A therapeutic dilemma: suppressive doses of thyroxine significantly reduce bone mineral measurements in both premenopausal and postmenopausal women with thyroid carcinoma

We measured lumbar spine, femoral neck, and forearm bone mineral (BMD) in 24 women (14 premenopausal and 10 postmenopausal) who had been treated with total thyroidectomy and 131 Iodine ablation therapy for nonanaplastic thyroid carcinoma and 24 case controls. At the time of the study, all patients were free of cancer (negative 131 Iodine whole body scan and serum thyroglobulin levels less than 0.3 micrograms/L) and all were receiving doses of T4 sufficiently high to prevent a rise in a serum thyroid-stimulating hormone concentration after an iv bolus of TRH. Femoral neck BMD were significantly reduced in both the premenopausal women (89 +/- 3.8% of case controls, 95% CI, 81 to 98) and postmenopausal women (77 +/- 3.9% of case controls; 95% CI, 68 to 86) receiving T4. Lumbar spine BMD and forearm BMD were unaffected in the premenopausal women, but significantly reduced in the postmenopausal women receiving T4 (lumbar spine BMD = 84 +/- 6.2% of case controls; 95% CI, 70 to 98 and forearm BMD = 89 +/- 5.6% of case controls; 95% CI, 76 to 101). Serum bone Gla-protein, a marker of bone turnover, was significantly increased in both the premenopausal and the postmenopausal women receiving T4 compared to case controls (P less than 0.001 for the difference between patient groups and controls). Whereas the cumulative dose of T4 was highly correlated with the femoral neck BMD in the premenopausal patients (r = 0.528; P less than 0.05); the presence of hypogonadism was the main determinant of the lumbar spine and forearm BMD. This data confirms that premenopausal and postmenopausal women receiving suppressive doses of T4 for thyroid carcinoma have diminished bone mineral measurements and are at risk for osteoporosis.     

Bone metabolism and mass in women with Cushing's syndrome and adrenal incidentaloma

OBJECTIVE: The aim of this study was to compare bone turnover and mass in women with either Cushing's syndrome (CS) or adrenal incidentaloma (AI), which is a possible model for minimal hypersecretion of cortisol. DESIGN AND PATIENTS: We studied 15 patients with CS (seven premenopausal and eight postmenopausal women); 23 patients with AI (five premenopausal and 18 postmenopausal women) and 20 matched controls (seven premenopausal and 13 postmenopausal women). Alkaline phosphatase (ALP), bone alkaline phosphatase (bALP), osteocalcin (BGP), 24-h urinary pyridinoline (Pyr) and deoxypyridinoline (D-Pyr) and serum and 24-h urinary calcium and phosphorus were determined in all subjects. Bone mineral density (BMD) at lumbar spine and proximal femur was measured by dual energy X-ray absorptiometry (DEXA). RESULTS: We found a significant reduction of BGP and serum phosphorus in CS and AI (P < 0.05) vs. controls and significantly lower levels of Pyr only in CS (P < 0.05) vs. AI and controls. Spinal and femoral BMD z-values were significantly lower (P < 0.05) in patients with CS (z-score: lumbar spine -1.44 +/- 1.5 and femoral neck -1.07 +/- 1; mean +/- SD) compared to AI and controls. CONCLUSIONS: Our data show that hypercortisolism reduces osteoblastic function and bone resorption and that osteocalcin can contribute to the precocious diagnosis of silent glucocorticoid excess. Patients with active CS were found to have lower BMD, particularly at vertebral level.     

Alendronate increases bone mass and reduces bone markers in postmenopausal African-American women

Previous studies indicated that aminobisphosphonate alendronate sodium, a potent inhibitor of bone resorption, increases bone mineral density (BMD) at the hip and spine, reduces markers of bone turnover, and reduces the risk of fractures in Caucasian postmenopausal women. The purpose of the present study was to investigate whether alendronate increases BMD and reduces markers of bone turnover in African-American postmenopausal women. In a multicenter, randomized, double-blind, placebo-controlled study, 65 African-American women, aged 45 to 88 yr, were randomly assigned to either placebo (n = 33) or alendronate 10 mg daily (n = 32) for 2 yr. Mean BMD T scores of the lumbar spine at baseline were -3.18 in the placebo-treated group and -3.09 in the alendronate-treated group. All women took 500 mg elemental calcium daily in the form of calcium carbonate and 500 IU vitamin D. Alendronate significantly increased BMD and reduced markers of bone formation and resorption, compared with placebo. At 2 yr, mean changes +/- SE in BMD were 6.5% +/- 0.7% for the lumbar spine (P < 0.001), 4.5% +/- 1.0% for the femoral neck (P < 0.001), 6.4% +/- 0.6% for the femoral trochanter (P < 0.001), 4.1% +/- 0.7% for the total hip (P < 0.001), 0.7% +/- 0.5% for the one third forearm (NS), and 2.0% +/- 0.4% for the total body (P < 0.001) in women treated with alendronate, compared with 0.9% +/- 0.6% (NS), 0.5% +/- 1.1% (NS), -0.2 +/- 0.8 (NS), -1.1 +/- 0.7% (NS), -0.8% +/- 0.6% (NS), and -1.2% +/- 0.6% (P < 0.05) for the lumbar spine, femoral neck, trochanter, total hip, one third forearm, and total body, respectively, in women treated with placebo. At 2 yr, mean serum bone-specific alkaline phosphatase had declined by 46.3% with alendronate (P < 0.001) and 13.6% with placebo (P < 0.01), and mean urinary N-telopeptide of type I collagen/creatinine ratio had declined by 70.5% with alendronate (P < 0.001) and 6.7% with placebo (NS). The incidence of adverse experiences was not different between the two groups. We conclude that in postmenopausal African-American women with osteoporosis, alendronate, 10 mg daily for 2 yr, increases BMD at the lumbar spine, hip, and total body and reduces markers of bone remodeling and is well tolerated.     

Simvastatin increases bone mineral density in hypercholesterolemic postmenopausal women

Statins are able to reduce cardiovascular morbility and mortality mainly through their hypocholesterolemic effect. Beyond the inhibition of cholesterol synthesis, the identification of "ancillary" mechanisms has motivated studies evaluating the relationship between the use of statins and the modification of bone mineral density (BMD). To date, clinical trials have provided discordant results. The aim of our study was to evaluate whether simvastatin treatment (40 mg/d) could modify BMD in hypercholesterolemic women (n = 40) after a 2-year treatment as compared with a control group treated only with diet (n = 20) and matched by gender, age, body mass index (BMI), lipids, menopausal age, and BMD and the number of osteopenic, osteoporotic, and normal women (on the basis of T-score value). Exclusion criteria were secondary hyperlipemias and osteoporosis and current or previous therapy with statins, bisphosphonates, and estrogens. The BMD was measured at the lumbar spine and hip by dual energy x-ray absorpiometry (DEXA). In the group treated by simvastatin, BMD, both on the spine and femoral hip, showed a significant increase after 8 and 24 months, respectively (0.878 +/- 0.133 v 0.893 +/- 0.130 and 0.907 +/- 0.132; 0.840 +/- 0.101 v 0.854 +/- 0.101; and 0.863 +/- 0.10, P <.001); there was a percentage increase of 1.7% after 8 months and 3.3% after 24 months at the spine; at the femoral hip, BMD increased 1.6% after 8 months and 2.7% after 24 months. The group treated only with hypolipidic diet demonstrated after 8 and 24 months a slight decrease in BMD both on the spine and femoral hip (respectively, 0.884 +/- 0.175 v 0.872 +/- 0.174 and 0.861 +/- 0.164; 0.860 +/- 0.110 v 0.853 +/- 0.096 and 0.847 +/- 0.095; P <.05). In conclusion, as partly suggested by retrospective or observational data, this longitudinal study indicates that simvastatin treatment exerts a beneficial effect on BMD.     

Disease damage and low bone mineral density: an analysis of women with systemic lupus erythematosus ever and never receiving corticosteroids

OBJECTIVES: To evaluate the relationship between disease damage and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE). METHODS: A cross-sectional study was conducted among 307 women with SLE. Patients attended a single clinic visit that included an interview, physical examination, laboratory testing and BMD measurements (hip and/or lumbar spine). Women were stratified by the Systemic Lupus International Collaborating Clinics/American College of Rheumatology cumulative disease damage index (SDI) > or =1 (Damage) vs SDI=0 (No Damage), and prior use of corticosteroids (CS), yielding four groups: (1) Damage/CS(+) (n=138), (2) Damage/CS(-) (n=23), (3) no Damage/CS(-) (n=100), and (4) no Damage/CS(-) (n=46). RESULTS: Mean age at SLE diagnosis was 32.7 +/- 11.8 yr, 24.4% were African American, 65.0% were premenopausal, and mean SDI +/- S.D. was 1.3 +/- 1.8. In the unadjusted and adjusted models controlling for significant univariate risk factors for osteoporosis, the reference group (Group 1) had significantly lower mean BMD T-scores at the hip and lumbar spine than groups having no disease damage (Groups 3 and 4) independent of CS use status. Similar hip and lumbar spine mean BMD T-scores were observed in women with disease damage with and without CS exposure (Groups 1 and 2). CONCLUSIONS: Women with SLE having disease damage and no CS use had BMD T-scores at the hip and lumbar spine similar to those of women with disease damage and prior CS use. These findings suggest an association between disease damage and lower BMD T-scores in women with SLE.     

High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women.

Animal studies demonstrated that phytoestrogen had a protective effect against bone loss after ovariectomy. However, data on dietary phytoestrogen intake as well as its relationship with bone mineral density (BMD) in human are not available. Six hundred fifty southern Chinese women, aged 19 to 86 yr, were recruited to determine their dietary phytoestrogen intake by a food frequency questionnaire. BMDs at the lumbar spine and hip region were measured using dual energy x-ray absorptiometry. The subjects were analyzed according to various tertiles of phytoestrogen intake. Among the postmenopausal women (n = 357), significant differences in the lumbar spine (L2-4) BMD (0.820 +/- 0.145 vs. 0.771 +/- 0.131 g/cm2, P < 0.05) and Ward's triangle BMD (0.450 +/- 0.151 vs. 0.415 +/- 0.142 g/cm2; P < 0.05) were found between the highest and lowest intake of isoflavone after adjusting for age, height, weight, years since menopause, smoking, alcohol consumption, HRT usage, and daily calcium intake. Women with the highest intake of isoflavone had significantly lower levels of serum PTH (19.38 +/- 14.61 vs. 26.56 +/- 11.19 pg/ml; P < 0.05), osteocalcin (4.95 +/- 3.61 vs. 6.69 +/- 5.05 mg/liter; P = 0.05), and urinary N-telopeptide (34.18 +/- 25.31 vs. 49.66 +/- 41.00 nmol bone collagen equivalents/mmol creatinine; P < 0.05) when compared with those with the lowest intake of isoflavone. No association between dietary phytoestrogen intake and BMDs was seen in the premenopausal women with high endogenous E (n = 293). In conclusion, postmenopausal women with habitually high intake of dietary isoflavone are associated with higher BMD values at both the spine and hip region. Customarily high isoflavone intake may help to reverse the state of secondary hyperparathyroidism associated with E withdrawal and hence lower the rate of bone turnover in postmenopausal women.     

Bone mineral density in premenopausal women with systemic lupus erythematosus

OBJECTIVE: To study bone mineral density (BMD) in premenopausal women with systemic lupus erythematosus (SLE) and to evaluate the influence of disease activity and use of corticosteroids. METHODS: A cross-sectional study on BMD of 118 premenopausal women with SLE. Patients were divided into 2 groups, 74 who had been treated with corticosteroids and 44 who had not. BMD at lumbar spine, femoral neck, and trochanter was measured. RESULTS: BMD in patients without and with corticosteroid treatment was 1.13 +/- 0.13 vs 1.05 +/- 0.14 g/cm2 (p = 0.005) at lumbar spine, 0.92 +/- 0.12 vs 0.86 +/- 0.12 g/cm2 (p = 0.005) at femoral neck, and 0.78 +/- 0.13 vs 0.72 +/- 0.12 g/cm2 (p = 0.014) at trochanter, respectively. Stepwise multilinear regression analysis showed that corticosteroid exposure was independently associated with decreased BMD in the corticosteroid treated patients (r2 = 7% for lumbar and 6.6% for trochanter model). No significant difference in BMD in corticosteroid treated patients appeared when they were subgrouped according to whether they were taking calcium supplements. Prevalence of osteoporosis at lumbar spine in corticosteroid treated patients was 1.4%, and was lower than reported for age and sex matched Caucasians. CONCLUSION: BMD measurements were significantly lower in premenopausal SLE patients who had had corticosteroid treatment than those who had not. There was a negative correlation between BMD and corticosteroid therapy, but not disease activity. Prevalence of osteoporosis, based on lumbar spine BMD, was lower than that reported in Caucasians.     

Prolactinomas in adolescents: persistent bone loss after 2 years of prolactin normalization

OBJECTIVE: To evaluate the effect of hyperprolactinaemia and its treatment with dopamine-agonists on bone mass and turnover in adolescent patients compared to adults. PATIENTS: Forty patients with hyperprolactinaemia (20 with disease onset during adolescence and 20 during adulthood) and 40 healthy control subjects. DESIGN: Open transverse (in patients and controls) and open longitudinal (in the patients). MEASUREMENTS: Bone mineral density (BMD) at lumbar spine and femoral neck, serum osteocalcin (OC) and urinary cross-linked N-telopeptides of type-1 collagen (Ntx) levels were evaluated in patients and controls. In the 40 patients, bone mass and turnover were re-evaluated after 12 and 24 months of treatment with bromocriptine (BRC, dose 2.5-10 mg daily), quinagolide (CV, dose 0.075-0.3 mg daily) or cabergoline (CAB, dose 0.5-1.5 mg weekly). RESULTS: Transverse study: BMD values were significantly lower in hyperprolactinaemic patients than in controls, both at lumbar spine (0.81 +/- 0.01 vs. 1.010 +/- 0.01 g/cm2; P < 0.001) and femoral neck (0.71 +/- 0.01 vs. 0.873 +/- 0.03 g/cm2; P < 0.001). Thirty-two patients (80%) had osteoporosis and/or osteopenia at one or both skeletal sites. A significant inverse correlation was found between T score values measured at lumbar spine and femoral neck and the estimated disease duration. BMD was significantly lower in young than adult patients both at lumbar spine (T score, -2.4 +/- 0.1 vs. -1.4 +/- 0.3, P < 0.01) and at femoral neck (T score, -2.1 +/- 0.05 vs. -1.5 +/- 0.2, P < 0.05). Similarly, serum OC levels were significantly lower (2.0 +/- 0.11 vs. 9.1 +/- 2.4 micrograms/l, P < 0. 01) while Ntx levels were significantly higher in patients than in controls (129.2 +/- 1.7 vs. 80.7 +/- 2.9 nmol Bone collagen equivalent (BCE)/mmol creatinine; P < 0.001). A significant inverse correlation was found between prolactin (PRL) levels and OC levels, lumbar and femoral T score values, as well as between disease duration and OC levels, lumbar and femoral T score values. A significant direct correlation was also found between Ntx levels and PRL levels and disease duration. Longitudinal study: Normalization of serum PRL levels was obtained in all patients after 6-12 months of treatment. A significant increase of serum OC levels together with a significant decrease of Ntx levels was observed after 12 and 24 months of treatment (P < 0.01). Urinary and serum calcium, phosphorus, creatinine, and serum alkaline phosphatase and parathyroid hormone levels did not change during the study period in all patients. After 12 months of therapy OC and Ntx concentrations were restored to normal. A slight but not significant increase of BMD values was recorded after 12 and 24 months of treatment. After 12 months of treatment the percent increment of BMD values in the whole group of patients was 1.13 +/- 0.6% at lumbar spine and 1.2 +/- 0.4% at femoral neck level, whereas after 24 months, it was 2.8 +/- 0.7% at lumbar spine and 3.5 +/- 0.7% at femoral neck level. After 12 months of treatment, the percent increment of BMD values was 0.7 +/- 0.2% and 1.6 +/- 1.1% at lumbar spine and 0.9 +/- 0.5% and 1.6 +/- 0.5% at femoral neck level in the young and adult patients, respectively, whereas after 24 months, it was 2.1 +/- 0.8% and 3.4 +/- 1.3% at lumbar spine and 2.6 +/- 0.8% and 4.4 +/- 1.0% at femoral neck level in the young and adult patients, respectively. CONCLUSIONS: Adolescents with prolactinoma have osteopenia or osteoporosis, a finding that strengthens the need for a prompt diagnosis. Since normalization of PRL concentrations by dopamine agonist therapy is unable to restore the bone mass, other therapeutic approaches should be considered in order to prevent further long-term problems.     

Bone density in a population-based cohort of premenopausal adult women with early onset inflammatory bowel disease

OBJECTIVE: We aimed to determine the bone mineral density (BMD) using dual energy x-ray absorptiometry in a population-based sample of women with inflammatory bowel disease who were diagnosed before age 20 yr and who are currently premenopausal and less than 45 yr. METHODS: The University of Manitoba Inflammatory Bowel Disease Epidemiology Research Registry was accessed to find eligible women. Of 171 eligible subjects, 82 agreed to participate, and 70 appeared for dual energy x-ray absorptiometry. All subjects completed demographic, clinical, and lifestyle questionnaires and underwent dual energy x-ray absorptiometry with analyses for both areal and volumetric BMD. RESULTS: The mean areal T scores at the lumbar spine, femoral neck, total hip, and total body were -0.14 +/- 1.05, -0.15 +/- 1.04, -0.25 +/- 1.17, and +0.09 +/- 1.04, respectively. Forty-five subjects had normal BMD, and 25 had a T score < -1. There were no significant differences between these groups for predictive variables. Only three (4%) had osteoporosis (T score < -2.5 at any site). There were 12 with disease onset before puberty and 58 after puberty. There were no differences between these groups for BMD. Volumetric BMD was slightly higher than areal BMD at the lumbar spine (p < 0.0002), femoral neck (p < 0.01), and total hip (p < 0.001). CONCLUSIONS: In a population-based sample of women diagnosed with IBD before 20 yr of age and who are currently premenopausal, their average BMD is normal and the prevalence of osteoporosis is very low. Despite the potential for children with IBD to develop osteoporosis, their BMD as adults is generally normal.     

以生物电阻法检测的身体组成成分与女性骨量的关系

目的 探讨体内的体脂和非体脂对绝经前和绝经后妇女骨密度(BMD)的作用。方法 282例绝经前和205例绝经后妇女参加本研究,用双能X线骨密度仪测定腰椎和股骨颈BMD,用生物电阻法测定体脂和非体脂,同时测量身高、体重、腰围、臀围,并计算体重指数(BMI)和腰臀围比(WHR)。结果 体脂和非体脂与绝经前、绝经后妇女腰椎和股骨颈BMD均呈显著正相关(P＜0．01),多元逐步回归分析显示,在绝经前妇女中,非体脂和年龄是腰椎BMD的独立影响因素(R^2=0．077,P=0．000),非体脂、年龄和BMI是影响股骨颈BMD的决定因素(R^2=0．130,P=0．000),在绝经后妇女中,体脂和年龄是影响腰椎和股骨颈BMD的决定因素(R^2分别为0．153和0．184,P=0．000)。结论 体脂和非体脂对绝经前和绝经后妇女BMD的作用不同,非体脂是决定绝经前妇女骨量的重要因素,而体脂是影响绝经后妇女骨量的重要因素。     

Bone mineral density in adults with Marfan syndrome

OBJECTIVES:Reduced bone mineral density (BMD) has been reported in pre-menopausal women and children with Marfan syndrome (MFS). The bone mineral status of adult men with MFS is unknown. The objective of this study was to determine the BMD of adult men and women with MFS. METHODS:BMD (g/cm(2)) was measured by dual-energy X-ray absorptiometry (DXA) of the lumbar spine (L1-L4), femoral neck and total hip in 25 adults (12 male) who fulfilled the 1996 MFS diagnostic criteria. The results were compared with age- and sex-matched controls and expressed as S.D. from the population mean (z score). RESULTS:Overall, BMD was significantly reduced in the lumbar spine (z = -0.42 +/- 0.97, P < 0.05), total hip (z = -0.57 +/- 0.88, P < 0.005) and femoral neck (z = -0.51 +/- 0.88, P < 0. 005). In women alone, BMD was reduced at the femoral neck (z = -0.53 +/- 0.95, P < 0.05) and at the hip (z = -0.64 +/- 0.77, P < 0.005). In men, BMD was reduced at the femoral neck (z = -0.48 +/- 0.84, P < 0.05) with a non-significant trend to lower BMD at the hip (z = -0. 49 +/- 1.01, P = 0.054) and lumbar spine (z = -0.59 +/- 1.02, P = 0. 09). CONCLUSION:Axial BMD is lower than normal in Marfan adults. This reduction may contribute to fractures seen in the Marfan population.     

Osteopenia in eugonadal men with acquired immune deficiency syndrome wasting syndrome

Multiple endocrine and metabolic consequences of human immunodeficiency virus (HIV) infection exist that may contribute to bone loss in men with the acquired immune deficiency syndrome (AIDS) wasting syndrome. Recent studies suggest that anabolic strategies can increase lean body mass in men with AIDS wasting. Prior studies have not examined the effects of anabolic agents on bone mineral density (BMD) or bone turnover in these men. To determine the effects of testosterone and progressive resistance training on BMD and bone turnover in eugonadal men with AIDS wasting, we randomly assigned 54 eugonadal men with AIDS wasting (weight < 90% IBW or weight loss >10% from preillness baseline) to receive either testosterone enanthate (200 mg/week, im) or placebo and to progressive resistance training (3 times/week) or no training in a 2 x 2 factorial study design for 3 months. The BMD of the lumbar spine, proximal femur, and total body; lean body mass; and fat mass were measured by dual energy x-ray absorptiometry. Total body scans were repeated after 12 weeks of therapy. Baseline bone turnover and BMD were compared with those in 35 age-matched healthy non-HIV-infected control subjects. Compared with controls, lumbar spine BMD (1.021 +/- 0.018 vs. 1.084 +/- 0.025 g/cm(2); P = 0.04) and total hip BMD (0.951 +/- 0.017 vs. 1.070 +/- 0.019 g/cm(2); P < 0.0001) were reduced in men with AIDS wasting. T-scores were lower in men with AIDS wasting at the lumbar spine (-0.62 +/- 0.17 vs. -0.07 +/- 0.23, P = 0.05) and total hip (-0.65 +/- 0.11 vs. +0.20 +/- 0.014, P < 0.0001). Total hip T scores were less than -1.0 in 33% of men with AIDS wasting. Neither the use of protease inhibitors nor the duration of protease inhibitors use correlated with BMD. Serum osteocalcin levels were lower (3.63 +/- 0.29 vs. 4.54 +/- 0.31 nmol/L; P < 0.04) and urinary N-telopeptide excretion was higher (45.4 +/- 4.5 vs. 26.8 +/- 3.0 nmol BCE/mmol creatinine; P = 0.004) in men with AIDS wasting than in controls. Lumbar spine BMD, as assessed on regional total body dual energy x-ray absorptiometry scan, increased over the 12-week treatment period in response to testosterone (+2.4 +/- 1.3 vs. -1.3 +/- 1.0%, testosterone vs. placebo, respectively; P = 0.02), but not in response to training (+0.8 +/- 1.0 vs. +0.4 +/- 1.3%, training vs. no training; P = 0.70). Lumbar spine and total hip BMD are reduced in eugonadal men with AIDS wasting. Biochemical markers of bone turnover suggest that bone formation and bone resorption are uncoupled in these men. Testosterone administration, but not resistance training, over 3 months increases lumbar spine BMD in eugonadal men with AIDS wasting.     

Secondary hyperparathyroidism due to hypovitaminosis D affects bone mineral density response to alendronate in elderly women with osteoporosis: a randomized controlled trial

OBJECTIVES: To determine whether secondary hyperparathyroidism (HPTH) due to hypovitaminosis D affects bone mineral density (BMD) response to alendronate (ALN) in elderly women with osteoporosis. DESIGN: Randomized, controlled trial with 1-year follow-up. SETTING: Two osteoporosis centers in northern Italy. PARTICIPANTS: Community-dwelling women aged 60 and older with a BMD T-score below -2.5 and secondary HPTH with vitamin D insufficiency. INTERVENTION: One hundred twenty subjects were randomly assigned to receive ALN 70 mg once a week alone or ALN 70 mg once a week plus calcitriol (1,25D3) 0.5 microg daily. MEASUREMENTS: BMD measured using dual-energy x-ray absorptiometry at the lumbar spine (L1-L4), femoral neck, and total hip and serum levels of intact PTH at baseline and 12 months. RESULTS: After 1 year, BMD of the lumbar spine, femoral neck, and total hip significantly increased from baseline in both groups (P<.001). Patients allocated to ALN plus 1,25D3 demonstrated a significantly higher increase in lumbar spine BMD than those receiving ALN alone (mean percentage+/-standard deviation 6.8+/-4.6 vs 3.7+/-3.2, P<.001). Serum levels of PTH did not change significantly at 1 year in the ALN group (mean percentage, -3.7+/-27.1, P=.13) but decreased significantly in the ALN plus 1,25D3 group (-32.1+/-22.1, P<.001). At 12 months, subjects with normalized PTH independent of therapy allocation had a greater increase in lumbar spine BMD than those with persistent HPTH (6.5+/-4.6% vs 3.7+/-3.4%, P<.001). Lumbar spine BMD changes showed a significant negative correlation with PTH at 1 year (correlation coefficient (rho) =-0.399, P<.001) and a positive correlation with PTH changes (i.e., baseline value - 1 year value; rho=0.295, P=.005). CONCLUSION: Persistence of secondary HPTH reduces BMD response to ALN in older women with osteoporosis.     

Bone mineral density in women with ankylosing spondylitis

OBJECTIVE: To determine bone mineral density (BMD) in premenopausal women with early ankylosing spondylitis (AS). METHODS: Eighteen premenopausal women with AS without syndesmophytes, interapophysiary arthritis, and/or coxofemoral joint destruction were studied. BMD was analyzed at lumbar spine and femoral neck by dual energy x-ray absorptiometry (Hologic QDR 1000). Z scores and T scores related to the general Spanish population were recorded. Comparisons were performed using the Student t test. Pearson's correlation coefficients were used to study the correlation between BMD and the variables. Following the WHO classification, osteopenia was diagnosed in patients with T score between -1 and -2.5 and osteoporosis in those with T score < -2.5 at lumbar spine or femoral neck. RESULTS: The mean Z score for spine BMD was -0.19+/-0.7, and -0.03+/-0.85 for femoral neck BMD. There were no significant differences of Z score values compared to the general population. No significant correlation was found between BMD and disease duration, radiology sacroiliac score, and spine mobility. Densitometry showed osteopenia in 2 patients and osteoporosis in none. CONCLUSION: We found a slight reduction in BMD in premenopausal women with early AS, but the difference was not statistically significant. We discuss the factors related to its pathogenesis.     

Comparison of alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women

This study compared the effects of oral alendronate and intranasal calcitonin for treatment of osteoporosis in postmenopausal women. Women at least 5 yr postmenopause (n = 299) were randomized to either 10 mg alendronate, matching alendronate placebo, or open-label intranasal calcitonin 200 IU daily for 12 months. Hip and spine bone mineral density (BMD) and markers of bone turnover were measured, and safety and tolerability were assessed. Alendronate produced greater increases in BMD than calcitonin at 12 months at the lumbar spine (5.16% vs. 1.18%; P < 0.001), trochanter (4.73% vs. 0.47%; P < 0.001), and femoral neck (2.78% vs. 0.58%; P < 0.001). Changes in BMD with calcitonin were greater than with placebo at the femoral neck, but were not different from placebo at either the trochanter or lumbar spine. Greater decreases in bone turnover were seen with alendronate than with calcitonin (serum bone-specific alkaline phosphatase, 43% vs. 9%, P < 0.001; urinary N-telopeptide, 62% vs. 11%, P < 0.001). Similar percentages of patients in each group reported an adverse experience during the study. We conclude that, in postmenopausal women with osteoporosis, 12 months of therapy with alendronate produced significantly greater increases in BMD of the hip and spine and greater decreases in bone turnover than intranasal calcitonin.     

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.     

Pattern of bone mineral density in patients with sporadic idiopathic hypoparathyroidism

OBJECTIVE: Measurement of bone mineral density (BMD) in patients with hypoparathyroidism directly addresses the effect of chronic under-exposure of bone to PTH. Because post-thyroidectomy hypoparathyroidism is potentially complicated by the pre-existence of thyrotoxicosis and the need for postoperative thyroxine replacement, we have studied a large group of patients with sporadic hypoparathyroidism who have been followed up in our endocrine clinic. Studies conducted in limited number of patients with sporadic idiopathic hypoparathyroidism (SIH) have suggested an increase in BMD in such patients. In this current study, we have measured BMD in a large cohort of patients with SIH and have assessed the relationship of BMD with duration of disease and with the adequacy of treatment, as indicated by follow-up serum calcium, phosphate and alkaline phosphatase levels. DESIGN: Case control study and intra-group comparison. SUBJECTS: Forty-seven patients (M : F ratio 23 : 24) with SIH who had been reviewed during 2003-2004 in our endocrine clinic were recruited for this study. Their mean age (+/- SD) was 34.6 +/- 13.6 years and the duration from the time of initial diagnosis was 9.6 +/- 8.5 years. Forty-eight match healthy volunteers were recruited from hospital staff and from normocalcaemic relatives. METHODS: Bone mineral density was measured at total lumbar spine (L1-L4), hip and forearm by dual energy X-ray absorptiometry (DXA). The relationship of BMD was analysed with duration of disease symptoms (group I, < or = 1 year, group II, > 1 and < 5 years and group III, > or = 5 years) and mean serum total calcium observed during follow-up (group A, calcium < or = 1.79 mmol/l and group B, > or = 1.80 mmol/l). RESULTS: Patients with SIH showed significantly higher BMD at total lumbar spine and hip when compared to controls (1.098 +/- 0.187 vs. 0.936 +/- 0.131 g/cm2 and 0.967 +/- 0.141 vs. 0.882 +/- 0.149 g/cm2, P < 0.001 for both). BMD in the forearm was not significantly different in patients and controls. The age- and BMI-adjusted lumbar spine BMD showed correlation with duration of disease (r = 0.348 and P = 0.019). Patients with longer duration of hypoparathyroidism had higher BMD at lumbar spine (group I vs. group III, 0.951 +/- 0.132 vs. 1.156 +/- 0.180 g/cm2, P < 0.05). There was no significant correlation between BMD values in patients with SIH and their mean serum total calcium levels during the period of follow-up (r = 0.192, P = 0.206). Neither was the mean BMD significantly different between group A and B. Serum total alkaline phosphatase showed a significant negative correlation with BMD at lumbar spine (r = -0.445, P = 0.012). CONCLUSIONS: Patients with sporadic idiopathic hypoparathyroidism have increased mean BMD in the lumbar spine and hip but not in the forearm, compared to normal matched healthy controls. The increase in BMD is related to the duration of the disease rather than the serum calcium levels.     

Association between African American race/ethnicity and low bone mineral density in women with systemic lupus erythematosus

OBJECTIVE: To determine the association between race/ethnicity and bone mineral density (BMD) in women with systemic lupus erythematosus (SLE). METHODS: Women with SLE (n = 298), including 77 African Americans and 221 whites, completed this cross-sectional study conducted from 1996 to 2002. Hip and lumbar spine BMD were measured by dual-energy x-ray absorptiometry. Study participants completed a self-administered questionnaire and a physician completed the Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). BMD results were expressed as Z scores. Analyses were performed to identify factors, including race/ethnicity, associated with low BMD defined as a Z score -1.0 or less at the hip or lumbar spine. RESULTS: African Americans compared with whites were younger at study visit (mean +/- SD 39.7 +/- 8.4 years versus 42.9 +/- 11.6 years) and had higher SDI (mean +/- SD 1.8 +/- 2.0 versus 1.0 +/- 1.6), but similar proportions of women were postmenopausal (31.2% versus 38.0%). African Americans had significantly lower mean BMD Z scores at the hip (-0.49 versus -0.07; group difference -0.41; 95% confidence interval [95% CI] -0.70, -0.13) and at the lumbar spine (-1.03 versus 0.10; group difference -1.13; 95% CI -1.48, -0.78) compared with whites. African American race/ethnicity was strongly associated with low BMD at the lumbar spine (adjusted odds ratio 4.42; 95% CI 2.19, 8.91) but not at the hip, adjusting for factors associated with low BMD. CONCLUSION: African American women compared with white women with SLE had lower BMD at the hip and lumbar spine. African American race/ethnicity was associated with low BMD at the lumbar spine controlling for relevant clinical covariates.     

Alendronate for the treatment of osteopenia in anorexia nervosa: a randomized, double-blind, placebo-controlled trial

Osteopenia is a serious medical complication of anorexia nervosa, with no known effective treatment. We conducted a double-blinded, randomized trial comparing alendronate (10 mg daily) with placebo in 32 adolescents with anorexia nervosa (mean age, 16.9 +/- 1.9 yr). All subjects received 1200 mg elemental calcium and 400 IU vitamin D daily and received the same multidisciplinary treatment for their eating disorder. Bone mineral densities (BMDs) of the lumbar spine and femoral neck were measured by dual energy x-ray absorptiometry at baseline and after 1 yr of treatment. Twenty-nine subjects completed the study. Femoral neck and lumbar spine BMDs increased 4.4 +/- 6.4% and 3.5 +/- 4.6% in the alendronate group compared with increases of 2.3 +/- 6.9% and 2.2 + 6.1% in the control group (P = 0.41, femoral neck; P = 0.53, lumbar spine). From baseline to follow-up, BMD increased significantly at the femoral neck (P = 0.02) and lumbar spine (P = 0.02) in those receiving alendronate, but did not increase in those assigned placebo (P = 0.22, femoral neck; P = 0.18, lumbar spine). At follow-up, body weight was the most important determinant of BMD. BMD was significantly higher in subjects who were weight-restored compared with those who remained at low weight (P = 0.002, femoral neck; P = 0.04, lumbar spine). After controlling for body weight, treatment group assignment still had an independent effect at the femoral neck. We conclude that in adolescents with anorexia nervosa, weight restoration is the most important determinant of BMD, but treatment with alendronate did increase the BMD of the lumbar spine and femoral neck within the group receiving alendronate, but not compared with placebo in the primary analysis. Until additional studies have demonstrated efficacy and long-term safety, the use of alendronate in this population should be confined to controlled clinical trials.