The effect of teriparatide compared with risedronate on reduction of back pain in postmenopausal women with osteoporotic vertebral fractures.

UNLABELLED: The effect of teriparatide and risedronate on back pain was tested, and there was no difference in the proportion of patients experiencing a reduction in back pain between groups after 6 or 18 months. Patients receiving teriparatide had greater increases in bone mineral density and had fewer vertebral fractures. INTRODUCTION: This study aimed to understand the effect of teriparatide in reducing back pain in patients with prevalent back pain and vertebral fracture compared to risedronate. METHODS: In an 18-month randomized, double-blind, double-dummy trial, we investigated the effects of teriparatide (20 µg/day) vs. risedronate (35 mg/week) in postmenopausal women with back pain likely due to vertebral fracture. The primary objective was to compare the proportion of subjects reporting ≥30% reduction in worst back pain severity from baseline to 6 months as assessed by a numeric rating scale in each treatment group. Pre-specified secondary and exploratory outcomes included assessments of average and worst back pain at additional time points, disability and quality of life, bone mineral density, incidence of fractures, and safety. RESULTS: At 6 months, 59% of teriparatide and 57% of risedronate patients reported ≥30% reduction in worst back pain and there were no differences between groups in the proportion of patients experiencing reduction in worst or average back pain at any time point, disability, or quality of life. There was a greater increase from baseline in bone mineral density at the lumbar spine (p = 0.001) and femoral neck (p = 0.02) with teriparatide compared to risedronate and a lower incidence of vertebral fractures at 18 months (4% teriparatide and 9% risedronate; p = 0.01). Vertebral fractures were less severe (p = 0.04) in the teriparatide group. There was no difference in the overall incidence of adverse events. CONCLUSIONS: Although there were no differences in back pain-related endpoints, patients receiving teriparatide had greater skeletal benefit than those receiving risedronate.

The reversible effects of raloxifene on luteinizing hormone levels and ovarian morphology in mice.

Raloxifene is a selective estrogen receptor modulator that has estrogen agonist effects on bone and serum lipids and estrogen antagonist effects on breast and uterine tissues. This study assessed the effects of raloxifene hydrochloride (HCl) treatment on circulating luteinizing hormone (LH) levels and ovarian morphology in sexually mature, 15-week-old, female CD-1 mice. Mice were maintained on diets providing average daily doses of 0 or 233 mg/kg raloxifene for 2 weeks (Study 1) or 0, 7.9, or 236 mg/kg raloxifene for 4 weeks (Study 2). At the end of the treatment period, blood samples were collected every 2 hours for 24 h in Study 1 (5 mice per group) and at 10:00 a.m. and 10:00 p.m. in Study 2 (8 mice per group). Serum LH levels were measured by radioimmunoassay. Ovarian histomorphology was evaluated in the 10 mice per group (Study 1) and the 8 mice per group (Study 2). For the reversibility phase (Study 2), mice were fed untreated diets for 3 weeks; serum LH levels and ovarian histomorphology were then assessed. Raloxifene treatment at 233 mg/kg/day for 2 weeks (Study 1) significantly elevated circulating LH levels by 4- to 7-fold compared with control. Raloxifene-treated mice had elevated LH levels sustained over the 24-h sampling period and did not exhibit the preovulatory LH surge evident in some control mice at the 4:00 p.m., 6:00 p.m., and 8:00 p. m. time points. Mice treated with 236 mg/day raloxifene for 4 weeks (Study 2) had elevated LH levels (4.4-fold compared to control), whereas mice exposed to 7.9 mg/kg/day raloxifene had a slight, nonsignificant increase in LH (2-fold compared to control). In both dose groups, LH levels were indistinguishable from controls 3 weeks after raloxifene treatment was discontinued. The ovaries in six of the eight mice treated with 7.9 mg/kg/day raloxifene had dilated and/or anovulatory follicles. One mouse in this group had a single hemorrhagic follicle; however, corpora lutea distribution was normal, indicating that ovulation was occurring. Raloxifene-treated mice in Study 1 and mice treated with a comparable raloxifene dose (236 mg/day) in Study 2 had histomorphological changes in the ovary indicative of arrested follicular maturation, including anovulatory hemorrhagic follicles, some developing follicles, and very few corpora lutea. At the end of the reversibility phase, hemorrhagic follicles were no longer evident and follicular maturation and corpora lutea distribution were normal. Raloxifene treatment in mice produces a dose-dependent, sustained elevation in serum LH levels and is associated with changes in ovarian follicular morphology. These changes are reversible upon discontinuation of raloxifene treatment.

Healthcare use among U.S. women aged 45 and older: total costs and costs for selected postmenopausal health risks.

The purpose of this study is to estimate the level of healthcare use and costs incurred by postmenopausal women overall and for these selected conditions: cardiovascular disease, osteoporosis, breast cancer, and gynecological cancers. National healthcare survey and discharge data were used to estimate healthcare use by women aged 45 and older. Clinical Classification for Health Policy Research (CCHPR) codes were used to identify patients whose primary diagnosis or procedure corresponded with the selected conditions. National weights were used to estimate resource use. Treatment costs were estimated using cost/charge ratios or the Medicare fee schedule to calculate costs for each individual procedure. Estimated total annual medical care treatment costs for women 45 and older were about $186 billion in 1997 dollars, including about $60.4 billion for cardiovascular disease, $12.9 billion for osteoporosis, and $5.0 billion for breast and gynecological cancers. For each condition, estimated resource use and costs are reported for hospitalization, outpatient, nursing home, and home healthcare services. Resource use and costs are also reported by age and expected source of payment. The economic burden of disease for conditions commonly affecting postmenopausal women is substantial. Prior research establishes that hormone replacement therapy (HRT) may be effective in reducing the burden of disease among women who continue preventive therapy for many years, but few at-risk women do so. New alternatives for prevention, such as selective estrogen receptor modulators (SERMs), may be effective in reducing the burden of disease among postmenopausal women.

Lithium as a potential adjuvant to 131I therapy of metastatic, well differentiated thyroid carcinoma.

As lithium inhibits the release of iodine from the thyroid but does not change iodine uptake, it may potentiate 131I therapy of thyroid cancer. The effects of lithium on the accumulation and retention of 131I in metastatic lesions and thyroid remnants were evaluated in 15 patients with differentiated thyroid carcinoma. Two 131I turnover studies were performed while the patients were hypothyroid. One was performed while the patient received lithium; the second served as a control study. From a series of gamma-camera images, it was found that lithium increased 131I retention in 24 of 31 metastatic lesions and in 6 of 7 thyroid remnants. A comparison of 131I retention during lithium with that during the control period showed that the mean increase in the biological or retention half-life was 50% in tumors and 90% in remnants. This increase occurred in at least 1 lesion in each patient and was proportionally greater in lesions with poor 131I retention. When the control biological half life was less than 3 days, lithium prolonged the effective half-life, which combines both biological turnover and isotope decay, in responding metastases by more than 50%. More 131I also accumulated during lithium therapy, probably as a consequence of its effect on iodine release. The increase in the accumulated 131I and the lengthening of the effective half-life combined to increase the estimated 131I radiation dose in metastatic tumor by 2.29 +/- 0.58 (mean +/- SEM) times. These studies suggest that lithium may be a useful adjuvant for 131I therapy of thyroid cancer, augmenting both the accumulation and retention of 131I in lesions.

Neuropsychiatric manifestations of altered thyroid state.

The authors assessed the mood and cognitive effects of sequential T4, T3, and withdrawal of thyroid hormone replacement on 25 patients who had had thyroidectomies for thyroid cancer. The patients experienced increased sadness and anxiety when they were without medication, but not significant difference in mood was noted between T4 and T3. The patients who experienced increased affective symptoms when not taking medication were more likely to have histories of affective illness or mood lability.

Thoracic stimulation and prolactin secretion.

Although galactorrhea and/or enhanced prolactin (PRL) secretion have been reported with a variety of thoracic stimuli, the effect of thoracic stimulation on dynamic prolactin secretion is not clear. A 49-year-old woman with ventilatory muscle weakness from polio presented with galactorrhea, and intermittent hyperprolactinemia but regular menses. The galactorrhea was noted following the use of a new, tight fitting cuirass (thoracic apparatus which assists ventilation). To determine if the new, "tight" cuirass elicited enhanced PRL secretion, and to assess more extensively the effect of such thoracic stimulation on PRL secretion, serum PRL was measured during brief and prolonged stimulation, sleep, and pharmacological manipulation of PRL. Basal PRL was normal (less than 25 ng/ml) and increased during brief stimulation (1 hour) with the "tight" (137%) and "loose" cuirass (140%). Although the absolute increments were similar, the "tight" cuirass elicited an earlier PRL peak than the "loose" cuirass and the PRL began to decrease while the "tight" cuirass was still functioning. Several hours of thoracic stimulation resulted in a transient rise in PRL and a fall to normal, prestimulatory levels despite persistent stimulation. During this stimulation, PRL did not rise after sleep nor after insulin-induced hypoglycemia despite normal cortisol and GH increments, but the PRL response after TRH was exaggerated.(ABSTRACT TRUNCATED AT 250 WORDS)

Changes in blood pressure and plasma noradrenaline in short-term hypothyroidism.

Thirteen patients who had undergone thyroidectomy for thyroid cancer stopped thyroid hormone replacement prior to follow-up radioactive iodine scans. Thyroxine was replaced by triiodothyronine (T3) for 4 weeks and T3 was stopped 2 weeks before the scan and 16 to 19 days before blood pressure measurement and venipuncture for obtaining plasma noradrenaline samples. During this time, a small but significant decrease in systolic blood pressure occurred, both supine and standing, while the corresponding plasma noradrenaline levels increased significantly. These findings indicate that the acute cardiovascular effect of brief thyroid hormone withdrawal is a decrease in blood pressure rather than the increase often observed in chronic hypothyroidism, and that plasma noradrenaline levels may increase much sooner than previously reported after onset of hypothyroidism.

Hospital admissions caused by iatrogenic disease.

Complications of medical therapy requiring hospitalization affect the costs and quality of medical care. We studied all admissions to the medical services of a public teaching hospital to characterize current incidence and cause of iatrogenic admissions. We studied 834 admissions resulting in 47 distinct iatrogenic events and 45 iatrogenic admissions (5.4%). Thirty-five cases were caused by medications, nine by procedures, one by radiotherapy, one by transfusional therapy, and one by nosocomial infection. Almost 50% of these admissions were avoidable. Though the incidence of iatrogenic admissions in this study is similar to that in previous reports, the profile of the responsible agents is different. We did not find relationships with age, number or type of diagnoses, or number of medications on admission. Study of other patient and physician characteristics may be more rewarding in reducing the number of iatrogenic complications.

Enzymic profiles of bovine pancreatic ductal and acinar tissues.

The plasma membrane enzymes, alkaline phosphatase, bicarbonate-dependent adenosine triphosphatase, 5'-nucleotidase, and carbonate dehydratase, were measured in ductal and acinar preparations of bovine pancreas. Epithelial cells were scraped from the main duct and a piece of acinar tissue was dissected from the whole pancreas for homogenization. All enzymes studied demonstrated higher levels in the duct per milligram protein than in the acinus: bicarbonate-dependent adenosine triphosphatase was 2.8 times higher; 5'-nucleotidase, 4.1 times higher; carbonate dehydratase, 16.9 times higher, while alkaline phosphatase showed only a slight increase in the duct compared to acini.