Biomedical subjects

I Fogelman

Publications and source records attributed to I Fogelman.

At least 19 recordsLinked to original sources

PubMed2006

Late low-dose steroid withdrawal in renal transplant recipients increases bone formation and bone mineral density.

Corticosteroids have been the most widely used immunosuppressive agents since the first clinical transplantation in the 1950s. There are few studies of late steroid withdrawal in renal transplantation and none have prospectively assessed bone mineral density (BMD). The study aim was to assess the impact of corticosteroid withdrawal, in stable renal transplant recipients, on BMD and bone turnover. BMD, osteocalcin (OC) and cross-linked telopeptide of type I collagen (CTx) were measured in 92 patients randomized into a trial of steroid withdrawal. Patients with functioning renal transplants for more than 1 year with a serum creatinine below 200 micromol/L entered the trial. All patients were on triple immunosuppression (Cyclosporin microemulsion, Azathioprine and prednisolone), corticosteroids were withdrawn at 1 mg/month. BMD was measured twice annually with serum CTx and OC. One year following withdrawal of glucocorticoids there was no significant difference in creatinine. BMD increased in the withdrawal group (2.54% per year L1-L4, p < 0.01), there was a slight reduction in the control group. Mean OC increased from 5.3 to 12.2 ng/mL (p < 0.05) in the withdrawal group, but was unchanged in the controls. No change was seen in CTx. Corticosteroid withdrawal in renal transplant recipients results in an increase in BMD with a corresponding increase in serum OC.

Absorptiometry, Photon↗

PubMed2005

Predicting the risk of fracture at any site in the skeleton: are all bone mineral density measurement sites equally effective?

The ability to assess a patient's risk of fracture is fundamental to the clinical role of bone densitometry. Fracture discrimination is quantified by the relative risk (RR), defined as the increased risk of fracture for a 1 standard deviation decrease in bone mineral density (BMD). The larger the value of RR, the more effective measurements are at identifying patients at risk of fracture. Epidemiological studies show that RR values for predicting the risk of any fracture are approximately the same for all BMD measurement sites. In this study, we show theoretically that this interesting observation is predictable and a consequence of two related observations: (1) that fracture prediction by BMD measurement sites distant from the fracture site is quantitatively explained by the correlation of BMD measurements and (2) that all correlation coefficients between distant BMD sites are comparable, with values in the range r = 0.55-0.65. The first of these conditions (referred to as the correlation hypothesis) is important because it sets a lower limit on the RR values at distant BMD sites on the assumption that measurements at these sites contain no independent information about fracture risk over and above that provided by their correlation with the fracture site BMD. If the correlation hypothesis is true, the present study points to the importance of the correlation coefficient between BMD sites as a key index that is indicative of the ability of different types of measurement to predict fracture risk. If, on the contrary, the correlation hypothesis is not valid, there is scope to improve bone densitometry by further studies to better identify those measurements that do provide independent information about fracture risk and how best to integrate this information with existing techniques to improve decision making.

Absorptiometry, Photon↗

PubMed2005

Changes in RANKL/OPG/RANK gene expression in peripheral mononuclear cells following treatment with estrogen or raloxifene.

The RANKL/OPG/RANK pathway is the key mediator of osteoclastogenesis. Mononuclear cells may be implicated in post-menopausal osteoporosis. The effect of estrogen or raloxifene on bone resorption and the expression of RANKL/OPG/RANK in peripheral blood mononuclear cells (PBMCs) was examined. Twenty-nine women with post-menopausal osteoporosis were treated with estrogen (HRT) or raloxifene for 12 months. Bone mineral density (BMD) was measured at baseline and at 12 months at the spine and hip. Serum C-terminal telopeptide (CTX) and OPG were measured at baseline and at 1, 3, 6 and 12 months. PBMCs were isolated from 17 women and changes in RANKL, OPG and RANK mRNA were determined. The effects of estrogen or raloxifene in PBMCs in vitro were also assessed. BMD increased following treatment (lumbar spine % change mean [S.E.M.]: 4.3% [0.9], p<0.001). Serum CTX decreased (6 months: -43.7% [6.0], p<0.0001). Serum OPG declined gradually (12 months: -26.4% [4.4], p<0.001). RANKL, OPG and RANK gene expression decreased (6 months: RANKL 50.0% [24.8] p<0.001, OPG: 21.7% [28] p<0.001, RANK: 76.6% [10.2] p=0.015). Changes in OPG mRNA correlated with changes in BMD (r=-0.53, p=0.027) and CTX (r=0.7, p=0.0044). Down-regulation in RANKL, OPG, RANK mRNA and reduction in bone resorption was also seen in vitro. These results suggest that the expression of RANKL/OPG/RANK in PBMCs are responsive to the slowing in bone turnover/remodeling associated with treatment with estrogen or raloxifene. Further confirmatory studies are needed.

Aged↗

PubMed2005

Dual X-ray absorptiometry: clinical evaluation of a new cone-beam system.

The DMS Lexxos is the first cone-beam dual X-ray absorptiometry (DXA) system capable of performing bone mineral density (BMD) measurements of the spine and hip. By using a two-dimensional (2-D) detector array rather than the linear array used with conventional fan-beam DXA systems, image acquisition time on Lexxos is only 1.5 s. However, the need to correct for the large signal from scattered radiation reaching the detector is a potential source of error in cone-beam DXA. The aim of this clinical evaluation of the Lexxos bone densitometer was to investigate the relative accuracy of cone-beam BMD measurements compared with conventional DXA by performing an in vivo cross-calibration study with an established fan-beam system, the Hologic QDR-4500. Spine (L1-L4) and hip BMD measurements were performed in 135 patients (111 women, 24 men) referred for a bone densitometry examination. Duplicate Lexxos measurements were performed in 27 female patients to evaluate precision. On average, Lexxos spine and femoral neck BMD measurements were 2% lower than those on the QDR-4500, whereas total hip BMD was 5% higher. Larger differences were found for the trochanter and Ward's triangle regions. For all sites, Lexxos BMD measurements showed a strong linear relationship with those measured on the QDR-4500 with correlation coefficients in the range r = 0.95 to 0.97 for the clinically important spine, femoral neck, and total hip regions. The root mean standard error (RMSE) between Lexxos and QDR-4500 BMDs ranged from 0.037 g/cm(2) for the femoral neck to 0.060 g/cm(2) for the spine, whereas Lexxos precision was 1.3% for total hip, 2.0% for femoral neck, and 2.3% for spine BMD. Although for the hip BMD sites the RMSE and precision of Lexxos measurements were similar to studies of pencil-beam and fan-beam DXA systems, the results for the spine were poorer than expected. The findings of this study suggest that Lexxos corrects accurately for the effects of scattered radiation at the detector, but that the precision of spine BMD measurements may be limited by involuntary patient movement between the high and low energy X-ray exposures.

Absorptiometry, Photon↗

PubMed2004

Comparison of myocardial gated single photon emission computerised tomography, planar radionuclide ventriculography and echocardiography in evaluating left ventricular ejection fraction, wall thickening and wall motion.

Left ventricular ejection fraction (LVEF) and wall thickening are fundamental aspects of cardiac function. Recently, gated single photon emission computerised tomography (GSPECT) and anatomical M-mode echocardiography are new techniques, which have been introduced for the evaluation of left ventricular wall thickening and ejection fraction. These, however, have not been evaluated against established techniques, including equilibrium radionuclide ventriculography (ERNV), which remains the current gold standard for the evaluation of LVEF. We examined the concordance between LVEF, wall motion and wall thickening scores derived from GSPECT, echocardiography and ERNV, in a group of 16 patients with suspected ischaemic heart disease. Estimated ejection fraction correlated better between ERNV and gated SPECT (R2 = 0.93) than between echocardiography and either gated SPECT (R2 = 0.62) or ERNV (R2 = 0.71). There was poor correlation between gated SPECT and anatomical M-mode echocardiography in the assessment of wall thickening (83/150, 56%; kappa= 0.31, p < 0.05) and similar correlation (100/150, 66%; kappa = 0.29, p < 0.01) for wall motion analysis. In conclusion, estimations of ejection fraction by all the three studied modalities agreed to a degree sufficient for routine clinical practice. However, estimates of wall thickening from echocardiography cannot be used interchangeably with those derived from gated myocardial perfusion SPECT.

Adult↗

PubMed2003

Can the WHO definition of osteoporosis be applied to multi-site axial transmission quantitative ultrasound?

Osteoporosis is a highly prevalent but preventable disease and, as such, it is important that there are appropriate diagnostic criteria to identify those at risk of low trauma fracture. In 1994 the World Health Organization (WHO) introduced definitions of osteoporosis and osteopenia using T-scores, which identified 30% of all Caucasian post-menopausal women as having osteoporosis. However, the use of the WHO T-score thresholds of -2.5 for osteoporosis and -1.0 for osteopenia may be inappropriate at skeletal sites other than the spine, hip and forearm or when other modalities, such as quantitative ultrasound (QUS) are used. The aim of this study was to evaluate the age-dependence of T-scores for speed of sound (SOS) measurements at the radius, tibia, phalanx and metatarsal by use of the Sunlight Omnisense, to evaluate the prevalence of osteoporosis and osteopenia at these sites by use of the WHO criteria, and calculate appropriate equivalent T-score thresholds. The study population consisted of 278 healthy pre-menopausal women, 194 healthy post-menopausal women and 115 women with atraumatic vertebral fractures. All women had SOS measurements at the radius, tibia, phalanx and metatarsal and bone mineral density (BMD) measurements at the lumbar spine and hip. A group of healthy pre-menopausal women aged 20-40 years from the pre-menopausal group were used to estimate the population mean and SD for each of the SOS and BMD measurement sites. Healthy post-menopausal women were classified into normal, osteopenic or osteoporotic, based upon the standard WHO definition of osteoporosis and expressed as a percentage. We investigated the age-related decline in T-scores from 20-79 by stratifying the healthy subjects into 10-year age groups and calculating the mean T-score for each of these groups. Finally, we estimated appropriate T-score thresholds, using five different approaches. The prevalence of osteoporosis in the post-menopausal women aged 50 years and over ranged from 1.4 to 12.7% for SOS and 1.3 to 5.2% for BMD. The age-related decline in T-scores ranged from -0.92 to -1.80 for SOS measurements in the 60 to 69-year age group and -0.60 to -1.19 for BMD measurements in the same age group. The WHO definition was not suitable for use with SOS measurements, and revised T-score thresholds for the diagnosis of osteoporosis of -2.6, -3.0, -3.0 and -2.2 and for osteopenia of -1.4, -1.6, -2.3, and -1.4, for the radius, tibia, phalanx and metatarsal, respectively, were recommended.

Adult↗

PubMed2003

Periprosthetic bone remodelling of two types of uncemented femoral implant with proximal hydroxyapatite coating: a 3-year follow-up study addressing the influence of prosthesis design and preoperative bone density on periprosthetic bone loss.

Periprosthetic bone loss is a major cause of concern in patients undergoing total hip arthroplasty (THA). Further studies are required to identify the factors determining the pattern of bone remodelling following THA and obtain improvements in the design and durability of prostheses. In this study, we monitored periprosthetic bone loss around two different types of hydroxyapatite coated femoral implant over a 3-year period to evaluate their design and investigate the relationship with the preoperative bone mineral density (BMD) at the spine, hip and forearm. Sixty patients (35 F, 25 M, mean age 63 years, range 46-75 years) undergoing THA were randomised to either the Anatomic Benoist Girard (ABG) or Mallory-Head (MH) femoral stem. Preoperative dual-energy X-ray absorptiometry (DXA) scans were acquired of the posteroanterior (PA) and lateral lumbar spine, the contralateral hip and the non-dominant forearm. Postoperative DXA scans were performed to measure periprosthetic BMD at 10 days (treated as baseline), 6 weeks, and 3, 6, 12, 24 and 36 months after THA using a standard Gruen zone analysis. Results were expressed as the percentage change from baseline and the data examined for the differences in bone loss between the different Gruen zones, between the ABG and MH stems, and the relationship with preoperative BMD. A total of 50 patients (24 ABG, 26 MH) completed the study. Three months after THA there was a statistically significant BMD decrease in every Gruen zone that varied between 5.6% and 13.8% for the ABG prosthesis and between 3.8% and 8.7% for the MH prosthesis. Subsequently, in most zones BMD reached a plateau or showed a small recovery. However, BMD continued to fall in Gruen zones 1 and 7 in ABG patients and Gruen zone 1 in MH patients. Bone loss was less in every Gruen zone in MH patients compared with ABG with the largest difference (10%, P=0.018) in Gruen zone 7. Highly significant relationships were found between periprosthetic bone loss and preoperative BMD measured at the PA spine ( P<0.001), total hip ( P=0.004) and total distal radius ( P<0.001). This study showed differences between two different designs of hydroxyapatite-coated implant that confirmed that prosthesis design influences periprosthetic bone loss. The study also showed that patients' bone density measured at the spine, hip or forearm at the time of operation was a major factor influencing bone loss around the femoral stem.

Absorptiometry, Photon↗

PubMed2003

Bone mineral density in premenopausal women treated for node-positive early breast cancer with 2 years of goserelin or 6 months of cyclophosphamide, methotrexate and 5-fluorouracil (CMF).

The purpose of this study was to compare changes in bone mineral density (BMD) in premenopausal patients with node-positive early breast cancer treated with goserelin (Zoladex) or cyclophosphamide, methotrexate and 5-fluorouracil (CMF). Patients ( n=1640) were randomized to goserelin (3.6 mg every 28 days for 2 years) or CMF (sixx28-day cycles) treatment. In a protocoled sub-study involving 96 patients from eight centers (goserelin: n=53; CMF: n=43), lumbar spine (L2-L4) and femoral neck BMD were assessed by dual X-ray absorptiometry at baseline and then annually for 3 years. At the end of the 2-year goserelin-treatment period, mean BMD losses for goserelin-treated and CMF-treated patients were -10.5% and -6.5% ( P=0.0005) for lumbar spine and -6.4% and -4.5% ( P=0.04) for femoral neck, respectively. At 3 years, partial recovery of BMD was observed in goserelin recipients. In contrast, mean BMD losses for the CMF group indicated persistent BMD loss. No significant differences in BMD were observed between groups at the 3-year assessment of the spine or femoral neck. In the CMF group, based on amenorrhea status at 48 weeks, BMD losses at the lumbar spine were greater for amenorrheic than non-amenorrheic patients. Ovarian suppression resulting in amenorrhea was closely related to BMD loss in both treatment groups. Overall, patients who received CMF did not show recovery of BMD throughout follow-up, whereas partial recovery was observed 1 year after cessation of goserelin therapy, associated with the return of ovarian function in the majority of patients.

Adult↗

PubMed2003

Differential effects of hormone replacement therapy on bone mineral density and axial transmission ultrasound measurements in cortical bone.

The menopause has a large effect on bone density, and hormone replacement therapy (HRT) has been shown to be an effective treatment for preventing postmenopausal bone loss. The aim of this study was to compare the effects of HRT use on speed of sound (SOS) measurements at the radius, tibia, phalanx, and metatarsal with bone mineral density (BMD) measurements of the lumbar spine and proximal femur. The study population consisted of 278 healthy premenopausal women, 194 healthy postmenopausal women, and 126 healthy postmenopausal women currently receiving HRT for one or more years. SOS measurements were taken at the radius, tibia, phalanx, and metatarsal using the Sunlight Omnisense, and BMD measurements at the lumbar spine and proximal femur using Hologic QDR-4500 densitometers. Z-scores were calculated using the postmenopausal control group. Z-score differences between the postmenopausal controls and HRT group, for the entire group and with the HRT group subdivided into three groups based on duration of HRT usage, were calculated. Significant postmenopausal bone loss was found for all SOS and BMD measurements. A positive effect of HRT usage was found for all SOS measurement sites and lumbar spine BMD, although only the radius and tibia SOS and lumbar spine BMD reached statistical significance. The Z-score differences between the two groups were 0.44, 0.37, 0.15, and 0.26 for the radius, tibia, phalanx, and metatarsal SOS respectively, and 0.28, 0.00, and -0.03 for the lumbar spine, femoral neck, and total hip BMD respectively. A clear effect of the duration of HRT use was seen for the radius measurements, the differences being less marked elsewhere. In conclusion, these results demonstrate a positive effect of HRT on SOS measurements at the radius and tibia and BMD measurements of the lumbar spine.

Absorptiometry, Photon↗

PubMed2003

Survival analyses from the ZEBRA study. goserelin (Zoladex) versus CMF in premenopausal women with node-positive breast cancer.

The Zoladex Early Breast Cancer Research Association (ZEBRA) trial compared the efficacy and tolerability of goserelin (Zoladex) with cyclophosphamide, methotrexate and 5-fluorouracil (CMF) chemotherapy in pre-/perimenopausal women with node-positive early breast cancer. The results of disease-free survival (DFS) analyses have already been published. Here we present an update including data on overall survival (OS) from the ZEBRA trial at a median follow-up of 7.3 years. In patients with oestrogen receptor (ER)-positive tumours, non-inferiority of goserelin versus CMF for OS was shown; goserelin was again shown to be equivalent to CMF for DFS. This updated analysis has demonstrated that the two treatments are also equivalent for distant disease-free survival (DDFS). In patients with ER-negative disease, goserelin was inferior to CMF for DFS, DDFS and OS. This follow-up analysis confirms the previously reported outcomes from the ZEBRA trial and demonstrates that goserelin offers an effective alternative to CMF chemotherapy for adjuvant therapy of premenopausal patients with ER-positive, node-positive early breast cancer.

Aged↗

PubMed2003

A direct in vivo measurement of 99mTc-methylene diphosphonate protein binding.

Quantitative studies of the kinetics of 99mTc-methylene diphosphonate (99mTc-MDP) in metabolic and metastatic bone disease require the measurement of free tracer in plasma to derive the input function. We describe a simple method of determination of free 99mTc-MDP in vivo based on measurements of the ratio of the renal plasma clearances of total 99mTc-MDP and 51Cr-ethylenediaminetetraacetic acid (51Cr-EDTA). The method is based on evidence that free MDP is cleared through the kidneys by glomerular filtration. Measurements of the fraction of free 99mTc-MDP were made between 0 and 4 h after injection in 70 postmenopausal women enrolled in a study of the effect of hormone replacement therapy on the whole-skeleton plasma clearance of 99mTc-MDP (K(bone)). The glomerular filtration rate (GFR) was measured simultaneously from the plasma clearance of 51Cr-EDTA. The mean fractions (and SD) of free MDP measured were 0.757 (0.050), 0.663 (0.062), 0.550 (0.052) and 0.472 (0.053), respectively, at 17, 90, 150 and 210 min after injection. The results agreed closely with data using protein precipitation with trichloroacetic acid. Between 2 and 4 h after injection, the biological half-life of free 99mTc-MDP in plasma was 92 min, compared with 540 min for bound MDP. Highly significant relationships were found between the fraction of free MDP measured in each patient at each of the four time points and the total plasma clearance of free 99mTc-MDP (K(total)=GFR+K(bone)), such that a larger value of K(total) was associated with a smaller fraction of free MDP. Multivariate regression analysis confirmed that this relationship held individually for both GFR and K(bone). A strong inverse relationship was found between K(total) and the plasma concentration of free 99mTc-MDP, but a much weaker relationship with the bound MDP concentration, a finding that is consistent with the slow re-equilibration of bound MDP in the circulation. The results confirm that the fraction of free 99mTc-MDP varies with time and shows significant differences between individuals, which are dependent on GFR and K(bone) amongst other factors.

Aged↗

PubMed2003

Interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin production by human osteoblastic cells: comparison of the effects of 17-beta oestradiol and raloxifene.

Oestrogen inhibits bone resorption, at least in part, by regulating the production of several cytokines, including interleukin-6 (IL-6), IL-1, receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) by cells of the osteoblastic lineage. The selective oestrogen receptor modulator raloxifene (RAL) acts on bone in a similar manner to oestrogen, although the mechanisms of action of RAL on osteoblasts still remain unclear. We investigated and compared the effects of 17-beta oestradiol (E(2)) and RAL on the regulation of IL-6, IL-1, RANKL and OPG in vitro in primary human osteoblastic (HOB) cells and in an immortalised clonal human bone marrow stromal cell line (HCC1) with osteoblastic characteristics. We tested E(2) and RAL at concentrations ranging from 10(-12) to 10(-6) M. IL-6, IL-1alpha and IL-1beta, OPG and RANKL were measured by ELISA. RANKL and OPG mRNA steady state level was assessed by quantitative PCR analysis. Both E(2) and RAL led to a significant reduction in IL-6 production in the HOB cells, although the effect was more marked with E(2) (P<0.05). IL-1alpha and IL-1beta also decreased significantly following treatment with E(2) and RAL in the HCC1 cells (E(2) (10(-8), 10(-7) and 10(-6) M), % reduction (means+/-S.E.M.) compared with vehicle-treated cells - IL-1alpha: 84+/-7.4, 70.8+/-2.9*, 78.2+/-4.8*; IL-1beta: 79+/-10, 72.8+/-8.2*, 66.6+/-2.8*; RAL (10(-8), 10(-7) and 10(-6) M) - IL-1alpha: 72.4+/-5*, 79+/- 5.2*, 102+/-7.7; IL-1beta: 67.9+/-3.2*, 69+/-2.5*, 73.8+/- 6.2*; *P<0.05). OPG protein concentration decreased significantly in a dose-dependent manner following treatment with E(2) and RAL (% reduction E(2) (10(-8), 10(-7) and 10(-6) M) - HOB: 72.5+/-8.4*, 80+/-6.7*, 62.8+/-8.9*; HCC1: 109+/-4, 98.8+/-6, 54.5+/-3.4*; RAL (10(-8), 10(-7) and 10(-6) M) - HOB: 81.5+/-5.5*, 62.7+/-7.4*, 55.2+/-10.9*; HCC1: 92.7+/-7.4, 67+/-12.2*, 39+/-4.5*; *P<0.05). In the HCC1 cells, RANKL protein did not change significantly following E(2). In contrast, a significant reduction in RANKL was seen with RAL at 10(-7) and 10(-6) M (66+/-6.4% and 74+/-3% respectively). There was no change in OPG mRNA expression following E(2) or RAL in the HCC1 cells, although in the HOB cells we observed a significant reduction in OPG mRNA. RANKL mRNA decreased significantly in the HCC1 cells following RAL (10(-8), 10(-7)and 10(-6) M) treatment (% change from controls: 52+/-2*, 62+/-1*, 53+/-5.8*; *P<0.05). Similar results were seen in the HOB cells with RAL at 10(-6) M (RANKL mRNA: 72+/-5.5, P<0.05). In addition, there was a significant decrease in the RANKL/OPG ratio after RAL at 10(-6) M (HOB: 65.6+/-5*, HCC1: 56.9+/-20*; *P<0.05). RANKL/OPG ratio did not change significantly in the HCC1 cells following E(2). However, in contrast to RAL, we observed an increase in the RANKL/OPG ratio in the HOB cells following treatment with E(2). In conclusion, the study shows that RAL and E(2) have divergent cell-specific effects on the regulation of cytokines. The data also suggest that, in contrast to E(2), RAL may exert its anti-resorptive actions, at least in part, via the RANKL/OPG pathway. Further in vivo studies are required to confirm this.

Carrier Proteins↗

PubMed2002

Goserelin versus cyclophosphamide, methotrexate, and fluorouracil as adjuvant therapy in premenopausal patients with node-positive breast cancer: The Zoladex Early Breast Cancer Research Association Study.

PURPOSE: Current adjuvant therapies have improved survival for premenopausal patients with breast cancer but may have short-term toxic effects and long-term effects associated with premature menopause. PATIENTS AND METHODS: The Zoladex Early Breast Cancer Research Association study assessed the efficacy and tolerability of goserelin (3.6 mg every 28 days for 2 years; n = 817) versus cyclophosphamide, methotrexate, and fluorouracil (CMF) chemotherapy (six 28-day cycles; n = 823) for adjuvant treatment in premenopausal patients with node-positive breast cancer. RESULTS: Analysis was performed when 684 events had been achieved, and the median follow-up was 6 years. A significant interaction between treatment and estrogen receptor (ER) status was found (P =.0016). In ER-positive patients (approximately 74%), goserelin was equivalent to CMF for disease-free survival (DFS) (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.84 to 1.20). In ER-negative patients, goserelin was inferior to CMF for DFS (HR, 1.76; 95% CI, 1.27 to 2.44). Amenorrhea occurred in more than 95% of goserelin patients by 6 months versus 58.6% of CMF patients. Menses returned in most goserelin patients after therapy stopped, whereas amenorrhea was generally permanent in CMF patients (22.6% v 76.9% amenorrheic at 3 years). Chemotherapy-related side effects such as nausea/vomiting, alopecia, and infection were higher with CMF than with goserelin during CMF treatment. Side effects related to estrogen suppression were initially higher with goserelin, but when goserelin treatment stopped, reduced to a level below that observed in the CMF group. CONCLUSION: Goserelin offers an effective, well-tolerated alternative to CMF in premenopausal patients with ER-positive and node-positive early breast cancer.

Amenorrhea↗

PubMed2002

A comparison of fracture discrimination using calcaneal quantitative ultrasound and dual X-ray absorptiometry in women with a history of fracture at sites other than the spine and hip.

The aim of this study was to determine whether calcaneal quantitative ultrasound can discriminate between women with and those without fragility fracture at (1) the wrist or (2) at sites other than the spine, hip, or forearm, as well as axial DXA measurements of BMD can. The study population consisted of 342 postmenopausal Caucasian women who were placed into one of three groups: (1) healthy women with no clinical risk factors for osteoporosis (n = 240); (2) women with a history of atraumatic fracture at the wrist (n = 50); (3) women with a history of atraumatic fracture at a skeletal site other than the spine, hip, or wrist (n = 52). Subjects had DXA measurements of the lumbar spine (LS), femoral neck (FN), and total hip (THIP), and calcaneal broadband ultrasound attenuation (BUA) and speed of sound (SOS) measurements on the Hologic Sahara (s) and Osteometer DTUone (d). Z-scores were calculated using the mean and SD obtained from the healthy postmenopausal group. All the BMD and QUS variables were significantly reduced in women reporting a fracture of the wrist or at a site other than the spine, hip, or forearm. When the group of women with a history of wrist fracture were compared with the postmenopausal controls, age-adjusted logistic regression yielded odds ratios associated with a 1 SD decrease, that were significant for both BMD and QUS, averaging 2.2. The AUC values ranged from 0.65 for FN BMD to 0.75 for BUAd. BMD and QUS measurements were also significantly reduced in women reporting a skeletal fracture at a site other than the spine, hip, or wrist, and odds ratios for BMD and QUS were significant, averaging 1.7. BMD and QUS showed similar fracture discriminatory abilities that were not significantly different from one another. In conclusion, calcaneal QUS can discriminate between women with and those without fracture at the wrist or at sites other than the spine, hip, or forearm as well as axial DXA measurements of BMD can.

Absorptiometry, Photon↗

PubMed2002

COLIA1 Sp1 polymorphism predicts response of femoral neck bone density to cyclical etidronate therapy.

Genetic factors are important in the pathogenesis of osteoporosis but less is known about their possible role in predicting response to anti-osteoporotic therapy. Previous studies have shown that a polymorphic Sp1 binding site in the collagen type 1 alpha 1 gene (COLIA1) is associated with bone mineral density (BMD) and osteoporotic vertebral fracture. In this study we sought to determine if the COLIA1 Sp1 polymorphism might also act as a predictor of the response to treatment of osteoporosis with bisphosphonate therapy. The study group comprised 108 perimenopausal women with osteopenia who had been randomized to receive cyclical etidronate therapy for 2 years with a 1-year treatment-free follow-up as part of a randomized placebo controlled trial. Bone mineral density was measured at the lumbar spine and femoral neck by dual X-ray absorptiometry and genotyping performed on DNA extracted from peripheral blood leukocytes using standard techniques. The distribution of COLIA1 genotypes was similar to that previously reported in Caucasians with 69 (63.9%) "SS" homozygotes, 38 (35.2%) "Ss" heterozygotes, and 1 (0.9%) "ss" homozygote. There was no association between COLIA1 genotype and response of lumbar spine BMD during etidronate treatment or the follow-up phase. The response of femoral neck (FN) BMD, however, differed significantly between the genotype groups throughout the study period, such that FN BMD increased by 0.56%, 2.36%, 1.82%, and 1.32 % after 1, 2, 2.5, and 3 years, respectively in the "SS" genotype group, compared with -1.56%, -0.62%, -0.37%, and -0.66% in the "Ss/ss" genotype groups (P = 0.002). The data presented here show that site-specific heterogeneity exists in the response of BMD to cyclical etidronate therapy, which is related to COLIA1 genotype. Our data raise the possibility that COLIA1 genotyping could be used to target etidronate therapy to those most likely to respond in terms of FN BMD, with potential benefits in terms of economic cost and clinical outcome.

Absorptiometry, Photon↗

PubMed2002

Multisite quantitative ultrasound: Colles' fracture discrimination in postmenopausal women.

Distal forearm fractures are the most common perimenopausal fracture and are generally associated with osteoporosis. The aim of this study was to evaluate the capability of speed of sound (SOS) measurements in cortical bone at the phalanx, radius, tibia and metatarsal to discriminate Colles' fracture cases from controls in postmenopausal women and to compare this with bone mineral density (BMD) measurements obtained by dual-energy X-ray absorptiometry (DXA). Sixty-three postmenopausal Colles' fracture cases and 191 postmenopausal controls had SOS measurements of the radius, tibia, phalanx and metatarsal using a semi-reflection ultrasound technique and BMD measurements of the lumbar spine and proximal femur using DXA. The age-adjusted odds ratios (ORs) for fracture for the SOS measurement sites were 1.50 [95% CI 1.07-2.10] for the radius, 1.23 [0.86-1.76] for the tibia, 1.85 [1.06-3.23] for the phalanx and 1.74 [1.12-2.71] for the metatarsal site. For the BMD measurements the ORs were 1.95 [1.34-2.85] for the lumbar spine, 2.21 [1.43-3.40] for the femoral neck and 2.62 [1.69-4.08] for the total hip. The benefits of combining sites either by taking their average Z-score or by using the manufacturer's ORI algorithm were evaluated. The two methods yielded similar results and the ORs for the combination of the radius and phalanx were 2.00 [1.21-3.33], for the radius and metatarsal 1.67 [1.05-2.67], for the phalanx and metatarsal 1.86 [1.11-3.08] and for the radius, phalanx and metatarsal 1.81 [1.07-3.06]. Combinations of DXA sites gave 2.22 [1.44-3.41] for the lumbar spine and femoral neck and 2.41 [1.57-3.70] for the lumbar spine and total hip. In conclusion, semi-reflection ultrasound measurements at the radius, phalanx or metatarsal demonstrated an ability to discriminate fracture cases from controls in postmenopausal Colles' fracture patients, although the odds ratios were lower than with spine and femur BMD.

Absorptiometry, Photon↗

PubMed2002

Risedronate reduces the risk of first vertebral fracture in osteoporotic women.

Risedronate treatment reduces the risk of vertebral fracture in women with existing vertebral fractures, but its efficacy in prevention of the first vertebral fracture in women with osteoporosis but without vertebral fractures has not been determined. We examined the risk of first vertebral fracture in postmenopausal women who were enrolled in four placebo-controlled clinical trials of risedronate and who had low lumbar spine bone mineral density (BMD) (mean T-score = -3.3) and no vertebral fractures at baseline. Subjects received risedronate 5 mg ( n = 328) or placebo ( n = 312) daily for up to 3 years; all subjects were given calcium (1000 mg daily), as well as vitamin D supplementation (up to 500 IU daily) if baseline serum 25-hydroxyvitamin D levels were low. The incidence of first vertebral fracture was 9.4% in the women treated with placebo and 2.6% in those treated with risedronate 5 mg (risk reduction of 75%, 95% confidence interval 37% to 90%; P = 0.002). The number of patients who would need to be treated to prevent one new vertebral fracture is 15. When subjects were stratified by age, similar significant reductions were observed in patients with a mean age of 64 years (risk reduction of 70%, 95% CI 8% to 90%; P = 0.030) and in those with a mean age of 76 years (risk reduction of 80%, 95% CI 7% to 96%; P = 0.024). Risedronate treatment therefore significantly reduces the risk of first vertebral fracture in postmenopausal women with osteoporosis, with a similar magnitude of effect early and late after the menopause.

Aged↗

PubMed2002

Low circulating estradiol and adrenal androgens concentrations in men on glucocorticoids: a potential contributory factor in steroid-induced osteoporosis.

Reductions in circulating estradiol concentrations could be implicated in the pathogenesis of steroid-induced osteoporosis (SIOP) in men. We assessed serum estradiol and adrenal androgens (dehydroepiandrosterone sulfate [DHEAS] and androstenedione) in 77 men (group A: idiopathic osteoporosis [IOP], n = 38, aged [mean +/- SD] 57.7 +/- 12.1 years; group B: SIOP, n = 39, aged 55.3 +/- 13.1 years). We also studied the relationship between bone mineral density (BMD) and serum estradiol in the group of men with SIOP. In group B, we observed a higher prevalence of low serum testosterone concentrations (<9.0 nmol/L) (P =.0052), which was significantly correlated with steroid dosage (r = -0.42, P =.0089) and estradiol concentrations (r = 0.42, P =.012). There was a significant positive association between BMD at the lumbar spine and serum estradiol (P =.004) in the men with SIOP (group B). A high proportion of subjects had low serum estradiol concentrations (<48 pmol/L) in both groups (group A: 44.7 %, group B: 36 %). Serum adrenal androgens concentrations were also significantly suppressed in group B (serum androstenedione-group A: 4.99 +/- 1.8; Group B: 2.1 +/- 1.6 nmol/L; P =.0001). Serum DHEAS was undetectable in 59% of patients in group B versus 6% in group A (P =.001). Reductions in androstenedione also correlated with steroid dosage (r = -0.35, P =.01). In conclusion, the data show that adrenal androgens synthesis is markedly suppressed in men with SIOP. The clinical relevance of this finding remains to be determined. This study also shows a positive association between serum estradiol and BMD and a high prevalence of low serum estradiol in men with SIOP. Low serum estradiol may contribute to bone loss in men with SIOP.

Adult↗