were studied in basal conditions; six patients also were investigated after successful parathyroid surgery. Mean serum PICP values of patients with primary hyperparathyroidism (194.5 +/- 27 SEM micrograms/l) were significantly higher (p < 0.001) with respect to those found in normal subjects. However, deviations from the norm (Z score values) were significantly less with respect to deviations of serum osteocalcin, alkaline phosphatase and urinary hydroxyproline/creatinine ratio. Following parathyroidectomy, it was possible to observe a discrepancy between markers of bone resorption and those of bone formation. The former tend to decrease, while the latter either do not show any significant change (serum alkaline phosphatase and serum osteocalcin) or increase (serum procollagen). The results of our investigation indicate that in basal conditions the assay of serum procollagen may be of clinical value but it would be better to use it in combination with other biomarkers of skeletal remodelling. The results obtained after parathyroidectomy are the opposite of those obtained following parathyroid hormone infusion and should be ascribed to the effect of acute hormone deficiency on collagen synthesis. The positive biochemical uncoupling following surgery might lend support to the rise of bone mineral density consistently reported in the first few months following parathyroidectomy.

Adenoma↗

Effect of estrogen deficiency on IGF-I plasma levels: relationship with bone mineral density in perimenopausal women.

Bone tissue is a source of growth factors; among them, insulinlike growth factor I (IGF-I) is probably an important local regulator of bone formation. This study has been carried out in order to assess the effects of natural menopause on plasma concentrations of IGF-I in the first 6 years after the cessation of gonadal function independent of age. We also examined the relationship between plasma IGF-I levels and bone mineral density (BMD) measured at the lumbar spine (LS), at the ultradistal radius (UDR), and at the junction of the distal and middle thirds of the radius (MR). Sixty-seven healthy nonobese women, aged 45-55, were studied (premenopausal n = 21; postmenopausal n = 46, from 1 to 6 years since menopause). Plasma IGF-I levels were measured by RIA, after acid-ethanol extraction. BMD of the forearm was measured by dual-photon densitometer and BMD of the LS was assessed by quantitative digital radiography. Mean values of IGF-I plasma levels were significantly reduced in postmenopausal women compared to the premenopausal group. Menopausal duration did not influence IGF-I plasma levels in postmenopausal women. We also found a positive correlation between IGF-I levels and BMD measured at MR both in pre- and postmenopausal women, while a correlation with LS and UDR-BMD was found only in fertile subjects. The results show that IGF-I plasma levels decrease immediately after menopause, since significantly lower levels are reached in the first years. The correlations found between plasma IGF-I levels and BMD suggest a possible role of reduced IGF-I in bone loss at particular skeletal sites.

Aging↗

Serum osteocalcin in metabolic bone diseases: what is its real significance?

This study has been carried out in order to elucidate the clinical significance of serum osteocalcin measurement. The changes of this marker paralleled those of serum total alkaline phosphatase activity (a marker of bone formation) following parathyroidectomy in hyperparathyroid patients with skeletal involvement. Furthermore, the percentage decrease of serum osteocalcin levels in respect to basal values (85 +/- 12), and the percentage decrease of serum alkaline phosphatase activity levels (82 +/- 7) were significantly lower (p < 0.001) in respect to that of the 24-h hydroxyproline/creatinine ratio (42 +/- 14) one week after parathyroid surgery. Instead, changes of serum osteocalcin levels were similar to those of serum free hydroxyproline (considered to be a marker of bone resorption) following acute calcitonin infusion in normal subjects. These results imply that the antibody used in our assay might recognize not only the entire osteocalcin molecule, but also small epitopes released during the process of bone matrix resorption. Alternatively, if we consider serum osteocalcin only as a marker related to some processes of bone formation, the experiment carried out on normal subjects strongly supports the evidence of calcitonin receptors in osteoblastic surfaces.

Adult↗

Trabecular bone mineral density in primary hyperparathyroidism: relationship to clinical presentation and biomarkers of skeletal turnover.

This study was carried out in order to investigate the entity of trabecular bone involvement in 62 patients with primary hyperparathyroidism (PHPT). Bone mineral density (BMD) was measured in all patients at the ultradistal radius (UDR) of the non-dominant arm by a dual photon densitometer and also at the lumbar spine (L) in 40 of the patients by means of quantitative dual energy radiography. Mean Z score values of UDR-BMD (-2.4 +/- 0.4) and L-BMD (-3.5 +/- 0.2) in patients with the skeletal variety of the disease (n = 6) were significantly reduced in respect to values of both asymptomatic (n = 31) and kidney stone patients (n = 25). As far as the comparison between the two sites of trabecular bone mass measurement in each hyperparathyroid subgroup of patients was concerned, a significant difference (P < 0.05) was found in patients with skeletal manifestations of the disease. Either serum total alkaline phosphatase activity, or osteocalcin and the 24-h hydroxyproline/creatinine ratio were significantly inversely related to the entity of bone mass evaluated at these two sites. Z score changes following surgery in 14 patients showed a positive trend in 13 of them at L compared to 7 out of 14 at UDR (P < 0.036 by chi square analysis). There was a very good inverse correlation between basal Z score values and the changes following surgery at the L (r = -0.851; P < 0.001) but not at the UDR. Our results demonstrate firstly that, in PHPT skeletal sites with almost similar composition of trabecular bone are differently involved in patients with more severe skeletal damage and that different skeletal sites may be divergently affected by the cessation of parathyroid gland hyperfunction.

Absorptiometry, Photon↗

Serum ionized calcium, parathyroid hormone and related variables: effect of age and sex.

This study was carried out in order to determine interrelationships of age and sex on parameters within the parathyroid endocrine system in healthy men and women. One hundred and fifteen normal subjects (70 females and 45 males) subdivided into three groups aged 25-35, 45-55 and 65-75 years were studied. Female subjects aged between 45 and 55 were further subdivided into two age-matched groups in relation to gonadal functional status. Serum intact parathyroid hormone (PTH) concentrations were measured using a two-site immunoradiometric assay. We found that there was a significant decrease of serum ionized calcium with ageing only in men (r = -0.666, P < 0.001) and a significant increase of serum PTH with age in both men (r = 0.488, P < 0.001) and women (r = 0.279, P < 0.019). A significant inverse correlation was found between serum ionized calcium and PTH in male subjects (r = -0.661, P < 0.001) and in fertile females (r = -0.353, P < 0.037) but not in postmenopausal women or in the entire female population. Furthermore, we found a significant decline of serum phosphate (r = -0.484, P < 0.001) and TmP/GFR (r = -0.492, P < 0.001) with advancing age in men, but not in women. We believe that the decrease of serum ionized calcium, as a likely consequence of the physiological reduction of intestinal calcium absorption, is the pivotal factor responsible for the increased PTH levels we observed with advancing age. The phenomenon is clear in men and in premenopausal women, but is masked in the female sex at menopause by the effects of a shortage of oestrogen on the calcium-phosphorus metabolism. These may also be responsible for the differences observed between the two sexes as far as phosphate metabolism is concerned. In conclusion, this study has, for the first time, taken relationships between serum ionized calcium and PTH, over a wide age range, into consideration. The results obtained show a marked difference of serum ionized calcium values between sexes with ageing, while serum parathyroid hormone levels increase in both men and women. Important differences also exist, as far as phosphate metabolism is concerned, between males and females.

Adult↗