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Biomedical subjects

S Adami

Publications and source records attributed to S Adami.

At least 55 records · Page 3Linked to original sources
PubMed2000

Influence of growth hormone on a new marker of cartilage metabolism (chondrex).

The aim of this study was to evaluate the usefulness of a major secretory protein of human chondrocytes (chondrex) as a potential serum marker of bone responsiveness to growth hormone (GH). The study included 18 children (10 F, 8 M), aged 10.9 +/- 2.3 years, bone age 8.8 +/- 2.7 years, height -2.3 +/- 0.22 SDS, affected by isolated idiopathic GH deficiency (GHD). Serum samples for evaluation of chondrex, total, and bone alkaline phosphatase were taken before and 3 and 6 months following treatment with rhGH. The basal serum level of chondrex did not differ between patients (37 +/- 22 ng/ml) and controls (33 +/- 9.8 ng/ml). Following 6 months of treatment with rhGH, a significant increase of height velocity SDS (from -2.8 +/- 0.5 to 1.3 +/- 0.7), total (from 195 +/- 47 to 264 +/- 79 U/liter) and bone alkaline phosphatase (from 81 +/- 21 to 108 +/- 30 U/liter) was observed, while chondrex serum level remained unchanged (from 37 +/- 22 to 36 +/- 29 ng/ml). It was concluded that chondrex cannot be considered a reliable marker of bone responsiveness to GH in the growing child.

Adipokines↗
PubMed2000

Weekly administration of alendronate: rationale and plan for clinical assessment.

OBJECTIVE: This paper describes the rationale and supporting data for once-weekly dosing of alendronate. BACKGROUND: Alendronate sodium, a bisphosphonate that potently inhibits bone resorption, has been shown to increase bone mass and substantially reduce the incidence of osteoporotic fractures, including fractures of the hip. The standard regimen of daily administration has generally been well tolerated. However, weekly administration may provide greater convenience to patients without compromising efficacy or tolerability. The pharmacokinetics of alendronate and bone remodeling theory predict similar efficacy for weekly and daily administration if the cumulative dose is the same. Bone resorption in individual remodeling units normally proceeds for approximately 2 weeks; alendronate inhibits the rate and extent of resorption. Because the half-life of residence on bone surfaces is several weeks, weekly administration of alendronate should inhibit bone resorption to an overall extent similar to that of daily dosing, thereby producing similar effects on bone mass and strength. Animal studies demonstrate that both weekly and daily parenteral administration of alendronate effectively increase bone mass and strength, but confirmation of efficacy is needed for weekly oral dosing in humans. Although daily bisphosphonates (alendronate and risedronate) elicited esophageal irritation in a canine model of gastroesophageal reflux, weekly dosing with alendronate at a higher unit dose did not. Thus, the lower frequency of weekly dosing with a higher unit dose may actually reduce the risk of upper gastrointestinal irritation compared with daily administration of a lower dose. CONCLUSIONS: Current safety and efficacy data justify further investigation of once-weekly dosing of alendronate. Two positive-control, double-blind, randomized trials of osteoporosis treatment and prevention are currently being performed to assess the comparability of weekly, biweekly, and daily dosing of alendronate with regard to effects on bone density, safety, and tolerability.

Alendronate↗
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

Background for studies on the treatment of male osteoporosis: state of the art.

Male osteoporosis represents an important, although long underestimated, public health problem. Both in men and in women aging is accompanied by continuous bone loss and by an exponential increase in the incidence of osteoporotic fracture, with a female to male incidence ratio of about 2 to 3 to 1 in the elderly for hip and vertebral fractures. Morbidity after osteoporotic fractures appears to be more serious and mortality more common in men than in women. To date, no single treatment has been proved to be effective and safe in published prospective studies. The present report, based on a systematic search of the literature on male osteoporosis, summarises the state of the art on the clinical consequences of male osteoporosis and its risk factors, in relation to the present state of knowledge about female osteoporosis. This constitutes the background for the design of rational clinical development strategies for therapeutic interventions in male osteoporosis. From this review of the literature it is apparent that notwithstanding the existing sex differences in pathophysiology of osteoporosis and the difference in age-specific incidence of osteoporotic fractures, there are also important similarities between osteoporosis in women and men. The higher incidence of fracture in women than in men results from quantitative differences in risk factors rather than from different risk factors. Even though there are sex differences in bone geometry, incidence of fracture seems to be similar in men and women for a same absolute areal bone mineral density. However, the lack of data on the changes in fracture rates in men resulting from pharmacological intervention, leading to changes in bone mineral density or bone turnover, remains the main limitation for extrapolation of established treatment outcomes from women to men.

Age Factors↗
PubMed2000

Height, bone mineral density and bone markers in congenital adrenal hyperplasia.

AIM: To evaluate height, bone growth, areal bone mineral density (aBMD), volumetric bone mineral density (vBMD) and markers of bone turnover in a group of patients affected by congenital adrenal hyperplasia (CAH). PATIENTS: There were 50 patients (23 males, 27 females), aged 1-28 years, affected by CAH due to 21-hydroxylase deficiency: 27 with the salt-wasting (SW); 14 with the simple virilizing (SV), and 9 with the nonclassical (NC) forms. METHODS: Bone morphometry was evaluated with the metacarpal index (MI) and lumbar aBMD and vBMD (L2-L4) by dual energy X-ray absorptiometry. Serum osteocalcin was used as a marker of bone formation, while urinary cross-linked N-telopeptides of type-I collagen and free deoxypyridinoline levels were evaluated as indexes of bone resorption. RESULTS: The height standard deviation score (SDS) was -0.41 +/- 1.4 in SW patients, -0.01 +/- 1.9 in SV patients, and -0.01 +/- 2.3 in NC patients. There was no significant difference among groups and against zero. The MI SDS was also not different between groups and against zero. aBMD was significantly lower in the pubertal patients compared with normal values, but only when patients with the SW and SV forms were considered together (p < 0.05). vBMD was significantly reduced in all patients with the classical form. Bone markers were not different in patients and controls. CONCLUSION: Our study shows that normal height can be attained in CAH patients; however, an impairment in bone growth and mineralization may be found in adolescents and young adults affected by the classical form.

Absorptiometry, Photon↗
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↗
PubMed2000

Efficacy and safety of daily risedronate in the treatment of corticosteroid-induced osteoporosis in men and women: a randomized trial. European Corticosteroid-Induced Osteoporosis Treatment Study.

Long-term use of high-dose corticosteroids often results in bone loss, which may lead to osteoporosis-related fractures. This was a multicenter, double-blind study in which 290 ambulatory men and women receiving high-dose oral corticosteroid therapy (prednisone > or = 7.5 mg/day or equivalent) for 6 or more months were randomized to receive placebo, risedronate 2.5 mg/day, or risedronate 5 mg/day for 12 months. All patients received calcium 1 g and vitamin D 400 IU daily. The primary endpoint was lumbar spine bone mineral density (BMD) at month 12. Additional measurements included BMD at the femoral neck and trochanter and the incidence of vertebral fractures. Overall, there were statistically significant treatment effects on BMD at 12 months at the lumbar spine (p < 0.001), femoral neck (p = 0.004), and trochanter (p = 0.010). Risedronate 5 mg increased BMD at 12 months by a mean (SEM) of 2.9% (0.49%) at the lumbar spine, 1.8% (0.46%) at the femoral neck, and 2.4% (0.54%) at the trochanter, whereas BMD was maintained only in the control group. Although not powered to show fracture efficacy, we observed a reduction in the incidence of vertebral fractures of 70% in the combined risedronate treatment groups, relative to placebo (p = 0.042). Risedronate was well tolerated, had a good safety profile, and was not associated with gastrointestinal adverse events. We conclude that risedronate increases BMD and potentially reduces the incidence of vertebral fractures in patients with corticosteroid-induced osteoporosis.

Adolescent↗
PubMed2000

A four year dose-response study of recombinant human growth hormone treatment of growth hormone deficient children: effects on growth, bone growth and bone mineralization.

To evaluate the effects of two regimens of recombinant human GH (rhGH) on growth, bone growth and bone mineralization in GH deficient children, we studied two groups (A and B), each including 16 GH deficient children matched for sex, age, body mass index, height, height velocity and bone age/chronological age ratio (BA/CA). Group A was treated with a weekly rhGH dose of 1IU/kg and group B with 0.5IU/kg. After four years of therapy, we evaluated the auxological outcome, bone morphometry (metacarpal index: MI) and bone mineralization by quantitative roentgen microdensitometry at the middle region of the II metacarpal and ultra-distal radius. Height increased significantly in both groups, being significantly higher in group A after four years of therapy, while BA/CA remained similar in the two groups. Bone growth (measured by the MI), and bone mineral density at the metacarpal (mostly trabecular bone) and at the ultra-distal radial (mostly cortical bone) site did not differ in the two groups, nor did these three parameters differ from normal controls. In conclusion, after four years a greater height gain was achieved by the higher dose of rhGH compared with the conventional dose, but there were no differences in bone growth and mineralization.

Body Height↗
PubMed2000

Therapeutic equivalence of alendronate 70 mg once-weekly and alendronate 10 mg daily in the treatment of osteoporosis. Alendronate Once-Weekly Study Group.

Dosing convenience is a key element in the effective management of any chronic disease, and is particularly important in the long-term management of osteoporosis. Less frequent dosing with any medication may enhance compliance, thereby maximizing the effectiveness of therapy. Animal data support the rationale that once-weekly dosing with alendronate 70 mg (7 times the daily oral treatment dose) could provide similar efficacy to daily dosing with alendronate 10 mg due to its long duration of effect in bone. In addition, dog studies suggest that the potential for esophageal irritation, observed with daily oral bisphosphonates, may be substantially reduced with once-weekly dosing. This dosing regimen would provide patients with increased convenience and would be likely to enhance patient compliance. We compared the efficacy and safety of treatment with oral once-weekly alendronate 70 mg (N=519), twice-weekly alendronate 35 mg (N=369), and daily alendronate 10 mg (N=370) in a one-year, double-blind, multicenter study of postmenopausal women (ages 42 to 95) with osteoporosis (bone mineral density [BMD] of either lumbar spine or femoral neck at least 2.5 SDs below peak premenopausal mean, or prior vertebral or hip fracture). The primary efficacy endpoint was the comparability of increases in lumbar spine BMD, using strict pre-defined equivalence criteria. Secondary endpoints included changes in BMD at the hip and total body and rate of bone turnover, as assessed by biochemical markers. Both of the new regimens fully satisfied the equivalence criteria relative to daily therapy. Mean increases in lumbar spine BMD at 12 months were: 5.1% (95% CI 4.8, 5.4) in the 70 mg once-weekly group, 5.2% (4.9, 5.6) in the 35 mg twice-weekly group, and 5.4% (5.0, 5.8) in the 10 mg daily treatment group. Increases in BMD at the total hip, femoral neck, trochanter, and total body were similar for the three dosing regimens. All three treatment groups similarly reduced biochemical markers of bone resorption (urinary N-telopeptides of type I collagen) and bone formation (serum bone-specific alkaline phosphatase) into the middle of the premenopausal reference range. All treatment regimens were well tolerated with a similar incidence of upper GI adverse experiences. There were fewer serious upper GI adverse experiences and a trend toward a lower incidence of esophageal events in the once-weekly dosing group compared to the daily dosing group. These data are consistent with preclinical animal models, and suggest that once-weekly dosing has the potential for improved upper GI tolerability. Clinical fractures, captured as adverse experiences, were similar among the groups. We conclude that the alendronate 70 mg once-weekly dosing regimen will provide patients with a more convenient, therapeutically equivalent alternative to daily dosing, and may enhance compliance and long-term persistence with therapy.

Administration, Oral↗
PubMed2000

A multicenter cross sectional study on bone mineral density in rheumatoid arthritis. Italian Study Group on Bone Mass in Rheumatoid Arthritis.

OBJECTIVE: To determine the frequency of osteoporosis in a large cohort of women with rheumatoid arthritis (RA) and to investigate the main determinants of bone mineral density (BMD) and risk factors for vertebral fractures in this population. METHODS: We recruited 925 consecutive female patients with RA at 21 Rheumatology Centers in Italy. For each patient pre-registered demographic, disease, and treatment-related variables were collected. BMD was measured at lumbar spine and proximal femur by dual x-ray absorptiometry technique. Collected variables underwent a univariate and multivariate statistical procedure. Osteoporosis was defined as BMD > -2.5 T score. RESULTS: The frequency of osteoporosis in the whole sample was 28.8% at lumbar spine and 36.2% at femoral neck and increased linearly from Steinbrocker's functional stage I to IV (p = 0.0001). Patients with spinal or femoral osteoporosis were significantly older (p = 0.0001), had a lower body mass index (BMI) (p < 0.02), a significantly longer disease duration (p < 0.02) and a significantly higher Health Assessment Questionnaire (HAQ) score (p = 0.0001). These differences were significant, even after adjusting for age. Steroid use was associated with significantly lower lumbar and femoral BMD (p = 0.0001) even after adjusting for the main confounding covariates. Analysis of lateral spine radiographs revealed 74 women with at least one vertebral fracture. These women had a significantly lower lumbar and femoral BMD (p = 0.0001). The generalized linear model showed that steroid use, menopause, BMI, age, and HAQ were all significant independent predictors of lumbar and femoral BMD. The logistic procedure showed that age (OR 1.05, 95% CI 1.03-1.07), HAQ (OR 1.3, 95% CI 1.07-1.7), menopause (OR 1.9, 95% CI 1.1-3.2), use of steroids (OR 1.5, 95% CI 1.07-2.1), and BMI (OR 0.8, 95% CI 0.8-0.9) were significantly associated with the risk for osteoporosis. The only variables associated with an increased risk for vertebral fracture were age (OR 1.04, 95% CI 1.01-1.08), HAQ (OR 1.7, 95% CI 1.08-2.09), and cumulative steroid intake (OR for 1 g of prednisone 1.03, 95% CI 1.006-1.07). CONCLUSION: To prevent osteoporosis and its dramatic complications in RA the therapeutic challenge is to preserve functional capacity using the lowest possible dosage of corticosteroids.

Absorptiometry, Photon↗
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↗
PubMed1999

Model citizens. Outsourcing helps start-up Medicare HMO.

UNLABELLED: Health Plans of Pennsylvania (HPP), the managed care arm of Crozer-Keystone Health System, in Media, Pa. PROBLEM: Selecting the information systems and building the infrastructure to support the start-up of a new Medicare HMO product. SOLUTION: HPP chose to outsource the information systems needed to integrate all the components of managed care administration into a cost-effective and cohesive program. RESULTS: Because of its aggressive programming and start-up of the MedCarePlus product offering, HPP became the first plan in the country to submit Medicare claims data electronically for encounter reporting to the Health Care Financing Administration (HCFA). KEYS TO SUCCESS: "Through an integrated team approach, an organization truly can benefit from the economies of scale gained through outsourcing."

Centers for Medicare and Medicaid Services, U.S.↗
PubMed1998

Modification of serum apolipoprotein A-I, apolipoprotein B and lipoprotein(a) levels after bisphosphonates-induced acute phase response.

Lipoprotein(a) (Lp(a)) is a low density lipoprotein-like particle displaying strong atherothrombotic properties. Although the concentration of Lp(a) in plasma is under strong genetic regulation, there are emerging evidences that several other factors, such as hormonal disorders, acute phase, liver and renal failure may affect its metabolism. The aim of the present study was to investigate whether bisphosphonates, an effectual drug in the treatment of malignant hypercalcemia and Paget's disease of bone, known to induce a concomitant acute phase, may have a significant influence on Lp(a) concentrations. Nine subjects (four men and five women), with plasma Lp(a) concentrations in the range between 6.4 and 17.7 mg/dl, were subjected to a single intravenous infusion of bisphosphonates (7.5 mg of aminohydroxybutylidene and 5.0 mg of aminohydroxylidene), previously dissolved in 250 ml of saline. Lp(a), apo A-I, apo B, C reactive protein (CRP) and erythrocyte sedimentation rate (ESR) were measured at the baseline and after days one, two, four and seven. CRP, ESR and Lp(a) started to increase after two days from the treatment, reaching statistical significance after day two, four and seven, respectively. Apo B and apo A-I decreased significantly after days one and two, respectively. Although patterns and relative amounts of the increase of CRP were substantially different among the subjects studied, the increase of Lp(a) was more homogeneous; the peak of Lp(a) concentrations was reached only seven days after treatment in the group as a whole, in agreement with previous observations. In univariate regression analysis, significant correlations were found only between apo A-I and ESR, and apo A-I and Lp(a). The present study suggest that Lp(a) behaves as an acute phase protein. Besides, we observed a slight but significant decrease of apo A-I and apo B after administration of bisphosphonates.

Acute-Phase Proteins↗