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Biomedical subjects

S Adami

Publications and source records attributed to S Adami.

At least 73 records · Page 4Linked to original sources
PubMed1998

Instrumental diagnosis of osteoporosis.

Considerable progress in the development of methods for assessing the skeleton now makes it possible to detect osteoporosis non-invasively and early. There is a variety of techniques available at present: single-photon (SPA) and single X-ray absorptiometry (SXA), dual-photon (DPA) and dual X-ray absorptiometry (DXA), quantitative computed tomography (QCT), radiographic absorptiometry (RA), and quantitative ultrasound (QUS), and their development has certainly been driven by the need to overcome the inherent shortcomings of plain radiography for this purpose. Both SPA and SXA methods make a quantitative assessment of the bone mineral content (BMC) or density (BMD) at peripheral sites of the skeleton possible. Single energy measurements are not possible at sites with variable soft tissue thickness and composition, i.e., the axial skeleton. For these purposes, DPA and DXA techniques were introduced. The main advantages of an X-ray system over a radionuclide system are shortened examination time, greater accuracy and precision limited to higher resolution, and removal of errors due to source decay correction. Low radiation dose, availability, capacity to evaluate multiple sites, and ease of use have made DXA the most widely used technique for measuring bone mineral density. QCT can determine the true volumetric density of trabecular or cortical bone in three dimensions at any skeletal site. Recently developed new computer-assisted methods have improved RA precision, thus providing a simple and inexpensive technique for screening of bone mineral status of large populations. QUS was reported to provide information regarding the structural characteristics of bone, which may be relevant to the appearance of osteoporotic fractures; indeed, some studies suggest a relationship between QUS and bone strength beyond that which can be explained by BMD. Recent experimental studies suggested that magnetic resonance might also constitute a promising tool for assessing osteoporosis.

Absorptiometry, Photon↗
PubMed1998

Bone measurements in asymptomatic primary hyperparathyroidism.

A large proportion of patients with asymptomatic primary hyperparathyroidism (PHPT) have some degree of bone involvement which appears to be relatively greater for cortical than trabecular bone. However, the clinical meaning and pathophysiologic basis of this observation are unknown. In 77 postmenopausal women with asymptomatic PHPT, bone mineral density (BMD) was measured at the proximal and ultradistal forearm, the lumbar spine, the femoral neck, and Ward's triangle by dual-energy X-ray absorptiometry. The digitalized X-ray pictures of the nondominant hand were obtained from all patients and from 680 healthy postmenopausal women, to measure the outer (D) and inner (d) diameter of the second metacarpus. The cortical area per total area (CA/TA) and a bending breaking resistance index (D4-d4/D) were then calculated. In 29 of the patients not operated on and in 30 healthy pair-matched women, a second X-ray of the hand was obtained 5-12 years afterward. In patients with PHPT, the z score of CA/TA was significantly lower than zero [-0.97+/-0.99, standard deviation (SD)]. This is due to an enlargement of the inner diameter, despite a significant increase in the z score for the outer diameter. The z score of the DXA measurements was significantly lower than zero for the lumbar spine (-0.59+/-1.26), ultradistal radius (-1.03+/-0.91), proximal radius (-1.91+/-1.80), and Ward triangle (-1.81+/-1.07), but not for the femoral neck (-0.36+/-1.03). In subjects in whom two X-rays were obtained, per-decade endosteal resorption and periosteal apposition were statistically significant only in the PHPT patients. Both endosteal resorption and periosteal apposition were significantly greater in PHPT patients compared to healthy controls. The mean BBRI in PHPT patients was not different from that in controls, but the longitudinal changes were significantly greater than those observed in control subjects. Our radiogrammetry data may provide an original clue for understanding preferential cortical bone loss in PHPT patients. In cross-sectional and longitudinal studies, we have shown that in PHPT, both endosteal bone resorption and periosteal apposition are augmented. The former effect is predominant, which leads to significant diminution of cortical thickness. As a consequence of the enlargement of long bones, the areal BMD is somewhat underestimated, since the same amount of cortical bone is divided by a greater diameter. Furthermore, in term of mechanical properties, the increases in the cross-sectional area of appendicular bone segments might compensate in part for both the diminution of cortical thickness and a greater porosity of cortical bone.

Absorptiometry, Photon↗
PubMed1998

Effect of hyperandrogenism and menstrual cycle abnormalities on bone mass and bone turnover in young women.

OBJECTIVE: Prolonged period of amenorrhoea are regarded as a risk factor for the appearance of osteoporosis. Amenorrhoea is a feature of different pathological conditions with heterogeneous endocrine profiles. We evaluated bone mineral metabolism in patients with polycystic ovary syndrome (PCOS), hypothalamic amenorrhoea and idiopathic hirsutism in order to establish the relative importance for the maintenance of normal bone mass of ovulatory cycles and androgen and oestrogen production. PATIENTS AND MEASUREMENTS: Bone mineral density (BMD), bone turnover markers and endocrine profile were evaluated in 51 patients with PCOS, 24 patients with idiopathic hirsutism, 26 patients with hypothalamic amenorrhoea and 35 healthy women. Body mass index (BMI) ranged between 20.1 and 31.0 kg/m2, and age from 17 to 33 years. Thirty-eight of the PCOS patients were amenorrhoeic (< 4 menstrual cycles/year). RESULTS: Spine and femoral BMD were significantly decreased and bone markers (serum osteocalcin, and urinary excretion of free deoxypyridinoline, cross-linked N-telopeptide and hydroxyproline) significantly increased in the patients with hypothalamic amenorrhoea, when compared to control subjects and the other two patient groups. In the sub-group of PCOS patients with amenorrhoea, spine and femoral neck BMD was significantly lower than in patients with idiopathic hirsutism and the non-amenorrhoeic PCOS patients. In all PCOS patients, spine and neck BMD were positively correlated (P < 0.05) with serum androstenedione and free testosterone levels. CONCLUSIONS: The results of this study suggest that in patients with polycystic ovary syndrome the deleterious effect on bone of amenorrhoea is balanced by androgen overproduction.

Adolescent↗
PubMed1997

Bisphosphonates in prostate carcinoma.

The majority of the patients with advanced prostate carcinoma have painful skeletal metastases, which are responsible for significant skeletal morbidity and disability. Most of these metastases are osteosclerotic, but it has been shown that the abnormal osteoblastic bone formation within metastases is preceded by osteoclastic activation, which appears to be associated with bone pain. This provides the rationale for using bisphosphonates, which are powerful and selective inhibitors of osteoclastic bone resorption. Several bisphosphonates have been shown to be clinically useful for the treatment of several conditions characterized by abnormal osteoclastic bone resorption, including Paget's disease, primary hyperparathyroidism, myelomatosis, and skeletal metastases. Its efficacy in relieving pain in patients with skeletal metastases due to prostate carcinoma has been confirmed in a few studies. The bisphosphonate clodronate was extensively investigated in the study unit. When infused intravenously i.v. (300 mg/day) relief of bone pain become appreciable within 3 days, sometimes preceded by a transient pain flare. These clinical results are very consistent and the residual pain usually is of extraosseous origin. Thus, with regard to pain of strictly bone origin, unresponsive patients are quite rare. Oral administration also is effective, but due to its limited intestinal absorption the effective dose is on the order of 1600-3200 mg/day. These doses usually are well tolerated, but they may be a problem for severely ill patients. Furthermore, the efficacy of treatment becomes apparent only after a few days. Thus, oral clodronate usually is adopted as a continuation of an i.v. course. The duration of the i.v. therapy should be individualized, but usually the more prolonged the treatment the longer the duration of the effect. For practical reasons, clodronate is infused daily for 5 days (Monday-Friday) and the treatment course is repeated at the time of any significant recurrence. The oral continuation prevents or delays the recurrence of bone pain in most patients, but in some patients this therapy has to be integrated occasionally with i.v. infusion. The duration of the effect for the same bioavailable dose is somewhat related to the degree of malignancy of the primary tumor. In an uncontrolled study, the author also evaluated the effectiveness of alendronate given either i.v. or orally. A single infusion of 5 mg alendronate i.v. produces roughly the symptomatic effect of 5 i.v. infusions of 300 mg clodronate. Alendronate, 40 mg orally/day, was effective in reducing bone pain in 11 of 12 patients with bone metastases due to prostate carcinoma but who were not confined to bed. In some patients with prostate carcinoma and a diffuse metastatic invasion of the skeleton, there is indirect biochemical and histologic evidence of osteomalacia. This can be aggravated by bisphosphonate administration because of the transient striking prevalence of osteoblastic activity over bone resorption, which also occasionally causes the appearance of symptomatic hypocalcemia. Therefore, the use of large oral supplements of calcium is recommended, particularly at the start of therapy. It is conceivable that these calcium supplements also may be able to improve the final clinical outcome of the bisphosphonate therapy. In conclusion, administration of large doses of bisphosphonates is one of the most cost-effective palliation treatments for patients with prostate carcinoma with bone metastases, both as first-line therapy and in the long term. With appropriate doses, a large proportion of patients can be maintained free of bone pain until death. Studies of the ability of lower doses to prevent skeletal morbidity in patients without metastases or with asymptomatic bone lesions are warranted.

Alendronate↗
PubMed1997

Prevention of nonvertebral fractures by alendronate. A meta-analysis. Alendronate Osteoporosis Treatment Study Groups.

OBJECTIVE: To evaluate the effect of treatment with alendronate sodium, a potent aminobisphosphonate, on the incidence of nonvertebral fractures in postmenopausal women with osteoporosis. DATA SOURCES: Published data and data on file at Merck Research Laboratories. STUDY SELECTION: All completed prospective, randomized, placebo-controlled alendronate trials of at least 2 years' duration (5 studies). DATA EXTRACTION: All subjects were women with osteoporosis between the ages of 42 and 85 years, postmenopausal at least 4 years, with lumbar spine bone mineral density (measured using dual-energy x-ray absorptiometry) at least 2.0 SD below the mean for young adult women. All women randomized to treatment with placebo or alendronate at a dose higher than 1 mg per day for at least 2 years were included. DATA SYNTHESIS: In the placebo group (n=590), 60 women reported nonvertebral fractures during 1347 patient-years at risk (overall rate, 4.45 women with fractures per 100 patient-years at risk). In the alendronate group (n = 1012), 73 women reported nonvertebral fractures during 2240 patient-years-at risk (overall rate, 3.26 women with fractures per 100 patient-years at risk). The estimated cumulative incidence of nonvertebral fractures after 3 years was 12.6% in the placebo group and 9.0% in alendronate group. The relative risk for nonvertebral fracture estimated using the Cox proportional hazards model was 0.71 (95% confidence interval,0.502-0.997) (P=.048). A reduction in risk was consistent across each of the studies and at each major site of osteoporotic fracture, including the hip and wrist. CONCLUSION: In postmenopausal women with osteoporosis, treatment with alendronate reduces the risk of nonvertebral fractures over at least 3 years.

Adult↗
PubMed1997

Ipriflavone prevents radial bone loss in postmenopausal women with low bone mass over 2 years.

Two hundred and fifty-five postmenopausal women with distal forearm bone mineral density (BMD) 1 SD below the mean value for normal age-matched postmenopausal subjects were randomly allocated to a 2-year treatment with oral ipriflavone (200 mg t.i.d) or a matched placebo, according to a double-masked, parallel group design. All patients also received a 1 g/day calcium supplement. Distal radius BMD and bone metabolism markers were measured at baseline, and every 6 months. Blood haematology and chemistry and physical parameters were monitored at the same time. One hundred and ninety-six patients completed 2 years of treatment. BMD changes from baseline were analysed according to valid completers (VC) and intention to treat (ITT) analyses. In both cases radial BMD was maintained in patients treated with ipriflavone while in decrease in those receiving the placebo, the between-treatment difference being significant at year 1 and year 2. Urinary hydroxyproline/creatinine levels were decreased in the ipriflavone-treated group and increased in the placebo group, with a significant between-treatment difference. Adverse reactions, mainly gastrointestinal, occurred to a similar extent in the two treatment groups.

Aged↗
PubMed1997

Intermittent Etidronate partially prevents bone loss in hirsute hyperandrogenic women treated with GnRH agonist.

Treatment with gonadotropin-releasing hormone (GnRH) agonist leads to enhanced bone turnover and accelerated bone loss in premenopausal women with endometriosis, uterine leiomyomatomas and hirsutism. Sodium etidronate is a powerful inhibitor of bone resorption which had been proven efficacious in the prevention and treatment of postmenopausal osteoporosis. The objective of this study was to evaluate the skeletal effects of 6 months of therapy with the depot preparation of the GnRH agonist triptorelin (decapeptil 3.75 mg intramuscularly every 4 weeks) in 24 hirsute patients, aged 24-33 years, with hyperandrogenic chronic anovulation. Ten patients also received cyclical etidronate in an oral dose of 400 mg/day for 2 weeks, followed by an 11-week period of 500 mg/day elemental oral calcium (one cycle). The remaining 14 patients received 500 mg/day of elemental calcium continuously. After 6 months all treatments were discontinued for at least a further 6 months. Bone mineral density (BMD) at lumbar spine and hip (dual-energy X-ray absorptiometry, Sophos LXRA, France) and biochemical markers (serum alkaline phosphatase, osteocalcin, urinary N-telopeptide and hydroxyproline/creatinine ratio) were evaluated at baseline, 6 months and 12 months. In the group given GnRH agonist alone BMD fell significantly at all measured skeletal sites during the first 6 months. In the patients treated with etidronate a significant decrease in BMD was observed at lumbar spine but not in the femoral neck and trochanter, and the changes at lumbar spine and trochanter were significantly smaller than those in the control group. At 6 months bone turnover was also increased in patients treated with GnRH and calcium. Cyclical etidronate prevented the increase in biochemical markers of bone formation and resorption, with the exception of calcium/creatinine excretion, which was significantly increased in both groups. Six months after treatment withdrawal BMD did not recover in either group. Biochemical markers (N-telopeptide, serum alkaline phosphatase) remained increased in those patients previously treated with calcium alone while they remained close to baseline values in the patients treated with cyclical etidronate. Our study indicates that: (1) GnRH agonist therapy causes remarkable bone loss in young individuals with androgen excess who are expected to have increased bone mass; (2) this bone loss can be partially prevented by intermittent cyclical etidronate therapy.

Adult↗
PubMed1997

Age-related cortical bone loss at the metacarpal.

In order to evaluate in vivo the entity of endosteal and periosteal changes with age in the two sexes, and their relative contribution to age-related cortical bone loss, we undertook a cross-sectional study on a population of normal Caucasian subjects. The group included 189 women and 107 men who were studied by photodensitometry and radiogrammetry of the second metacarpal bone, derived from the same standard hand X-ray. Of the subjects, 134 were 65 years of age or older (75 women and 59 men). Metacarpal bone mineral density (BMD) correlated with age in both sexes, with an annual bone loss rate of 0.5% in women and 0.15% in men. In the over 65 group, correlation was significant only in women, who underwent an acceleration in the rate of bone loss (1% per year). Marrow cavity width (M), cortical index at the second metacarpal shaft (MI) and external width (W) all correlated with age in both sexes, although generally better in the female than in the male sex. M almost doubled from the fourth to the ninth decade in women and increased 50% in men. In the same age interval, MI showed an annual decrease of 0.49% in females and 0.33% in males. In the over 65 group, cortical thinning rate was significant in women (0.39% per annum) but not in men (0.14% per annum), whereas correlation of W was not significant in either sex. Finally, MI correlated with BMD in the whole study population and in the over 65, with a female prevalence in correlation strength maintained throughout life. The following conclusions can be derived for metacarpal aging: (1) an acceleration in cortical bone loss occurs in females after age 65; (2) age-related growth in periosteal diameter, although significant in the whole population, is negligible in the elderly of both sexes; (3) age-related cortical bone loss is generally more dependent on cortical thinning in women than in men.

Adult↗
PubMed1997

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↗
PubMed1997

Bisphosphonate therapy of reflex sympathetic dystrophy syndrome.

OBJECTIVE: The reflex sympathetic dystrophy syndrome (RSDS) is a painful limb disorder, for which a consistently effective treatment has not yet been identified. The disease is associated with increased bone resorption and patchy osteoporosis, which might benefit from treatment with bisphosphonates, powerful inhibitors of bone resorption. METHODS: Twenty patients with RSDS of foot and hand, were randomly assigned to blind administration of either alendronate intravenously (Istituto Gentili, Pisa, Italy) 7.5 mg dissolved in 250 ml saline solution or placebo saline infusions daily for three days. Two weeks later all patients had an identical treatment course with open labelled alendronate (7.5 mg/day for three days), independent from the results of the first blind treatment. RESULTS: In the patients treated with blind alendronate the diminution in spontaneous pain, tenderness, and swelling (circumference of the affected limb) and the improvement in motion were significantly different from baseline (p < 0.001), from those observed within the first two weeks in the control group (p < 0.01), and from week 2 to week 4 (p < 0.01). In the patients given blind placebo infusions no relevant symptomatic changes were observed after the first two weeks of follow up, but they responded to the open alendronate therapy given afterwards. In 12 patients with RSDS of the hand the ultradistal bone mineral content (BMC) of the affected arm was considerably lower than that of the controlateral arm (mean (SD)) (426(82) mg/cm versus 688(49)). Six weeks after the beginning of the trial BMC rose by 77(12) mg/cm (p < 0.001) in the affected arm, but it did not change in the controlateral. CONCLUSIONS: These results indicate that bisphosphonates should be considered for the treatment of RSDS, producing consistent and rapid remission of the disease.

Adult↗
PubMed1997

Effects of nandrolone decanoate (Decadurabolin) on serum Lp(a), lipids and lipoproteins in women with postmenopausal osteoporosis.

Although lipoprotein(a) (Lp(a)) concentrations are mainly regulated genetically, it has been reported that variations in sex hormone concentrations may have effects on serum Lp(a). We evaluated the effect of nandrolone decanoate, a testosterone-derived synthetic anabolic steroid, on serum Lp(a), lipids and lipoproteins in 19 postmenopausal women who were given parenteral nandrolone decanoate (Decadurabolin) once a week for 3 weeks. At the 4th week, a significant decrease was observed for total cholesterol (p = 0.003), Lp(a) (p = 0.0003), apolipoprotein A-I (apo A-I) (p < 0.0001), and high density lipoprotein-cholesterol (HDL-C) (p < 0.0001). Moreover, a significant decrease in serum albumin concentration (p = 0.002) was concomitantly observed. We conclude that the administration of nandrolone decanoate significantly affects the lipid profile of postmenopausal women, showing controversial effects in terms of cardiovascular risk.

Anabolic Agents↗
PubMed1996

Effect of aging on trabecular and compact bone components of proximal and ultradistal radius.

Bone densitometry has become a major tool for osteoporosis risk assessment. The traditional dual-energy X-ray absorptiometry (DXA) methods are able to evaluate the bone mineral content (BMC; mg/cm) and the areal density (BMD; mg/cm2), but only quantitative computed tomography (QCT) has the potential to measure the true volumetric bone density in the sense of mass per unit volume (mg/cm3). Peripheral QCT (pQCT) measurements were carried out at the nondominant radius using a Stratec XCT 960 (Unitrem, Roma) in 241 postmenopausal and 29 premenopausal women. The sites of evaluation were both the ultradistal and the proximal radius. The technique used has a coefficient of variation of 2% and it allows separation of the bone section into trabecular and cortical bone on the basis of density threshold. Bone mass of radius, hip and spine was also evaluated by DXA procedures. The bone density data obtained by pQCT were significantly correlated with all DXA measurements. The correlation coefficients between their respective BMD values ranged from 0.48 to 0.75, but for the BMC values of the radius the correlation coefficients ranged from 0.82 to 0.93. The BMD values measured by DXA, but not by pQCT, were positively related with patient heights. All pQCT density measurements, including those obtained at the proximal radius and containing exclusively cortical bone, where negatively related with age and years since menopause. A partial volume effect, which is increasingly relevant the thinner are the bone cortices, might explain that. However, by applying increasing density thresholds, cortical bone density seems to decrease with age as a consequence of a gradual density diminution from the inner part of the bone cortex outwards. Trabecular bone density decreases with aging, but its overall mass does not change as a consequence of an age-related enlargement of trabecular area. Thus, the proportion of trabecular bone over total bone rises, and this might be relevant for our understanding of the age-related changes in bone turnover and rate of bone loss.

Absorptiometry, Photon↗
PubMed1996

Computed radiographic absorptiometry and morphometry in the assessment of postmenopausal bone loss.

The best method for the diagnosis of osteoporosis and assessment of fracture risk is currently considered to be bone densitometry. The most commonly used dual-energy X-ray absorptiometry (DXA) methods may sometimes not predict bone mass accurately in every skeletal site, are expensive and not widely available. The recent development of computed analysis of a plain radiograph of the hand might provide a practical, inexpensive and rapid method for evaluation of bone mineral status. In this study we evaluated 20 healthy premenopausal and 660 postmenopausal women. In 36 of these subjects a second evaluation was carried out after 2 years of therapy with calcium supplements. The internal and external diameters of the second metacarpal and the metacarpal and ultradistal radial bone density were evaluated using a technical device developed in our laboratory and marketed by NIM, Verona, Italy (Osteoradiometer). The radiographic images, captured by a video camera, were digitized and studied by computed analysis. In 150 subjects bone density at the level of the lumbar spine, femur, and ultradistal and proximal radius was also measured by DXA techniques. Both external (D) and internal (d) diameters increase significantly with age and years since menopause (YSM), whereas metacarpal index (D--d/D) and metacarpal and ultradistal radial bone density decrease significantly with age and YSM. The ratio between metacarpal bone mineral content and the cortical area (volumetric metacarpal bone density) did not change with age. Significant correlations were found between radiometric findings and DXA measurements. The best correlation coefficients were between bone density measured at the level of the ultradistal radius by DXA and radiographic absorptiometry. In the 2-year follow-up study, a 4.9% and 6.2% decline in radial metacarpal bone density respectively were observed, but the difference was statistically significant only for the latter. In conclusion, computed radiogrammetry is closely correlated with all DXA measurements and may be useful in screening of large populations, providing a simple, inexpensive and sufficiently precise method for evaluation of bone mineral status. Further studies are warranted for assessing the accuracy of radiogrammetry for longitudinal investigations and its capacity to predict fracture risk.

Absorptiometry, Photon↗
PubMed1996

Evaluation of cortical thickness and bone density by roentgen microdensitometry in growing males and females.

UNLABELLED: The bone mineral content (BMC) and the cortical thickness at the distal radius and at the II metacarpal were assessed in growing individuals (167 females and 158 males) by radiometric and quantitative roentgen microdensitometric methods. BMC adjusted for age and pubertal status was significantly higher in males than in females. However, the BMC corrected for bone volume (volumetric bone density, g/cm3) and the metacarpal cortical index (cortical area/total area) were identical in males and females. BMC rose progressively with age, approaching a plateau by the end of puberty. Lower but still significant increases with age were also observed for volumetric bone density of the metacarpus and the metacarpal index. These increases were also most marked by the end of pubertal maturation and might be related to diminution of bone turnover. CONCLUSION: This study provides the normative data of bone mass in growing individuals by making use of a reasonably accurate and easily available technique. The results obtained indicate that most of the differences between males and females and the changes with age are related to changes in skeletal dimension rather than density.

Absorptiometry, Photon↗
PubMed1996

Adverse effects of bisphosphonates. A comparative review.

The bisphosphonates comprise a new class of drugs, and are increasingly being used to treat bone diseases characterised by increased osteoclastic bone resorption. These compounds are generally well tolerated, but toxicity may vary considerably from one compound to another. Dosages of etidronic acid above 800 mg/day impair the normal skeletal mineralisation and this may be associated with the appearance of fractures, but at the doses used for the treatment of osteoporosis, none of the bisphosphonates induce clinical or histological signs of impaired mineralisation. The skeletal half-life of bisphosphonates is of the order of several years, but this appears to be of little clinical consequence since the pharmacological effect is of relatively short duration. The mechanical properties of the skeleton of animals treated over long periods with high doses of various bisphosphonates have been shown to be perfectly preserved. However, in growing individuals, excess inhibition of bone remodelling might induce osteopetrotic-like alterations. When high doses of amino-bisphosphonates are given to patients who have never received bisphosphonate therapy, the patients may experience fevers up to 39 degrees C for 1 to 3 days, associated with transient haematological changes resembling a typical acute-phase response. Rapid intravenous injection of bisphosphonates at doses greater than 200 to 300 mg may cause severe renal failure; this can be prevented by slowing the rate of infusion (< 200 mg/h). Administration of high doses of bisphosphonates to patients with high bone turnover may induce a rapid and transient drop in serum calcium which is seldom symptomatic. The gastrointestinal absorption of bisphosphonates is low, and they must be taken without food. Oral amino derivatives may induce dose-related serious gastrointestinal lesions, with the sporadic appearance of erosive oesophagitis. Amino-bisphosphonate administration has been also associated with the sporadic occurrence of uveitis, scleritis and phlebitis and, in single cases, with irritative reactions at the skin, peritoneum and pericardium.

Acute Kidney Injury↗
PubMed1996

[Diphosphonates: and alternative to estrogen therapy in postmenopausal osteoporosis. Experience with alendronate].

The post-menopausal osteoporosis represents an important complication during the climateric period; its clinical, economic and social weight is destined to increase with the aging of the population. The lack of oestrogens is the main etiopathogenetic element; this is the reason why the substitutive therapy during the menopause represents the most appropriate approach. However, the possibility of clinical contra-indications to the oestrogenic treatment, the compliance of the patient not always adequate, the possibility of side-effects, and the doubt about the real opportunity of this treatment in the advanced years, require therapeutic alternatives. Between these, the "inhibitors of the bone reuptake" are actually the more realistic and justified approach knowing the pathogenetic aspect of the disease. In this group of drugs, the biphosphonates are particularly useful because of their pharmacologic properties: a strong affinity for the bone, a specific action only in the area of the bone rearrangement, a strong and selective inhibition of the osteoclastic activity. Because of their long half-life in the bone tissue, it seemed interesting to evaluate mineral bone density and metabolic effects using the alendronate. A double blind controlled study was performed in order to evaluate the effect of this drug: two groups of 15 women in post-menopause with vertebral bone mineral density (BMD) > 2 S.D. behind the mean peak of the adult and without vertebral fractures, were randomized to receive a 20 mg/die dose of alendronate or a placebo for six months. The first treatment significantly reduced all the bone turnover indexes (idrossiprolin, collagen cross links, phosphatase alkalin activity) in three months; another slight reduction was observed in the next three months. After the interruption of the treatment all the indexes of the bone turn over were slowly increased and reached the pre-treatment values in six-nine months. The lumbar BMD is increased of 3.7% (+/- 1.7 SD) after six months of aleandronate treatment; there were no modifications 6 and 12 months after the interruption of the treatment (respectively +4.6 +/- 2.8 and +4.7 +/- 2.67 referred to the basal values). The control group presents a slow reduction of the lumbar BMD, but this was significative only at the 18 degrees month of the study. The femoral BMD was not modified in a relevant measure in the group treated with the drug, while a significative reduction of the neck value was observed in the control group. We conclude that a short treatment with the alendronate is able to increase the lumbar BMD and to prevent the femoral reduction in the woman affected by post-menopausal osteoporosis. Finally, in our experience the alendronate represents a promising alternative to the oestrogen treatment of the post-menopausal osteoporosis; this approach however should be verified in the reduction in the incidence of fractures with larger studies.

Aged↗