Bone turnover and its relationship with bone mineral density in pre- and postmenopausal women with or without fractures.

OBJECTIVE: This work was carried out in order to investigate possible relationships between bone turnover rate, as evaluated by bone biomarkers and skeletal mass, as evaluated by bone mineral density (BMD). METHOD: Fifty-eight normal women and 30 female patients with osteoporotic fractures were enrolled. Three groups were defined: (1) fertile subjects (n = 24), mean age 33.7 +/- 8.1 years; (2) postmenopausal women (n = 32, including 11 patients with fractures) whose BMD values, in terms of T score, were less than -2.5 S.D. below the young adult mean obtained in our laboratory (mean age 61.7 +/- 7.9 years; and years since menopause (ysm), 12.6 +/- 8.3); (3) postmenopausal women (n = 32, including 19 patients with fractures) whose BMD values in terms of T score, were below -2.5 S.D. (mean age 62.9 +/- 8.6 years; and ysm 15.9 +/- 9.0). Groups II and III characterised, by inclusion criteria, by significant different mean BMD values, were similar as far as chronological and menopausal age were considered. Metabolic tests included a short urine collection to determine calcium, hydroxyproline, cross-linked N-telopeptides of type I collagen (NTx) and creatinine (Cr); half-way through this collection, a blood sample was taken for the measurement of total alkaline phosphatase activity (ALP) and tartrate-resistant acid phosphatase activity (TRAP). BMD at lumbar spine was evaluated. RESULTS: There were significant differences amongst the three groups in mean ALP (P < 0.001, by analysis of variance) TRAP (P < 0.006) and NTx/Cr (P < 0.001) values, but not as far as mean values of calcium/Cr or hydroxyproline/Cr ratios were concerned. Considering the group as a whole, there were significant inverse correlations between NTx/Cr, ALP, TRAP and BMD controlling for both age (r = -0.392, P < 0.001; r = -0.447, P < 0.001 and r = -0.327, P < 0.002, respectively) and ysm (r = -0.374, P < 0.001; r = -0.474, P < 0.001 and r = -0.333, P < 0.002). CONCLUSIONS: Our results indicate, that, even after controlling for both ageing and oestrogen status, there is an inverse relationship between bone mass (that at a given time represents the balance of all previous metabolic events) and a biochemical marker (which reflects bone turnover at the time of examination). These findings are in line with the belief that increased bone turnover should be regarded as a risk factor for osteoporosis. Furthermore, our results indicate that, unless there is no increase of hepatic isozyme, total ALP still maintains a possible role as a first analysis to evaluate bone turnover before requesting markers with greater specificity, sensitivity but also more expensive and whose analysis is sometimes time-consuming.

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.

[Dilated myocardiopathy and polymyositis. A clinical case and critical review of the literature]. / Miocardiopatia dilatativa e polimiosite. Caso clinico e revisione critica della letteratura.

A patient affected by a "limb-girdl syndrome" type of polymyositis shows clinical symptoms and signs of progressively worsening dilatative myocardiopathy. The diagnosis was based on well established criteria, such as the following: EF < 45-55%, left ventricular telediastolic diameter higher than 2.7 cm/mq, and normal wall thickness (L. Mestroni 1994, W.H. Abelmann 1989, et al.). The above-mentioned clinical picture was further complicated by amiodarone induced thyrotoxicosis. After the case presentation, and having exhaustively and critically revised the existing literature on polymyositis associated dilatative myocardiopathy and on eventual joint pathogenetic mechanisms, the essay in question focuses on the discussion of the clinical data brought forth in the first part.

[Correlations between the efficacy of thrombolytic therapy and appearance of abnormal Q waves in the early stages of acute myocardial infarction]. / Correlazione tra efficacia della terapia trombolitica e comparsa di onde Q patologiche nella fase precoce dell'infarto miocardico acuto.

BACKGROUND: The purpose of this study was to determine the time course of the appearance of abnormal Q waves on the electrocardiogram (ECG) over the first 6 hrs of the symptoms of acute myocardial infarction (AMI) and to determine what implications, if any, such Q waves have for the efficacy of thrombolytic therapy. Severe myocardial ischemia can produce early QRS changes in the absence of infarction. Abnormal Q waves on the baseline ECG may not be an accurate marker or irreversibly injured myocardium. METHODS: A study of 232 patients with AMI consecutively admitted to our coronary care units was carried out. Patients with previous AMI were not included. The presence and number of abnormal Q waves, as defined by Selvester, on the initial ECG was determined for each patient. The presence or absence and magnitude of ST segment elevation and depression were recorded and these data were used to estimate the left ventricular infarct size should thrombolytic therapy not be given (Aldrich score). Quantitative thallium-201 tomographic imaging was performed after a mean of 42 +/- 40 days from hospital discharge in 145 patients. RESULTS: In patients admitted within 1 hr of symptoms, 53% had abnormal Q waves on the initial ECG independent of the duration of symptoms before therapy (p < 0.001). Despite this finding, the presence of abnormal Q waves on the admission ECG did not eliminate the effect of thrombolytic therapy on reducing final infarct size (p < 0.001). CONCLUSIONS: Abnormal Q waves are a common finding early in the course of AMI. However, there is no evidence that abnormal Q waves are associated with less benefit in terms of reduction of infarct size after thrombolytic therapy.

Age- and menopause-related changes in speed of sound and ultrasound attenuation of the os calcis in a healthy Italian female population.

This study assessed changes in ultrasonometric variables of bone (speed of sound, broadband ultrasound attenuation and stiffness) related to age and years since menopause in a normal Italian female population. Two hundred and thirty-one healthy female subjects, age range 18-78 years, divided into two groups (113 pre-menopausal, age range 18-51 years, and 118 post-menopausal, age range 46-78 years), were investigated. The results obtained show that there was a linear decrease in speed of sound, broadband ultrasound attenuation and stiffness with age; a similar pattern was also observed in post-menopausal women as far as the correlations between ultrasonometric variables and both age and years since menopause were concerned. In particular, speed of sound declined at a rate of 0.86 m/s for each year post-menopause, while broadband ultrasound attenuation declined at 0.4 dB/MHz, and stiffness at 0.5 units. These findings suggest that ultrasound variables might be able to detect characteristics of bone that are barely influenced by estrogen deficiency, and depend on other factors. Therefore, ultrasound measurement should be considered as a possible alternative to x-ray densitometry for the assessment of the skeleton.