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Biomedical subjects

G F Mazzuoli

Publications and source records attributed to G F Mazzuoli.

At least 19 recordsLinked to original sources

Primary hyperparathyroidism and osteoporosis.

Primary hyperparathyroidism (PHPT) is considered a cause of secondary osteoporosis as a consequence of its known catabolic effect promoting osteoclast activity and bone resorption. However, recent in vitro and in vivo studies have shown that parathyroid hormone (PTH) may also have an anabolic effect on the mammalian skeleton. These two paradoxical effects of parathyroid hormone are discussed in the light of recent results of basic research, and of bone densitometric and histomorphometric data collected in patients affected by PHPT. Review of the literature leads to the conclusion that in PHPT skeletal damage involves prevalently cortical bone, while the mineral content of trabecular bone is preserved or even increased. On the basis of bone mineral density (BMD) measurements, osteoporosis prevalence in the early postmenopausal period seems to be significantly higher in women affected by PHPT than in the general population. As age progresses, osteoporosis prevalence seems to decrease in PHPT, while it increases exponentially with age in the general population. Similarly in PHPT, vertebral and appendicular fractures occur prevalently in the earlier decades of life with a higher frequency than in normal subjects, while with advancing age the fracture incidence becomes equal to that of the general population. When bone density is measured in lateral projection at lumbar level, BMD values in patients with mild asymptomatic PHPT are significantly higher than in controls. We conclude that PTH hypersecretion may represent a risk factor for osteoporosis and fractures in the young and in the early postmenopausal period, while it may have a protective effect on trabecular bone in elderly postmenopausal women.

Aged

Relationship between spine bone mineral density and vertebral body heights.

The aim of this study was to investigate the correlation between lumbar spine bone mineral density (LS-BMD) and the vertebral body heights with advancing age and years since menopause. One hundred and sixty-three women ages 39-74 years (77 normal premenopausal, ages 39-54, and 86 normal postmenopausal, ages 46-74 years) were studied. LS-BMD was measured by dual energy X-ray absorptiometry. Vertebral heights were evaluated, using morphometry, as the sum of anterior (AHs), middle (MHs), and posterior (PHs) vertebral body heights from T4 to L5. The AHs/PHs ratio at the same level was also calculated. AHs, MHs, PHs, and AHs/PHs ratio directly correlated with LS-BMD; the correlations are AHs r = 0.80, P < 0.0001, MHs r = 0.75, P < 0.0001, PHs r = 0.76, P < 0.0001, and AHs/PHs r = 0.66, P < 0.001. Both LS-BMD and AHs are inversely correlated with age, and the regressions fit with both linear and cubic curves. The statistical significance of the correlations persists while maintaining age constant. The linear regression curve of AHs with age indicates that the spine height decrement rate is 2.12 mm/year, corresponding to 7.4 cm in 35 years. AHs decreases immediately after menopause fitting with a cubic curve model, with a decrement rate of about 3 cm in the first 5 years after menopause. We conclude that the measurement of the sum of vertebral body heights could usefully integrate LS-BMD evaluation in the clinical and epidemiological investigation of osteoporosis.

Adult

Tartrate-resistant acid phosphate activity as osteoclastic marker: sensitivity of cytochemical assessment and serum assay in comparison with standardized osteoclast histomorphometry.

Tartrate-resistant acid phosphatase (TRAP) activity is regarded as an important cytochemical marker of osteoclasts; its concentration in serum is utilized as a biochemical marker of osteoclast function and degree of bone resorption. This study was carried out to assess the sensitivity of TRAP activity both as a cytochemical marker in histological sections and as a biochemical marker in serum in comparison with the standardized histomorphometric variables of osteoclasts. To this end we investigated 24 patients (21 women, 3 men; 60 +/- 17 years of age) affected with various metabolic bone diseases. Osteoclast surface (OcS/BS) and osteoclast number (OcN/BS) were evaluated by standardized histomorphometry in iliac crest biopsies. On the basis of TRAP cytochemical activity, TRAP-positive osteoclast surface (TRAP + OcS/BS) and number (TRAP + OcN/BS) were measured. TRAP-positive cells adjacent to bone and showing one nucleus or no nuclei at all in the plane of section were included in the counts as osteoclasts. Serum TRAP activity was determined by spectrophotometric assay. Values of OcS/BS and OcN/BS were much lower than those of TRAP + OcS/BS (-50%) and TRAP + OcN/BS (-60%), respectively. Correlations between OcS/BS and TRAP + OcS/BS, and between OcN/BS and TRAP + OcN/BS, were highly significant. Serum TRAP was significantly correlated with OcS/BS, OcN/BS, and TRAP + OcN/BS. These correlations, however, were rather low. Moreover, serum TRAP did not correlate with TRAP + OcS/BS. From these results, the conclusion can be drawn that while TRAP activity is confirmed as a valid cytochemical marker for identification of osteoclasts, serum TRAP activity is an osteoclastic marker of weak sensitivity. This may be due to known factors, such as synthesis of the enzyme not being unique to osteoclasts, enzyme instability, and the presence of inhibitors in serum. Mononucleated osteoclasts do not significantly influence the serum enzyme levels.

Acid Phosphatase

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.

Adolescent

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

Effect of chronic treatment with ipriflavone in postmenopausal women with low bone mass.

We present the results of two multicenter, double-blind, placebo-controlled, 2-year studies to evaluate the efficacy and tolerability of ipriflavone in postmenopausal women (PMW) with low bone mass. 453 PMW (aged 50-65 years) with a vertebral (VMD) or radial (RMD) mineral density value 1 SD lower compared with age-matched controls, were randomly selected to receive oral ipriflavone (200 mg T.I.D. at meals) or matching placebo, plus 1 g oral calcium daily. Vertebral (study A, by dual X-ray absorptiometry-DXA) and radial (study B, by dual photon absorptiometry-DPA) bone density, serum bone Gla-protein (BGP), and urinary hydroxyproline/creatinine (HOP/Cr) were measured every 6 months. In both studies, the Valid Completers (VC) analysis showed a maintenance of bone mass in ipriflavone-treated women, whereas in the placebo group, bone mineral density (BMD) was significantly decreased. The final outcome was a bone-sparing effect of 1.6% in study A, and of 3.5% in study B after 2 years. The Intention to Treat (ITT) analysis confirmed the decrease in the placebo group, with no changes in ipriflavone-treated women. A significant (P < 0.05) between-treatment difference was found in both studies. Biochemical markers of bone turnover decreased in patients treated with ipriflavone, thus suggesting a reduction of bone turnover rate. Twenty-six women treated with ipriflavone and 28 receiving the placebo dropped out because of side effects, mainly gastrointestinal. The compliance to the oral long-term treatment was good. The results of these studies show that ipriflavone is able to prevent both axial and peripheral bone loss in PMW with low bone mass, and is well tolerated.

Absorptiometry, Photon

Aging changes in vertebral morphometry.

We analyzed the vertebral morphometry of healthy premenopausal women and their changes with age and menopause in order to better define the reference population for the clinical and epidemiological evaluation of vertebral fractures. Vertebral morphometry has been performed on lateral thoracic and lumbar spine films from 50 premenopausal and 76 postmenopausal normal women, age range 39-74 years. Vertebral heights and the anterior height/posterior height ratio are significantly lower in postmenopausal compared with premenopausal women. Vertebral anterior height decreases about 1.5 mm/year, whereas middle and posterior height decreases about 1.3 and 1.2/mm year, respectively. A statistically significant reduction of vertebral heights by around 1 mm/vertebra was observed in postmenopausal (n = 16) compared with premenopausal women (n = 20) of the same age (P < 0.05). The results demonstrate that vertebral heights are lower with advancing age and menopause and that the vertebral heights difference in elderly people is not only the consequence of a cohort effect. The results also contribute to better defining the reference population to be chosen for evaluating vertebral deformation.

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 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

Hip fracture in Italy: epidemiology and preventive efficacy of bone-active drugs.

In this paper we report the results on the epidemiology of hip fracture and the preventive efficacy of bone-active drugs in Italy, observed in men and women aged 50 years or over, recruited in the three Italian centres participating in the Mediterranean Osteoporosis Study (MEDOS), namely Parma, Rome, and Siena. The number of fractures observed was 1,437 in a catchment area population of 847,508 individuals, with a total incidence of 169.6/100,000--a female-to-male ratio of 3.5 and a doubling-time of about 5.5 years. The female excess becomes evident in the age groups over 60 years. The mean age of fractures was 77 years in females and 73 in males. From the data collected, the estimated number of fractures per year in the Italian population aged over 50 years is 32,000. The pattern of use and the preventive efficacy of bone-active drugs was examined in women. Calcitonin and calcium were the drugs mainly used; less than 3% had taken vitamin D or oestrogen and only a minor percentage had taken anabolic steroids. Fluorides were not used at all. As seen in the European sample, the protective effect of calcium and calcitonin is statistically significant even in Italy, while vitamin D is not. The use of anabolic steroids was associated with a decrease in risk. Oestrogen administration does not seem to reduce the relative risk of hip fracture in Italian women, probably due to the small sample size.

Aged

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

Hypocalcemia and hypomagnesemia in cancer patients.

The aim of this study was to evaluate the incidence of hypocalcemia and hypomagnesemia and the relationship between calcium and magnesium serum levels in 82 hospitalized cancer patients, 61 of whom were in the terminal phase of the disease. The frequency of hypocalcemia and hypomagnesemia was 13.4% and 17.1% respectively. The incidence of hypocalcemia in patients with hypomagnesemia was 28.6%, while in those with normal or high magnesium serum levels it was 10.3%. The lowest magnesium serum level was observed in hypocalcemic patients. It may thus be concluded that hypocalcemia and hypomagnesemia are a frequent complication of malignant tumors mostly in the terminal stage of the disease, and that even hypomagnesemia could contribute to the development of tumor-associated hypocalcemia.

Aged

Clinical usefulness of serum tartrate-resistant acid phosphatase activity determination to evaluate bone turnover.

The study was carried out to evaluate the clinical validity and usefulness of serum tartrate-resistant acid phosphatase (TRAP) activity determined using an improved spectrophotometric assay. Enzyme activity was measured in 84 normal subjects and in 109 patients with common metabolic bone diseases. Mean values of serum TRAP activity in male subjects (n = 19; 10.4 +/- 2.15 U l-1) were not significantly different from those found in female subjects (n = 65; 10.8 +/- 1.8 U l-1). In the latter group mean values were significantly raised in post-menopausal subjects (10.5 +/- 2.0 U l-1; p less than 0.01) compared with mean values in pre-menopausal women (8.45 +/- 1.8 U l-1). We found a significant inverse correlation between serum TRAP activity values and bone mineral density (BMD) measured both at an ultradistal radial point (n = 33, r = -0.506; p less than 0.01), and at the lumbar spine (n = 57, r = -0.261; p less than 0.05). Mean serum TRAP activity values in patients with metabolic bone diseases were: primary hyperparathyroidism, n = 30: 14.2 +/- 4.89 U l-1, p less than 0.001 vs normal subjects; chronic maintenance haemodialysis, n = 19: 17.4 +/- 6.7, p less than 0.001; metastatic cancer, n = 13: 21.2 +/- 6.3, p less than 0.001; post-surgical hypoparathyroidism, n = 10: 9.9 +/- 1.8, NS; involutional osteoporosis, n = 20: 12.5 +/- 2.3 p less than 0.001; Paget's disease, n = 10: 16.8 +/- 3.5, p less than 0.001; osteomalacia, n = 7: 19.5 +/- 3.31, p less than 0.001.(ABSTRACT TRUNCATED AT 250 WORDS)

Acid Phosphatase

Effects of salmon calcitonin on the bone loss induced by ovariectomy.

We present the results of a 12-month clinical study assessing the effects of synthetic salmon calcitonin (sCT) on a group of fertile white women who had undergone ovariectomy for uterine fibromatosis. The study was performed to verify whether CT can prevent the loss of bone mass and the changes in calcium-phosphorus metabolism associated with acute estrogen deficiency. The study consisted of an initial double-blind phase of 6 months, followed by a 6-month open period. Treated patients were given 100 MRC U of synthetic salmon CT injected i.m. in the morning, every other day, starting on the 7th day after the operation and continued for 12 months. Control patients received a placebo injection for the first 6 months; subsequently, they too were treated with sCT i.m. every other day for 6 months at the same dose as the 12 month-treated group. All patients received 500 mg of elementary calcium p.o., b.i.d. Bone mineral content (BMC) was measured at the extreme distal radius of the nondominant arm by a dual photon bone densitometer which utilizes two radio nuclides, 241 Am and 125 I, with energies of about 60 and 30 KeV. Biochemical parameters of the calcium-phosphorus metabolism were also measured. After 12 months of study, no significant changes of BMC were observed in the 12 months sCT treated group, while control patients, treated 6 months after the ovariectomy, showed a significant decrease in BMC values.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult

Acute hypocalcemia enhances prolactin levels: a study before and after oophorectomy.

The effect of acute hypocalcemia on serum prolactin values was investigated in 13 female subjects before and after oophorectomy. An infusion of disodium-EDTA (50 mg/kg b.w., for 120 min) was administered to each patient. Ionized calcium, immunoreactive parathyroid hormone and prolactin serum levels were determined 15 min prior to the infusion, at the beginning of each infusion and thereafter at every 30 min interval. The decrease in serum ionized calcium induced by Na2-EDTA infusion was not influenced by surgery. Serum prolactin and parathyroid hormone values before and after oophorectomy showed a significant (p less than 0.01) increase at 90 and 120 min. The maximum serum prolactin increase was achieved at 120 min and was not influenced by oophorectomy. The results demonstrate that acute hypocalcemia increases serum prolactin levels in female subjects and suggest a possible role for parathyroid hormone and dopaminergic system, even if their interaction remains speculative.

Adult