Outcome and prognosis of isolated carotid vasculitis.

OBJECTIVE: To assess the prognosis and outcome of patients with isolated carotid vasculitis. METHODS: We performed a retrospective multicenter study of 36 patients (median age at diagnosis was 37 [IQR 27-45] years and 11 [31 %] patients were men) with initial presentation as isolated carotid vasculitis. Study endpoints included vascular complications, relapses, and progression to large vessel vasculitis (i.e. Giant cell arteritis or Takayasu). RESULTS: The most frequent involvement was the left internal carotid artery (39 %), and 81 % had stenosis. After a median follow-up of 32 months [IQR 12-96], 21 (58 %) patients had a vascular event, including 31 % of new onset vascular lesions and 25 % of stroke/transient ischemic attack. Patients with stroke had less carotidynia at diagnosis (33 % vs 74 %, p = 0.046), higher significant carotid stenosis (i.e. > 50 %) (89 % vs. 30 %, p = 0.026) and higher severe carotid stenosis (i.e. >70 %) (67 % vs 19 %, p = 0.012), compared to those without stroke. Twenty (52 %) patients experienced relapses. High CRP at diagnosis was associated with relapses (p = 0.022). At the end of follow-up, 21 (58 %) patients were classified as having Takayasu arteritis, 13 (36 %) as isolated carotid vasculitis, and two (6 %) as giant cell arteritis. CONCLUSION: Carotid vasculitis may occur as a topographically limited lesion and is associated with significant rate of vascular complications.

Behçet's disease uveitis.

Uveitis in Behçet's disease (BD) is frequent (40% of cases) and is a major cause of morbidity. The age of onset of uveitis is between 20 and 30 years. Ocular involvement includes anterior, posterior or panuveitis. It is non-granulomatous. Uveitis may be the first sign of the disease in 20% of cases or it may appear 2 or 3 years after the first symptoms. Panuveitis is the most common presentation and is more commonly found in men. Bilateralisation usually occurs on average 2 years after the first symptoms. The estimated risk of blindness at 5 years is 10-15%. BD uveitis has several ophthalmological features that distinguish it from other uveitis. The main goals in the management of patients are the rapid resolution of intraocular inflammation, prevention of recurrent attacks, achievement of complete remission, and preservation of vision. Biologic therapies have changed the management of intraocular inflammation. The aim of this review is to provide an update previous article by our team on pathogenesis, diagnostic approaches, identification of factors associated with relapse and the therapeutic strategy of BD uveitis.

EULAR/EFORT recommendations for management of patients older than 50†years with a fragility fracture and prevention of subsequent fractures.

The European League Against Rheumatism (EULAR) and the European Federation of National Associations of Orthopaedics and Traumatology (EFORT) have recognised the importance of optimal acute care for the patients aged 50 years and over with a recent fragility fracture and the prevention of subsequent fractures in high-risk patients, which can be facilitated by close collaboration between orthopaedic surgeons and rheumatologists or other metabolic bone experts. Therefore, the aim was to establish for the first time collaborative recommendations for these patients. According to the EULAR standard operating procedures for the elaboration and implementation of evidence-based recommendations, 7 rheumatologists, a geriatrician and 10 orthopaedic surgeons met twice under the leadership of 2 convenors, a senior advisor, a clinical epidemiologist and 3 research fellows. After defining the content and procedures of the task force, 10 research questions were formulated, a comprehensive and systematic literature search was performed and the results were presented to the entire committee. 10 recommendations were formulated based on evidence from the literature and after discussion and consensus building in the group. The recommendations included appropriate medical and surgical perioperative care, which requires, especially in the elderly, a multidisciplinary approach including orthogeriatric care. A coordinator should setup a process for the systematic investigations for future fracture risk in all elderly patients with a recent fracture. High-risk patients should have appropriate non-pharmacological and pharmacological treatment to decrease the risk of subsequent fracture.

DXA-based variables and osteoporotic fractures in Lebanese postmenopausal women.

INTRODUCTION: The aim of this study was to assess DXA-based variables (bone mineral density, bone mineral apparent density, compressive strength index of the femoral neck and trabecular bone score) in Lebanese postmenopausal women having presented a previous fracture. MATERIALS AND METHODS: One thousand Lebanese postmenopausal women between 45 and 89 years participated in this study. The women were recruited by advertisements offering bone mineral density measurements at a reduced cost. Subjects with previous history of radiotherapy or chemotherapy were excluded. Informed written consent was obtained from all the participants. RESULTS: Femoral neck compressive strength index (FN CSI) was significantly (P<0.001) associated with the presence of fracture using a simple logistic regression (odds ratio=0.51 [0.385-0.653]). When a multivariate logistic regression analysis was performed with the presence of fracture as a dependent variable and each of age, FN BMD and FN CSI as independent variables, only FN BMD (P=0.005) and FN CSI (P=0.004) were found to be associated with the presence of fracture. CONCLUSION: This study suggests that FN CSI is associated with history of osteoporotic fractures in postmenopausal women. The use of FN CSI in clinical practice may help to identify patients with high risk of fracture. LEVEL OF EVIDENCE: Epidemiological study, level IV.

Epidemiology of hip fractures in Lebanon: a nationwide survey.

INTRODUCTION: Hip fractures are a reliable indicator of osteoporosis. Despite their importance, few studies have assessed their epidemiology in Lebanon and the Middle East. HYPOTHESES: Hip fracture incidence rates in Lebanon approximate those of Northern countries, and show the same characteristics, particularly the exponential increase with age, higher incidence in women, and a recent trend of rate leveling in women but not in men. MATERIALS AND METHODS: A national database of hip fracture cases admitted to hospitals in Lebanon in 2007 was created. Crude and age-adjusted incidence rates were calculated at 5-year intervals for individuals over age 50. These rates were also standardized to the 2000 United States population, and compared to those of other countries. Projected incidence rates in Lebanon in 2020 and 2050 were also calculated. RESULTS: A total of 1199 patients were included in the study. The crude annual incidence rate in individuals over 50 was 147 per 100,000 individuals, 132 per 100,000 males and 160 per 100,000 females, with a female-to-male ratio of 1.2. The age-standardized annual incidence rates (per 100,000) were 180 in males and 256 in females. Assuming unchanged healthcare parameters, the projected crude incidence rates for people over 50 are expected to reach 174 and 284 per 100,000 in 2020 and 2050 respectively. CONCLUSIONS: Lebanese hip fracture rates are lower than Northern countries, but show many similar characteristics such as an exponential increase with age, a higher incidence in women, and clues of a leveling of rates in women but not in men. Numbers are expected to increase substantially in the coming decades. LEVEL OF EVIDENCE: Level IV. Epidemiological study.

Developmental dysplasia of the hip: is acetabular retroversion a crucial factor?

OBJECTIVE: The objective of this study was to investigate a possible relation between congenital hip dysplasia and acetabular retroversion and to explore the eventual influence of the latter in the surgical decision for periacetabular osteotomy. MATERIALS AND METHODS: We assessed the classical morphological characteristics of both hips, with an additional newly described retroversion index. The study was conducted in 174 patients with uni- or bilateral congenital hip dysplasia having undergone unilateral (153 patients) or bilateral (21 patients) periacetabular osteotomy when respectively one or both dysplastic hips remained symptomatic. RESULTS: In the group of operated hips (195 hips in total), 53% of the acetabuli were anteverted, 42% retroverted, and 5% neutral orientations. The group of nonoperated hips (153 hips) included 24% normal hips, 22% hips with normal coverage but retroverted, 35% dysplastic hips with anteverted or neutral orientation, and 19% dysplastic retroverted hips. Comparing the two hips in the subgroup of patients in whom the operated and nonoperated sides were both dysplastic failed to demonstrate statistically significant difference in the mean retroversion index. However, all the other variables measured were significantly different; with the operated side more dysplastic. Comparing the two hips in the other subgroups showed that acetabular retroversion was nearly always bilateral and symmetrical, even in presence of unilateral congenital dysplasia. DISCUSSION: Our data suggest that the presence of acetabular retroversion is probably independent of the congenital hip dysplasia and that this abnormality seems at best a secondary factor in the appearance of dysplastic hip symptoms. LEVEL OF EVIDENCE: Level IV, retrospective diagnostic study.

Dysplasia epiphysealis hemimelica with involvement of the hip and spine in a young girl.

Dysplasia epiphysealis hemimelica of the left proximal femur was diagnosed in an eight-month-old girl. At the age of 18 months, radiographs of the hip and MRI showed overgrowth and loss of containment of the femoral head. She underwent resection of the superior portion of the head and neck of the femur at the age of 2.5 years. Six months later further radiographs and an MR scan show that the mass has increased in size and that hip containment has been lost. Further plain radiographs have shown that the left knee, ankle and spine were involved. To the authors' knowledge, this is the first report of dysplasia epiphysealis hemimelica involving both the lower limb and the spine. A review of the literature is presented.

[Neonatal osteomyelitis of the proximal femur: a case with ten-year follow-up and review of the literature]. / Ostéomyélite néonatale du col du fémur avec contamination articulaire.

Acute hematogenous osteomyelitis most frequently occurs in children, generally around 6 to 9 years of age. If it occurs in early infancy, the infection usually involves both the bone and the joint, nearly simultaneously. Neonatal osteomyelitis is another presentation, with an osteomyelitic focus in the metaphysis. We report a case of septic arthritis following osteomyelitis of the hip joint in a neonate caused by a virulent pathogenic organism. Despite late diagnosis and treatment, outcome was very satisfactory with few sequelae for the joint and epiphysis. It should be emphasized that early diagnosis, with prompt and adequate treatment is essential to achieve good outcome. We discuss this case and present a review of the literature.

Middle East and North Africa consensus on osteoporosis.

With the increasing life expectancy, osteoporosis is becoming a major worldwide health problem. The magnitude of the disease may become larger in developing countries, more particularly in the Middle East region where the prevalence of low bone mass is higher than in western countries. Although several local organizations and countries have developed guidelines for osteoporosis, no previous regional guidelines have been developed encompassing all Middle-Eastern and North African countries. The present document reviews all the regional published data on bone mineral density, risk factors, fracture prevalence and vitamin D status. It also gives simple recommendations applicable to all these countries. This document was endorsed by leading members of all the different regional countries including, Iran, Egypt, Tunisia, Jordan, Palestine, Syria, Iraq, Libya, Oman, Kuwait, Saudi Arabia and Bahrain.

The spinal curvature irregularity index independently identifies vertebral fractures.

INTRODUCTION AND HYPOTHESIS: The spinal curvature irregularity index (SCII) is a quantitative measure of the irregularity of the spinal curvature. We evaluated the predictive ability of SCII to identify subjects with vertebral fractures (VF). METHODS: Vertebral heights were measured by quantitative vertebral morphometry in 461 Lebanese women 20-89 years of age and VFs were ascertained by the grade 1 Eastell method. SCII scores were log-transformed and expressed as Z-SCII, the number of standard deviations above or below the mean ln(SCII) of young patients without VF. Univariate and multivariate binary logistic regression models were used to identify clinical predictors of VF. RESULTS: Women with a higher SCII were more likely to have prevalent VF. A higher SCII was associated with a greater prevalence of VF within each category of femoral neck BMD (normal, osteopenia, osteoporosis). In univariate analysis, predictors of VF included Z-SCII (odds ratio, OR: 2.21, 95% CI: 1.80-2.71) and femoral neck T-score (OR: 1.35, 95% CI: 1.12-1.63). In multivariate analysis, predictors of VF were: Z-SCII (OR: 1.54, 95% CI: 1.02-2.32), femoral neck T-score (OR: 1.41, 95% CI: 1.11-1.78) and age(3) (OR: 1.40, 95% CI 1.10-1.82). At a cutoff SCII of 9.5%, the sensitivity and specificity of SCII for VF were 71 and 64% respectively, and higher SCII cutoffs identified VFs with greater specificity. CONCLUSION: The SCII is a robust, simple and independent indicator of the presence of VFs.

The prevalence of vitamin D inadequacy amongst women with osteoporosis: an international epidemiological investigation.

INTRODUCTION: Vitamin D is essential for calcium metabolism as well as for fracture prevention, and a recent review suggested that the optimal serum 25(OH)D lies in the region of 50-80 nmol L-1 (20-32 ng mL-1). A high prevalence of inadequacy has been reported in many studies but the prevalence of inadequacy amongst women with osteoporosis in different regions of the world has not been well characterized. SETTING AND SUBJECTS: A multinational study of 18 countries at various latitudes (range 64N-38S) was conducted in 2004 and 2005 to determine the average levels of serum 25(OH)D and the prevalence of vitamin D inadequacy. A total of 2606 postmenopausal women with osteoporosis (low bone mineral density, history of fragility fracture) seeking routine medical care were enrolled and serum 25(OH)D levels were measured at a single laboratory visit. RESULTS: Mean serum 25(OH)D level was 26.8 ng mL-1 (SE 0.3) and ranged from 7 to 243 ng mL-1. Regional mean values were highest in Latin America (29.6 ng mL-1, SE 0.6) and lowest in the Middle East (20.4 ng mL-1, SE 0.5). Overall, 64% of women had serum levels<30 ng mL-1. Serum parathyroid hormone reached a nadir at serum 25(OH)D levels>35 ng mL-1. In nonequatorial countries, women recruited during the winter months had somewhat lower serum 25(OH)D levels than those recruited during the summer months in some, but not all, countries. CONCLUSIONS: Low levels of serum 25(OH)D are common amongst women with osteoporosis. The results underscore the value of assuring vitamin D adequacy in these women.

Effects of levothyroxine suppressive therapy on bone mineral density in premenopausal women.

BACKGROUND: Levothyroxine (L-T4) is widely prescribed for treating thyroid disorders, but its effect on bone mineral density (BMD), is being debated. OBJECTIVES: We studied the effect of supraphysiologic doses of L-T4 on BMD in a group of premenopausal women. PATIENTS AND METHODS: We included 50 women (mean age=36.8 +/- 7.6 years) receiving L-T4 for at least 1 year for treating their benign cold thyroid nodules. Serum T3, T4, thyroid-stimulating hormone (TSH), parathyroid hormone (PTH), calcium, and phosphate and urine calcium and sodium levels of all patients were measured. Bone density at femoral neck and lumbar (L1-L4) regions was measured, using dual energy X-ray absorptiometry (DXA). RESULTS: No significant decrease was detected in the bone density of the subjects treated with L-T4 compared with the control group. CONCLUSION: L-T4 treatment for 1 year is not associated with increased risk of osteoporosis in premenopausal women but other potential adverse effects still need to be monitored in women receiving L-T4 especially long-term.

[Effect of alendronate on periprosthetic bone loss after cemented primary total hip arthroplasty: a prospective randomized study]. / Action de l'Alendronate sur l'état osseux péri-prothétique après prothèse totale de hanche cimentée: étude prospective randomisée en double aveugle.

PURPOSE OF THE STUDY: Bone remodeling and osteolysis around total hip prostheses, with its inevitable corollary, prosthesis loosening, remains a difficult problem in orthopedic surgery. Alendronate (bisphosphonate) has proven its efficacy for the treatment of osteoporosis of the lumbar spine and femoral neck. A few in vitro studies have pointed out its inhibiting effect on particle-induced osteolysis. In vivo, one study has demonstrated its usefulness in preventing osteolysis around non-cemented total hip arthroplasties (THA). The purpose of this work was to study the efficacy of this agent for the prevention of changes in peri-prosthetic bone mineral density (BMD) after primary THA. MATERIAL AND METHODS: The study series included 38 patients with degenerative hip disease who underwent THA. The patients were randomized in double-blind fashion to two treatment arms: 10 alendronate and 600 mg calcium per day for 2 years (20 patients) or placebo and 600 mg calcium per day for 2 years (18 patients). Conventional x-rays and x-ray biphotonic absorptiometry (DPX) was performed on day four postop and at 3, 6, 12, and 24 months postop. The periprosthetic zones described by Grüen were used for analysis. RESULTS: DPX demonstrated a significant reduction in BMD in all patients included in the study. The bone loss was the same in both groups during the early postoperative period reaching maximum loss at 3 months. Differences were observed after this time. In the placebo group, bone loss reached a plateau at 6 months then BMD started to increase progressively, reaching 12.7% bone loss at 2 years follow-up (p<0.002). In the alendronate group, there was no plateau, BMD increased continuously starting from three months and reached 6.857% bone loss at 2 years (p<0.003). DISCUSSION: Administration of alendronate led to a significant reduction in peri-prosthetic bone loss at 2 years follow-up. These results are the first to our knowledge demonstrating the beneficial effect in vivo of alendronate on bone behavior around cemented THAs. CONCLUSION: This beneficial effect observed in vivo should be confirmed in further studies including a larger number of patients and longer follow-up. The action of alendronate could facilitate and even retard revision surgery by preserving bone stock.

Naturally occurring fatal herpes simplex virus 1 infection in a family of white-faced saki monkeys (Pithecia pithecia pithecia).

A family of three white-faced saki monkeys (Pithecia pithecia pithecia) died 48-96 hours after the onset of anorexia, nasal discharge, pyrexia and oral ulceration. One animal also had clonic seizures. Lesions found post-mortem consisted of oral and esophageal ulcers, hepatic and intestinal necrosis, meningoencephalitis and sporadic neuronal necrosis. Intranuclear inclusion bodies and syncytial cells were present in oral lesions and affected areas of liver. Herpes simplex virus 1 (HSV-1) was identified as the etiology of disease by virus isolation, polymerase chain reaction, or in situ hybridization in all three animals. Immunohistochemistry for detection of apoptotic DNA and activated caspase-3 showed significant levels of apoptosis in oral and liver lesions and occasional apoptotic neurons in the brain. These findings demonstrate the vulnerability of white-faced saki monkeys to HSV-1 and provide initial insight into the pathogenesis of fatal HSV-1-induced disease, indicating that apoptosis plays a significant role in cell death.

Age-associated changes in quantitative ultrasonometry (QUS) of the os calcis in Lebanese women-assessment of a Lebanese reference population.

OBJECTIVE: This study was aimed to assess age changes in quantitative ultrasonometry (QUS) in a large sample of Lebanese women to determine a Lebanese reference population. DESIGN: Cross-sectional study. SUBJECTS AND METHODS: Broadband ultrasound attenuation (BUA) and speed of sound (SOS) and the stiffness index (SI) of the os calcaneus was measured in 4,320 women with a mean age of 52.5 years (age range 20 to 79 years) using three identical Achilles Express (GE/Lunar) and one Achilles Plus (GE/Lunar) ultrasonometry devices. Women were randomly selected and asked to participate in a nationwide screening program using the media, conferences, telephone calls etc. Measurements were performed at Red Cross centers located all over the country. No inclusion or exclusion criteria were used. RESULTS: There was an overall decline of 19.2% for BUA, 3.1% for SOS and 30.3% for SI between late adolescence and old age. In premenopausal women, BUA decreased only slightly by 3%, while postmenopausal women showed a significant decline of 16.2%. In contrast, SOS continuously decreased from the age of 42; there was a decline of 0.8% from adolescence to the menopause; postmenopausal women showed a larger decline of 2.4%. The SI of premenopausal women decreased by 6%, while postmenopausal women showed a significantly larger decline of 24.3%. SI value for the female Lebanese young adult reference is 8% lower than that of the American and European women (92 SI units compared to 100). At the age of 42, SI value for the Lebanese women is 10.4% lower than the American women and 7.5% lower than the European women (86 SI units compared to 96 and 93, respectively). At the age of 75, SI values for the Lebanese women is 4.4% lower than the American women and the European women (65 SI units compared to 68). The decline in stiffness index for the Lebanese women between age 20 and 75 years is about 30.3% compared to 32% for the American or European reference curves. The rate of decrease for the Lebanese women was 0.2 SI units per year for the premenopausal period, and 0.7 SI units per year for the postmenopausal period. CONCLUSION: The age-related female, Lebanese reference curve was significantly different from the American and the European reference curves used by the manufacturer. Therefore, the use of our standardized reference data instead of the proposed US or European database reduces the risk of overestimating osteoporosis in the Lebanese population. The impact of our results on the prevalence of osteoporotic fracture in Lebanon has to be evaluated later on.

Osteoporosis: combination therapy for better or worse.

Osteoporosis is a condition that is associated with an increased susceptibility for fractures. In the past few years, several drugs have become available that can reduce the incidence of fractures in patients with osteoporosis. Since these drugs work through different cellular mechanisms, combining agents of different classes may have an additive or multiplicative effect on fracture risk reduction. Combination treatments that have been evaluated in clinical trials include bisphosphonates with estrogen, raloxifene or PTH/ bisphosphonates and PTH/ estrogen. In general, these trials have shown increases in bone mineral density over that observed with each agent alone. However, whether anti-fracture efficacy is improved, or worsened remains to be established. This article reviews the combination treatments that have been evaluated in clinical trials, with a discussion of the potential benefits and risks that those treatments entail. Integrating safety and cost issues will eventually determine whether those combinations will become the standard of care.

Bone mineral density in beta - thalassemic Lebanese children.

Osteoporosis has been described extensively in adult thalassemics. Fewer studies have been reported in thalassemic children. In this article, we measured the bone mineral density (BMD) of Lebanese beta-thalassemic children before institution of a balanced transfusion-chelation regimen, in comparison with that of healthy controls, and studied its correlation with various demographic and biological parameters. Both groups, controls and thalassemics were comparable with respect to age, sex, socioeconomic and regional distribution. On the other hand, thalassemics had a significantly lower height age (p<0.001), lower bone age (p=0.001), lower sexual maturation (p=0.004), lower absolute BMD values and larger negative BMD-Z scores (p<0.001). Within the thalassemic group, BMD correlated significantly with luteinizing hormone (LH) and follicle stimulating hormone (FSH), estradiol and testosterone values, as well as with the pretransfusion hematocrit, but not with other endocrine or bone metabolism parameters. We conclude that Lebanese beta-thalassemic children have a significantly lower BMD than their healthy counterparts due, in part, to their slower physical development. A major contributor seems to be the low-transfusion regimen followed by these patients, as well as the endocrine dysfunction which was detected in about 25% of them.

Molecular modeling, affinity labeling, and site-directed mutagenesis define the key points of interaction between the ligand-binding domain of the vitamin D nuclear receptor and 1 alpha,25-dihydroxyvitamin D3.

We have combined molecular modeling and classical structure-function techniques to define the interactions between the ligand-binding domain (LBD) of the vitamin D nuclear receptor (VDR) and its natural ligand, 1alpha,25-dihydroxyvitamin D(3) [1alpha,25-(OH)(2)D(3)]. The affinity analogue 1alpha,25-(OH)(2)D(3)-3-bromoacetate exclusively labeled Cys-288 in the VDR-LBD. Mutation of C288 to glycine abolished this affinity labeling, whereas the VDR-LBD mutants C337G and C369G (other conserved cysteines in the VDR-LBD) were labeled similarly to the wild-type protein. These results revealed that the A-ring 3-OH group docks next to C288 in the binding pocket. We further mutated M284 and W286 (separately creating M284A, M284S, W286A, and W286F) and caused severe loss of ligand binding, indicating the crucial role played by the contiguous segment between M284 and C288. Alignment of the VDR-LBD sequence with the sequences of nuclear receptor LBDs of known 3-D structure positioned M284 and W286 in the presumed beta-hairpin of the molecule, thereby identifying it as the region contacting the A-ring of 1alpha, 25-(OH)(2)D(3). From the multiple sequence alignment, we developed a homologous extension model of the VDR-LBD. The model has a canonical nuclear receptor fold with helices H1-H12 and a single beta hairpin but lacks the long insert (residues 161-221) between H2 and H3. We docked the alpha-conformation of the A-ring into the binding pocket first so as to incorporate the above-noted interacting residues. The model predicts hydrogen bonding contacts between ligand and protein at S237 and D299 as well as at the site of the natural mutation R274L. Mutation of S237 or D299 to alanine largely abolished ligand binding, whereas changing K302, a nonligand-contacting residue, to alanine left binding unaffected. In the "activation" helix 12, the model places V418 closest to the ligand, and, consistent with this prediction, the mutation V418S abolished ligand binding. The studies together have enabled us to identify 1alpha,25-(OH)(2)D(3)-binding motifs in the ligand-binding pocket of VDR.

Bone mineral density of the Lebanese reference population.

We determined the bone mineral density (BMD) of normal Lebanese subjects and compared results with US/European reference data. The investigation was conducted at one center, and included 858 women and 165 men aged 20-79 years. Spine, femoral and radial BMD measurements were made using dual-energy X-ray absorptiometry. Age-related changes in BMD were similar in form to those of US/European reference data. However, BMD values of Lebanese were generally lower than US/European values. Spine BMD of Lebanese women was about 8% lower than US/European values between ages 20 and 59 years, and 5-6% lower for ages 60-79 years. Femoral neck BMD values for Lebanese women were 8% lower in the young adult years (age 20-39 years), but only 2-3% lower in the postmenopausal years, compared with US/European women. There were smaller postmenopausal decreases in femoral and radial BMD in Lebanese women compared with US/European women, which led to a convergence of BMD after age 70 years. The BMD of Lebanese men was 5-8% lower than US/European values throughout the age range (20-79 years). The effect of weight on BMD ranged from 0.2% to 0.4% per kilogram. Height was not significantly associated with BMD when both height and weight were entered in multiple regression analyses. The prevalence of osteoporosis appeared to be overestimated if the US/European reference data, rather than Lebanese reference data, were used to calculate T-scores.

Homology model for the ligand-binding domain of the human estrogen receptor.

We have modeled the ligand-binding domain (LBD) of the human estrogen receptor protein (hER) by homology to the known crystal structure of the LBD of the alpha isoform of human retinoate-X receptor (hRX). Alignment of hER with members of the nuclear receptor superfamily defined probable secondary structures which we used to constrain backbone torsion angles and hydrogen bonds. From published studies we identified key interactions between hER and estradiol to use to dock the hormone in its ligand-binding pocket. Since the hRX crystal structure corresponds to the unliganded form of the LBD, we adopted the "mousetrap" mechanism proposed by Renaud et al to predict the structure of the E2-bound hER. Refinement by molecular dynamics and energy minimization gave a model which matches well the known facts about the estradiol phamacophore. It also provides a possible explanation for how hER discriminates between estradiol and testosterone.