Biomedical subjects

F Bertoldo

Publications and source records attributed to F Bertoldo.

29 records · Page 2Linked to original sources

PubMed1994

Duration of the effects of intravenous alendronate in postmenopausal women and in patients with primary hyperparathyroidism and Paget's disease of bone.

The effect of a single intravenous (i.v.) infusion of 5 mg alendronate was studied in ten patients with Paget's disease, six patients with primary hyperparathyroidism and ten osteopenic postmenopausal women. Urinary hydroxyproline excretion significantly decreased within few days in all patients (from 113 +/- 67.9 to 58 +/- 35 mmol/mol Cr in Paget's disease, from 21.8 +/- 9 to 12.9 +/- 6 mmol/mol Cr in hyperparathyroidism, from 18.7 +/- 9.5 to 8.5 +/- 4.3 mmol/mol Cr in postmenopausal women). In the patients with Paget's disease urinary hydroxyproline remained suppressed over the 6 months of follow-up, whereas it rose toward pretreatment values within 4 and 6 weeks in the patients with primary hyperparathyroidism and in postmenopausal osteopenic women, respectively. Plasma alkaline phosphatase significantly fell only after 4-6 weeks in patients with primary hyperparathyroidism and in Pagetic patients. In the latter group alkaline phosphatase continued to decline thereafter and a plateau became apparent after 2 months. In postmenopausal women the serum alkaline phosphatase remained unchanged. Thus, the same dose of alendronate induces comparable fractional decreases of bone resorption in the three groups of patients, but the effect is persistent only in Paget's disease. This is consistent with the hypothesis that alendronate inhibits osteoclastic activity only at the level of the existing resorption sites. In osteoporotic and primary hyperparathyroid patients, as soon as the treatment is withdrawn, the appearance of new sites of resorption is not inhibited and bone turnover is resumed to pre-treatment values.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗

PubMed1994

Effect of bisphosphonate therapy and parathyroidectomy on the urinary excretion of galactosylhydroxylysine in primary hyperparathyroidism.

BACKGROUND: In patients with mild or asymptomatic primary hyperparathyroidism a reliable index of bone resorption might be useful for appropriate management. Hydroxyproline is the most commonly used marker of bone resorption but its low specificity and sensitivity are known. Galactosylhydroxylysine, an amino acid mainly represented in bone collagen, has been proposed as a more suitable index of bone resorption. In this study we evaluated the sensitivity of galactosylhydroxylysine and hydroxyproline assays in following the changes of their urinary levels in 12 patients with mild primary hyperparathyroidism before and after treatment with bisphosphonate and surgery. METHODS: Serum and fasting urine specimens were obtained from 12 women with mild primary hyperparathyroidism before and after bisphosphonate treatment (2.5 mg daily for 5 days, intravenously) and after a further 25 days; in 7 patients biochemical tests were also performed 1 and 6 days after parathyroidectomy. Galactosylhydroxylysine was assayed by an HPLC method and hydroxyproline by a RIA commercial kit. RESULTS: Baseline galactosylhydroxylysine urinary levels were far above the normal range in all the patients whilst in 8 of them baseline hydroxyproline levels were normal. Bisphosphonate treatment significantly decreased bone turnover as shown by a significant fall in serum calcium (from 2.9 to 2.6 mmol/l; P < 0.001) and in galactosylhydroxylysine and hydroxyproline (-55 and -31% respectively). Twenty-five days after the end of treatment, resorption increased again and serum calcium and galactosylhydroxylysine, but not hydroxyproline, rose significantly towards basal levels. One day after parathyroidectomy serum calcium, galactosylhydroxylysine and PTH showed reduction below normal ranges. PTH and galactosylhydroxylysine returned to normal values at day 6 after parathyroidectomy. No changes in hydroxyproline levels were seen. Galactosylhydroxylysine, but not hydroxyproline, correlated significantly with serum calcium and PTH. CONCLUSION: Galactosylhydroxylysine appears to be a sensitive index of bone resorption, useful in the clinical assessment of bone involvement and in the management of patients with mild primary hyperparathyroidism.

Aged↗

PubMed1993

Long-term effects of transdermal and oral estrogens on serum lipids and lipoproteins in postmenopausal women.

The transdermal and oral administration of estrogens for one year were compared with respect to the effects on lipid metabolism. Eighty-one postmenopausal women (1.5-3 years after menopause) were randomly divided into three groups. The first two groups received sequential estrogen treatment with either transdermal estradiol (Estraderm TTS, Ciba Geigy; 50 micrograms/day; 24 women) or 0.625 mg/day conjugated estrogens (Premarin, Wyeth; 20 subjects), respectively. In both groups medroxyprogesterone (10 mg/day per os) was added for 12 days of each cycle. Thirty-five subjects served as control group without therapy. No significant changes in the lipid profile was observed in control subjects after 1 year of follow-up. Serum triglycerides decreased significantly (-10.9 +/- 26% S.D.; P < 0.05) in transdermal treated women, whereas it slightly rose in oral estrogen group. Comparable significant decreases in total and low density lipoprotein (LDL) cholesterol (mean range -6.5/-18.0%) were observed in women on estrogen replacement therapy. High density lipoprotein (HDL) cholesterol significantly diminished in transdermal estradiol group, but it rose slightly in the oral estrogen group. Thus the fraction of HDL cholesterol over LDL cholesterol did not change in the transdermal group whereas it significantly rose in subjects treated with oral estrogens. It remains to be established to what extent these differences on lipid metabolism are relevant for the prevention of cardiovascular diseases.

Administration, Cutaneous↗

PubMed1993

[The medical treatment of primary hyperparathyroidism].

The first-choice treatment of primary hyperparathyroidism is surgical removal of abnormal parathyroid gland(s) and the medical management is usually reserved only to control severe hypercalcemia. However, asymptomatic primary hyperparathyroidism with mild hypercalcemia and renal and bone status close to normal is now the more common picture of the disease and in this situation conservative management can be considered, because many of those patients may have a prolonged benign course. Management guidelines are therefore devised to minimize the risk for deterioration of renal, skeletal or gastrointestinal complications of hyperparathyroidism. General medical management includes recommendation to avoid dehydration, immobilization or excessive dietary calcium intake and therapy with thiazides; intravenous infusion with isotonic saline combined to furosemide or etacrinic acid are recommended to treat acute or threatening hypercalcemia. Many other drugs as phosphate, mithramycin, gallium nitrate and calcitonin have been reported to be useful in reversing hypercalcemia but their transient effects, toxicity and side effects limit their clinical use. The bisphosphonates, a new class of bone resorption inhibitors, have been shown to be particularly safe so they result especially effective on controlling acute hypercalcemia and on preventing "hungry bone" disease. However, their effect is not sustained because the serum calcium tends to return toward pretreatment levels despite continued therapy; therefore their consistent beneficial effect on long-term treatment seems unlike.

Fluid Therapy↗

PubMed1992

The effects of menopause and estrogen replacement therapy on the renal handling of calcium.

Mineral metabolism was studied in 99 premenopausal and 80 postmenopausal women both before and after 9-14 months of treatment with 50 micrograms/day transdermal estradiol. In estrogen-repleted subjects (premenopausal women and postmenopausal women on estrogen replacement therapy) total serum calcium was significantly lower (0.065 mmol/l; p less than 0.001) than in those who were estrogen-depleted (untreated postmenopausal women). This difference was smaller but still significant for calculated ultrafiltrable calcium (UFCa: 0.02-0.03 mmol/l; p less than 0.001). However, ionized calcium (both calculated and measured) was not different in the two groups of women. This finding explains why estrogen repletion does not induce changes in the serum level of intact parathyroid hormone (PTH), despite lower total or ultrafiltrable serum calcium. In a parallel study we have shown that intravenous administration of aminobutane bisphosphonate, a powerful inhibitor of bone resorption, produces similar decreases in serum calcium which were associated with significant increases in intact PTH. Estrogen-depleted women had, on the one hand, significantly higher serum levels of bicarbonate, anion gap, complexed calcium, pH, phosphate and alkaline phosphatase, and higher rates of tubular reabsorption of phosphate and urinary excretion of calcium and hydroxyproline. On the other hand they had lower serum chloride levels and lower rates of tubular reabsorption of calcium. Altogether these findings might indicate that estrogen deficiency decreases renal sensitivity to PTH. This is responsible for the higher serum phosphate and bicarbonate levels, the resulting mild metabolic alkalosis leading to higher serum levels of complexed ultrafiltrable calcium and higher rates of urinary excretion of calcium, but unchanged serum levels of ionized calcium and PTH.

Adult↗

PubMed1991

The prevention of corticosteroid-induced osteoporosis with nandrolone decanoate.

The effects of nandrolone decanoate (ND; 50 mg IM every three weeks) on calcium metabolism and forearm bone density were studied in a randomized trial in 35 women receiving long-term therapy with corticosteroids (CST) for rheumatic disease. The 17 patients who served as controls were on CST therapy for less years and their bone density was higher. Thus a second control group, pair-matched with the active treatment group for age, duration of CST therapy and bone density, was selected retrospectively. At the end of the 18 months' treatment course with ND, forearm bone density was increased by 5.1% (P less than 0.01) but fell by 11.3% (P less than 0.01) and 6.7% respectively in the first and second control group. The patients on ND differed significantly from both control groups in the changes at 6, 12 and 18 months (P less than 0.01). Urinary excretion of hydroxyproline fell significantly in patients receiving ND, whereas the biochemical indices of bone formation did not change (alkaline phosphatase) or increased (osteocalcin; P less than 0.01). In conclusion, nandrolone decanoate therapy may be used in the prevention of CST-induced osteoporosis. It also seems to exert mild inhibition of bone resorption without affecting or even stimulating bone formation.

Absorptiometry, Photon↗

PubMed1990

Regulation of calcium-parathyroid hormone feedback in primary hyperparathyroidism: effects of bisphosphonate treatment.

Dichloromethylene bisphosphonate (C12MBP), a powerful inhibitor of bone resorption, was administered to 27 patients with primary hyperparathyroidism. It was given by either intravenous infusion (six patients, 500-100 mg day), or by intramuscular injection (six patients, 100-200 mg/day) or by mouth (15 patients, 1600-2400 mg/day) for 20-180 days. Sustained suppression of bone resorption was observed in all patients, as judged by a fall in the urinary hydroxyproline excretion. In contrast, the hypocalcaemic effect was inconsistent and short-lived, particularly in the patients without overt bone disease. The fall in serum calcium seemed largely to be due to a transient dissociation between bone resorption and bone formation and was associated with increases in circulating parathyroid hormone (PTH). In ten patients given the bisphosphonate orally for 6 months, serum calcium was unchanged but serum PTH was significantly raised. These results suggest that C12MBP may be of use for short-term correction of severe hypercalcaemia due to hyperparathyroidism, particularly in the patients with overt bone disease. However, its long-term use should not be recommended because of increased PTH secretion.

Adult↗

PubMed1989

Transdermal estradiol in the treatment of postmenopausal bone loss.

The effects on calcium metabolism and forearm bone mineral density of sequential transdermal estradiol (ESTRADERM TTS-50), 50 micrograms/day and medroxyprogesterone (10 mg/day for 12 days) was studied in a randomised controlled trial in 34 healthy females 2-4 years after the menopause. At the end of the 18 months' treatment course with transdermal estradiol, bone density was increased by 4.31% (P less than 0.01) but was decreased by 3.5% (P less than 0.01) in the control group. In the treated group, serum calcium, calcium excretion and hydroxyproline excretion significantly fell during the first 2 months with no significant changes thereafter. Serum alkaline phosphatase significantly decreased only after 4 months, it continued to fall until the fourteenth month when a plateau became apparent. Serum phosphate and tubular maximum for urinary phosphate progressively fell until the tenth month of therapy but thereafter they rose up to initial values. Serum intact parathyroid hormone did not show any significant change. In conclusion, small doses of transdermal estradiol are as effective as oral estrogens. This suggests that the bone sparing effects of estrogens may be due only to low circulating estradiol concentrations, but not to supraphysiological estrone levels. It seems also that estrogens exert both a straight inhibition of bone resorption and a partial inhibition of parathyroid responsiveness.

Administration, Cutaneous↗

PubMed1987

The use of dichloromethylene bisphosphonate and aminobutane bisphosphonate in hypercalcemia of malignancy.

54 patients with malignant hypercalcemia were treated with either dichloromethylene bisphosphonate (Cl2MBP) or aminobutane bisphosphonate (AHButBP). Both compounds infused intravenously (i.v.) were rapidly effective in lowering serum calcium to normal range and a potency ratio between Cl2MBP and AHButBP could be roughly estimated as 1:100-250. 600 mg of Cl2MBP infused in one day over 9 h in nine patients were only slightly less effective (serum calcium from 12.3 +/- 1.7 to 10.1 +/- 1.1 SE, mg/dl) than 3300 mg infused in 11 consecutive days (13.4 +/- 1.9 to 9.3 +/- 1.2 SE, mg/dl). Thus the effectiveness of treatment with Cl2MBP was related better to the overall time of infusion than to the cumulative dose administered. This could not be demonstrated in a similar trial using AHButBP. 1600 mg Cl2MBP daily p.o. was unable to prevent the relapse of hypercalcemia in four patients after a treatment course with i.v. bisphosphonates. 100 mg of Cl2MBP intramuscularly maintained serum calcium within the normal range in two out of eight patients; however, weekly infusions of either Cl2MBP or AHButBP prevented the relapse of hypercalcemia in eight similarly treated patients for several weeks. Providing that adequate dosages are adopted, parenteral Cl2MBP and AHButBP may be a useful measure for controlling hypercalcemia in patients with carcinoma.

Administration, Oral↗

PubMedDate not supplied

Effects of two oral doses of alendronate in the treatment of Paget's disease of bone.

Twenty patients with mild Paget's disease of bone were given either 20 (10 patients) or 40 mg alendronate daily for 6 months. The 20-mg dose was well tolerated, but in 3 patients on 40 mg/d alendronate, the treatment was withdrawn after 3-5 months because of gastric and oesophageal disturbances. Urinary hydroxyproline excretion fell within the first month to 77 +/- 5% (SD) and to 47 +/- 5% of pretreatment values in the 20- and 40-mg dosing group, respectively (p < 0.001 between group comparison). The serum alkaline phosphatase fell more slowly with the maximum suppression of disease activity reached at 4 months, when it attained a plateau in both groups of patients. However, the decrease in serum alkaline phosphatase was significantly more pronounced in the patients treated with 40 mg/d tablets (50 +/- 10% of pretreatment values) than in those given 20 mg alendronate per day (76 +/- 9% of initial value), in none of whom a disease remission was observed. It appears, therefore, that while 20 mg/d oral doses of alendronate are insufficient, 40 mg/d are associated with a high incidence of side effects. Furthermore, the suppression of disease activity depends on the dose of bisphosphonate given daily or over a short period of time and lower doses cannot be compensated by a longer duration of the treatment course.

Administration, Oral↗

PubMedDate not supplied

[Use of nonsteroidal anti-inflammatory drugs in patients with vertebral osteoporotic fractures].

OBJECTIVE: The aim of the study was to assess the use of Non Steroidal Anti-Inflammatory Drugs (NSAIDs) in patients with a history of osteoporotic vertebral fractures. METHODS: We investigated 119 patients with postmenopausal osteoporosis complicated by one or more non recent vertebral fractures. RESULTS: More than 60% of the patients took at least one dose of NSAID weekly. The most prescribed NSAID was nimesulide, at a dose with an exclusively antalgic effect. Patients with wedge fracture and those with a documented vertebral fracture in the last 12 months were those taking NSAIDs more frequently. 77% of the patients that used NSAIDs had concomitant features of osteoarthritis, mainly at the spine or at the knee. The use of NSAIDs was negatively related to the use of specific therapy for osteoporosis, particularly for oral daily tablets. CONCLUSIONS: This study highlights the significant use of NSAIDs in patients with osteoporotic vertebral fractures and the overlap between osteoporosis, osteoarthritis and related treatments.

Aged↗