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E Siris

Publications and source records attributed to E Siris.

At least 19 recordsLinked to original sources
PubMed2003

Severity of prevalent vertebral fractures and the risk of subsequent vertebral and nonvertebral fractures: results from the MORE trial.

Prevalent vertebral fractures and baseline bone mineral density (BMD) predict subsequent fracture risk. The objective of this analysis is to examine whether baseline vertebral fracture severity can predict new vertebral and nonvertebral fracture risk. In the randomized, double-blind 3-year Multiple Outcomes of Raloxifene Evaluation (MORE) trial, 7705 postmenopausal women with osteoporosis (low BMD or prevalent vertebral fractures) were randomly assigned to placebo, raloxifene 60 mg/day, or raloxifene 120 mg/day. Post hoc analyses studied the association between baseline fracture severity and new fracture risk in the placebo group and the effects of placebo, raloxifene 60 mg/day, and raloxifene 120 mg/day on new fracture risk in women with the most severe prevalent vertebral fractures (n = 614). Vertebral fracture severity was visually assessed using semiquantitative analysis of radiographs and categorized by estimated decreases in vertebral heights. Reported new nonvertebral fractures were radiographically confirmed. Baseline vertebral fracture severity predicted vertebral and nonvertebral fracture risk at 3 years. In women without prevalent vertebral fractures, 4.3 and 5.5% had new vertebral and nonvertebral fractures, respectively. In women with mild, moderate, and severe prevalent vertebral fractures, 10.5, 23.6, and 38.1% respectively had new vertebral fractures, whereas 7.2, 7.7, and 13.8% respectively experienced new nonvertebral fractures. Number of prevalent vertebral fractures and baseline BMD also predicted vertebral fracture risk, but the severity of prevalent vertebral fractures was the only predictor of nonvertebral fracture risk and remained a significant predictor after adjustment for baseline characteristics, including baseline BMD. In patients with severe baseline vertebral fractures, raloxifene 60 mg/day decreased the risks of new vertebral [RR 0.74 (95% Cl 0.54, 0.99); P = 0.048] and nonvertebral (clavicle, humerus, wrist, pelvis, hip, and leg) fractures [RH 0.53 (95% CI 0.29, 0.99); P = 0.046] at 3 years. To prevent one new fracture at 3 years in women with severe baseline vertebral fractures with raloxifene 60 mg/day, the number needed to treat (NNT) was 10 for vertebral and 18 for nonvertebral fractures. Similar results were observed in women receiving raloxifene 120 mg/day. In summary, baseline vertebral fracture severity was the best independent predictor for new vertebral and nonvertebral fracture risk. Raloxifene decreased new vertebral and nonvertebral fracture risk in the subgroup of women with severe vertebral fractures at baseline. These fractures may reflect architectural deterioration, independent of BMD, leading to increased skeletal fragility.

Aged↗
PubMed2002

Effects of raloxifene on fracture severity in postmenopausal women with osteoporosis: results from the MORE study. Multiple Outcomes of Raloxifene Evaluation.

Raloxifene reduces the risk of new vertebral fractures, but its effect on the severity of these new fractures has not been determined. The MORE (Multiple Outcomes of Raloxifene Evaluation) trial studied the effects of placebo, raloxifene 60 or 120 mg/day in 7,705 postmenopausal women with osteoporosis. Radiologists assessed new vertebral fractures from radiographs and graded the fracture severity as normal (no fracture) or mild, moderate or severe. New clinical vertebral fractures were defined as new vertebral fractures associated with symptoms, such as back pain, and confirmed in radiographs. In the total study population, the majority (76.4%) of the women who experienced clinical vertebral fractures were diagnosed with new moderate/severe vertebral fractures. In turn, women with moderate/severe vertebral fractures in the overall population were more likely to experience clinical symptoms suggestive of fracture than were women who had new mild-only vertebral fractures. The incidence of new mild-only and moderate/severe fractures was the same in women without prevalent vertebral fractures, but the incidence of new moderate/severe fractures was 2 to 3 times higher than that for new mild-only fractures in women with prevalent vertebral fractures. Raloxifene 60 mg/day decreased the risk of at least 1 new moderate/severe vertebral fracture by 61% in women without prevalent vertebral fractures [RR 0.39 (95% CI 0.17, 0.69)], and by 37% in women with prevalent vertebral fractures [RR 0.63 (95% CI 0.49, 0.83)] at 3 years. The risk reductions for at least 1 new moderate/severe vertebral fracture were not significantly different between the raloxifene doses, in women with and without prevalent vertebral fractures. The effects of raloxifene on significantly decreasing the risk of new moderate/severe vertebral fractures may explain the risk reduction for new painful clinical vertebral fractures observed with raloxifene, and is particularly important in postmenopausal women with severe osteoporosis who are at higher risk for moderate or severe fractures.

Aged↗
PubMed2001

Importance of precision in bone density measurements.

Bone densitometry, regardless of the specific technique, is not perfectly reproducible even when consistently performed in exact accordance with the manufacturer's recommendations. Precision must be quantified at each densitometry facility in precision studies of the various skeletal sites used for monitoring. The precision, as the root-mean-square standard deviation or root-mean-square coefficient of variation, is then used to determine the change in bone density that constitutes the least significant change and the minimum interval between follow-up measurements. Until precision studies are performed, the least significant change cannot be determined for any level of statistical confidence, making the interpretation of serial studies impossible.

Absorptiometry, Photon↗
PubMed2000

Comparison of bone mineral density of the phalanges, lumbar spine, hip, and forearm for the assessment of osteoporosis in postmenopausal women.

The objective of this study was to compare peripheral bone mineral density (BMD) of the phalanges with BMD of the lumbar spine, total hip, femoral neck, and forearm and to determine the clinical value of measuring a single peripheral site (phalanges) in identifying postmenopausal women with osteoporosis. BMD was measured by dual energy X-ray absorptiometry using the accuDEXA((R)) (ADXA-finger) (Schick, New York, NY) and the QDR-4500 (DXA-lumbar spine, hip, forearm) (Hologic, Waltham, MA). Correlation coefficients between ADXA and DXA of the lumbar spine, total hip, femoral neck and one third radial site ranged from 0.53 to 0.73. The sensitivity of an ADXA T-score of -2.5 in identifying patients with a DXA T-score of < or = -2.5 at the femoral neck was 35%. An ADXA T-score cut point of -1.0 improved the sensitivity of ADXA in identifying patients with a femoral neck T-score of < or = -2.5 (85%), but the specificity declined from 88 to 49%. There was substantial discordance in the diagnosis of osteoporosis when a single site was measured, regardless of technique. Within the limitations of single-site measurements, BMD measured by ADXA has adequate sensitivity to identify women with low BMD at the femoral neck, if an appropriate T-score criterion is used.

Absorptiometry, Photon↗
PubMed1999

A 10-year prospective study of primary hyperparathyroidism with or without parathyroid surgery.

BACKGROUND AND METHODS: In the United States, most patients with primary hyperparathyroidism have few or no symptoms. The need for parathyroidectomy to treat all patients with this disorder has therefore been questioned. We studied the clinical course and development of complications for periods of up to 10 years in 121 patients with primary hyperparathyroidism, 101 (83 percent) of whom were asymptomatic. There were 30 men and 91 women (age range, 20 to 79 years). During the study, 61 patients (50 percent) underwent parathyroidectomy, and 60 patients were followed without surgery. RESULTS: Parathyroidectomy in patients with or without symptoms led to normalization of serum calcium concentrations and a mean (+/-SE) increase in lumbar-spine bone mineral density of 8+/-2 percent after 1 year (P=0.005) and 12+/-3 percent after 10 years (P=0.03). Bone mineral density of the femoral neck increased 6+/-1 percent after 1 year (P=0.002) and 14+/-4 percent after 10 years (P=0.002). Bone mineral density of the radius did not change significantly. The 52 asymptomatic patients who did not undergo surgery had no change in serum calcium concentration, urinary calcium excretion, or bone mineral density. However, 14 of these 52 patients (27 percent) had progression of disease, defined as the development of at least one new indication for parathyroidectomy. All 20 patients with symptoms had kidney stones. None of the 12 who underwent parathyroidectomy had recurrent kidney stones, whereas 6 of the 8 patients who did not undergo surgery did have a recurrence. CONCLUSIONS: In patients with primary hyperparathyroidism, parathyroidectomy results in the normalization of biochemical values and increased bone mineral density. Most asymptomatic patients who did not undergo surgery did not have progression of disease, but approximately one quarter of them did have some progression.

Adult↗
PubMed1999

Alendronate in the treatment of Paget's disease of bone.

This review reports the results of 2 recently completed long-term, randomised, double-blind, multicentre, controlled studies in which men and women with moderate to severe Paget's disease received oral alendronate 40 mg daily for 6 months One study conducted in the United States, compared the effects of alendronate 60 mg/day (n=41) with those of oral etidronate 400 mg/day (n=47); the other, conducted in the United Kingdom, Australia, and New Zealand, compared the effects of alendronate (n=27) with those of placebo (n=28). In both studies alendronate significantly reduced serum concentrations of alkaline phosphatase by more than 70%, which was significant in comparison with baseline (P < 0.001) and the comparator regimens (P < 0.001). Response to treatment (i.e. a > 60% decrease in or normalisation of serum alkaline phosphatase) was seen in more than three-quarters of patients treated with alendronate in both trials, compared with less than one-third of patients treated with etidronate and no patients treated with placebo. Radiologic scores, reflecting the status of osteolytic lesions, improved in a greater proportion of patients receiving alendronate than in those receiving etidronate or placebo. Histomorphometric analysis performed at 6 months showed that bone formed during alendronate treatment was of normal quality, without evidence of impaired mineralisation or other abnormalities. Alendronate was well tolerated, with an adverse event profile comparable with those of etidronate and placebo. These studies therefore showed that 6 months of treatment with oral alendronate suppresses disease activity in patients with Paget's disease of bone, with beneficial effects on biochemical, radiologic, and histomorphometric indices superior to those of etidronate and placebo.

Alendronate↗
PubMed1998

Design of NORA, the National Osteoporosis Risk Assessment Program: a longitudinal US registry of postmenopausal women.

NORA is an observational registry of postmenopausal US women with periodic collection of event and treatment data that will create a database including several hundred thousand subjects. It will utilize peripheral and central measurements of bone density and relate these to other risk factors, treatment patterns, and the natural history of osteoporosis. Initiated in the fall of 1997, the registry will be open to women throughout the United States who agree to complete baseline and on-going surveys. The database created by NORA will provide a resource that is unmatched in size and scope in the medical field and will allow for future research in a number of areas including patient outcomes, types of follow-up employed in clinical practice, diagnostic cost modelling, and osteoporosis therapy use (type, patient compliance, persistence and satisfaction). In addition, upon approval by the Steering Committee, women enrolled in the registry may be randomly selected to receive additional educational materials or questionnaires on a variety of topics of interest to specific researchers.

Bone Density↗
PubMed1996

Comparative study of alendronate versus etidronate for the treatment of Paget's disease of bone.

Alendronate, an aminobisphosphonate, is much more potent than etidronate, an older bisphosphonate, in inhibiting osteoclast-mediated bone resorption, and unlike etidronate, therapeutic doses of alendronate are not associated with abnormal mineralization. In the present study, we compared the effectiveness, safety, and tolerability of 6 months of daily oral administration of alendronate (40 mg) with those of etidronate (400 mg) in 89 patients with clinically active Paget's disease. The primary efficacy end point was the percent change in serum alkaline phosphatase. Other end points included changes in urinary deoxypyridinoline excretion, pain, functional impairment scores, and radiological osteolysis. Tetracycline-labeled bone biopsies were obtained for histomorphometric analysis from a subset of 43 patients at the 6-month visit. The alendronate-treated group had significantly greater decreases in both serum alkaline phosphatase (79% vs. 44%) and urinary deoxypyridinoline (75% vs. 51%) than the etidronate-treated group (P < 0.001 in both cases). Normalization of serum alkaline phosphatase was much more frequent in alendronate-treated patients (63.4% vs. 17.0%; P < 0.001). Alendronate was well tolerated and had a safety profile similar to that of etidronate. Histomorphometry revealed decreased bone turnover and no qualitative abnormalities, including no direct negative effects on bone mineralization, with alendronate treatment. One patient receiving etidronate developed frank osteomalacia. Alendronate appears to be a highly effective treatment for Paget's disease of bone that offers an important therapeutic advance over etidronate.

Administration, Oral↗
PubMed1995

Teenage and current calcium intake are related to bone mineral density of the hip and forearm in women aged 30-39 years.

The relation between diet and bone mineral density in premenopausal women was evaluated in a cross-sectional study of 139 women aged 30-39 years. The population consisted of volunteers recruited in Rockland County, New York, between September 1988 and August 1992. A food frequency questionnaire was used to determine nutrient intake for both the year prior to bone density measurement and for ages 13-17 years. Physical measurements included height, weight, grip strength, and percent body fat. Bone mineral density was measured in the lumbar spine, hip, and forearm. Multiple regression equations were used to relate nutrient intake to bone density while controlling for age, height, weight, and grip strength. There were no relations between lumbar spine or distal forearm bone density and any nutrient studied from either the current or teenage diet. Current dietary calcium intake was modestly related to hip bone density (beta = 0.077; p = 0.074). When fiber intake was added to the multiple regression model, the association between calcium and hip bone density was strengthened (beta = 0.101; p = 0.037); this would be expected, because fiber interferes with calcium absorption. In the teenage diet, phosphorus and calcium intake were related to hip bone density. A higher lifetime calcium intake was associated with a higher hip bone density compared with low lifetime calcium intake. An increase in teenage calcium intake from 800 to 1,200 mg per day is estimated to increase hip bone density by 6 percent.

Adolescent↗
PubMed1995

A multicenter trial of low dose gallium nitrate in patients with advanced Paget's disease of bone.

Gallium nitrate is a potent antiresorptive drug that has been extensively tested in patients with accelerated bone turnover. We have evaluated the effects of this new agent in a pilot multicenter trial of 49 patients with advanced Paget's disease of bone. Patients were randomized to receive 0.05, 0.25, or 0.5 mg/kg.day gallium nitrate administered by sc injection in two 14-day cycles. Serum alkaline phosphatase, fasting 2-h urinary hydroxyproline and N- telopeptide collagen cross-links excretion, and quality of life were assessed every 2 weeks for 12 weeks. The group mean alkaline phosphatase activity at baseline was 854 +/- 100 (+/- SEM) IU/L. The mean changes from baseline to week 12 in serum alkaline phosphatase were +0.5%, -24%, and -31%, respectively, for the three doses tested. The differences for each of the higher dose levels (0.25 and 0.5 mg/kg.day) was statistically significant (P < or = 0.05), and nearly half of the patients treated with the 0.5 mg/kg.day dose achieved a 50% or more reduction in enzyme activity. The nadir value in hydroxyproline excretion occurred at 10 weeks, with mean changes of +9%, -10%, and -17% for the 0.05, 0.25, and 0.5 mg/kg.day doses, respectively; the difference was significant only at the 0.5 mg/kg.day level (P < 0.01). Urinary collagen cross-link excretion showed a significant decrease at the 0.25 and 0.5 mg/kg.day doses. We also observed a definite, but nonsignificant, trend for improved quality of life in patients treated at the highest drug dose. Minor discomfort at the injection site was frequently reported, but did not lead to interruption of therapy. Our results in these patients who had received moderate to extensive prior therapies with other drugs show that cyclical, low dose, sc administration of gallium nitrate is safe and effective for treating patients with advanced Paget's disease of bone.

Adult↗
PubMed1995

Longitudinal measurements of bone density and biochemical indices in untreated primary hyperparathyroidism.

A large number of patients with primary hyperparathyroidism today do not undergo parathyroidectomy. In this prospective study, we evaluated the effect of untreated disease on biochemical and bone densitometric indices. In 66 patients, seven annual measurements showed no change in serum calcium, phosphorus, PTH, vitamin D, or alkaline phosphatase; in urinary calcium, hydroxyproline or hydroxypyridinium cross-link excretion; or lumbar spine, femoral neck, and radial bone mineral density. The subset of postmenopausal women also showed no change in biochemical indices or bone density at any of the three sites. Twenty-four patients met guidelines for surgery as established by the NIH Consensus Conference, 1990. They differed from those who did not meet these guidelines only by being younger (50 +/- 3 vs. 62 +/- 2 yr; P = 0.0005) and by having higher urinary calcium excretion [7.7 +/- 0.9 vs. 5.4 +/- 0.3 mmol/L (310 +/- 37 vs. 215 +/- 14 mg/g creatinine); P < 0.01]. No longitudinal changes in biochemical profile or bone mineral density at any site were noted in this subgroup. Conservative management of patients with mild primary hyperparathyroidism does not lead to progression of disease, as reflected by biochemical indices. Bone density is maintained over 6 yr of observation at sites reflecting both cortical (radius) and cancellous (lumbar spine) bone.

Adult↗
PubMed1995

Increased bone mineral density after parathyroidectomy in primary hyperparathyroidism.

Skeletal involvement in primary hyperparathyroidism is characterized by preferential loss of cortical bone, whereas cancellous bone is relatively spared. Little data are available concerning changes in bone density, particularly at sites containing more cancellous bone, after successful parathyroidectomy. Most patients with primary hyperparathyroidism are asymptomatic, but approximately 50% meet one or more criteria for surgery. In a prospective study of 34 patients who met one or more such criteria, bone density rose at all skeletal sites (lumbar spine, femoral neck, and the radius) in the 4 yr after surgery. The lumbar spine, with most cancellous bone, showed a rapid (mean +/- SE, yr 1, 8.2 +/- 2.0%; P < 0.005) and sustained (yr 4, 12.8 +/- 2.8%; P < 0.001) rise. Post-menopausal patients were similar (by yr 4, 12.5 +/- 2.7%; P < 0.005). At the femoral neck, with intermediate cancellous and cortical composition, a similar increase was noted (12.7 +/- 3.8% by yr 4; P < 0.01). The distal radius, containing mostly cortical bone, rose modestly (4.0 +/- 1.5% by yr 3; P < 0.05), except in patients with lowest preoperative bone density, where the increase was marked (12.3 +/- 2.6% by yr 3; P < 0.05). In patients meeting surgical guidelines, parathyroidectomy is associated with improved bone mineral density.

Adult↗
PubMed1994

Hereditary hyperphosphatasia: 20 year follow-up and response to disodium etidronate.

We provide a 20 year follow-up of a family with three siblings affected by hereditary hyperphosphatasia (HH). An iliac crest bone biopsy was performed on one of the siblings following double-tetracycline labeling, with results reported quantitatively in a standard histomorphometric format. Biochemical parameters of disease activity were monitored in the patient before and after treatment with oral etidronate disodium, 20 mg/kg/day taken for 5 weeks. Biochemical evidence of intense disease activity continued 20 years after the initial diagnosis of HH in the sibling studied. His bone biopsy specimen also revealed extremely high bone turnover but low cancellous bone volume and osteoclasts unlike those found in Paget's disease. Treatment with etidronate disodium resulted in a temporary 40% reduction in serum alkaline phosphatase and 24 h urine hydroxyproline excretion, with reduction in serum osteocalcin from two times the upper limit of normal to a subnormal level. We conclude that disease activity in HH can continue unabated for two decades. Our bone biopsy finding of low cancellous bone volume, the consistent lack of pagetic-looking osteoclasts in our and other studies, plus the clinical features of HH (childhood onset and extremely diffuse disease with gross skeletal deformation) serve to distinguish HH from Paget's disease. Bisphosphonates may be of value in treating HH.

Adult↗
PubMed1989

Effects of tamoxifen on spinal bone density in women with breast cancer.

Bone densitometry (L2-L4) was performed on 10 postmenopausal women with breast cancer after 0, 6, and 12 months of tamoxifen treatment; the results were compared with data from 10 normal controls. The patients and controls differed significantly at 6 (P less than .05) and 12 (P less than .003) months. The tamoxifen group showed a nonsignificant mean gain in bone mineral density after 6 and 12 months of treatment (+0.024 +/- 0.014 and +0.022 +/- 0.018 g/cm2, respectively), whereas the controls showed a nonsignificant mean loss of bone mass at 6 months (-0.012 +/- 0.018 g/cm2) and a statistically significant loss of bone density after 12 months (-0.024 +/- 0.01 g/cm2). These preliminary data suggest that tamoxifen use is associated with preservation of bone mass during the first year of treatment.

Aged↗