HMG-CoA reductase inhibitors increase BMD in type 2 diabetes mellitus patients

Recently, it was reported that 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors increased bone mineral density (BMD) in mice. We studied the effect of HMG-CoA reductase inhibitors on BMD of type 2 diabetes mellitus by a retrospective review of medical records. Sixty-nine type 2 diabetic patients were included. The control group (n = 33) did not take HMG-CoA reductase inhibitors. The treatment group (n = 36) was administered either lovastatin, pravastatin, or simvastatin. BMD of the spine, femoral neck, femoral trochanter, and total hip were measured by dual-energy X-ray absorptiometry. There were no significant differences between control and treatment groups in age, sex, body mass index, glycemic control, and serum insulin levels. In the control group, BMD of the spine significantly decreased (from 1.116 +/- 0.165 to 1.081 +/- 0.178 g/cm2) after 14 months. In the treatment group, BMD of the femoral neck significantly increased (from 0.853 +/- 0.139 to 0.878 +/- 0.147 g/cm2) after 15 months. In male subjects treated with HMG-CoA reductase inhibitors, there was a significant increase in BMD of the femoral neck and femoral trochanter (from 0.899 +/- 0.139 to 0.934 +/- 0.139 and from 0.801 +/- 0.145 to 0.833 +/- 0.167 g/cm2, respectively), but in female subjects, only BMD of the femoral neck increased (from 0.819 +/- 0.132 to 0.834 +/- 0.143 g/cm2). Percentage increments of BMD of the femoral neck, femoral wards triangle, femoral trochanter, and total hip in the treatment group were significantly higher than in the control group (2.32% vs. -0.99, 1.77% vs. -1.25%, 1.40% vs. -1.21%, 0.88% vs. -1.03%, respectively). The proportion of subjects who had an increase in BMD of the spine and total hip more than two percentages was significantly larger in the treatment group than in the control group (30.6% vs. 15.2% and 30.6% vs. 9.1%, respectively). The increased increment in BMD of the treatment group was significantly greater than those in the control group after adjustment for age and body mass index (P < 0.05). These results suggest that HMG-CoA reductase inhibitors may increase BMD of the femur in male patients with type 2 diabetes mellitus.     

Regional bone mineral density after orthotopic liver transplantation

OBJECTIVES: Although there is a fall in lumbar spine bone mineral density (BMD) after liver transplantation, little is known about femoral neck or total body BMD. Therefore we determined: (a) the proportion of patients with preexisting hepatic osteopenia before transplantation and (b) the effects of transplantation on global and regional BMD. DESIGN: Retrospective analysis of BMD measurements of patients before and up to 2 years after liver transplantation. METHODS: BMD was assessed by dual energy X-ray absorptiometry in 56 patients, before and at regular intervals after liver transplantation, for up to 24 months, to measure total body, lumbar spine (L2-L4) and femoral neck BMDs. RESULTS: Pre-transplant, 23% of patients had osteoporosis (a negative Z score > 2). Paired data before and after transplantation revealed no change in total body BMD. However, there was a fall in lumbar spine BMD (1.04+/-0.03 to 1.02+/-0.03 g/cm2; P < 0.04) at 1 month after transplantation. The reduction in lumbar spine BMD was seen up to 12 months, BMD at 18-24 months being similar to pre-transplant values. Femoral neck BMD also fell (0.96+/-0.06 to 0.83+/-0.04 g/cm2; P < 0.03), but only after 6-9 months, thereafter remaining below pre-transplant values until the end of the follow-up period. CONCLUSIONS: Although osteopenia is common in patients with liver disease, total bone density does not fall after transplantation. Nonetheless regional lumbar spine and femoral neck bone density does fall after transplantation with a risk period for femoral neck fracture which may extend for up to 2 years.     

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 loss in patients treated with pulses of methylprednisolone is not negligible: a short term prospective observational study

OBJECTIVE: To examine the influence of intravenous pulsed methylprednisolone (MP) on bone mass. METHODS: 38 patients (30 women) with various rheumatic disorders requiring intravenous MP pulse treatment were examined at baseline and after 6 months with dual energy x ray absorptiometry (DXA), measuring hip and lumbar spine bone mineral density (BMD). Demographic and clinical data were collected. RESULTS: Demographics showed: mean (SD) age 48.4 (16.3) years, body mass index 24.9 (5.1) kg/m(2), and median (range) disease duration 3.2 (0.1-40.0) years. During follow up patients received a mean cumulative MP dose of 3.0 (1.6) g given as 5.7 (2.0) pulses over a median period of 5.7 (2.3-33.7) months. 34/38 (89%) patients were also pulsed with cyclophosphamide, 20 (53%) were taking oral corticosteroids, and 8 (21%) were using either bisphosphonates or oestrogen. At the end of the study mean BMD was reduced by -2.2% at the femoral neck, -1.1% at the total hip, and -1.0% at the spine L2-4. In subgroups BMD increased in patients treated with bisphosphonates or oestrogen (femoral neck +1.6%, total hip +3.2%, spine L2-4 +4.5%), whereas BMD decreased at all sites in patients not treated with antirersorptive treatment, both for users (femoral neck -4.4%, total hip -2.4%, spine L2-4 -2.1%) and non-users of concomitant oral prednisolone (femoral neck -1.7%, total hip -1.9%, spine L2-4 -2.6%). CONCLUSION: Treatment with intravenous pulses of MP leads to a high rate of bone loss. Prevention of bone loss in these patients with bisphosphonates and oestrogens should be considered.     

Effect of alendronate on bone mineral density in male idiopathic osteoporosis

Idiopathic osteoporosis in men is an increasingly recognized disorder accounting for up to 200,000 hip fractures worldwide each year. Although there is no widely accepted or proven efficacious treatment for men with idiopathic osteoporosis, we attempted to examine the effectiveness of alendronate in this disorder. We retrospectively compared the clinical records of male patients with osteopenia (hip or spine T scores less than -1.0, with or without low-trauma fractures) treated either with alendronate 10 mg orally/day and calcium and vitamin D replacement versus conservative treatment with calcium and vitamin D alone. Review included analysis of laboratory studies and bone turnover markers in a subset of patients. We documented bone mineral density (BMD) by dual-energy x-ray absorptiometry (DXA) and repeated BMD after an average follow-up of 1.9 and 2.7 years in the alendronate-treated and conservative treatment groups, respectively. At baseline, conservatively-treated and alendronate-treated patients had similar BMD at the lumbar spine and hip. Over the period of observation, the conservatively-treated patients exhibited insignificant changes in BMD at all measured sites. In contrast, alendronate treatment resulted in a significant increase in BMD of the spine (+4.6%, P =.002), trochanter (+6.4%, P =.002), and total hip (+4.7%, P =.002). Indeed, compared with conservative treatment, alendronate-treated patients sustained a significant annualized percent increment of the BMD in the spine (2.7 +/- 0.6 v 1.1 +/- 0.3, P =.025), trochanter (4.7 +/- 1.7 v 0.7 +/- 0.6, P =.025), and total hip BMD (3.3 +/- 0.9 v 0.1 +/- 0.4, P =.0009). These data are among the first that illustrate the potential efficacy of alendronate in the management of idiopathic osteoporosis in men.     

Increased urinary N-telopeptide cross-linked type 1 collagen predicts bone loss in patients with inflammatory bowel disease

OBJECTIVE: Reduced bone mineral density (BMD) is common in patients with inflammatory bowel disease (IBD), but the factors associated with its longitudinal rate of change have not been established. We prospectively assessed the rate of change in BMD, and its association with biochemical markers of bone turnover. METHODS: Twenty-two patients with Crohn's disease and 14 ulcerative colitis patients age 37.1 +/- 11.6 yr were followed for 2 yr. Lumbar spine (L2-L4) and femoral neck BMD were measured by dual x-ray absorptiometry at baseline and 24 months. Bone-specific alkaline phosphatase, osteocalcin, urinary N-telopeptide crosslinked type 1 collagen (NTx), parathyroid hormone, and 25-hydroxyvitamin-D were determined at baseline. RESULTS: At baseline, 59% of Crohn's patients and 43% of ulcerative colitis patients were osteoporotic, with spine or femoral neck BMD T-score < -2.5. Spine BMD, and spine and femoral neck T-scores were lower and disease duration was longer in nine patients with ileal resection compared with nonoperated patients (0.84 +/- 0.15 g/cm2 vs 0.96 +/- 0.11 g/cm2, -3.0 +/- 1.5 vs -1.7 +/- 1.3, -3.2 +/- 1.5 vs -2.2 +/- 1.0, respectively; all p < 0.05). At 24 months, 13/36 (36%) and 14/36 (39%) patients experienced spinal and femoral neck bone loss, respectively, with mean annual percent BMD changes of -2.0% and -1.5%, respectively. NTx, a bone resorption marker, inversely correlated with spinal BMD rate of change (r = -0.4, p < 0.05). Using quartiles analysis, patients with the highest NTx (Q4) experienced the greatest decrease in spine BMD compared with patients with the lowest NTx (Q1). CONCLUSIONS: Spine and femoral neck bone loss continues over time in more than one-third of IBD patients. Increased NTx level predicts spinal bone loss in IBD patients.     

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.     

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.     

Alendronate in primary hyperparathyroidism: a double-blind, randomized, placebo-controlled trial

Primary hyperparathyroidism (PHPT) is often associated with reduced bone mineral density (BMD). A randomized, double-blind, placebo-controlled trial was conducted to determine whether alendronate (ALN), 10 mg daily, maintains or improves BMD in patients with PHPT. Eligible patients had asymptomatic PHPT and did not meet surgical guidelines or refused surgery. Forty-four patients randomized to placebo or active treatment arms were stratified for gender. At 12 months, patients taking placebo crossed over to active treatment. All patients were on active treatment in yr 2. The primary outcome index, BMD, at the lumbar spine (LS), femoral neck, total hip, and distal one third radius was measured every 6 months by dual-energy x-ray absorptiometry. Calcium, phosphorous, PTH, bone-specific alkaline phosphatase (BSAP) activity, urinary calcium, and urinary N-telopeptide (NTX) excretion were monitored every 3 months. Treatment with alendronate over 2 yr was associated with a significant (6.85%; micro(d) = 0.052; +/-0.94% se; P < 0.001) increase in LS BMD in comparison with baseline. Total hip BMD increased significantly at 12 months with alendronate by 4.01% (micro(d) = 0.027; +/-0.77% se; P < 0.001) from baseline and remained stable over the next 12 months of therapy. BMD at the one third radius site did not show any statistically significant change in the alendronate-treated group at 12 or 24 months of therapy. At 24 months, the alendronate-treated group showed a 3.67% (micro(d) = 0.022; +/-1.63% se; P = 0.038) gain in bone density at the femoral neck site in comparison with baseline. The placebo group, when crossed over to alendronate at 12 months, showed a significant change of 4.1% (micro(d) = 0.034; +/-1.12% se; P = 0.003) in the LS BMD and 1.7% (micro(d) = 0.012; +/-0.81% se; P = 0.009) at the total hip site in comparison with baseline. There was no statistically significant change seen in the placebo group at 12 months at any BMD site and no significant change at 24 months for the distal one third radius or femoral neck sites. Alendronate was associated with marked reductions in bone turnover markers with rapid decreases in urinary NTX excretion by 66% (micro(d) = -60.27; +/-13.5% se; P < 0.001) at 3 months and decreases in BSAP by 49% at 6 months (micro(d) = -15.98; +/-6.32% se; P < 0.001) and by 53% at 9 and 12 months (micro(d) = -17.11; +/-7.85% se; P < 0.001; micro(d) = -17.36; +/-6.96% se; P < 0.001, respectively) of therapy. In the placebo group, NTX and BSAP levels remained elevated. Serum calcium (total and ionized), PTH, and urine calcium did not change with alendronate therapy. In PHPT, alendronate significantly increases BMD at the LS at 12 and 24 months from baseline values. Significant reductions in bone turnover occur with stable serum calcium and PTH levels. Alendronate may be a useful alternative to parathyroidectomy in asymptomatic PHPT among those with low BMD.     

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.     

Low bone mass in premenopausal women with depression

BACKGROUND: An increased prevalence of low bone mineral density (BMD) has been reported in patients with major depressive disorder (MDD), mostly women. METHODS: Study recruitment was conducted from July 1, 2001, to February 29, 2003. We report baseline BMD measurements in 89 premenopausal women with MDD and 44 healthy control women enrolled in a prospective study of bone turnover. The BMD was measured by dual-energy x-ray absorptiometry at the spine, hip, and forearm. Mean hourly levels of plasma 24-hour cytokines, 24-hour urinary free cortisol, and catecholamine excretion were measured in a subset of women. We defined MDD according to the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition). RESULTS: The prevalence of low BMD, defined as a T score of less than -1, was greater in women with MDD vs controls at the femoral neck (17% vs 2%; P = .02) and total hip (15% vs 2%; P = .03) and tended to be greater at the lumbar spine (20% vs 9%; P = .14). The mean +/- SD BMD, expressed as grams per square centimeters, was lower in women with MDD at the femoral neck (0.849 +/- 0.121 vs 0.866 +/- 0.094; P = .05) and at the lumbar spine (1.024 +/- 0.117 vs 1.043 +/- 0.092; P = .05) and tended to be lower at the radius (0.696 +/- 0.049 vs 0.710 +/- 0.055; P = .07). Women with MDD had increased mean levels of 24-hour proinflammatory cytokines and decreased levels of anti-inflammatory cytokines. CONCLUSIONS: Low BMD is more prevalent in premenopausal women with MDD. The BMD deficits are of clinical significance and comparable in magnitude to those resulting from established risk factors for osteoporosis, such as smoking and reduced calcium intake. The possible contribution of immune or inflammatory imbalance to low BMD in premenopausal women with MDD remains to be clarified.     

Effects of prasterone on bone mineral density in women with systemic lupus erythematosus receiving chronic glucocorticoid therapy

OBJECTIVE: To assess the effects of treatment with prasterone (dehydroepiandrosterone) on bone mineral density (BMD) in female patients with mild to moderate systemic lupus erythematosus (SLE) receiving chronic treatment with glucocorticoids. METHODS: Fifty-five female patients with SLE who had received prednisone (or glucocorticoid equivalent) /= 6 months were treated for 1 year with either prasterone 200 mg/day (n = 24) or placebo (n = 31) in this randomized, double blind trial. Prasterone or placebo was added to each patient's one or more concomitant standard SLE medications, including glucocorticoids, nonsteroidal antiinflammatory drugs, antimalarials, methotrexate, azathioprine, and other immunosuppressives, which were to be maintained at fixed doses for the duration of the study. RESULTS: BMD was significantly improved in patients who received prasterone compared to placebo. At the lumbar spine, there was a mean (SEM) gain in BMD of 1.7 +/- 0.8% in the prasterone group compared to a mean loss in BMD of -1.1 +/- 0.5% in the placebo group (p = 0.003 between groups). For the total hip, mean gain was 2.0 +/- 0.9% in the prasterone group vs a mean loss of -0.3 +/- 0.4% in the placebo group (p = 0.013 between groups). In the prasterone treatment group, the mean gains from baseline at both lumbar spine and hip were statistically significant. CONCLUSION: Prasterone treatment prevented BMD loss and significantly increased BMD at both the lumbar spine and total hip in female patients with SLE receiving exogenous glucocorticoids.     

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.     

Three-monthly ibandronate bolus injection offers favourable tolerability and sustained efficacy advantage over two years in established corticosteroid-induced osteoporosis

OBJECTIVE: Corticosteroids are widely prescribed, although treatment-related side-effects are common. Of these adverse events (AEs), osteoporosis is considered the most serious. Currently, oral bisphosphonates are the standard treatment for corticosteroid-induced osteoporosis (CIO). However, intermittent intravenous (i.v.) therapy may have advantages, including lack of gastrointestinal AEs, improved bioavailability and increased compliance. This study investigated the efficacy and safety of 3-monthly i.v. ibandronate bolus injections in patients with established CIO. The results from a planned 2-yr interim analysis are reported. METHOD: In this controlled, prospective, open-label, parallel-group study, 104 patients (49 men and 55 women) with established CIO (mean T-score <-2.5 s.d. at the lumbar spine (L2-L4) received daily calcium (500 mg) plus either 3-monthly i.v. ibandronate (2 mg) bolus injections or oral daily alfacalcidol (1 micro g). The primary end-point was bone mineral density (BMD) change at the lumbar spine, femoral neck and calcaneus after 24 months. RESULTS: Compared with oral daily alfacalcidol, i.v. ibandronate produced significantly superior gains in mean (+/-s.d.) BMD at the lumbar spine (2.2+/-3.1 vs 11.9+/-7.4%; P<0.001), femoral neck (1.3+/-1.8 vs 4.7+/-4.0%; P<0.001) and calcaneus (7.6+/-3.8 vs 15.5+/-10.7%; P<0.0001) after 2 yr. Consistent with these BMD gains and, although the study was not powered for fractures, a trend towards a reduction in vertebral fractures and greater back pain relief was seen in the ibandronate group. The overall incidence of AEs was similar in the two treatment arms. CONCLUSIONS: Three-monthly i.v. ibandronate bolus injections are significantly superior to alfacalcidol in the treatment of CIO. These data confirm the potential of ibandronate for the treatment of osteoporosis associated with corticosteroid use. The ease of administration, lack of AEs and good compliance associated with intermittent i.v. ibandronate make it a potentially valuable alternative to oral bisphosphonate therapy for the treatment of CIO.     

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.     

Increases in bone mineral density after discontinuation of daily human parathyroid hormone and gonadotropin-releasing hormone analog administration in women with endometriosis

Intermittent PTH administration increases spinal bone mineral density (BMD) and prevents bone loss from the hip and total body in young women treated with a long acting GnRH analog for endometriosis. To establish whether these beneficial effects on BMD persist after PTH administration is discontinued, we remeasured BMD and biochemical markers of bone turnover in 38 women with endometriosis who had been treated with a GnRH analog alone (nafarelin acetate; 200 microg, intranasally, twice daily; n = 23; group 1) or who had received nafarelin plus human PTH-(1-34) (40 microg/day, s.c.; n = 15; group 2) for 6-12 months 1 yr after therapy was completed. Cyclic menstrual function returned promptly after nafarelin therapy was discontinued. In group 1, BMD increased significantly at all sites [P < 0.001 for the anterior-posterior (AP) and lateral spine; P = 0.014 for the femoral neck; P = 0.004 for the trochanter], except the proximal radius (P = 0.065) and total body bone density (P = 0.069) after nafarelin therapy was stopped. In group 2, BMD increased significantly at the AP spine (P < 0.001), lateral spine (P = 0.012), femoral neck (P = 0.002), and trochanter (P = 0.029) after nafarelin therapy was stopped. BMD of the spine in the AP projection increased more in group 2 and than in group 1 after therapy was stopped (P = 0.045). Despite these increases after discontinuation of nafarelin therapy, BMD was still significantly below baseline values at the AP spine (P < 0.001) and femoral neck (P = 0.006) and tended to be lower than baseline values at the trochanter (P = 0.057) and total body (P = 0.101) at the end of the 1-yr follow-up period in group 1. In contrast, BMD was significantly above baseline values at the AP and lateral spine (P < 0.001) sites and was similar to baseline values at the other skeletal sites at the end of the 1-yr follow-up period in group 2. Bone turnover returned to baseline values in both groups when therapy was stopped. We conclude that the beneficial effects of PTH on bone persist in women who regain cyclic menstrual function. Although part of the increases in BMD are probably due to restoration of ovarian function, additional increases in BMD most likely represent a further anabolic effect of PTH on bone that is not detected until after PTH administration is stopped.     

Osteoporosis in a north american adult population with celiac disease

OBJECTIVE: Osteoporosis, common in European and South American adults with celiac disease, has not been reported in those patients with celiac disease residing in North America. We therefore evaluated bone density in a group of patients from the United States. METHODS: Patients (105 women and 23 men) with celiac disease, who had completed a questionnaire and had bone mineral density (BMD) measured by dual energy x-ray absorptiometry, were evaluated. The patients were an average age of 56 yr old (range 21-83 yr) and had been on a gluten-free diet from 0 months to 46 yr (mean 7.5 yr). RESULTS: Osteoporosis (T score < -2.5) was present in 34% of the patients at the lumbar spine, 27% at the femoral neck, and 36% at the radius. Low bone mass (T score between -1.0 and -2.5) was present in 38% at the lumbar spine, 44% at the femoral neck, and 32% at the radius. When compared to age-matched controls, men were more severely affected than women. BMD did not differ between those on a gluten-free diet and those who had not begun therapy. BMD was remeasured 16 +/- 2 months after beginning a gluten-free diet in 5 patients; it increased by 7.5% at the femoral neck (p < 0.02). In 16 patients who had followed a gluten-free diet for an average of 12 yr, BMD remained stable over an additional 2 yr of observation. CONCLUSIONS: Osteoporosis and low bone mass often affect North American adults with celiac disease, whether or not they are on dietary therapy. Routine screening for osteoporosis is indicated in patients with celiac disease.     

Bone mass in young adults: relationship with gender, weight and genetic factors

OBJECTIVES: To determine the relationship of the bone mass attained in young adults with anthropometric and genetic factors. DESIGN: Cross-sectional study of normal individuals. METHODS: We studied 341 healthy subjects between 22 and 45 years of age. Bone mineral density (BMD) was measured by dual-energy X-ray absorptiometry (DXA) and correlated with body weight, height and nine polymorphisms in six genes involved in sex steroid metabolism (17-hydroxylase, aromatase and 5-reductase) and activity (oestrogen receptors (ER)-alpha and -beta, and androgen receptor). RESULTS: The BMD was higher in men than in women (spine: 1.048 +/- 0.120 vs. 1.034 +/- 0.112; hip: 0.907 +/- 0.131 vs. 0.822 +/- 0.104 g cm(-2), P < 0.001). However, the difference was due, at least in part, to the larger body size in men and diminished markedly after height adjustment. There was a negative correlation between age and hip BMD. Body weight was the single most influential factor on spine and hip BMD in both sexes, explaining 8-9% of BMD variance. Amongst the genetic factors studied, a common CA repeat polymorphism in ER-beta showed a significant association with BMD in women (P = 0.03 at the spine, and 0.008 at the hip). The relationship between ER-beta genotype and BMD persisted after adjustment by body weight and age, explaining a further 2-3% of BMD variance. Allelic variants of other genes studied were not related with BMD. CONCLUSIONS: Body weight and allelic variants of ER-beta are associated with BMD in young adults.     

停用他汀类药物对血管内皮一氧化氮合成的影响

目的　观察停用他汀类药物对人脐静脉内皮细胞 (HUVECs)NO合成的影响。方法　HUVECs分别用辛伐他汀和洛伐他汀 (10 -6mmol/L)孵育 2 4h ,然后停药 6、12、18、2 4h ,用Griess试剂的方法测定NO的合成 ,并用RT PCR方法测定对内皮型一氧化氮合酶 (eNOS)mRNA表达的影响。结果　辛伐他汀和洛伐他汀作用 2 4h后均可使NO的合成分别增加 (173± 33) %和 (170±4 4 ) % ,而停药 2 4h后NO的产量分别下降约 (6 4± 9) %和 (49± 10 ) %。同样 ,上述药物也可使eNOSmRNA的表达增加 ,并在停药后的短期内下调其表达。结论　停用他汀类药物可显著减少NO的合成和eNOS的表达 ,可能是临床试验中停用他汀类药物后心血管事件增加的原因之一。