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Biomedical subjects

D Gatti

Publications and source records attributed to D Gatti.

At least 19 recordsLinked to original sources
PubMed2007

Quantitative ultrasound in adults with cystic fibrosis: correlation with bone mineral density and risk of vertebral fractures.

In several conditions, including cystic fibrosis (CF) and corticosteroid-induced osteoporosis, bone mineral density (BMD) measurements provide a modest prediction of fracture risk. We investigated in adult CF patients whether quantitative ultrasound (QUS) parameters were able to discriminate between patients with and without prevalent vertebral fractures. One hundred seventy-two adults with CF, 91 men and 81 women, often on chronic oral or inhaled corticosteroid therapy, were studied. BMD at the lumbar spine, proximal femur, and total body were measured by dual-energy X-ray absorptiometry (DXA). QUS parameters were assessed by Achilles Express at the calcaneus and by the DBM Sonic 1200 at the phalanges. All bone measurements by DXA and QUS were significantly correlated with each other, with the exception of phalangeal amplitude-dependent speed of sound versus spine BMD. The mean T-score values in CF patients with and without prevalent vertebral fractures were similar for all DXA measurements and for stiffness index. A significant difference between the two groups was observed only for phalangeal ultrasound bone profile index (UBPI) values (relative risk = 1.25, 95% confidence interval 1.05-1.49 for each decrease in T score), and this difference was maintained after adjusting the values for age, body weight, forced expiratory volume in 1 second, gender, and corticosteroid use. In conclusion, only a phalangeal QUS parameter (UBPI), in contrast with calcaneus QUS or DXA measurements, was able to discriminate CF patients with from those without vertebral fractures, possibly as a result of qualitative alterations of bone tissue independent of BMD.

Absorptiometry, Photon↗
PubMed2004

Prevalence and correlates of vertebral fractures in adults with cystic fibrosis.

INTRODUCTION: Osteoporosis associated with cystic fibrosis (CF) is becoming increasingly important as the life expectancy of patients continues to increase. MATERIALS AND METHODS: We studied 191 adults with CF (18-50 years old; 100 men, 91 women). Total body, lumbar spine, and total proximal femur bone mineral density (BMD) were measured by dual-energy X-ray absorptiometry, and lateral spinal radiographs were taken for assessment of vertebral fractures. A range of anthropometric, clinical and biochemical variables were evaluated as potential correlates. RESULTS: BMD T score values at the lumbar spine lower than -2.5 SD were observed in 27.3% and 11.2% of male and female patients, respectively. These proportions fell to 14% and 9.9% for total hip and 10.4% and 12.1% for total body, in men and women, respectively. Vertebral deformities were identified in 26.7% of the patients with a slightly higher prevalence in males (32%) than in females (21%, P = 0.058). Multiple vertebral deformities were observed in 12% and 7.7% of men and women, respectively. BMD values were significantly related to body weight, FEV1, age of puberty and occasionally to cumulative steroid dose in both genders. BMD values were also significantly related with serum albumin, IgG and cholinesterase. Serum estradiol levels were found below the normal range in 23% of the women and 27% of the men, and was significantly related to femur BMD values in both women and men. Significantly lower serum estradiol and free testosterone levels were observed in men with vertebral fractures. Serum osteocalcin was below the normal range in 36% and urinary deoxypyridinoline above the normal range in 51% of the patients. CONCLUSIONS: This study indicates that osteoporosis is a common complication of CF, being related to disease progression and apparently due to both excess bone resorption and inadequate bone formation. Estradiol deficiency may have a significant role in the pathogenesis in both genders. Vertebral fracture prevalence is high and greater than expected from prevalent BMD values.

Adolescent↗
PubMed2003

Intravenous intermittent neridronate in the treatment of postmenopausal osteoporosis.

Bisphosphonates have been used with success in the treatment of osteoporosis, but oral therapy often lacks compliance. Here we report the results of clinical trial with aminobisphosphonate neridronate administered intravenously (i.v.). The study included 78 postmenopausal women with spine bone mineral density (BMD) at least -2.5 SD below peak. Patients were randomized to receive for 2 years either 50 mg i.v. neridronate bimonthly and 500 mg calcium plus 400 U vitamin D supplements daily (n=39) or calcium-vitamin D supplements alone (control group, n=39). Treatment was continued over 2 years with an additional 1 year follow-up of calcium-vitamin D supplements alone. Neridronate was well tolerated with the appearance of typical clinical signs of an acute phase reaction in only 3 of the patients after the first infusion. In the control group no significant changes in BMD or bone markers were observed. In the neridronate group BMD rose progressively at the spine rose up to 7.4% +/- 6.1% (SD) and at the femoral neck up to 5.8% +/- 8.2% (SD) at the end of the second year. In the succeeding follow-up these gains were maintained at both skeletal sites. Serum bone alkaline phosphatase (bone ALP) and serum type I collagen C-telopeptide (s-CTX) significantly decreased within 2 months. The bone ALP values reached a -35% plateau after 6 months, while s-CTX attained the lowest mean value (-47%) only by the end of the treatment with neridronate. Both bone markers returned almost to baseline values 1 year after treatment discontinuation. Treatment of postmenopausal osteoporosis with 50 mg i.v. neridronate bimonthly results in clinically relevant increases in BMD, among the largest so far observed with any other bisphosphonate.

Aged↗
PubMed2003

Intravenous neridronate in adults with osteogenesis imperfecta.

Osteogenesis imperfecta (OI) is a heritable disease of connective tissue, characterized by increased bone fragility. Bisphosphonates currently seems to be the most promising therapy, at least in children. We tested IV neridronate, an amino-bisphosphonate structurally similar to alendronate and pamidronate in adults with OI. Twenty-three men and 23 premenopausal women with OI were randomized to either iv neridronate (100 mg infused intravenously for 30 minutes every 3 months) or no treatment with a ratio of 2 to 1. Control patients were given the same bisphosphonate therapy at the end of the first year. Clinical evaluation included bone densitometry measurements using dual energy X-ray absorptiometry (DXA), fasting serum and urinary biochemistry every 6 months, and radiographs of the spine taken at baseline and after 12 and 24 months of follow-up. Spine and hip bone mineral density rose by 3.0 +/- 4.6% (SD) and by 4.3 +/- 3.9%, respectively, within the first 12 months of treatment, whereas small insignificant changes were observed in the control group. During the second year of follow-up, additional 3.91% and 1.49% increases were observed at the spine and hip, respectively. Markers of skeletal turnover significantly fell during neridronate treatment. Fracture incidence during neridronate treatment was significantly lower than before therapy and compared with controls. Neridronate iv infusions, administered quarterly, significantly increase bone mineral density and lowered the risk of clinical fracture in adults with OI. Bisphosphonate therapy seems to provide clinical benefits, not only to children with OI, but also to adult patients.

Adult↗
PubMed2002

Relationship among VDR (BsmI and FokI), COLIA1, and CTR polymorphisms with bone mass, bone turnover markers, and sex hormones in men.

Osteoporosis is a disease characterized by low bone mineral density (BMD) and up to 80% of its variance is under genetic control. Although osteoporosis is more frequent in women, one-third of hip fractures also occur in men. Much information on genetic factors and bone density has been obtained in women, but only a few studies have been performed in osteoporotic men. We have evaluated the relationship between polymorphisms for several candidate genes such as vitamin D receptor (VDR), collagen type Ia1 (COLIA1), and calcitonin receptor (CTR) in a sample of unrelated Italian men (n = 253, mean age 58.41 +/- 15.64 SD). We found no significant differences in BMD when subjects were stratified for their VDR (BsmI and FokI) and COLIA1 genotypes. BMD both at the lumbar spine and at the femoral neck were associated with polymorphism of CTR gene. The CC genotype of CTR gene had the lowest BMD value (P <0.05 and P <0.01 at the spine and hip, respectively) and its prevalence was significantly over-represented in the subgroup of men with prior hip or vertebral fracture as compared with controls (P = 0.004% c2 = 11.10). The men with the CC genotype also showed significantly lower body mass index (BMI), serum sex hormone binding globulin (SHBG), estradiol, total alkaline phosphatase-(total AP) and bone alkaline phosphatase (bone AP) levels and significantly higher free androgen index (FAI). In conclusion, the polymorphism of CTR gene but not VDR and COLIA1 is associated with osteoporosis incidence and the levels of alkaline phosphatase and estradiol. The lower BMD in CC genotype is apparently associated in males with depressed bone formation and lower estradiol levels.

Adult↗
PubMed2001

Radial bending breaking resistance derived by densitometric evaluation predicts femoral neck fracture.

Bone mineral density (BMD) measurement by hip dual-energy X-ray absorptiometry (DXA) is considered the best predictor of osteoporotic fracture risk. BMD takes into account only in part the bone cross-sectional area that is an important determinant of both bone compression strength and of bending breaking resistance. From DXA measurements of proximal radius (Osteoplan, NIM, Verona, Italy) we obtained the projected outer diameter (D) and the mean diameter of the medulla (d), by an algorithm based on the assumption of a constant cortical volumetric density of 1050 g/cm3. The algorithm was validated by the good correlation found (r = 0.8) between calculated d and that actually measured by peripheral quantitative tomography (pQCT; XCT 960, Stratec, Unitrem, Italy) at the same radial site. The D and d values were used to calculate a bending breaking resistance index (BBRI) that is a component of the cross-sectional moment of inertia. The BBRI measured in 5460 women aged 35-89 years, was stable up to the age of 65-70 years and rapidly declined thereafter by 0.7% per year. This profile appears to be due to the fact that the increase in medullary area is compensated in terms of mechanical resistance by enlargement of cross-sectional area. In 68 women with either previous femoral neck (n = 41) or pertrochanteric fracture (n = 27) DXA measurements at proximal and ultradistal radius, lumbar spine and femoral neck were obtained together with the evaluation of proximal radius BBRI. The diagnostic accuracy of BBRI was somewhat comparable to that of spine and femoral neck BMD and significantly superior to that of ultradistal and proximal radius BMD, from which it was derived. Despite the obvious limitation of the cross-sectional nature of this study, our results indicate that a simple re-elaboration of the data obtained by peripheral radial densitometry may achieve diagnostic accuracy for hip fracture risk assessment only marginally lower than that of the direct measure of the BMD of the femoral neck. They also give additional support to the view that bone geometry, particularly for compact skeletal segments, is a determinant of its strength at least as important as bone density.

Absorptiometry, Photon↗
PubMed2001

Effects of oral alendronate in elderly patients with osteoporosis and mild primary hyperparathyroidism.

In a large proportion of the patients with primary hyperparathyroidism (PHPT), a variable degree of osteopenia is the only relevant manifestation of the disease. Low bone mineral density (BMD) in patients with PHPT is an indication for surgical intervention because successful parathyroidectomy results in a dramatic increase in BMD. However, low BMD values are almost an invariable finding in elderly women with PHPT, who are often either unwilling or considered unfit for surgery. Bisphosphonates are capable of suppressing parathyroid hormone (PTH)-mediated bone resorption and are useful for the prevention and treatment of postmenopausal osteoporosis. In this pilot-controlled study, we investigated the effects of oral treatment with alendronate on BMD and biochemical markers of calcium and bone metabolism in elderly women presenting osteoporosis and mild PHPT. Twenty-six elderly patients aged 67-81 years were randomized for treatment with either oral 10 mg alendronate on alternate-day treatment or no treatment for 2 years. In the control untreated patients a slight significant decrease was observed for total body and femoral neck BMD, without significant changes in biochemical markers of calcium and bone metabolism during the 2 years of observation. Urine deoxypyridinoline (Dpyr) excretion significantly fell within the first month of treatment with alendronate, while serum markers of bone formation alkaline phosphatase and osteocalcin fell more gradually and the decrease became significant only after 3 months of treatment; thereafter all bone turnover markers remained consistently suppressed during alendronate treatment. After 2 years in this group we observed statistically significant increases in BMD at lumbar spine, total hip, and total body (+8.6 +/- 3.0%, +4.8 +/- 3.9%, and +1.2 +/- 1.4% changes vs. baseline mean +/- SD) versus both baseline and control patients. Serum calcium, serum phosphate, and urinary calcium excretion significantly decreased during the first 3-6 months but rose back to the baseline values afterward. Increase in serum PTH level was statistically significant during the first year of treatment. These preliminary results may make alendronate a candidate as a supportive therapy in patients with mild PHPT who are unwilling or are unsuitable for surgery, and for whom osteoporosis is a reason of concern.

Absorptiometry, Photon↗
PubMed2000

Association of CTR and COLIA1 alleles with BMD values in peri- and postmenopausal women.

The variability of bone mass and bone strength is in part genetically determined. The pathophysiology of the disease is complex and its heritability is almost certainly polygenic. In a large group of women from north eastern Italy, homogeneous for calcium intake and other risk factors for osteoporosis, we investigated three different genetic polymorphic markers that have been associated with bone mineral density (BMD). The study includes 663 postmenopausal (aged 48-85 years) and 52 perimenopausal (aged 47-53 years) women. Lumbar spine and hip BMD were measured by dual energy X-ray absorptiometry (DXA). After DNA extraction, the restriction enzymes utilized were MscI for the SP1 site of the collagen type I regulatory region (COLIA1), AluI for the calcitonin receptor (CTR) gene, and BsmI for the Vitamin D receptor (VDR) gene. COLIA1 genotype was significantly associated with age-adjusted hip BMD, with the highest values in the SS group and the lowest in the ss group (p < 0.05). The COLIA1 effect was not visible until the sixth decade of life, but it increased thereafter with aging, becoming statistically significant also at the lumbar spine in subjects aged >70 years. CTR genotype was also significantly related to bone mass in the CC group, with the lowest age and weight-adjusted BMD values at the spine (p < 0.05). The CTR genotype effect was greater in the younger subset of women. This suggests that the CTR genotype might influence the process of acquiring peak bone mass rather than the process of bone loss along aging. No trend association was found between BMD values and VDR genotype. These findings suggest an association between the COLIA1 gene polymorphism more with the age-related rate of bone loss than with peak bone mass, which apparently is somewhat affected by CTR gene polymorphism.

Aged↗
PubMed2000

Effects of two intermittent alendronate regimens in the prevention or treatment of postmenopausal osteoporosis.

In clinical practice, a large proportion of patients have bone mass values for which a therapeutic intervention is considered necessary, but the accepted aim might be the sole preservation or marginal increases of the actual bone mass. These goals might be achieved with lower or intermittent doses of a powerful agent for the purpose of fewer side effects and improved compliance. The aim of this study was to assess the effects of two intermittent alendronate regimens in the treatment of postmenopausal osteoporosis. One hundred twenty-four postmenopausal women (age range 52-75 years, at least 7 years since last menopause) with a bone mineral density (BMD) at either the femoral neck or lumbar spine of 2 SD below the mean values of young healthy individuals, and without a history of previous osteoporotic fracture, were randomly assigned either to calcium/vitamin D supplements, alone or associated with two different intermittent oral alendronate regimens: 20 mg once a week (weekly alendronate group) or 10 mg daily (orally) for 1 month out of 3 (cyclical alendronate group). After 1 year, in both groups given intermittent alendronate, we observed significant increases in BMD at both the spine (+2.2 +/- 2.6 and +2.5 +/- 2.9) and femoral neck (+1.6 +/- 4.8 and +1.5 +/- 2.2) for the weekly and cyclical regimens, respectively. This was associated with a significant diminution of both serum bone-specific alkaline phosphatase and urinary N-telopeptides of collagen type I excretion. In the patients in the control group BMD decreased significantly at the lumbar spine, with a slight decline of serum bone-specific alkaline phosphatase. Compliance with treatment and drug tolerability were good in both alendronate groups. In conclusion, intermittent alendronate administration at cumulative doses (and costs) three times lower than those currently recommended for osteoporosis treatment is very well accepted, and is able to significantly increase BMD at the spine and femoral neck and to decrease the markers of bone turnover. These regimens can be clinically useful in the long-term treatment of postmenopausal osteoporosis without prevalent osteoporotic fractures, particularly in women with lower compliance for continuous administration.

Administration, Oral↗
PubMed2000

Chronic intravenous aminobisphosphonate therapy increases high-density lipoprotein cholesterol and decreases low-density lipoprotein cholesterol.

Nowadays, bisphosphonates are considered the drugs of choice for the treatment of several bone disorders. Their exact mechanism of action is not clear but recently it has been reported that the aminobisphosphonates inhibit cholesterol biosynthesis and that this might be relevant for their actions on bone osteoclasts. The study includes 87 postmenopausal women with moderate to severe osteoporosis. The patients were randomly assigned to intravenous (iv) infusion of 50 mg of the aminobisphosphonate Neridronate dissolved in 100 ml of saline solution every 2 months for a year (44 patients). The remaining 43 served as controls. At the time of each infusion blood samples were obtained for the evaluation of total cholesterol, triglycerides, high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C), apolipoprotein A-I (Apo A-I), apolipoprotein B (Apo B), and total and bone alkaline phosphatase (AP). Free deoxypyridinoline (f-DPD) was measured in fasting urine specimens. In the control group no significant changes were observed throughout the study period for any of the biochemical variables. In the Neridronate-treated patients both bone AP and f-DPD excretion fell significantly by 15-20%. In these patients serum total cholesterol and serum triglycerides showed marginal decreases, which were occasionally significant. LDL-C and Apo B fell by 5-6% and these changes were statistically significant at most time points. Apo A-I and HDL-C rose progressively with time. At the 12th month, HDL-C rose 17-18% (p < 0.0001) above the baseline values. Similar findings were obtained in four postmenopausal women given high iv doses of Pamidronate or Alendronate. In conclusion aminobisphophonates, at least when given iv, induce remarkable and unexpected effects on lipid metabolism with a final profile that might be clinically relevant.

Alendronate↗
PubMed1999

Structure-function correlations of the reaction of reduced nicotinamide analogues with p-hydroxybenzoate hydroxylase substituted with a series of 8-substituted flavins.

Structural and kinetic studies have revealed two flavin conformations in p-hydroxybenzoate hydroxylase (PHBH), the in-position and the out-position. Conversion between these two conformations is believed to be essential during catalysis. Although substrate hydroxylation occurs while the flavin in PHBH is in the in-conformation, the position of the flavin during reduction by NADPH is uncertain. To investigate the catalytic importance of the out-conformation of the flavin and to clarify the mechanism of flavin reduction in PHBH, we report quantitative structure-reactivity relationships (QSAR) using PHBH substituted separately with nine derivatives of FAD modified in the 8-position and four dihydronicotinamide analogues as reducing agents. The 8-position of the FAD isoalloxazine ring was chosen for modification because in PHBH it has minimal interactions with the protein and is accessible to solvent. The chemical sequence of events during catalysis by PHBH was not altered when using any of the modified flavins, and normal products were obtained. Although the rate of reduction of PHBH reconstituted with flavin derivatives is expected to be dependent on the redox potential of the flavin, no strict correlation was observed. Instead, the rate of reduction correlated with the kappa-substituent constant, which is based on size and hydrophobicity of the 8-substituent on the FAD. Substituents that sterically hinder attainment of the out-conformation decreased the rate of flavin reduction much more than expected on the basis of the redox potential of the flavin. The results of this QSAR analysis are consistent with the hypothesis that the flavin in PHBH must move to the out-conformation for proper formation of the charge-transfer complex between NADPH and FAD that is necessary for rapid flavin reduction.

4-Hydroxybenzoate-3-Monooxygenase↗
PubMed1999

Intramuscular clodronate therapy in postmenopausal osteoporosis.

Long-term daily administration of oral bisphosphonates has been effective in the treatment of postmenopausal osteoporosis, but the duration, mode and cost of the therapy may sometimes affect patient compliance. In Italy, the bisphosphonate clodronate is also available via the intramuscular (i.m.) route of administration, and the present study was performed to test its efficacy in postmenopausal osteoporosis. Ninety osteoporotic postmenopausal women were enrolled in a randomized, controlled 3 year study. The diet of all patients was adjusted to provide 1200-1300 mg of calcium daily, eventually by administration of supplements. Patients were randomly assigned to no therapy (30 patients) or to receive clodronate 100 mg i.m. either every 2 weeks (30 patients) or 1 week (30 patients). The i.m. injection caused substantial pain at the site of injection, which led to treatment withdrawal in almost 50% of the patients receiving weekly dosing. In control patients, a progressive, slow decline in spine and femoral bone mineral density (BMD), which became statistically significant at the end of the second year of observation, was observed. In the patients given weekly i.m. clodronate, spinal BMD rose by 3.8% (+/-7.3 SD) within 6 months. A slight, nonsignificant increase was observed thereafter, such that, at the completion of 3 years of observation, the mean gain was 4.5% (+/-6.3). In the patients treated with injections of 100 mg of clodronate every two weeks the increase in BMD was somewhat lower and slower, becoming significant only at month 24 (2.9+/-4.6%). In none of the two active groups was the femoral neck BMD changed significantly during the 3 years of the study. A significant increase in trochanter and Ward's triangle BMD was observed at month 12 only in the patients on the highest dose of clodronate. In both groups treated, the hip BMD changes were significantly different from those observed in control patients. The biochemical markers of bone turnover were suppressed in both clodronate groups. These results indicate that intermittent i.m. clodronate administration can provide clinically relevant benefits to skeletal bone density in osteoporotic postmenopausal women, but the in situ pain may limit its extensive use.

Aged↗
PubMed1999

Spironolactone, but not flutamide, administration prevents bone loss in hyperandrogenic women treated with gonadotropin-releasing hormone agonist.

GnRH agonists (GnRHa) have recently been proposed for the treatment of hirsutism in women with the polycystic ovary syndrome (PCOS). As most of these subjects have increased androgen secretion from both ovaries and adrenal glands, the association of GnRHa with antiandrogen drugs might enhance the clinical response to treatment. On the other hand, this association might also potentiate the adverse effects of GnRHa on bone metabolism, generating a potentially harmful situation at the skeletal level. In this study we investigated in 41 PCOS patients the skeletal effects of a 6-month course of GnRHa (tryptorelin, 3.75 mg, i.m., monthly), either alone (n = 12) or associated with the antiandrogen drugs spironolactone (100 mg, orally, once daily; n = 14) or flutamide (250 mg, once daily; n = 15). In all subjects bone mineral density was measured before and after treatment by dual energy x-ray absorptiometry at the lumbar spine (L2-L4) and at the femoral neck and Ward's triangle. In addition, at baseline and after 6 months of therapy, bone metabolism markers (serum and urinary calcium, serum phosphorus and alkaline phosphatase, plasma osteocalcin, and urinary hydroxyproline) and endocrine parameters (serum gonadotropins, estradiol, and free testosterone) were assayed. Women given either GnRHa alone or associated with spironolactone or flutamide were similar for age and body mass index. At baseline, the 3 groups of PCOS women were also similar for endocrine and bone parameters. After 6 months, all treatments determined similar striking suppressions of serum gonadotropins and sex steroids. Concurrently, bone mineral density was significantly reduced at all examined sites in subjects receiving either GnRHa alone or GnRHa plus flutamide. Conversely, women given GnRHa plus spironolactone did not show any change in skeletal mass from baseline values (P < 0.05-0.01 among groups). Biochemical parameters of bone metabolism were consistent with densitometric assessments. In conclusion, after a 6-month course of therapy, bone mineral density is reduced in PCOS women given either GnRHa alone or GnRHa plus flutamide, but not in those receiving GnRHa plus spironolactone. The mechanisms of the bone-sparing effect of spironolactone remain to be determined. Nevertheless, this drug could represent a useful tool to prevent skeletal loss in women given GnRHa as well as in other hypoestrogenic conditions, in particular when estrogens are not recommended.

Adult↗
PubMed1999

Site-specific effects of strength training on bone structure and geometry of ultradistal radius in postmenopausal women.

Knowledge of the effects of exercise on bone mass in postmenopausal women is limited and controversial. Animal studies have shown that the response of bone to bending strain is an alteration of bone geometry. We studied 250 postmenopausal women, aged 52-72 years, willing to participate in a 6-month exercise program. The first 125 started the program immediately and the remaining 125 served as controls. The training program included exercises designed to maximize the stress on the wrist. One hundred and eighteen of the active group and 116 of the control group completed the study and were reassessed 6 months later. Bone mineral density (BMD) of the femoral neck, lumbar spine, ultradistal and proximal radius was measured by dual-energy X-ray absorptiometry (DXA) both before and at the end of the exercise program. The forearm was also evaluated by peripheral quantitative computed tomography, which measures the area, bone mineral content (BMC), and volumetric density for both the cortical and the trabecular component. The results showed that the DXA measurements at the femoral neck, lumbar spine, ultradistal and proximal radius were similar between the two groups. No significant difference was detected after the exercise program at the proximal radius. At the ultradistal radius, the cross-sectional area of cortical bone rose by 2.8 +/- 15.0% (SD, p < 0.05), apparently for both periosteal apposition and corticalization of the trabecular tissue. The volumetric density of cortical bone rose by 2. 2 +/- 15.8% (p < 0.1), and that of trabecular bone decreased by 2.6 +/- 10.7% (p < 0.01). The combined changes in both bone volume and density in the exercise group were associated with marked increase in cortical BMC (3.1 +/- 10.7%, p < 0.01) and decrease in trabecular BMC (-3.4 +/- 14.2%, p < 0.05), which were statistically different from those observed in the control group (p < 0.05). In conclusion, these results confirm that site-specific moderate physical exercises have very little effect on bone mass. However, it appears that some exercises may reshape the bone segment under stress by increasing both the cross-sectional area and the density of the cortical component. These structural changes are theoretically associated with increases in the bending strength.

Absorptiometry, Photon↗
PubMed1999

New bisphosphonates in the treatment of bone diseases.

Bisphosphonates are pyrophosphate analogues, in which the oxygen in P-O-P has been replaced by a carbon, resulting in a P-C-P structure. They are characterised by a strong anti-osteoclastic activity and for this pharmacological property they are now considered the treatment of choice for Paget's disease of the bone, malignant hypercalcaemia and bone metastases. Etidronate, clodronate and pamidronate have been registered in several countries for these indications. Etidronate and alendronate are also extensively used for the prevention and treatment of postmenopausal and senile osteoporosis. In this article, we review the most recent findings on the newest bisphosphonates, which will become available in the near future. The aminobisphosphonate risedronate is undergoing a huge programme of clinical development for the treatment of osteoporosis. In a study of the prevention of early postmenopausal bone loss, oral risedronate 5 mg fully prevented the bone loss observed in the placebo group. Similar effects have been observed with an intermittent dosage regimen of oral risedronate 30 mg/day for 2 out of 12 weeks, which corresponds to 5 mg/day in terms of cumulative dose. With lower doses [5 mg on alternate fortnights (2 weeks)] the prevention of bone loss was half that observed with continuous 5 mg/day therapy, indicating that this might not yet be the maximum effective dose. The use of intermittent intravenous bisphosphonates for osteoporosis therapy has been pioneered by studies with clodronate, pamidronate and alendronate. This treatment regimen has been chosen for an extensive clinical development programme for ibandronate. In a phase 2 study, this new bisphosphonate was administered as an intravenous bolus (0.25, 0.5, 1 or 2 mg) every 3 months for a year, with increases in spinal bone mass of 5.2%. Tiludronate, alendronate and risedronate have been recently introduced for the treatment of Paget's disease of bone. Daily doses of tiludronate 400 mg, alendronate 40 mg and risedronate 30 mg for 3 to 6 months have been shown to be superior to etidronate 400 mg/day. The intravenous administration of ibandronate, zoledronate and alendronate (40 mg, 10 mg and 5 mg, respectively) have achieved the normalisation of serum alkaline phosphatase in more than 70% of the patients and these treatments may provide an alternative for patients intolerant oral bisphosphonates. Intravenous ibandronate has been also developed for the treatment of hypercalcaemia of malignancy. The effective doses ranged from 2 to 4 mg. Zoledronate appears to be the most powerful bisphosphonate under investigation, and the effective doses used in cancer hypercalcaemia are as low as 1 to 2 mg. The new generation of bisphosphonates are likely to increase clinical options in terms of administration regimens, but their real advantage over those already available in terms of clinical efficacy remains uncertain.

Bone Diseases↗