CYP2R1 polymorphisms are important modulators of circulating 25-hydroxyvitamin D levels in elderly females with vitamin insufficiency, but not of the response to vitamin D supplementation.

We studied the association between CYP2R1 genetic polymorphisms and circulating 25-hydroxyvitamin D [25(OH)D] before and after supplementation with vitamin D3 in 218 elderly. We found differences between 3 and 8 ng/ml in circulating levels at baseline in women but not in the response after 1 year of supplementation. INTRODUCTION: This study evaluated the association between polymorphisms in four single nucleotide polymorphisms (SNPs) of the CYP2R1 gene and 25(OH)D levels before and 1 year after supplementation with two different doses of vitamin D3 (600 IU daily or a dose equivalent to 3750 IU daily), in a cohort of 218 (96 men and 122 women) Lebanese elderly overweight subjects. METHODS: Genotyping was performed for rs12794714, rs10741657, rs1562902, and rs10766197 SNPs using real-time PCR. The 25(OH)D levels were measured by liquid chromatography tandem mass spectrometry. RESULTS: At baseline, the mean ± SD age was 71.0 ± 4.7 years, BMI 30.3 ± 4.6 kg/m2, and 25(OH)D level was 20.5 ± 7.6 ng/ml. There were significant differences in mean 25(OH)D levels between genotypes in women, but not in men. After adjustment for age, season, and BMI, the homozygous for the low frequency gene variant (HLV) of rs1562902 and rs10741657 SNPs had the highest mean 25(OH)D levels with difference of 7.6 ng/ml for rs1562902 SNP (p < 0.01) and of 5.9 ng/ml for rs10741657 (p = 0.05) compared to the homozygous for the major polymorphisms (HMPs). Conversely, for rs10766197 and rs12794714 SNPs, HMP had the highest mean 25(OH)D levels with difference of 6 ng/ml for rs10766197 (p = 0.003) and of 4.8 ng/ml (p = 0.02) for rs12794714, compared to the HLV. CYP2R1 genetic polymorphisms explained 4.8 to 9.8 % of variability in 25(OH)D in women. After 1 year, there was no difference in the response to vitamin D3 supplementation between genotypes in either gender. CONCLUSION: This study showed a difference in 25(OH)D levels between CYP2R1 genotypes that equates a daily supplementation of 400-800 IU vitamin D, depending on genotype. It underscores possible important genetic contributions for the high prevalence of hypovitaminosis D in the Middle East.

PTH level but not 25 (OH) vitamin D level predicts bone loss rates in the elderly.

UNLABELLED: We assessed the impact of calciotropic hormones on bone loss in 195 elderly subjects. After a median follow up of 4 years, parathyroid hormone (PTH) correlated negatively with changes in bone mineral density (BMD) at all skeletal sites. After adjustment for potential predictors of bone loss in the elderly, PTH level alone explained 3% of the variance in BMD changes at the hip. INTRODUCTION: This study assessed the impact of calciotropic hormones on bone loss rates in an elderly population-based cohort of 195 ambulatory men and women, aged 65-85 years and followed up for a median of 4 years. METHODS: Calcium intake, serum calcium, and phosphorus were assessed at baseline. Serum creatinine was measured at follow up visit. The 25 (OH) vitamin D [25-OHD] and PTH were measured at baseline and at follow up. Bone mass at the lumbar spine, hip, forearm and total body, as well as body composition was measured at baseline and at follow up by dual energy X-ray absorptiometry. RESULTS: Mean 25-OHD level was 14.7 ± 6.4 ng/ml and mean PTH level was 47.9 ± 30.4 pg/ml. Age correlated negatively with percent changes in BMD at all skeletal sites (p < 0.05). Changes in body mass index (BMI) and in body composition correlated positively with BMD changes at all sites, except at the forearm. There was no correlation between 25-OHD and changes in BMD except at the trochanter (r = 0.19, p < 0.008). Conversely, PTH negatively correlated with changes in BMD at all skeletal sites (r = -0.14 to -0.27, p < 0.05). This correlation persisted after adjustment for age, changes in BMI, changes in fat mass and lean mass, serum creatinine, calcium intake, and 25-OHD levels. PTH level alone explained 3% of the variance in BMD changes at all hip subregions. CONCLUSIONS: Serum PTH, but not 25-OHD, predicted bone loss rates in the elderly. Thus, it is important to normalize PTH level when correcting hypovitaminosis D in the elderly.

Osteoporotic fractures, DXA, and fracture risk assessment: meeting future challenges in the Eastern Mediterranean Region.

The purpose was to report on the burden of osteoporotic fractures in the Eastern Mediterranean Region (EMR) and the use of bone mineral density (BMD) dual-energy X-ray absorptiometry (DXA) databases for osteoporosis diagnosis. PubMed electronic database was reviewed using the following MeSH terms: "Hip fractures," "Fractures, Compression," "Radius Fractures," "Osteoporosis," "Bone density," and "Middle East" up to July 2009. Incidence of hip fractures varied across the EMR between 100 and 295 per 100,000 person-years in women and 71 and 200 per 100,000 person-years in men. No data were found on other nonvertebral osteoporotic fractures. Prevalence of radiographic vertebral fractures older than 65 yr ranged between 15% and 25% in women and 7.3% and 18% in men. By 2020, the number of hip fractures older than 50 yr would increase by 20%. DXA manufacturer's reference curves for the spine were higher than population-specific ones. At the hip, National Health and Nutrition Examination Survey (NHANES) and population-based curves were comparable. Estimates of the relative risk of vertebral fracture per SD decrease in BMD using NHANES and local data set were similar, that is, 1.61 (1.17-2.23) and 1.49 (1.14-1.95), respectively. The EMR is similar to southern Europe regarding incidence rates of hip fracture, suggesting the health burden to be significant. Using DXA at the hip, population-specific reference databases did not perform better than NHANES on which the FRAX model has been developed highlighting the need for reviewing fracture risk assessment strategies in the EMR.

An audit of bone densitometry practice with reference to ISCD, IOF and NOF guidelines.

INTRODUCTION: The impact of osteoporosis guidelines on clinical practice has not been fully evaluated. OBJECTIVES: To estimate the positive predictive value (PPV) of the National Osteoporosis Foundation (NOF), the International Osteoporosis Foundation (IOF) and the International Society for Clinical Densitometry (ISCD) guidelines for osteoporosis and compare it to the PPV of clinical judgement alone. METHODS: All subjects tested for bone mineral density during the fall of 2001 in three teaching hospitals in Beirut were invited to participate. The reference databases used for the calculation of the T-score were the NHANES database for the hip and the manufacturer's database for the spine. The impact of using guidelines was measured by the increment in PPV. Osteoporosis was defined as a T-score < or =-2.5 at either the spine or hip. RESULTS: A total of 307 post-menopausal women were tested with dual-energy X-ray absorptiometry (DXA). In current practice (clinical judgement alone), the PPV for osteoporosis was 42.4%; using NOF guidelines, 236 women would have been tested, and the PPV would have been 46.2%. Similarly, using IOF or ISCD guidelines, 236 women would have been tested, and the PPV would have been 47.1%. CONCLUSION: Compared to current clinical practice, application of the ISCD, IOF and NOF guidelines may increase the predictive value of a central DXA for osteoporosis.

Overweight children in Beirut: prevalence estimates and characteristics.

OBJECTIVE: To estimate, for the first time, overweight prevalence and associated characteristics in a representative sample of prepubertal children in Beirut, Lebanon's capital. DESIGN: A cross-sectional study with a home interview including measurements of weight and height and a structured questionnaire. SUBJECTS: A total of 234 children aged 6-8 years in Beirut: 131 boys, 103 girls. METHODS: Prevalence of overweight and obesity was based on the international cut-off points for body mass index (BMI) by age and gender proposed by the International Obesity Task Force. The characteristics of overweight examined were: age, gender, household and family size, single- vs. two-parent family, parents' level of education and profession, physical activity and dietary intake of children. RESULTS: Prevalence of overweight and obesity was 26% and 7% respectively in boys, 25% and 6% in girls. Overweight was significantly associated with low physical activity (P < 0.05) and mother's BMI (P < 0.05). CONCLUSIONS: This study identified a high proportion of overweight in 6- to 8-year-old children in Beirut. Reduced physical activity was the most significant factor associated with childhood overweight. Further studies in different regions in Lebanon are necessary to identify national characteristics; prevention efforts will be designed accordingly.

Effects of a short-term calcium and vitamin D treatment on serum cytokines, bone markers, insulin and lipid concentrations in healthy post-menopausal women.

In vitro studies have shown that 1,25 dihydroxyvitamin D3 [1,25(OH)2D3] decreases cytokine production by monocytes and lymphocytes. In addition, intravenous or oral pulse calcitriol treatment suppresses interleukin 6 (IL6) and interleukin1beta (IL1beta) in hemodialysis patients. We studied the effect of a daily 12-week course of 1000 mg calcium and 800 U cholecalciferol on circulating 25 hydroxyvitamin D [25(OH)D], PTH, cytokines, osteoprotegerin (OPG), C-reactive protein (CRP), bone markers, lipid parameters and insulin levels in 47 healthy post-menopausal women. Thirty-nine women completed the study. A significant increase in 25(OH)D and a significant decrease in PTH were observed (p=0.0043 and p<0.0001, respectively). In addition, alkaline phosphatase, osteocalcin and, to a lesser extent, urinary free deoxypiridinoline (DPD) decreased significantly (p<0.0001, p=0.0002 and p=0.026, respectively). No change in circulating IL6, tumor necrosis factor alpha (TNFalpha), CRP, OPG, triglycerides, LDL- and HDL-cholesterol, and insulin levels was observed. Correlation studies in the 47 women enrolled in the study revealed inverse significant correlations between OPG on one side and body mass index, LDL-cholesterol, IL6, CRP and insulin levels on the other (p=0.002, p=0.002, p=0.004, p=0.023 and p=0.0001). Also, IL6 was significantly correlated with insulin levels (p=0.0005). In a multivariate model, both insulin and LDL-cholesterol were independently associated with OPG, while only insulin was independently associated with IL6. Our results showed no effect of a short-term calcium-vitamin D treatment on circulating cytokines, CRP, insulin levels and lipid parameters. This could be related to the low circulating cytokine concentrations in healthy subjects or to the short duration of treatment. The interesting association we found between OPG and some cardiovascular risk markers deserves further investigation.

Low peak bone mineral density in healthy Lebanese subjects.

Osteoporosis is a major public health problem in Western countries and is projected to have a similar impact in the Middle East. It has been suggested that peak bone mineral density (BMD), a major determinant of osteoporotic fractures later in life, may be lower in this part of the world compared with the Western world. However, subjects have not been randomly selected or systematically screened to rule out secondary causes of bone loss. The purpose of this study was to determine peak bone mass and lifestyle risk factors for bone loss in a randomly chosen sample of healthy Lebanese subjects from the greater Beirut area. Subjects 25-35 years of age were randomly selected from greater Beirut, which comprises one third of the Lebanese at large, and studied during the Fall of 1999. BMD was measured at the lumbar spine, hip, forearm, and total body. A questionnaire on lifestyle factors was administered to all subjects. Results were compared with the database of subjects from the USA provided by the manufacturer, and to the NHANES database for the total hip. Two hundred thirteen subjects were studied; 45 subjects rotated at all three centers for cross-calibration purposes. Peak BMD in Lebanese subjects was 0.2-0.9 SD below that of peak BMD in American subjects, depending on skeletal site, gender, and densitometer. These differences persisted after attempting to adjust for body size. Osteoporosis and osteopenia were more prevalent than in healthy young Americans. Height, weight, and total body fat were the most significant correlates of BMD/bone mineral content (BMC), accounting for 0.3-0.7 of the variance in bone mass measurement. Lifestyle factors had a very modest but significant contribution to bone mass variance. This is the first population-based study from the Middle East demonstrating that peak BMD is slightly lower in Lebanese subjects compared as with an established database from the USA. Due to the selection of relatively healthier subjects in our study than in the NHANES study, the actual differences between the two populations may be even greater. The impact of our findings on the epidemiology of osteoporotic fractures in Lebanon remains to be determined.

Hepatitis B and C seroprevalence in the Lebanese population.

We aimed to evaluate exposure to hepatitis B and C viruses (HBV and HBC) and candidate risk factors among the Lebanese population. All individuals presenting to all laboratory units in the country over a 2-week period were asked for a 5-mL whole blood sample and answered a questionnaire addressing risk factors. For individuals under 15 years of age the mother was interviewed. In all, 2893 blood samples were examined. Refusal rate was 2.9%. Exposure to HBV antigen was 18.9%; 1.9% were carriers and acute hepatitis B point prevalence was 0.1%. Exposure to HCV antigen was 0.7%. Exposure to both HBc and HCV antibodies was 0.2%. HBc prevalence increased with age and was higher among men. Significant risk factors included blood transfusion, haemodialysis and gastrointestinal endoscopy.

[Incidence of fractures after the age of 50 years in the Lebanese population and implications in terms of osteoporosis]. / Incidence fracturaire après 50 ans et implications en termes d'ostéoporose dans la population libanaise.

BACKGROUND: No comprehensive population-based data is available on the incidence of fractures in Lebanon and the Middle-East. The aim of this study was to estimate the incidence of osteoporotic fractures in the Lebanese population aged 50 years and over. METHODS: In 1997, a cross-sectional population-based random sample of individuals aged 50 years and over was selected using a multiple level cluster sampling technique. Selected individuals responded to an Arabic version of the EULAR questionnaire. A fracture was defined as incident if it had occurred within the last year. The lifetime risk of osteoporotic fracture was estimated using the incidence rate by ten-year age groups assuming that each individual counts on the average for half the interval. RESULTS: 1003 individuals were included. There were 496 men (49.5%) and 507 women (50.5%). Mean age was 61.3 years (CI: 60.8-61.8) with a maximum of 88 years. The observed number of fractures was 111, giving an absolute risk of osteoporotic fractures of 11.1% (CI: 9.1-12.9). It was higher in women, 13.0% (CI: 10.9-15.1) than in men, 8.6% (CI: 6.9-9.3). Female to male ratio was 1.6. The estimated annual incidence was 2.6% (CI: 2.0-3.2), higher in women, 3.8% (CI: 2.2-5.5) than in men, 1.4% (CI: 0.4-2.5). Incident cases were distributed as follows: 4-hip, 4-forearm, 3-spine, and 15 other sites. Annual incidence was higher in women than in men for all sites. Estimated lifetime risk of osteoporotic fracture was 9.3% (CI: 6.7-11.9) in men and 16.7% (CI: 13.4-19.9) in women. CONCLUSION: Our figures are lower than those found in Northern Europe but are higher than in Asian countries, possibly reflecting a west-east gradient in risk factors.

Incidence of hip fractures in the Lebanese population.

This is the first prospective study to estimate the incidence of hip fractures in the general population in Lebanon. All orthopaedic surgeons in Beirut reported on hip fracture cases between 1 October and 31 December 1996. Data were extrapolated to 1 year and standardized for the whole population. The estimated annual incidence rate was 0.129% (women: 0.153%, men: 0.100%), increasing with age and remaining higher in women. Our figures are comparable with larger studies in other Mediterranean countries. The incidence rate of hip fractures in our population falls within a gradient of risk between the west and the east and the north and the south, highlighting the importance of environmental and genetic factors as risk factors for osteoporotic fractures.

Prevalence of tobacco use among the adult Lebanese population.

To determine the prevalence of smoking in Lebanon, 727 individuals aged > or = 19 years were randomly selected for study using Emile Roux and Fagerstrom questionnaires. Smokers were defined as those answering "yes" to the question, "Do you currently smoke?" A Fagerstrom score > or = 6 indicated strong nicotine addiction. The prevalence of smoking was 53.6%. The male/female ratio was 1.23, with 67.0% of smokers categorized as addicted. Failure to quit was related to withdrawal symptoms, mostly irritability (57%) and weight gain (20%). Recommendations are given for combating this high prevalence of tobacco use.

Clinical, radiological, and laboratory findings in Lebanese spondylarthropathy patients according to HLA-B27 status.

UNLABELLED: To evaluate clinical, radiologic, and laboratory features in Lebanese spondylarthropathy patients according to HLA-B27 status. METHODS: We retrospectively compared demographic, clinical, radiologic, and severity data in 40 HLA-B27-positive and 58 HLA-B27-negative patients. All 98 patients met Amor's or European Spondylarthropathy Study Group criteria for spondylarthropathy, and 51.7% met New York modified criteria for ankylosing spondylitis. RESULTS: Onset before 16 years of age, hip involvement, and an elevated mean erythrocyte sedimentation rate were significantly associated with the presence of the HLA-B27 (32.5 vs 13.8%, P=0.02; 45 vs 7.5%, P=0.001; and 47.7 vs 25.4, P=0.02; respectively). The two groups were comparable for age, sex ratio, prevalence and distribution of spondylarthropathy types, family history, sacroiliitis, bamboo spine, syndesmophytes, peripheral joint involvement, enthesopathies, extra-articular involvement, response to nonsteroidal anti-inflammatory drugs, and need for other medications. CONCLUSION: In Lebanon, spondylarthropathy patients positive for HLA-B27 experience disease onset at an earlier age, are more likely to develop hip involvement, and have laboratory evidence of more severe inflammation than their HLA-B27-negative counterparts. None of the other clinical and radiologic parameters are modified by HLA-B27 status.

A general population survey on patterns of benzodiazepine use and dependence in Lebanon.

OBJECTIVE: In Lebanon, benzodiazepines are often available without medical prescription. We aimed to carry out the first community-based pharmaco-epidemiological study on benzodiazepine consumption in the Middle East Area. METHOD: The prevalence of past-month benzodiazepine use was assessed in a 1000-subject randomized sample from the Lebanese community, and risk factors were studied in a group of 496 current users. RESULTS: Benzodiazepine use during the past month was found in 9.6% of subjects. Four variables were significantly associated with use: age higher than 45 years, female sex, cigarette smoking and the existence of a recent life event. Benzodiazepine dependence was found in 50.2% of users. CONCLUSION: Benzodiazepine use in Lebanon is particularly high, and can be related to well-known factors such as female sex and age, but other potent specific variables, such as war stress or the lack of control on drug access, can be hypothesized.

[Epidemiological study of hyperlipemia in a Lebanese population]. / Etude épidémiologique des hyperlipémies dans une population libanaise.

An epidemiological study was conducted on 500 persons (60% women and 40% men) from the medico-technical staff of the "Hôtel-Dieu de France" (Lebanon center for hospitalization and medical formation) in order to establish the lipid profile of the Lebanese population. The following results were obtained (mean values): total cholesterol 5.27 mmol/l (SD = 1.04), HDLc 1.28 mmol/l (SD = 0.40), LDLc 3, 31mmol/l (SD = 0.94), Triglycerides 1.55 mmol/l (SD = 1.55), glucose 5 mmol/l (SD = 0.80), Fibrinogen 3.09 g/l (SD = 0.67) and Lipoprotein (a) 0.20 g/l (SD = 0.253) with 20% of the population having Lp(a) values greater than 0.3 g/l. The distribution of these parameters in regard to the sex, age, Lebanese regions origin, body mass index and the waist to hips ratio, as well as tobacco consumption, alimentary habits, personal and familial history of dyslipidemia or coronary diseases, are reported. The results of Lp(a) measurements and correlations to other parameters confirm its importance as an independent risk factor for coronary problems. The significant percentage of subjects with lipid levels higher than those recommended by the NCEP, 19% for total cholesterol, 27% for LDL cholesterol and 20% for Lp(a), has to be seriously considered.

Validation of the European Spondylarthropathy Study Group and B. Amor criteria for spondylarthropathies in Lebanon.

OBJECTIVES: 1) To validate European Spondylarthropathy Study Group (ESSG) and B. Amor's criteria for spondylarthropathies in Lebanon. 2) To evaluate the frequency of spondylarthropathies in rheumatological practice in Lebanon. PATIENTS AND METHODS: Cases of definite and probable spondylarthropathy were diagnosed based on the clinical judgement of participating rheumatologists, without reference to the two criteria sets under study. The first two patients without spondylarthropathy seen after each spondylarthropathy case were included into the control group. Criteria in the ESSG and B. Amor sets were looked for in the patient and control groups. The frequency of spondylarthropathy meeting each criteria set was determined. RESULTS: Of the 841 patients evaluated during the study period, 68 met B. Amor's criteria and 72 met ESSG criteria. There were 29 cases of ankylosing spondylitis (40.3%), ten of peripheral psoriatic arthritis (13.8%), two of reactive arthritis (2.8%), two of enteropathic arthropathy (2.8%), and 29 of undifferentiated spondylarthropathy (40.3%). In the definite spondylarthropathy group, sensitivity and specificity were 77.19% and 97.55% for B. Amor's criteria versus 91.23% and 100% for ESSG criteria. The frequency of spondylarthropathy was 8.1% (95% confidence interval [CI], 6.3-9.9) or 8.56% (CI 6.6-10.5) according to B. Amor and ESSG criteria, respectively. CONCLUSION: Our data validate both criteria sets in the Lebanese population, demonstrating that they are useful in populations that are genetically different from the European populations used to develop them. Spondyloarthropathy is the most common in our rheumatology practice.

[Validation of choice of experts for the spondylarthropathy study in Lebanon]. / Validation du choix d'experts pour l'étude des spondylarthropathies au Liban.

A study of the spondylarthropathies, their recent diagnostic criteria and the prevalence of HLA B27 in these affections in Lebanon will soon be started. Experts will have to include patients, prospectively, and to classify them as having or not a spondylarthropathy, according solely to their clinical judgement. The decision of the expert is of major importance in including patients in the study. We performed a clinical evaluation of inter-observer variability to select experts according to a significant concordance in the clinical diagnosis of different rheumatic diseases, especially spondylarthropathies. Results of the evaluation are presented and discussed.

[Value of the light-test histological study in photodermatoses]. / Intérêt de l'étude histologique du phototest dans les photodermatoses.

Clinic and histologic analysis of 92 phototests of various photodermatosis (14 benign summer light eruption (BSLE), 47 polymorphous light eruption (PMLE) 20 persistent light reactor photodermatitis (PLRP), 11 drug induced photodermatitis (DIP) has been performed. Clinically, a phototoxic aspect was observed in 30 cases, it was photoallergic in 36 cases and uncertain in 26 cases. Histologically, a phototoxic picture was present in 32 cases, a photoallergic one in 48 cases, and 12 cases exhibited unclassified aspect. Only one case of BSLE was associated with photoallergic aspect, clinically and histologically. Photoallergic type was observed in 70 p. 100 of iterative exposure phototest (IEP) of PMLE; clinical and histological aspects were concordant; in contrast phototoxic aspects were constantly observed when single exposure phototest (SEP) were used. In PLRP histological aspect of IEP was constantly of photoallergic type; whereas clinical aspect was uncertain in 50 p. 100 of the cases; 7 of the 10 biopsies of SEP exhibited a photoallergic picture. In DIP histological aspect of IEP was constantly photoallergic, whereas 5 of the 6 cases exhibited uncertain clinical aspect; only one of the 5 SEP gave a photoallergic reaction both clinically and histologically. Comparison of histological features revealed a more typical photoallergic picture in PLRP than in PMLE. We conclude that: the reproducibility of clinical and histological lesions is better with the iterative exposure phototest than with single exposure phototest; histologic examination is more reliable than clinical findings in persistent light reactor photodermatitis and drug induced photodermatitis.