Anesthetic management of hypothyroid patients for coronary artery bypass grafting

Six hypothyroid patients with ischemic heart disease underwent coronary artery bypass grafting (CABG). Three of them were in euthyroid state by preoperative thyroid supplementation. Although remaining three who had not received preoperative supplementation were in overt hypothyroid state at CABG, their intra- and postoperative courses were satisfactory without any complications. We, therefore, found no benefit from preoperative thyroid supplementation. Serum TSH levels in hypothyroid patients were suppressed for more than three days postoperatively despite concomitant low FT3 and FT4 concentrations. The inhibition of TSH secretion could have been produced by therapeutic dose of dopamine which had been infused from intraoperative through postoperative period. Postoperative thyroid replacement should be initiated as soon as possible in hypothyroid patients to counteract the low FT4 concentration that could be prolonged and aggravated by the infusion of dopamine.     

Diagnosis and management of the hypothyroid patient with chest pain

A retrospective analysis of 38 patients undergoing cardiac catheterization with the diagnoses of hypothyroidism and chest pain revealed 23 to be euthyroid while receiving replacement therapy and 15 to be hypothyroid. Cardiac index was significantly reduced (p less than 0.01) in hypothyroid and euthyroid patients with thyroxine values between 4 and 7 micrograms/dl (2.8 +/- 0.7 and 3.0 +/- 0.9 L/min/m2, respectively), compared to euthyroid patients with thyroxine values greater than 7 micrograms/dl with or without coronary artery disease (4.0 +/- 1.2 and 4.0 +/- 0.7 L/min/m2, respectively). Ten hypothyroid patients underwent coronary artery bypass. There were no deaths, and only one patient required prolonged postoperative intubation. With a mean follow-up of 36 months, there have been no myocardial infarctions and one late death, which occurred at 7 years secondary to stroke. We conclude that preoperative thyroid replacement therapy is theoretically dangerous and may not significantly improve hemodynamics until full replacement is achieved. Coronary bypass grafting can be performed safely despite hypothyroidism with excellent early results.     

甲状腺癌病人骨矿物质含量的研究

甲状腺癌病人在接受手术治疗和放射性碘清除残余甲状腺组织后，为了维持正常的甲状腺激素水平，必须接受激素替代治疗（HRT）。甲状腺激素能刺激骨骼的更新，加速骨质的形成和破坏，抑制剂量的甲状腺激素会引起骨矿物质的丢失。适当调整甲状腺癌病人的甲状腺激素替代治疗剂量，对于减少复发的可能和骨量的流失均十分重要。     

The comparative effect of ovarian hormone administration on bone mineral status in oophorectomized rats

The effect of oophorectomy and hormone replacement therapy on cortical and trabecular bone mass was assessed in Sprague-Dawley rats. Bone mineral density (BMD) of the femur and the lumbar spine was determined by dual photon absorptiometry 4 months after surgery. Femoral mineral content was also determined. A significant decrease in bone density and in calcium content was observed after surgical castration. Bone mineral loss was prevented by either progesterone or estrogen, while the combination of progesterone and estrogen had no effect on the bone mineral content. The present study suggests the possibility that estrogen-progestin treatment may be less effective than a therapy with estrogen alone, and that further study on the effect of progesterone alone would be worthwhile.     

Outcome of bariatric surgery on hypothyroidism: experience from a tertiary care center in India

BackgroundHypothyroidism is frequently found to be associated with morbid obesity. Effect of bariatric surgery on type 2 diabetes, hypertension, and sleep apnea has been studied extensively but there is a dearth of literature on its impact on thyroid function. We had published our experience of laparoscopic sleeve gastrectomy and its effect on hypothyroidism in morbidly obese patients previously. In this study, we have tried to evaluate the impact of bariatric surgery on the whole cohort of hypothyroid patients and compare the effect of various bariatric procedures on thyroid hormone replacement dose.ObjectiveTo assess outcome of bariatric surgery on the hypothyroid patients and to compare the outcomes of laparoscopic sleeve gastrectomy, Roux-en-Y gastric bypass, and one-anastomosis gastric bypass in terms of reduction of thyroid hormone replacement dosage.SettingTertiary care University Hospital, India; Government Practice.MethodsThis is a retrospective analysis of a database of all bariatric procedures done in a single unit at a tertiary care teaching hospital in India. Morbidly obese patients with hypothyroidism on thyroxine replacement were identified and their preoperative and postoperative thyroid hormone replacement dosage (THR) and thyroid stimulating hormone levels were compared.ResultsOf 883 patients undergoing bariatric surgery, 180 patients were hypothyroid (on thyroxine replacement). Ninety-three patients were included in the final analysis. The mean age of the study population was 42.2 ± 10.4 years and the mean preoperative body mass index was 47.8 ± 8.3 kg/m². Mean follow-up duration was 29.8 ± 19.6 months. The excess weight loss was 58.9%. Fifty-two (55.8%) patients had a decrease in the in THR dosage, 37 (39.8%) had no change in THR dosage, and 4 patients required an increase in THR dosage. Decrease of THR dose was observed in 61.7% patients in laparoscopic sleeve gastrectomy in comparison to 45.4% in bypass group.ConclusionBariatric surgery might cause reduction of thyroid replacement dosage in hypothyroid, morbidly obese patients.     

Thyroid Hormones: Beneficial or Deleterious for Bone?

The mechanism of action as well as the clinical effects of thyroid hormones on bone has been of interest for more than a century. With the appearance of new treatment modalities for thyroid function disorders, the accompanying alterations in bone metabolism appeared to be rare. However, the introduction of new diagnostic tools, such as osteodensitometry and biochemical bone markers, has changed our view since they were able to show smaller but important changes in bone mineral metabolism associated with thyroid function disorders. Now, we know that hyperthyroidism is associated with an increased life-time risk for fractures, even after achieving euthyroidism. This fact may play an important role in the higher mortality rate among previously hyperthyroid patients later in life. Subclinical hyperthyroidism may also affect bone density, however, its effect on fracture rate remains to be established. The lack of thyroid hormones will alter normal growth during childhood. Adult hypothyroid patients tend to exhibit higher than normal bone density. Despite rather increased bone quantity, hypothyroidism is accompanied with increased fracture risk before and after diagnosis. The effect of thyroid hormone treatment on bone tissue is somewhat controversial. Nevertheless, only patients with suppressed thyroid-stimulating hormone (TSH) appear to loose bone and have higher fracture incidence, whereas patients with a TSH level in the normal range seem to have similar bone mineral content and fracture rate as euthyroid subjects. In summary, most of thyroid function disorders may result in reduced bone density and/or increased fracture rate that should be taken into consideration at clinical evaluation.     

Effect of treatment of overt hypothyroidism on insulin resistance

AIM: To investigate the impact of hypothyroidism and thyroxine therapy on insulin sensitivity in patients with overt hypothyroidism.METHODS: The study included twenty seven overtly hypothyroid and fifteen healthy euthyroid South Western Asian females.Both groups had matching age and body mass index.Physiological and pathological conditions as well as medications that may alter thyroid function,glucose homeostasis or serum lipids were ruled out.Serum thyrotropin(TSH),free tetraiodothyronine(FT4),free triiodothyronine(FT3),fasting insulin(FI),fasting plasma glucose(FPG),total cholesterol and triglycerides were measured before and six months after initiating thyroxine therapy for hypothyroid patients and once for the control group.Insulin resistance(IR) was estimated using homeostasis model assessment(HOMA-IR) and Body mass index(BMI) was calculated.RESULTS: Both study groups,hypothyroid patients and euthyroid control subjects,had matching age and body mass index(P-value 0.444,0.607 respectively).No significant difference was found between the hypothyroid patients and the euthyroid control group regarding fasting plasma glucose,fasting insulin,insulin resistance,total cholesterol and triglycerides(P-values 0.432,0.621,0.883,0.586,0.05 respectively).In the hypothyroid patients,triglycerides showed direct correlation to TSH and inverse correlation to FT3.Similarly total cholesterol inversely correlated to FT3 but its direct correlation to TSH did not reach statistical significance.After thyroxine replacement and reaching an euthyroid state as confirmed by clinical and laboratory data,there was no significant change in fasting plasma glucose,insulin resistance or triglyceride level(P-value 0.216,0.204,0.175 respectively) while total cholesterol significantly decreased(P-value 0.043) and fasting insulin significantly increased(P-value 0.047).CONCLUSION: Hypothyroidism has no impact on insulin sensitivity.Correction of hypothyroidism is not associated with a significant change of insulin sensitivity or triglycerides,but with a significant reduction of total cholesterol.     

Laparoscopic Gastric Bypass in Patients on Thyroid Replacement Therapy for Subnormal Thyroid Function – Prevalence and Short-Term Outcome

Background: Hypothyroidism is associated with increased body weight. Weight gain may occur despite normal levels of serum thyroid stimulating hormone (TSH) and thyroxine (T4) achieved by replacement therapy. We evaluated the prevalence of patients on thyroid replacement for subnormal thyroid function who were operated on for morbid obesity and monitored their postoperative weight loss pattern. Methods: Data was identified from a prospectively accrued database of patients undergoing laparoscopic Roux-en-Y gastric bypass (LRYGBP) or laparoscopic adjustable gastric banding (LAGB) for morbid obesity from February 2000 to November 2001. All patients with subnormal thyroid function, diagnosed by past thyroid function tests and treated by an endocrinologist, who were on thyroid replacement therapy, were identified; 5 of these were matched for age, gender, preoperative body mass index (BMI) and surgical procedure (LRYGBP) to 5 non-hypothyroid patients. Weight loss at 3 and 9 months after surgery was compared between the 2 groups. Results: 192 patients underwent LRYGBP (n=155) or LAGB (n=37). Of the 21 patients (10.9%) on thyroid replacement identified, 14 were primary, 4 were postablative, and 3 were post-surgical; 17 underwent LRYGBP. All patients had normal preoperative serum levels of TSH and T4. Comparison of the 2 matched groups of patients revealed no difference in weight loss at 3 and 9 months after surgery (P=1.0). Conclusions: The prevalence of euthyroid patients on thyroid replacement for subnormal thyroid function who undergo surgical intervention for morbid obesity is high. Short-term weight loss in these patients is comparable to normal thyroid patients. Longer follow-up may be necessary to demonstrate the weight loss pattern in this group.     

Value of stimulated serum thyroglobulin levels for detecting persistent or recurrent differentiated thyroid cancer in high- and low-risk patients.

BACKGROUND: Serum thyroglobulin determination has been reported to be a sensitive indicator of persistent or recurrent differentiated thyroid cancer of follicular cell origin (DTC) after total thyroidectomy. The purpose of this investigation was to determine the accuracy of serum thyroglobulin levels in predicting persistent or recurrent DTC in euthyroid and hypothyroid patients. METHODS: One hundred ninety consecutive patients with DTC of follicular cell origin who had 4 or more thyroglobulin levels measured after total thyroidectomy were retrospectively evaluated. One hundred fifteen patients had serum thyroglobulin levels measured when hypothyroid for radioiodine scanning or ablation. Serum thyroglobulin levels were determined by commercial assays. One hundred twenty-two patients less than 45 years old were considered at low risk, whereas 68 patients more than or equal to 45 years old were considered at high risk on the basis of TNM classification. The mean follow-up period was 62 months. RESULTS: After thyroidectomy with or without central or modified radical neck dissection 120 patients had normal thyroglobulin levels (< or = 3 ng/mL) while receiving thyroid hormone. One hundred thirteen of the 120 patients (94%) with normal serum thyroglobulin levels had no evidence of recurrent tumor, whereas 6% (7 patients) had persistent or recurrent disease. Among 76 patients with persistent (28 patients) or recurrent (48 patients) disease, 70 had a serum thyroglobulin level > 3 ng/mL while receiving thyroid hormone. Overall, 14 of 115 patients, including 2 of 61 (3%) in the high-risk group and 12 of 54 (22%) in the low-risk group, only had elevated serum thyroglobulin levels when hypothyroid with high serum thyroid-stimulating hormone (TSH) levels documenting persistent or recurrent disease. In 1 patient the serum thyroglobulin level (240 ng/mL) was falsely elevated probably as a result of interfering antibodies because no tumor was identified surgically or pathologically, and the thyroglobulin concentration was < 3 ng/mL when analyzed in 3 other laboratories. CONCLUSION: Serum thyroglobulin testing is sensitive (91%) and specific (99%) for identifying patients with persistent or recurrent differentiated thyroid cancer. Serum thyroglobulin levels are most precise when patients are hypothyroid (high TSH) and may be unreliable in patients with antithyroglobulin antibodies. We recommend TSH-stimulated thyroglobulin testing for all patients after total thyroidectomy for differentiated thyroid cancer of follicular cell origin regardless of patient age or risk group.     

Micturition pattern in hyperthyroidism and hypothyroidism

Micturition pattern was investigated in 61 consecutive patients with thyroid disease. The patients were divided into three groups: hyperthyroid, hypothyroid, and euthyroid. Micturition pattern was examined after the first visit to the hospital and again six months later, when thyroid function had been restored to normal. Hyperthyroid patients had significantly increased micturition frequency as well as nocturia compared with their own control group when euthyroid (p less than 0.01). Hypothyroid patients had reduced micturition frequency compared with their own control group (p = 0.05). No significant changes were found in the euthyroid group. Which mechanisms might be responsible for the relationship between thyroid function and micturition pattern is debatable, and calls for further urodynamic and electrophysiologic studies. One conclusion is that thyroid disease should be borne in mind when patients present with unexplained urinary frequency or retention.     

RA患者肌肉含量与骨量变化的相关性分析

目的分析类风湿关节炎(rheumatoid arthritis,RA)患者的肌肉含量与其骨量变化特点的相关性,以及影响RA患者肌肉含量减少的相关因素。方法选取66名(男∶女=8∶25) RA患者为研究对象,平均年龄为60. 4岁。采用双能X线骨密度仪(dual energy X-ray absorptiometry,DXA)及法国MEDI-LINK超声骨密度仪对研究对象进行二维骨密度(bone mineral density,BMD)、3D体积骨密度(皮质骨、骨小梁及总体积骨密度)及肌肉含量的测定,根据T值将研究对象分为骨量正常组(41名)和骨量流失组(25名),并收集患者的一般资料和临床数据,包括性别、年龄、骨折史、吸烟史、糖尿病史、肾病史、甲状腺病史以及RA疾病活动度DSA28评分。结果与RA骨量正常组患者相比,RA骨量流失组患者的全身各部位的肌肉含量均明显降低(P0. 05); RA患者肌肉含量的减少与其BMD及总的体积骨密度的减低具有明显相关性(r=0. 342,P=0. 005及B=35022. 918,P0. 001);而RA患者的总体肌肉含量与激素的使用及RA疾病活动度(DSA28)无明显相关性。结论 RA合并骨量流失患者的肌肉含量明显减少,肌肉含量的改变与骨密度存在一定的相关性。     

Surgical treatment of ischemic heart disease combined with hypothyroidism

Treatment for patients with ischemic heart disease and hypothyroidism contains many difficulties, such as a dilemma that thyroid hormone to hypothyroid patients may worsen angina. The purpose of this study is to propose an appropriate control of thyroid function in these patients before coronary artery bypass grafting (CABG), and to clarify the change of thyroid function during postoperative period. Because of progressive angina pectoris, five hypothyroidism patients underwent CABG. Preoperatively, minimal dose of L-Thyroxine (0-75 micrograms, daily) was administered orally to keep thyroid function at slightly low level before CABG. Ten consecutive CABG patients with normal thyroid function were selected as control group. Between both groups, there was no significant difference in age, coronary artery disease, and the number of bypass grafts. Serum T4, free-T4, T3, free-T3, and TSH were measured at 1st, 2nd, 3rd, and 7th P.O.D. In control group, pituitary-thyroid function was suppressed transiently. In hypothyroid group, T4 revealed no change and was kept at slightly low level during observed period. There was no significant difference in postoperative hemodynamics between both groups. Postoperatively all of hypothyroid patients got free from angina and received an adequate thyroid hormone replacement therapy without complications. It is concluded that CABG for patients with angina and hypothyroidism can be performed safely by keeping preoperative thyroid function at slightly low level.     

Analysis of relationships between sex hormone dynamics and bone metabolism and changes in bone mass in surgically induced menopause

A 3-year follow-up study was performed of bone metabolism and bene changes induced by surgical menopause as a consequence of hysterectomy and oophorectomy (OVX) in 52 nonmenopausal women. We investigated 22 bone parameters and determined seven bone indices as indieators of bone mineral content by dual-energy X-ray absorptiometry (DXA), quantitative computed tomography (QCT), and microdensitometry (MD). The significant correlations between levels of sex hormones and/or bone parameters and bone indices demonstrated that marked sex-steroid deficiency after surgical menopause induced bone uncoupling during high bone turnover and subsequent rapid bone loss in the early period after OVX. Principal component analysis using correlation coefficients suggested a seven-loading-factor matrix composed of bone parameters and a two loading-factor matrix composed of bone indices. Two groups of parameters—estradiol and estriol, and androstenedione together, and luteinizing hormone and follicle-stimulating hormone together—indicated that the rate of bone loss was greater in the trabecular bone than in the cortical bone. Three other groups of parameters—urine calcium, urine hydroxyproline, and serum bone Gla-protein together; serum alkaline phosphatase, serum calcium, and 1,25-dihydroxy-cliolecalciferol [1,25(OH)₂D] together; and plasma tartrateresistant acid phosphatase—indicated that bone uncoupling, with a prevalence of resorption over formation of bone, was greater in trabecular bone than in cortical bone and also that the magnitude and rate of bone loss in the axial vertebrae surpassed those in the appendicular metacarpals after OVX. Two other groups of parameters, namely, trabecular bone mineral density (D_d) and bone mineral content (D_c), both measured by DXA, and bone mineral density (L₂, L₃), measured by QCT, together; and the cortical thickness index (MCI), cortical bone mineral density (GS/D), and the ratio of GSmin/max, measured by MD, indicated that the relative rates of bone reduction at the 3-year follow-up were greater in the axial vertebrae than in the appendicular metacarpals. Thus, bone change in the trabecular bone was associated with rapid loss during the early phase after OVX, whereas that in the cortical bone was slow during the late phase.     

Thyroid hormone replacement for nephrotic syndrome patients with euthyroid sick syndrome: a meta-analysis

Objective: To assess the efficacy of thyroid hormone replacement therapy for nephrotic syndrome (NS) patients associated with euthyroid sick syndrome (ESS). Materials and methods: The Cochrane library, ISI, Ovid, PubMed, Chinese Biomedicine Database were searched, and reference list of relevant articles were selected. Randomized controlled trials (RCTs) or quasi-RCTs with thyroid hormone replacement on NS patients associated with ESS were included in this analysis. Results: Six trials (329 participants) were included. Meta-analysis showed that thyroid hormone replacement therapy can significantly increase the completely remission rate [OR?=?3.04, 95% confidence interval (CI): 3.04–1.88, p?p?Conclusions: Thyroid hormone replacement therapy significantly increases the remission of ESS in patients with NS.     

Serum triiodothyronine,bone turnover,and bone mass changes in euthyroid pre- and postmenopausal women

Summary Hyperthyroidism and thyroid hormone substitutive therapy with serum iT₃ in the normal range of values are known to lead to increased bone remodeling and loss of bone mass. We looked for a relationship between serum iT₃ and bone metabolic or bone mass parameters in 402 euthyroid women aged 44–60. In a group of 93 premenopausal women, a group of 309 postmenopausal women, and a group of 118 untreated postmenopausal women, serum iT₃ was higher in the women classified as having “high” bone turnover according to both alkaline phosphatases and hydroxyprolinuria values. In postmenopausal women, serum iT₃ corrected for thyroid binding globulin (TBG) (T_3c) was higher in those receiving no estrogen replacement therapy. In a longitudinal study (n=131), the rate of changes in lumbar bone mineral content was associated with changes in T_3c. A less favorable bone mass evolution was associated with an increase in serum T_3c, and inversely. Data suggest that the relationship of iT₃/bone metabolism is direct and not merely the consequence of estrogen induced changes in both iT₃ and bone metabolism. iT₃ should be explored at the bone cellular level as a possible mediator in bone metabolic changes occurring in menopause and many other clinical situations.     

Prevalence of Hypothyroidism in Benign Breast Disorders and Effect of Thyroxine Replacement on the Clinical Outcome

Background

The aim of this study was to determine the prevalence of hypothyroidism in patients with benign breast disorders (BBD). We then asked if thyroxine replacement in hypothyroid patients has any impact on the clinical outcome of the BBD.

Methods

This prospective study included 201 women with BBD. None of the included patients had previously suspected hypothyroidism. Clinical, laboratory, and follow-up details of the patients were noted. Baseline serum thyroxine, thyroid-stimulating hormone (TSH), and prolactin estimation was done in all cases. Thyroid peroxidase antibody (TPOAb) estimation was done in hypothyroid patients and/or patients with a goiter. In addition to the standard conservative management protocol, hypothyroid patients were given thyroxine replacement therapy. Their response to treatment was assessed at 3-month intervals. The clinical outcomes of euthyroid and hypothyroid groups were compared.

Results

The mean age of the patients was 34 ± 8 years, and the mean length of follow-up was 13.0 ± 4.2 months. The overall prevalence of hypothyroidism was 23.2% (nipple discharge 37%, mastalgia 23%, lump/lumpiness 17.4%). The rate of hypothyroidism and the mean serum TSH concentration were significantly higher among patients with nipple discharge than among those with mastalgia (P = 0.001) or a lump (P = 0.01). In all, 39% of hypothyroid women had TSH concentrations >10 mIU/l, and 53% had an elevated TPOAb titer. BBD symptoms were alleviated in 83% of the hypothyroid patients with only thyroxine replacement. The final clinical outcomes of hypothyroid patients with nipple discharge and mastalgia were significantly better than that of their euthyroid counterparts (P = 0.028 and 0.001, respectively); no significant difference was noted in patients with lumpiness (P = 0.144).

Conclusions

All women with BBD should be screened for hypothyroidism because the prevalence of hypothyroidism is high among this group and correction of hypothyroidism results in significant clinical improvement of BBD in most of these patients.     

Radial bone mineral density in pre- and perimenopausal women: a prospective study of rates and risk factors for loss.

Radial bone mineral density (BMD) of 217 white women aged 22-54 years from a single rural community was evaluated in 1984 using single-photon absorptiometry. BMD was measured at a site one-third the distance from the wrist to the elbow, a site that represents predominantly cortical bone tissue. Most of these women (181; 83%) were reexamined 5 years later. The overall average 5 year radial BMD loss was -5.6%. The average rate of loss was -4.5% for women retaining positive estrogen status at follow-up (n = 108) and -7.4% for women who were in negative estrogen status at follow-up (n = 73). Baseline radial BMD measures were highly predictive of the follow-up BMD values (r = 0.80). Women with positive estrogen status and greater baseline BMD also had less BMD change. Greater baseline BMD did not predict the amount of change in women with negative estrogen status. The bone turnover markers osteocalcin and bone-specific alkaline phosphatase were significantly associated with BMD change in women with negative, but not positive estrogen status. There was no conclusive evidence of a "peak age" in the baseline and follow-up BMD measures. Based on rates of BMD change, "peak" bone mineral content appears to occur before age 25 years. Factors significantly associated with lower levels of BMD were menopause without estrogen replacement, nulliparity, smoking, and age at first pregnancy. Factors associated with more bone loss were menopause without estrogen replacement, smoking, shorter duration of oral contraceptive use, and older age. Quetelet index, muscle area, number of lost pregnancies, ever breast-feeding, or calcium intake were not associated with BMD level or its 5 year rate of loss. Physical activity and alcohol intake were not associated with BMD level or change after data were adjusted for age or estrogen status.     

Effects of raloxifene on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis

BACKGROUND: Premature amenorrhea and hypoestrogenism and lack of hormone replacement therapy after menopause have been frequently reported in uremic women on dialysis. Therefore, in addition to renal osteodystrophy, postmenopausal women on dialysis could be at risk of osteoporosis. In addition, these patients are at higher risk for hyperlipidemia, arteriosclerosis, and subsequent coronary heart disease and stroke. Recent evidence has suggested that hormone replacement therapy (HRT) in postmenopausal women could have several beneficial effects as well as potentially serious risks. Great efforts have been made to identify therapeutic alternatives that would have the benefits of estrogen on brain and bone without its adverse effects on breast and endometrium. In the present study, we evaluated the effect of raloxifene, a selective estrogen receptor modulator (SERM), on bone metabolism and serum lipids in postmenopausal women on chronic hemodialysis. METHODS: We performed a prospective, blind, placebo-controlled, and randomized study. Fifty postmenopausal women on chronic hemodialysis with proven severe osteopenia or osteoporosis by bone densitometry were selected. After a written informed consent, patients were randomized into two groups: 25 women on placebo and 25 women on the study drug, raloxifene hydrochloride, at a dose of 60 mg/day. In all patients, we performed a baseline bone mineral density (BMD) analysis and simultaneously evaluated different biochemical parameters, serum lipids (total low-density lipoprotein [LDL] and high-density lipoprotein [HDL] cholesterol and triglycerides) and serum markers of bone resorption (pyridinoline crosslinks). BMD was reassessed after 1 year of therapy. Bone resorption markers were determined every 3 months for 1 year. RESULTS: After 1 year on raloxifene therapy, lumbar spine BMD (trabecular bone) significantly improved, whereas femoral neck BMD (cortical bone) did not change significantly. No changes in BMD were observed at trabecular or cortical sites in the placebo group. Serum pyridinoline levels showed a significant decrease after 6 months on raloxifene that persisted thereafter. Low-density lipoprotein (LDL)-cholesterol decreased significantly in the raloxifene group with no changes in serum triglycerides, total cholesterol, or HDL cholesterol. No significant side effects were observed in the raloxifene group. CONCLUSION: The study demonstrates that after one year on raloxifene, postmenopausal women on hemodialysis have a significant increase in trabecular BMD, decrease in bone resorption markers and LDL-cholesterol values, suggesting that SERMs could constitute a therapeutic alternative to improve bone metabolism and control of hyperlipidemia in these patients. The possible long-term effects of raloxifene remain to be determined.     

Forearm bone loss in hemiplegia: a model for the study of immobilization osteoporosis

Hemiplegia is associated with excessive bone loss in the paralyzed arm. The forearm bone mineral content was measured at a proximal cortical site and a distal trabecular site of both the normal and hemiplegic arms in 74 patients with hemiplegia. By comparing the ratios of bone mineral content in the two arms, the effect of immobilization could be quantitated independently of the large population variance in bone mineral content. Bone loss, estimated from this single comparison of bone mineral content in the normal and hemiplegic arms, at the trabecular and cortical sites was positively correlated with the duration of stroke and negatively correlated with reduction in forearm function. At the trabecular site females had a proportionately greater bone loss than males, indicating an interaction between gender and immobilization associated bone loss at this site. The regression line of excess bone loss in the hemiplegic limb against time had a negative slope of 1.3% and 1.5% a year of the starting value for the trabecular and cortical sites, respectively, over the 15 years studied. This study indicates that a reduction in function is associated with significant bone loss occurring over prolonged periods that may account, at least in part, for the significant osteoporosis seen in elderly people and in subjects with conditions resulting in reduced mobility such as arthritis, obstructive airways disease, and neurological disease.     

Longitudinal Study of Bone Loss in Pre- and Perimenopausal Women: Evidence for Bone Loss in Perimenopausal Women

Bone loss before and around the time of menopause is not well characterized by longitudinal studies. We measured bone mineral density at various skeletal sites – total body, femoral neck, trochanter, anteroposterior (AP) and lateral spine, and forearm – with dual-energy X-ray absorptiometry in a large prospective cohort of 272 untreated pre- and perimenopausal women aged 31–59 years, at 1 year intervals for 3 years. Sex steroids and the following markers of bone remodeling were measured: serum osteocalcin (OC), procollagen I carboxyterminal extension peptide, bone alkaline phosphatase (BAP) and urinary crosslinks (CTX and NTX). Seventy-six women were classified as perimenopausal and 196 as premenopausal. Over the 3 years, premenopausal women had no significant bone loss at any site and a small but significant increase in bone mineral density at the trochanter, total hip, AP spine and radius. Perimenopausal women significantly lost bone from cancellous and cortical sites, i.e., the femoral neck, trochanter and lumbar spine. In perimenopausal women with increased follicle stimulating hormone, the rate of bone loss at the femoral neck correlated negatively with OC and BAP. In perimenopausal women, serum estradiol levels decreased during the 3 years of follow-up and bone loss from the trochanter and the AP spine was correlated with serum estradiol after 3 years. In conclusion, among premenopausal women there is no bone loss. In contrast, there is a rapid and diffuse bone loss in perimenopausal women, related to decreased estrogen secretion. Bone markers may be useful to identify these women losing bone. Received: 13 October 1997 / Accepted: 19 October 1998