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Biomedical subjects

R Rizzoli

Publications and source records attributed to R Rizzoli.

At least 127 records · Page 7Linked to original sources
PubMed1996

Effects of oral clodronate on bone mineral density in patients with relapsing breast cancer.

The high prevalence of bone metastases in breast cancer and the risk that spinal and femoral osteoporosis may add further morbidity provide a rationale for bisphosphonate therapy in patients with skeletal metastases from mammary carcinoma. We investigated the effects of oral clodronate given during 9 months, with a 24-month follow-up, on bone mineral density (BMD), on biochemical markers of bone remodeling, and on osseous complications in 67 women with documented relapsing breast cancer, aged 58.7 +/- 1.5 years (x +/- SEM). Patients with active cancer disease were randomly allocated to two groups, with or without clodronate treatment (1600 mg/day, orally). Twenty-six women considered in complete remission (52.4 +/- 2.4 years) were also studied. Expressed in deviation from gender- and age-matched normals (z score), base-line BMD at the levels of lumbar spine (LS), femoral neck (FN), and midfemoral shaft (FS) was +0.10 +/- 0.22 vs. -0.12 +/- 0.25, +0.03 +/- 0.19 vs. -0.54 +/- 0.24, and +0.08 +/- 0.14 vs. -0.02 +/- 0.22, in patients with active breast cancer and in subjects in remission, respectively. After 9 months of treatment, fasting urinary calcium to creatinine ratio was lower (0.26 +/- 0.04 vs. 0.40 +/- 0.04 mmol/mmol creatinine, p < 0.02) and serum osteocalcin was stabilized (-2.1 +/- 1.1 vs. +7.0 +/- 3.3 micrograms/L, as compared with pretreatment values, p < 0.02), in the clodronate-treated group. The rate of osseous complications (pathological fracture, hypercalcemic episode, scintigraphic or radiological evidence of metastasis development, chemo- or radiotherapy for bone disease progression) was 28.8 events per 100 patient-year in the clodronate-treated group vs. 39.0 in controls, and 31.5 vs. 40.5, after 9 and 15 months of follow-up, respectively. In 15 women without evident LS bone metastasis (7 clodronate-treated and 8 controls), LS BMD increased in the clodronate-treated group by +5.2 +/- 2.5% vs. -0.3 +/- 1.4%, and +8.1 +/- 4.7 vs. -0.9 +/- 1.7, after 10.3 +/- 0.4 and 17.3 +/- 1.2 months, respectively (p < 0.01), as compared with pretreatment values. These results indicate that clodronate treatment decreased bone turnover and attenuated cancer-related bone morbidity. In addition, clodronate increased LS BMD in apparently unaffected bone of women with relapsing breast cancer.

Administration, Oral↗
PubMed1996

Axial osteomalacia: report of a new case with selective increase in axial bone mineral density.

Axial osteomalacia was diagnosed in a 60-year-old white Caucasian male, on the basis of X-ray examination showing typical coarsened and sponge-like appearance of trabecular bone strictly located in the axial skeleton. Dual energy X-ray absorptiometry demonstrated a marked increase in axial bone density at lumbar spine levels in both anteroposterior and lateral views (T score: +7.9 and +5.5, respectively), contrasting with normal values at femoral neck, trochanter and midfemoral diaphysis (T score: +0.6, +0.3, and +0.8, respectively). Histomorphometry of iliac crest showed marked thickening of cortices (1730 and 2763 microns, N = 967 +/- 57), increased trabecular bone volume (28.9%, N = 17.4 +/- 5.6), normal eroded surface (3.5%, N = 3.6 +/- 1.1), and increased osteoid surface and volume (31.6%, N = 15.3 +/- 9.4 and 5.8%, N = 2.8 +/- 1.8). Osteoid thickness was increased (39.6 microns, N = 10.5 +/- 1.8, up to 120 microns in one site) and mineral apposition rate was decreased in the trabecular sites (0.43 micron/day, N = 0.72 +/- 0.12, down to < 0.2 micron/day, focally). Bone fluoride content was not increased (0.08%, N < 0.10%). All biochemical parameters of bone metabolism, including serum osteocalcin, PTH, calcidiol, calcitriol, and renal tubular reabsorption of calcium or phosphate were normal.

Absorptiometry, Photon↗
PubMed1996

Osteoporosis in patients undergoing lung transplantation.

The occurrence of osteoporotic fractures may seriously compromise the quality of life of lung transplant recipients. However, at present, the true risk of osteoporosis in such patients is unknown. We therefore prospectively evaluated bone mass changes in patients undergoing pulmonary transplantation. Bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and femoral shaft (FS), as well as whole body bone mineral content (WB-BMC) were measured in 21 consecutive candidates for lung transplantation (9 males and 12 females; mean+/-SD age 47+/-11 yrs). Twelve of the patients had their BMD remeasured within 6 months after surgery, and nine again after 1 year. Before transplantation, BMD at all sites as well as WB-BMC were significantly decreased as compared to the values in young healthy adults, FN being the most affected (FN -25+/-2%; LS, -12+/-4%; FS -9+/-2%, WB-BMC -15+/-4% (mean+/-SEM)). Seven out of 20 adult patients (35%) fulfilled World Health Organization (WHO) criteria for osteoporosis, i.e. BMD more than 2.5 SD below peak bone mass, whereas three had previously been diagnosed as having osteoporotic fractures of the spine or femoral neck. Within 6 months after transplantation, significant bone loss occurred, mostly at the LS level (-4.0+/-1.7%; p=0.04), despite calcium and vitamin D supplementation. Furthermore, two patients had new osteoporotic vertebral fractures. After 1 year, no further bone loss or new osteoporotic fractures were observed. In conclusion, evaluation of bone mass and prevention of bone loss should be considered early before lung transplantation. Further studies are needed to determine the efficacy of antiresorptive drugs on the prevention of accelerated bone loss and vertebral fractures after transplantation.

Adult↗
PubMed1995

The role of dual energy X-ray absorptiometry of lumbar spine and proximal femur in the diagnosis and follow-up of osteoporosis.

Dual energy x-ray absorptiometry techniques have been validated for the quantitative assessment of bone mass at two skeletal sites particularly at risk of osteoporotic fracture, i.e., lumbar spine and proximal femur. These measurements assess areal bone mineral density (BMD), which integrates the size of the bone and its thickness, as well as the true volumetric density. Areal density provides useful information relative to fracture risk, since there is an inverse relationship between incidence of osteoporotic fractures and areal BMD. Although lumbar spine BMD measurements by a lateral view could offer the advantage over conventional anteroposterior projection of avoiding osteophytes and posterior element osteoarthritis, it does not seem to be superior in diagnostic sensitivity, except possibly for corticosteroid-induced bone loss. Femoral neck BMD appears to be a significantly better predictor of fracture of the proximal femur. Since this measurement does not appear to be influenced by osteoarthritis, it would be the most suitable for the diagnosis of osteoporosis in the elderly. However, the potential for error in terms of both accuracy and precision for dual x-ray absorptiometry measurements of lumbar spine and proximal femur emphasizes the need for strictly controlled conditions of measurement.

Absorptiometry, Photon↗
PubMed1995

Vitamin-D-receptor-gene polymorphisms and change in lumbar-spine bone mineral density.

Common vitamin-D-receptor (VDR) gene allelic variants predict bone mineral density. We analysed VDR alleles and rate of change of lumbar-spine bone mineral density over 18 months in 72 elderly subjects. 9 BB homozygotes lost bone mineral density but 26 homozygotes for the alternative genotype (bb) did not (mean change -2.3 [SE 1.0] vs 0.9 [0.7]% per year, p < 0.05), irrespective of calcium intake. Among 37 heterozygotes (Bb), however, change in bone mineral density correlated with calcium intake (r = 0.35, p < 0.03). This association between a genetic marker and rate of bone loss in the elderly suggests that the effect of calcium intake on maintenance of bone mass could relate to VDR gene polymorphisms.

Aged↗
PubMed1995

Regulation of parathyroid hormone/parathyroid hormone-related protein receptor expression by osteoblast-deposited extracellular matrix in a human osteoblast-like cell line.

Parathyroid hormone (PTH) receptors and the biological response to PTH in osteoblasts have been shown to be influenced by glucocorticoids, growth factors, cytokines or PTH itself. Furthermore, components of extracellular matrix (ECM) appear to regulate the response to PTH as well. We investigated the effects of osteoblast-deposited ECM on PTH-related protein (PTHrP)-stimulated cAMP production, PTHrP binding and PTH/PTHrP receptor mRNA in the human osteoblast-like cell line SaOS-2. ECM was laid down by the human osteoblastic cell line MG-63. At confluence, maximal cAMP stimulation induced by 100 nmol/l PTHrP (1-34) was decreased in SaOS-2 cells grown on ECM as compared with cultures on plastic dishes, without any change in PTHrP concentration producing half-maximal stimulation. In contrast, cAMP production stimulated by PGE2 was increased in cells on ECM. Saturable 125I-PTHrP binding (as evaluated by Scatchard plot analysis) was markedly diminished in cells grown on ECM (5,600 +/- 2,010 vs. 20,700 +/- 1,710 binding sites/cell, x +/- S.E.M., P < 0.01, n = 4 experiments), without any significant change in affinity (1.3 +/- 0.4 vs. 2.5 +/- 0.5 nmol/l (NS), in cells on ECM and plastic, respectively). This apparent decrease in membrane receptor density was associated with markedly lower steady state PTH/PTHrP receptor mRNA levels as assessed by Northern blot analysis (ECM/control: 0.4 +/- 0.1). A difference in PTH/PTHrP receptor mRNA levels between cells on ECM or on plastic dishes was detectable by 8 hours but not by 4 hours, after seeding the cells at high density. By 24 hours after plating, PTH/PTHrP receptor mRNA levels were maximally decreased in cells on ECM. These results in the human osteoblast-like cell line SaOS-2 indicate that PTH/PTHrP receptors are down-regulated by growth on ECM. Thus, attachment of bone cells to bone surface could influence differentiation and function of osteoblasts.

Down-Regulation↗
PubMed1995

Sodium monofluorophosphate increases vertebral bone mineral density in patients with corticosteroid-induced osteoporosis.

Corticosteroid-induced osteoporosis, which particularly affects the axial skeleton and the proximal femur, is characterized by a state of low bone remodelling. Fluoride is a potent stimulator of trabecular bone formation which could potentially be useful in the treatment of corticosteroid-induced osteoporosis. We investigated the effects of sodium monofluorophosphate (26 mg/day of fluoride) combined with 1000 mg of calcium (MFP-calcium-treated group), or of calcium alone (control), given for 18 months, on bone mineral density (BMD) of lumbar spine (LS), femoral neck (FN) and midfemoral shaft (FS) in 48 patients with corticosteroid-induced osteoporosis. Mean ages were 49.4 +/- 3.1 and 51.6 +/- 3.0 years (mean +/- SEM), duration of corticosteroid therapy 7.5 +/- 1.8 and 9.3 +/- 1.7 years, and mean daily dose of prednisone 18.2 +/- 2.3 and 12.1 +/- 1.1 mg in the MFP-calcium-treated group and controls, respectively. Initial BMDs (expressed as the Z-score, i.e. the difference in standard deviations from age- and sex-matched normal subjects) were -1.5 +/- 0.2 and -1.2 +/- 0.2 for LS, -1.4 +/- 0.2 and -1.3 +/- 0.2 for FN, and -0.8 +/- 0.3 and -0.6 +/- 0.3 for FS, in the MFP-calcium-treated group and controls, respectively. Analysis by linear regression of 6-monthly measurement values revealed BMD changes of +7.8 +/- 2.2 versus +3.6 +/- 1.3% (p < 0.02) for LS, -1.5 +/- 1.8 versus +0.9 +/- 1.8% for FN, and -1.1 +/- 1.1 versus -0.5 +/- 1.4% for FS after 18 months of follow-up in the MFP-calcium-treated group and controls, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗
PubMed1995

[Peak bone mass: facts and uncertainties].

Peak bone mass, which can be defined as the amount of bony tissue present at the end of the skeletal maturation, is an important determinant of osteoporotic fracture risk in adulthood. The techniques of single or dual energy absorptiometry measure the so-called "areal" or "surface" bone mineral density (BMD), a variable which has been shown to be directly related to bone strength. During puberty the gender difference in bone mass becomes expressed. This difference appears to be essentially due to a more prolonged bone maturation period in males than in females, with a larger increase in bone size and cortical thickness, as there is no significant sex difference in the volumetric trabecular density at the end of pubertal maturation. At the beginning of the 3rd decade, there is a large variability in the normal values of areal BMD in axial and appendicular skeleton. This large variance, which is observed at sites particularly susceptible to osteoporotic fractures in adulthood, such as lumbar spine and femoral neck, is barely reduced after correction for statural height, and does not appear to substantially increase during adult life. It is generally accepted that peak bone mass at any skeletal site is attained in both sexes during the mid-thirties. However, recent studies indicate that in healthy caucasian females, bone mass accumulation can virtually be completed before the end of the second decade, for both lumbar spine and femoral neck. Several variables are supposed to influence bone mass accumulation during growth: heredity, sex, diet components, endocrine factors, mechanical forces, and exposure to risk factors.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1995

Tiludronate: bone pharmacology and safety.

The pharmacological properties of tiludronate (4-chlorophenyl)thiomethylene bisphosphonate), a sulfured bisphosphonate, have been characterized in a series of preclinical in vivo and in vitro studies. In vivo, tiludronate exerts a dose-dependent inhibitory activity on bone resorption. This property was demonstrated in several animal models, including rats, ewes, and dogs, when bone resorption was induced by administration of retinoid acid or parathyroid hormone, or by immobilization, ovariectomy or orchidectomy. By uncoupling bone resorption from bone formation, tiludronate can induce a positive calcium and phosphate balance. When administered either continuously or intermittently to ovariectomized osteoporotic rats, tiludronate promotes a significant increase in bone mass. This positive effect is associated with an increase in mechanical resistance. Bone tolerance studies indicate that tiludronate is a safe compound with an appreciable therapeutic margin since it can effectively inhibit bone resorption without reducing bone mineralization and strength. In vitro, tiludronate added to bone tissue culture inhibits calcium release, lysosomal enzyme secretion and collagen matrix degradation when induced by various stimulators of bone resorption. At the cellular level, tiludronate does not appear to exert its inhibitory effect on bone resorption by impairing either the recruitment, the migration or the fusion of osteoclast precursors. Tiludronate could act on mature osteoclasts by reducing their capacity to secrete proton into the resorption space and also by favoring their detachment from the bone matrix. The available preclinical data indicate that tiludronate should be an efficacious bisphosphonate in the management of clinical conditions characterized by excessive bone resorption.

Animals↗
PubMed1995

Potential role of IGF-1 in parathyroid hormone-related renal growth induced by high protein diet in uninephrectomized rats.

Recent studies indicate that parathyroidectomy (PTX) prevents the progression of kidney damage due to high protein diet in the subtotal nephrectomized rat model of chronic renal failure. Associated with this protection, the difference in the renal "compensatory" growth induced by high (HPr) as compared to normal protein diet (NPr) is completely abolished by PTX. To understand the physiological mechanism responsible for this protection, the changes in both circulating level and kidney content of IGF-1, a growth factor capable of influencing renal "compensatory" growth, was analyzed after unilateral nephrectomy (UNX). In UNX rats, HPr as compared to NPr diet given for five days significantly increased the kidney/body weight ratio (0.48 +/- 0.01%, N = 11 vs. 0.44 +/- 0.01%, N = 11, P < 0.005) and the plasma level of IGF-1 (365 +/- 10 ng/ml vs. 306 +/- 10 ng/ml, P < 0.001). In UNX rats fed HPr, PTX completely abolished the renal "compensatory" growth (0.38 +/- 0.02%, N = 7, P < 0.001) and the increased plasma level of IGF-1 (246 +/- 14 ng/ml, N = 7, P < 0.001). In PTX-UNX rats treated with physiological doses of 1,25-dihydroxyvitamin D3 which nearly normalized the calcemia, the renal growth and the increased plasma level of IGF-1 induced by HPr were restored towards those recorded in SHAM-UNX rats fed the HPr diet. Similar effects were observed in PTX-UNX rats in which the plasma calcium concentration was increased by the chronic administration of a retinoid derivative, used as an agent where the calcemic effect is essentially mediated by a stimulation of bone resorption.(ABSTRACT TRUNCATED AT 250 WORDS)

Animal Nutritional Physiological Phenomena↗
PubMed1995

Oral calcium tolerance test in extensive psoriasis treated with topical calcipotriol.

BACKGROUND: The vitamin D3 derivative calcipotriol (Daivonex) is an efficient topical treatment of psoriasis. When applied at a dose of about 25 g/week over a mean body surface of 16%, it is not associated with any detectable change in calcium metabolism. OBJECTIVE: Our purposes were (i) to analyze the effects of calcipotriol on various parameters of calcium metabolism when applied on a large body surface and (ii) to evaluate the usefulness of an oral calcium tolerance test in monitoring psoriatic patients under topical calcipotriol. METHODS: In group 1, 10 patients with psoriasis affecting 67.0 +/- 2.7% of total body surface (range 55-80%) were treated with calcipotriol for 6.5 weeks (mean 383 g/month). In group 2, 19 patients with psoriasis involving 15% of body surface were treated with calcipotriol for 9 weeks (mean 105 g/month). In group 3, 7 patients without topical calcipotriol for at least 1 week were given 1.5 micrograms of oral calcitriol for 7 days. An extended survey of blood and urinary parameters of calcium metabolism was performed before and after 45 days of treatment (group 1). Since one of the actions of vitamin D is to stimulate intestinal calcium absorption, an oral calcium-loading test (groups 1, 2 and 3) was done in order to detect more subtle changes possibly induced by calcipotriol. RESULTS: We did not detect any significant change in various parameters of calcium metabolism in group 1 (large body surface treated) patients. The urinary calcium responses to the oral calcium load were identical to controls in both group 1 (large body surface treated) and group 2 (limited body surface treated), whereas in group 3 (oral calcitriol therapy) an increased urinary calcium response to the calcium load was identified. CONCLUSIONS: No significant changes in calcium metabolism were detectable when calcipotriol was administered once a day over a large body surface with doses up to 100 g/week. The oral calcium tolerance test appears to be a cheap, simple and sensitive test to monitor patients exposed to high doses of calcipotriol as it detects increased intestinal calcium absorption induced by 1.5 micrograms of oral calcitriol.

Administration, Topical↗
PubMed1995

Immunocytochemical detection of phosphatidylinositol 4,5-bisphosphate localization sites within the nucleus.

Phosphatidylinositol 4,5-bisphosphate (PIP2) is a key element of signal transduction, being the preferential substrate of specific phospholipases that produce second messengers such as inositol trisphosphate (IP3) and diacylglycerol (DG). Because PIP2 has been cytochemically identified by monoclonal antibodies not only in the cytoplasmic membranes but also in the nuclear envelope and within the nucleus, we performed a study by immunoblotting and by confocal and electron microscopic immunocytochemistry to identify the nuclear sites of PIP2 localization and to exclude any cross-reactivity of the antibody with other nuclear molecules. The results confirm the specificity of the immunolabeling and indicate that PIP2 is localized at precise intranuclear sites both in in situ and in isolated nuclei. They also show that a significant amount of the phospholipid is retained by the cytoskeleton and by the inner nuclear matrix in in situ matrix preparations. Moreover the sensitivity of the immunocytochemical reaction is capable of detecting quantitative variations of PIP2 nuclear content induced by agonists that modulate the signal transduction system at the nuclear level.

3T3 Cells↗
PubMed1995

High-resolution FEISEM detection of DNA centromeric probes in HeLa metaphase chromosomes.

HeLa metaphase chromosome spreads were hybridized with centromeric biotinylated DNA probes and detected with gold-conjugated anti-biotin antibodies. Chromosomes were observed by an in-lens field emission scanning electron microscope (FEISEM), which permits detection of biological samples without any coating. DNA probes were well localized in the centromeric region of chromosomes and there was clear discrimination between 10 nm fibers that hybridized to DNA probes and those that did not hybridize. This approach shows that in situ hybridization can be directly visualized at the FEISEM level by evaluating only secondary electron emission, which allows physical localization of the hybridized probe with high resolution so that backscatter detection represents only a control. Because chromosomes maintain the 10-nm fiber organization after in situ hybridization procedures, our data suggest that this fiber represents the lowest order of chromatin arrangement that permits transitory DNA denaturation.

Centromere↗