A pilot study: effects of decreasing serum insulin with diazoxide on vitamin D levels in obese women with polycystic ovary syndrome.

INTRODUCTION: We conducted a pilot project to test the hypothesis that decreasing insulin concentrations with diazoxide would affect parameters of vitamin D in obese women with and without polycystic ovary syndrome (PCOS). MATERIALS AND METHODS: Eight obese women with PCOS and nine matched controls participated in the study. Diazoxide was administered orally 100 mg three times daily for 10 days, and parameters of vitamin D were measured at baseline and end-of-study. RESULTS: At baseline, women with polycystic ovary syndrome had significantly lower serum 25-hydroxyvitamin D (25[OH]D) levels than controls. After treatment with diazoxide, there were no significant changes in vitamin D parameters when PCOS and control women were evaluated separately. Diazoxide exhibited differential effects on 25(OH)D concentrations in PCOS as compared with normal women (P for interaction=0.045), and serum 25(OH)D levels converged after diazoxide treatment. CONCLUSIONS: Obese women with PCOS had significantly lower serum 25(OH)D levels at baseline than age- and body mass index-matched controls. Short-term administration with diazoxide seemed to have differential effects on 25(OH)D levels in PCOS as compared with control women. Further studies are necessary to confirm this finding.

Ten years' experience with alendronate for osteoporosis in postmenopausal women.

BACKGROUND: Antiresorptive agents are widely used to treat osteoporosis. We report the results of a multinational randomized, double-blind study, in which postmenopausal women with osteoporosis were treated with alendronate for up to 10 years. METHODS: The initial three-year phase of the study compared three daily doses of alendronate with placebo. Women in the original placebo group received alendronate in years 4 and 5 and then were discharged. Women in the original active-treatment groups continued to receive alendronate during the initial extension (years 4 and 5). In two further extensions (years 6 and 7, and 8 through 10), women who had received 5 mg or 10 mg of alendronate daily continued on the same treatment. Women in the discontinuation group received 20 mg of alendronate daily for two years and 5 mg daily in years 3, 4, and 5, followed by five years of placebo. Randomized group assignments and blinding were maintained throughout the 10 years. We report results for the 247 women who participated in all four phases of the study. RESULTS: Treatment with 10 mg of alendronate daily for 10 years produced mean increases in bone mineral density of 13.7 percent at the lumbar spine (95 percent confidence interval, 12.0 to 15.5 percent), 10.3 percent at the trochanter (95 percent confidence interval, 8.1 to 12.4 percent), 5.4 percent at the femoral neck (95 percent confidence interval, 3.5 to 7.4 percent), and 6.7 percent at the total proximal femur (95 percent confidence interval, 4.4 to 9.1 percent) as compared with base-line values; smaller gains occurred in the group given 5 mg daily. The discontinuation of alendronate resulted in a gradual loss of effect, as measured by bone density and biochemical markers of bone remodeling. Safety data, including fractures and stature, did not suggest that prolonged treatment resulted in any loss of benefit. CONCLUSIONS: The therapeutic effects of alendronate were sustained, and the drug was well tolerated over a 10-year period. The discontinuation of alendronate resulted in the gradual loss of its effects.

Skeletal sites for osteoporosis diagnosis: the 2005 ISCD Official Positions.

The International Society for Clinical Densitometry (ISCD) has developed Official Positions to assist healthcare providers in addressing some of the issues inherent with the use of bone mineral density (BMD) assessed by dual-energy X-ray absorptiometry (DXA) to diagnose osteoporosis, apply World Health Organization (WHO) T-score classifications, and monitor BMD changes over time. Differences exist, however, between the ISCD Official Position statement and that of the International Osteoporosis Foundation with respect to WHO criteria for skeletal sites. Consequently, a subcommittee of the ISCD was directed to address the application of the WHO classifications to specific skeletal sites and regions of interest. In 2005, the ISCD Position Development Conference reviewed the findings and prepared Official Positions, which address whether or not: (1) the lowest T-score of the total proximal femur, femoral neck, trochanter, and spine should continue to be used for diagnosis; (2) the WHO classification may be applied to a single vertebral body T-score; and (3) the ISCD should endorse the use of the National Health and Nutrition Examination Survey database for proximal femur T-score derivation. The resulting ISCD Official Positions, with their corresponding rationales and evidence are provided here, as well as questions that will need to be addressed in the future.

Effects of gastric bypass procedures on bone mineral density, calcium, parathyroid hormone, and vitamin D.

Weight loss after gastric bypass procedures has been well studied, but the long-term metabolic sequelae are not known. Data on bone mineral density (BMD), calcium, parathyroid hormone, and vitamin D were collected preoperatively and at yearly intervals after gastric bypass procedures. A total of 230 patients underwent preoperative BMD scans. Fifteen patients were osteopenic preoperatively, and three patients subsequently developed osteopenia postoperatively within the first year. No patient had or developed osteoporosis. At 1 year, total forearm BMD decreased by 0.55% (n = 91; P = .03) and radius BMD had increased overall by 1.85% (n = 23; P = .008); both total hip and lumbar spine BMD decreased by 9.27% (n = 22; P < .001) and 4.53% (n = 31; P < .001), respectively. By the second postoperative year, BMD in the total forearm had decreased an additional 3.62% (n = 14; P < .001), whereas radius BMD remained unchanged. Although total hip and lumbar spine BMD significantly decreased at 1 year, by year 2 both total hip and lumbar spine BMD only slightly decreased and were not significantly different from before the operation. Serum calcium decreased from 9.8 mg/dL to 9.2 during the first year (not significant [NS]) and then to 8.8 (NS) by the second year. Parathyroid hormone increased from 59.7 pg/mL (nl 10-65 pg/mL) preoperatively to 63.1 during year 1 (NS) and continued to increase to 64.7 by year 2 (NS). No difference was noted among levels of 25-hydroxy vitamin D preoperatively (25.2 ng/mL; nl 10-65 ng/mL), at 1 year (34.4), and at 2 years (35.4). Our data indicate that bone loss is highest in the first year after gastric bypass with stabilization, and that, in some cases, there is an increase in bone density after the first year.

Precision assessment and radiation safety for dual-energy X-ray absorptiometry: position paper of the International Society for Clinical Densitometry.

Measurement of bone mineral density (BMD) by dual-energy X-ray absorptiometry (DXA) is used to diagnose osteoporosis, assess the risk of fracture, and monitor changes in BMD over time. Because biological changes in BMD are usually small in proportion to the error inherent in the test itself, interpretation of serial BMD tests depends on knowledge of the smallest change in BMD that is beyond the range of error. This value, called the least significant change (LSC), varies according to the instrument used, the patient population being tested, the measurement site, the skill of the technologist at positioning the patient and analyzing the test, and the confidence interval used in the calculation. The precision and LSC values provided by the manufacturer cannot be applied to clinical bone densitometry centers because of the differences in the patients being tested and the technologist performing the test. Because harmful errors in clinical management may occur from incorrectly interpreting serial BMD tests, it is recommended that every DXA technologist conduct a precision assessment and calculate the LSC for each measurement site and DXA instrument used. Precision assessment provides direct benefit to patients by allowing clinicians to make clinical decisions based on genuine change or stability of BMD. The patient-care benefits of precision assessment outweigh the risk of exposure to trivial doses of ionizing radiation.

Significant differential effects of alendronate, estrogen, or combination therapy on the rate of bone loss after discontinuation of treatment of postmenopausal osteoporosis. A randomized, double-blind, placebo-controlled trial.

BACKGROUND: Combination therapy with alendronate and estrogen for 2 years increases bone mineral density at the spine and hip more than does therapy with either agent alone. Changes in bone mineral density after discontinuation of therapy have not been compared directly. OBJECTIVE: To determine the rate of bone loss when therapy with alendronate, estrogen, or both agents is discontinued. DESIGN: Double-blind, placebo-controlled discontinuation trial. SETTING: 18 U.S. centers. PATIENTS: 244 postmenopausal, hysterectomized women 44 to 77 years of age. INTERVENTION: 2 years of therapy with alendronate, 10 mg/d (n = 92); conjugated estrogen, 0.625 mg/d (n = 143); alendronate and conjugated estrogen (n = 140); or placebo (n = 50). At year 3, women were allocated into five groups: Twenty-eight women continued to take placebo and 44 women continued to take combination therapy, but 50 women taking alendronate, 81 taking conjugated estrogen, and 41 taking combination therapy were switched to placebo. MEASUREMENTS: Bone mineral density and biochemical markers of bone turnover. RESULTS: Women taking alendronate or combination therapy who were switched to placebo for year 3 of the study maintained bone mass. Bone mineral density in these women was 4.1% (CI, 2.6% to 5.7%) and 6.6% (CI, 5.0% to 8.2%) higher, respectively, at the spine (P < 0.001 for both treatment comparisons) and 3.5% (CI, 2.3% to 4.6%) and 3.0% (CI, 1.8% to 4.2%) higher, respectively, at the trochanter (P < 0.001 for both treatment comparisons) than that in women previously taking estrogen who were switched to placebo. In contrast, women who were taking estrogen and were switched to placebo during year 3 experienced a 4.5% decrease at the spine (95% CI, -5.0% to -4.0%) and a 2.4% decrease at the trochanter (CI, -2.7% to -2.1%) (P < 0.001 for both changes). Compared with women who took placebo for 3 years, women who took estrogen for 2 years and were then switched to placebo had a bone mineral density that was 2.9% higher (CI, 1.2% to 4.6%) at the spine (P < 0.05) and 2.9% higher (CI, 1.6% to 4.2%) at the trochanter (P < 0.001). Changes in biochemical markers during year 3 did not differ among the groups that discontinued active treatment. CONCLUSIONS: Accelerated bone loss is seen after withdrawal of estrogen therapy but not after withdrawal of alendronate or combination therapy. The differential effects after withdrawal of therapy should be considered in the management of postmenopausal osteoporosis.

Official positions of the international society for clinical densitometry.

The International Society for Clinical Densitometry (ISCD) periodically holds Position Development Conferences for the purpose of establishing standards and guidelines for indications, acquisition, and interpretation of bone density tests. Topics are selected for consideration by the ISCD Scientific Advisory Committee, reviewed by scientific working groups, and presented to an international panel of experts. Topic categories addressed to date include indications for bone density testing, selection of reference databases for T-scores and Z-scores, clinical applications for central and peripheral bone densitometry, serial bone density testing, instrument precision assessment, phantom scanning and calibration testing, requirements for a bone density report, nomenclature, and diagnosis of osteoporosis in postmenopausal women, premenopausal women, men, and children. After an open session for public comment and discussion, the panel convenes for consideration of each topic and makes recommendations for positions to the ISCD Board of Directors. Recommendations that are accepted become the Official Positions of the ISCD. This Special Report summarizes the methodology of the ISCD Position Development Conferences and presents selected Official Positions of general interest.

Effect of raloxifene on the risk of new vertebral fracture in postmenopausal women with osteopenia or osteoporosis: a reanalysis of the Multiple Outcomes of Raloxifene Evaluation trial.

Raloxifene reduces vertebral fracture risk in postmenopausal women with osteoporosis and established osteoporosis, but its efficacy in women with osteopenia has not been studied. The objective of this study was to evaluate the effect of raloxifene hydrochloride on the risk of vertebral fractures in postmenopausal women with osteopenia and to compare this effect with that in women with osteoporosis as defined by the bone mineral density (BMD) T-score at the hip. We studied the 3204 postmenopausal women with osteopenia or osteoporosis without vertebral fractures at baseline in the Multiple Outcomes of Raloxifene Evaluation trial. Compared with placebo, 60 mg/day raloxifene reduced the risk of new vertebral fractures at 3 years independent of baseline total hip BMD. The relative risk for new vertebral fractures for the raloxifene group compared with placebo was 0.53 (95% CI, 0.32-0.88) for those with osteopenia and 0.31 (0.06-0.71) for those with osteoporosis. In raloxifene-treated women the rate of vertebral fracture was similar in women with osteoporosis (2%) to that in women with osteopenia (1.9%). For clinically apparent vertebral fractures, the relative risk of fracture in the osteopenia group for raloxifene was 0.25 (0.04-0.63) compared with placebo. There were no new clinical vertebral fractures in women with osteoporosis receiving raloxifene, whereas four occurred in the placebo group. We conclude that treatment with 60 mg/day raloxifene significantly decreases the risk of new vertebral fractures and new clinical vertebral fractures in postmenopausal women without baseline vertebral fracture who have osteopenia or osteoporosis.

Complications of nephrogenic systemic fibrosis following repeated exposure to gadolinium in a man with hypothyroidism: a case report.

INTRODUCTION: Nephrogenic systemic fibrosis is a condition that has recently been recognized in patients with chronic renal disease and is associated with use of gadolinium-based contrast agents of ubiquitous use in magnetic resonance imaging scans. The condition is believed to arise through inadequate renal clearance of the gadolinium-based contrast agents, resulting in bodily deposition of the gadolinium; this is most widely recognized in the skin, but also occurs in other tissues. CASE PRESENTATION: We report the case of a 52-year-old Caucasian man with hypothyroidism and chronic renal disease who developed nephrogenic systemic fibrosis upon repeated exposure to gadolinium, and who presented with a subsequent malabsorption of levothyroxine. This malabsorption resolved only partially upon amelioration of other conditions that might contribute to malabsorption, including edema and infectious diarrhea. The presence of gadolinium was quantified in specimens from his gastrointestinal tract. Our patient otherwise demonstrated adequate gastrointestinal nutritive absorption, objectively shown by normal albumin levels, resolution of diarrhea, and maintenance of his bodily weight. CONCLUSIONS: Our observations suggest that nephrogenic systemic fibrosis can also affect tissue of the gastrointestinal tract, potentially contributing to partial malabsorption of levothyroxine in patients with hypothyroidism.

The long-term effects of gastric bypass on vitamin D metabolism.

OBJECTIVE: Alterations of the endocrine system in patients following Roux-en-Y gastric bypass (GBP) are poorly described and have prompted us to perform a longitudinal study of the effects of GBP on serum calcium, 25-hydroxy-vitamin-D (vitamin D), and parathyroid hormone (PTH). METHODS: Prospectively collected data were compiled to determine how GBP affects serum calcium, vitamin D, and PTH. Student t test, Fisher exact test, or linear regression was used to determine significance. RESULTS: Calcium, vitamin D, and PTH levels were drawn on 243 patients following GBP. Forty-one patients had long-limb bypass (LL-GBP), Roux >100 cm, and 202 had short-limb bypass (SL-GBP), Roux < or =100 cm. The mean (+/-SD) postoperative follow-up time was significantly longer in the LL-GBP group (5.7 +/- 2.5 years) than the SL-GBP group (3.1 +/- 3.6 years, P < 0.0001). When corrected for albumin levels, mean calcium was 9.3 mg/dL (range, 8.5-10.8 mg/dL), and no difference existed between LL-GBP and SL-GBP patients. For patients with low vitamin D levels (<8.9 ng/mL), 88.9% had elevated PTH (>65 pg/mL) and 58.0% of patients with normal vitamin D levels (> or =8.9 ng/mL) had elevated PTH (P < 0.0001). In individuals with vitamin D levels <30 ng/mL, 55.1% (n = 103) had elevated PTH, and of those with vitamin D levels > or =30 ng/mL 28.5% (n = 16) had elevated PTH (P = 0.0007). Mean vitamin D levels were lower in patients who had undergone LL-GBP as opposed to those with SL-GBP, 16.8 +/- 10.8 ng/mL versus 22.7 +/- 11.1 ng/mL (P = 0.0022), and PTH was significantly higher in patients who had a LL-GBP (113.5 +/- 88.0 pg/mL versus 74.5 +/- 52.7 pg/mL, P = 0.0002). There was a linear decrease in vitamin D (P = 0.005) coupled with a linear increase in PTH (P < 0.0001) the longer patients were followed after GBP. Alkaline phosphatase levels were elevated in 40.3% of patients and correlated with PTH levels. CONCLUSION: Vitamin D deficiency and elevated PTH are common following GBP and progress over time. There is a significant incidence of secondary hyperparathyroidism in short-limb GBP patients, even those with vitamin D levels > or =30 ng/mL, suggesting selective Ca malabsorption. Thus, calcium malabsorption is inherent to gastric bypass. Careful calcium and vitamin D supplementation and long-term screening are necessary to prevent deficiencies and the sequelae of secondary hyperparathyroidism.