Biomedical subjects

M Favus

Publications and source records attributed to M Favus.

11 recordsLinked to original sources

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

The contribution of testosterone to skeletal development and maintenance: lessons from the androgen insensitivity syndrome.

Although androgen status affects bone mass in women and men, an androgen requirement for skeletal normalcy has not been established. Women with androgen insensitivity syndrome (AIS) have 46,XY genotypes with androgen receptor abnormalities rendering them partially or completely refractory to androgen. Twenty-eight women with AIS (22 complete and 6 high grade partial), aged 11-65 yr, responded to questionnaires about health history, gonadal surgery, and exogenous estrogen use and underwent bone mineral density (BMD) assessment by dual energy x-ray absortiometry. BMD values at the lumbar spine and proximal femur were compared to age-specific female normative values and listed as z-scores. Average height for adults in this cohort, 174 cm (68.5 in.), was moderately increased compared with the average height of adult American women of 162.3 cm, with skewing toward higher values: 5 women exceeded 6 ft in height, and 30% of the 18 adult women with complete AIS exceeded 5 ft, 11 in. in height. The average lumbar spine and hip BMD z-scores of the 6 women with partial AIS did not differ from population norms. In contrast, the average lumbar spine BMD z-score of women with complete AIS was significantly reduced at -1.08 (P = 0.0003), whereas the average value for hip BMD did not differ from normal. When BMD was compared between women who reported good estrogen replacement therapy compliance and those who reported poor compliance, there was a significantly greater deficit at the spine for women with poor compliance (z = -2.15 +/- 0.15 vs. -0.75 +/- 0.28; P < .0001). Furthermore, hip BMD was also significantly reduced in the noncompliant group (z = -0.95 +/- .40). Comparison of BMD values to normative male standards gave z-score reductions (z = -1.81 +/- 0.36) greater than those observed with female standards. Because of the high prevalence of tall stature in this study sample, we calculated bone mineral apparent density, a variable that adjusts for differences in bone size. Even for the estrogen-compliant group, bone mineral apparent density z-scores were subnormal at both the spine (z = -1.3 +/- 0.43; P < 0.01) and the hip (z = -1.38 +/- 0.28; P = 0.017). Six women with complete AIS had sustained cortical bone fractures, of whom 3 reported multiple (>3) fractures. We conclude that even when compliance to exogenous estrogen use is excellent, women with complete AIS show moderate deficits in spine BMD, averaging close to 1 SD from normative means, and that with correction of BMD for bone size, skeletal deficits are magnified and include the proximal femur. The results suggest that severe osteopenia in some women with AIS probably reflects a component of inadequate estrogen replacement rather than androgen lack alone.

Adult↗

PubMed1999

Alendronate in the treatment of postmenopausal osteoporosis.

The following article reviews the results of 2 investigational Phase III trials of alendronate. Alendronate has been found to induce clinically significant increases in bone mineral density at the spine, hip and other cortical and trabecular sites while maintaining bone quality thereby reducing the rate of vertebral fracture. Alendronate was revealed to be well tolerated, with a good safety profile; a dose of 10 mg daily offers the best risk:benefit ratio and appears to be the optimal dosage for the treatment of established postmenopausal osteoporosis. The persistence of bone gain with extended treatment offers a considerable advantage over currently available forms of therapy.

Aged↗

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

Effect of oral alendronate on bone mineral density and the incidence of fractures in postmenopausal osteoporosis. The Alendronate Phase III Osteoporosis Treatment Study Group.

BACKGROUND: Postmenopausal osteoporosis is a serious health problem, and additional treatments are needed. METHODS: We studied the effects of oral alendronate, an aminobisphosphonate, on bone mineral density and the incidence of fractures and height loss in 994 women with postmenopausal osteoporosis. The women were treated with placebo or alendronate (5 or 10 mg daily for three years, or 20 mg for two years followed by 5 mg for one year); all the women received 500 mg of calcium daily. Bone mineral density was measured by dual-energy x-ray absorptiometry. The occurrence of new vertebral fractures and the progression of vertebral deformities were determined by an analysis of digitized radiographs, and loss of height was determined by sequential height measurements. RESULTS: The women receiving alendronate had significant, progressive increases in bone mineral density at all skeletal sites, whereas those receiving placebo had decreases in bone mineral density. At three years, the mean (+/- SE) differences in bone mineral density between the women receiving 10 mg of alendronate daily and those receiving placebo were 8.8 +/- 0.4 percent in the spine, 5.9 +/- 0.5 percent in the femoral neck, 7.8 +/- 0.6 percent in the trochanter, and 2.5 +/- 0.3 percent in the total body (P < 0.001 for all comparisons). The 5-mg dose was less effective than the 10-mg dose, and the regimen of 20 mg followed by 5 mg was similar in efficacy to the 10-mg dose. Overall, treatment with alendronate was associated with a 48 percent reduction in the proportion of women with new vertebral fractures (3.2 percent, vs. 6.2 percent in the placebo group; P = 0.03), a decreased progression of vertebral deformities (33 percent, vs. 41 percent in the placebo group; P = 0.028), and a reduced loss of height (P = 0.005) and was well tolerated. CONCLUSIONS: Daily treatment with alendronate progressively increases the bone mass in the spine, hip, and total body and reduces the incidence of vertebral fractures, the progression of vertebral deformities, and height loss in postmenopausal women with osteoporosis.

Aged↗

PubMed1994

Multifractal radiographic analysis of osteoporosis.

An important complication of osteoporosis is fracture. Alteration in bone structure, as well as decreased bone mass, contribute to the tendency to fracture in osteoporosis. Current methods that measure bone mass alone show substantial overlap of the measurements of osteoporotic patients who fracture with those that do not. Our aim is to develop noninvasive methods of evaluating bone structure on plain film radiographs to better predict fracture risk in osteoporosis. Regions of interest (ROIs) were selected from digitized lateral lumbar spine radiographs of 43 patients being seen in an osteoporosis clinic. The fractal dimension of these ROIs was estimated using a surface area method. The ability of fractal dimension to distinguish between cases that had fracture elsewhere in the spine from those that did not, was evaluated using receiver operating characteristic (ROC) analysis. These results were compared with ROC analysis for these same patients using bone mineral density (BMD) measurements (bone mass). Significantly larger Az (area under ROC curve) values were obtained using fractal dimension (0.87) than from using BMD (0.58), indicating a better test performance using fractal dimension. Therefore, computerized radiographic methods to evaluate bone structure, such as fractal analysis, may be helpful in better determining fracture risk in osteoporosis.

Adult↗

PubMed1985

Radiation-induced tumors of the head and neck following childhood irradiation. Prospective studies.

Nodules were found in 1108 subjects who received childhood radiation for benign conditions of the cervical area at our institution. This is 37.5% of 2958 subjects, out of a total of 5379, for whom there is follow-up information. Of the 848 subjects who have had thyroidectomies, 297 (35.0%) had thyroid cancer. In addition to thyroid tumors, salivary, neural, and probably parathyroid tumors also occurred as a late consequence of childhood radiation. Prospective studies of the subjects indicate that thyroid nodules are continuing to occur at a constant rate. The measurement of serum thyroglobulin is helpful in identifying individuals for whom the risk of developing a nodule is increased. Follow-up of patients with nonsurgically-treated nodules indicates that some of their nodules are progressive. At the present time there is no indication that radiation-induced cancers behave differently than ones in other settings. However, some of their characteristics, especially their multicentricity and occurrence in younger individuals, indicate that continued follow-up is necessary. On the basis of the data generated by the follow-up program at our institution and programs elsewhere, recommendations for screening, treatment, and follow-up are made. The recommendations stress the importance of estimating risk based on radiation dose, previous tumors, and serum thyroglobulin, in arriving at clinical decisions for these subjects.

Adult↗

PubMed1981

Continuing occurrence of thyroid nodules after head and neck irradiation. Relation to plasma thyroglobulin concentration.

We re-examined 158 subjects from a group of 226 previously normal persons who had received head and neck irradiation, 113 with elevated plasma thyroglobulin levels at their first visit and 113 with normal levels. Twenty-four subjects had thyroid scintigrams that had changed in the follow-up interval of 24 to 60 (mean = 45.3) months. Twelve subjects subsequently had thyroidectomy, and five malignancies were found. In the other 12 the changes tended to be more subtle, but in nine they very likely represented thyroid nodules. We conclude that the prevalence of radiation-induced nodules is not decreasing. More changes (17 of 24) occurred in subjects who initially had elevated plasma thyroglobulin levels (p less than 0.05). However, the difference was not significant when the analysis was limited to the almost certain development of a nodule. Longer follow-up will be needed to ascertain whether a high thyroglobulin level predicts a greater risk of developing thyroid nodules.

Child, Preschool↗

PubMed1980

Hyperparathyroidism in nephrolithiasis.

We found primary hyperparathyroidism in 56 of 1,132 consecutive patients with nephrolithiasis. We describe 48 of these patients who have undergone curative parathyroidectomy. Thirty of the 48 patients had extremely mild hypercalcemia (serum calcium level, 10.15 to 10.95 mg/dL), often accompanied by very substantial hypercalciuria. Stone disease was of equal severity in these 30 patients and in the 18 with more pronounced hypercalcemia (serum calcium level above 11 mg/dL). In all 48 patients, recurrent stone formation was virtually abolished by parathyroidectomy.

Female↗

PubMed1976

Thyroid scintigram. Sensitivity with sodium pertechnetate Tc 99m and gamma camera with pinhole collimator.

To evaluate the reliability of thyroid scintigraphy in the diagnosis of nodular growth, scintigrams of patients who later underwent thyroidectomy were reviewed and correlated with pathologic findings. The scintigrams were all obtained with a 5-mm single-hole collimator-equipped gamma-scintillation camera after intravenous injection of 5 millicuries of sodium pertechnetate Tc 99m. In the group of 92 patients, six of whom had two histologically different lesions, 149 nodules were identified pathologically. There were 26 nodules 2 to 5 mm in diameter, of which 22 were benign and four were malignant. None of the 22 benign nodules were delineated scintigraphically. Superior image quality and resolution, low radiation dose, technical simplicity, and speed make 99mTc pinhole-camera scintigraphy the best procedure available for routine thyroid imaging.

Adenocarcinoma↗

PubMed1975

99mTc-pertechnetate thyroid scintigraphy in patients predisposed to thyroid neoplasms by prior radiotherapy to the head and neck.

Histories, physical examinations and 99mTc-pertechnetate imaging were used to evaluate 1,452 persons who had had x-ray therapy to the neck region for benign conditions 18 to 35 years previously. Thyroid abnormalities were found in 301 patients (21%) and thyroid malignancy was found in 29% of 193 patients with abnormal studies who were explored surgically. Thyroid imaging detected 96% of these abnormalities, 40% of which would not have been unequivocally established by physical examination alone. Nuclear imaging could not distinguish benign from malignant lesions.

Adenocarcinoma↗